Patrice Wendling

CHICAGO – Switching from conventional to small-volume phlebotomy tubes is an easy step toward reducing iatrogenic blood loss in critically ill adults, a new study suggests.

“We were looking at the amount of blood we were drawing off these patients and when we asked the nurses, the numbers were crazy. It could be as high as 20 mL per time that they drew off the patient and we felt we had to do better. The common sense dictum is the more blood you draw off, the more harm you are causing the patient,” principal investigator Dr. Heather Dolman from Detroit Receiving Hospital, Wayne State University, said in an interview.

For patients staying only a day or 2 at the hospital, the type of blood tube used may not make a difference. But for the critically ill, who studies suggest can have an average of 5 to more than 24 samples drawn a day, the cumulative blood loss over an extended stay can be sizable.

Clinicians are also inclined to order more diagnostic tests as the severity of illness increases, thus putting their sickest patients at the greatest risk of iatrogenic anemia and transfusion. Anemia secondary to phlebotomy accounts for up to 40% of packed red blood cells transfused, Dr. Dolman noted at the annual meeting of the Central Surgical Association.

The process of blood sampling itself also involves a fair amount of waste. Conventional arterial line systems require that an initial blood sample be removed to “clear the line.” This typically results in 2-10 mL of blood being discarded before a second sample of undiluted blood can be obtained.

©Martynasfoto/thinkstockphotos.com

Some hospitals have turned to closed blood sampling devices that avoid the need for a second sample. The impact of blood-conserving devices on transfusion rates has been underwhelming, with only one study showing a positive impact leading to reduced blood product use.

As part of their blood-conserving strategy, Dr. Dolman and her colleagues asked the hospital to invest in small-volume phlebotomy tubes (SVTs), which are sized somewhere between a conventional-volume tube (CVT) and a pediatric blood tube.

SVTs reduce the amount of blood needed from 8.5 mL with a conventional tube to 5.0 mL for a basic metabolic panel, from 6.0 mL to 2.0 mL for a complete blood count (CBC) or cross-matching, and from 2.7 mL to 1.8 mL for a prothrombin time /internationalized ratio/partial thromboplastin time, Dr. Dolman said. The cost of an SVT is the same as a CVT, as is the cost of the machinery needed to analyze the samples.

“Everyone is worried about missing out on data, but if you look at the research on the amount of blood the machine really needs, it is only 0.1 mL, that’s less than a cc,” she said. “The technology has been there for a while, I just think the common sense aspect of all this, no one has ever thought of.”

The investigators then retrospectively compared 248 critically ill patients in the ICU, of whom 116 had blood drawn with an SVT and 132 with a CVT. The two groups were well matched with respect to age (55 years vs. 57 years), admission to the emergency surgery/trauma service (63% vs. 64%), and mean APACHE II scores (14.1 vs. 12.7).

Transfusion was at the discretion of the primary team using a restrictive hemoglobin threshold of < 7.0 gm/dL, unless hemodynamic instability or active bleeding were present.

Utilizing an SVT significantly reduced daily blood loss from phlebotomy from 31.7 mL with a CVT to 22.5 mL (P < .0001) and overall phlebotomy blood loss from 299 mL to 174 mL (P < .001), Dr. Dolman reported.

This translated into a nonsignificant trend for fewer units of packed red blood cells transfused in the SVT group (mean 4.4 vs. 6.0; P = .16).

The same pattern was observed in the 158 patients admitted to the emergency surgery/trauma service, with SVT also leading to significantly fewer episodes of severe anemia (6 vs. 20; P = .01) and a trend toward shorter ICU stays (9.2 days vs. 10.6 days; P = .46), she said.

Patients with an APACHE score of at least 20, a group one would anticipate to derive greater advantage from a blood-conserving strategy, did not benefit from use of an SVT vs. a CVT, but the number of patients was very low at just 27 and 19, respectively, Dr. Dolman noted.

Anemia, however, had a profound impact on the critically ill cohort. Patients with severe anemia were significantly more likely than those with a hemoglobin level of at least 7 gm/dL to have longer ICU stays (16 days vs. 7.7 days; P < .001), longer hospital stays (23.3 days vs. 13.6 days; P < .001), and to die in the hospital (29% vs. 13%; P = .01).

Using a small-volume tube cut the number of patients with more than one episode of severe anemia from 22 to 11 (P = .01) and those with more than two episodes from 6 to 4 (P = .53).

“Anemia in the critically ill is a significant problem,” Dr. Dolman said. “Phlebotomy waste contributes to anemia and should be recorded to decrease this hidden loss.”

The impact of transfusion vs. no transfusion was less pronounced with respect to ICU stay (12 days vs. 6 days; P < .001), hospital stay (19 days vs. 11 days; P = .44), and in-hospital mortality (17% vs. 15%; P = .60), but can lead to other negative sequelae such as increased risk of infection, circulatory overload transfusion reactions, and immune modulation, she added.

Detroit Receiving Hospital continues to use conventional tubes in its ICU and other units, although a switch to small-volume tubes is expected to be considered following peer review of the full results, Dr. Dolman said.

Dr. Dolman reported having no financial disclosures.

[email protected]

On Twitter @pwendl

CHICAGO – Switching from conventional to small-volume phlebotomy tubes is an easy step toward reducing iatrogenic blood loss in critically ill adults, a new study suggests.

“We were looking at the amount of blood we were drawing off these patients and when we asked the nurses, the numbers were crazy. It could be as high as 20 mL per time that they drew off the patient and we felt we had to do better. The common sense dictum is the more blood you draw off, the more harm you are causing the patient,” principal investigator Dr. Heather Dolman from Detroit Receiving Hospital, Wayne State University, said in an interview.

For patients staying only a day or 2 at the hospital, the type of blood tube used may not make a difference. But for the critically ill, who studies suggest can have an average of 5 to more than 24 samples drawn a day, the cumulative blood loss over an extended stay can be sizable.

Clinicians are also inclined to order more diagnostic tests as the severity of illness increases, thus putting their sickest patients at the greatest risk of iatrogenic anemia and transfusion. Anemia secondary to phlebotomy accounts for up to 40% of packed red blood cells transfused, Dr. Dolman noted at the annual meeting of the Central Surgical Association.

The process of blood sampling itself also involves a fair amount of waste. Conventional arterial line systems require that an initial blood sample be removed to “clear the line.” This typically results in 2-10 mL of blood being discarded before a second sample of undiluted blood can be obtained.

©Martynasfoto/thinkstockphotos.com

Some hospitals have turned to closed blood sampling devices that avoid the need for a second sample. The impact of blood-conserving devices on transfusion rates has been underwhelming, with only one study showing a positive impact leading to reduced blood product use.

As part of their blood-conserving strategy, Dr. Dolman and her colleagues asked the hospital to invest in small-volume phlebotomy tubes (SVTs), which are sized somewhere between a conventional-volume tube (CVT) and a pediatric blood tube.

SVTs reduce the amount of blood needed from 8.5 mL with a conventional tube to 5.0 mL for a basic metabolic panel, from 6.0 mL to 2.0 mL for a complete blood count (CBC) or cross-matching, and from 2.7 mL to 1.8 mL for a prothrombin time /internationalized ratio/partial thromboplastin time, Dr. Dolman said. The cost of an SVT is the same as a CVT, as is the cost of the machinery needed to analyze the samples.

“Everyone is worried about missing out on data, but if you look at the research on the amount of blood the machine really needs, it is only 0.1 mL, that’s less than a cc,” she said. “The technology has been there for a while, I just think the common sense aspect of all this, no one has ever thought of.”

The investigators then retrospectively compared 248 critically ill patients in the ICU, of whom 116 had blood drawn with an SVT and 132 with a CVT. The two groups were well matched with respect to age (55 years vs. 57 years), admission to the emergency surgery/trauma service (63% vs. 64%), and mean APACHE II scores (14.1 vs. 12.7).

Transfusion was at the discretion of the primary team using a restrictive hemoglobin threshold of < 7.0 gm/dL, unless hemodynamic instability or active bleeding were present.

Utilizing an SVT significantly reduced daily blood loss from phlebotomy from 31.7 mL with a CVT to 22.5 mL (P < .0001) and overall phlebotomy blood loss from 299 mL to 174 mL (P < .001), Dr. Dolman reported.

This translated into a nonsignificant trend for fewer units of packed red blood cells transfused in the SVT group (mean 4.4 vs. 6.0; P = .16).

The same pattern was observed in the 158 patients admitted to the emergency surgery/trauma service, with SVT also leading to significantly fewer episodes of severe anemia (6 vs. 20; P = .01) and a trend toward shorter ICU stays (9.2 days vs. 10.6 days; P = .46), she said.

Patients with an APACHE score of at least 20, a group one would anticipate to derive greater advantage from a blood-conserving strategy, did not benefit from use of an SVT vs. a CVT, but the number of patients was very low at just 27 and 19, respectively, Dr. Dolman noted.

Anemia, however, had a profound impact on the critically ill cohort. Patients with severe anemia were significantly more likely than those with a hemoglobin level of at least 7 gm/dL to have longer ICU stays (16 days vs. 7.7 days; P < .001), longer hospital stays (23.3 days vs. 13.6 days; P < .001), and to die in the hospital (29% vs. 13%; P = .01).

Using a small-volume tube cut the number of patients with more than one episode of severe anemia from 22 to 11 (P = .01) and those with more than two episodes from 6 to 4 (P = .53).

“Anemia in the critically ill is a significant problem,” Dr. Dolman said. “Phlebotomy waste contributes to anemia and should be recorded to decrease this hidden loss.”

The impact of transfusion vs. no transfusion was less pronounced with respect to ICU stay (12 days vs. 6 days; P < .001), hospital stay (19 days vs. 11 days; P = .44), and in-hospital mortality (17% vs. 15%; P = .60), but can lead to other negative sequelae such as increased risk of infection, circulatory overload transfusion reactions, and immune modulation, she added.

Detroit Receiving Hospital continues to use conventional tubes in its ICU and other units, although a switch to small-volume tubes is expected to be considered following peer review of the full results, Dr. Dolman said.

Dr. Dolman reported having no financial disclosures.

[email protected]

On Twitter @pwendl

CHICAGO – Switching from conventional to small-volume phlebotomy tubes is an easy step toward reducing iatrogenic blood loss in critically ill adults, a new study suggests.

“We were looking at the amount of blood we were drawing off these patients and when we asked the nurses, the numbers were crazy. It could be as high as 20 mL per time that they drew off the patient and we felt we had to do better. The common sense dictum is the more blood you draw off, the more harm you are causing the patient,” principal investigator Dr. Heather Dolman from Detroit Receiving Hospital, Wayne State University, said in an interview.

For patients staying only a day or 2 at the hospital, the type of blood tube used may not make a difference. But for the critically ill, who studies suggest can have an average of 5 to more than 24 samples drawn a day, the cumulative blood loss over an extended stay can be sizable.

Clinicians are also inclined to order more diagnostic tests as the severity of illness increases, thus putting their sickest patients at the greatest risk of iatrogenic anemia and transfusion. Anemia secondary to phlebotomy accounts for up to 40% of packed red blood cells transfused, Dr. Dolman noted at the annual meeting of the Central Surgical Association.

The process of blood sampling itself also involves a fair amount of waste. Conventional arterial line systems require that an initial blood sample be removed to “clear the line.” This typically results in 2-10 mL of blood being discarded before a second sample of undiluted blood can be obtained.

©Martynasfoto/thinkstockphotos.com

Some hospitals have turned to closed blood sampling devices that avoid the need for a second sample. The impact of blood-conserving devices on transfusion rates has been underwhelming, with only one study showing a positive impact leading to reduced blood product use.

As part of their blood-conserving strategy, Dr. Dolman and her colleagues asked the hospital to invest in small-volume phlebotomy tubes (SVTs), which are sized somewhere between a conventional-volume tube (CVT) and a pediatric blood tube.

SVTs reduce the amount of blood needed from 8.5 mL with a conventional tube to 5.0 mL for a basic metabolic panel, from 6.0 mL to 2.0 mL for a complete blood count (CBC) or cross-matching, and from 2.7 mL to 1.8 mL for a prothrombin time /internationalized ratio/partial thromboplastin time, Dr. Dolman said. The cost of an SVT is the same as a CVT, as is the cost of the machinery needed to analyze the samples.

“Everyone is worried about missing out on data, but if you look at the research on the amount of blood the machine really needs, it is only 0.1 mL, that’s less than a cc,” she said. “The technology has been there for a while, I just think the common sense aspect of all this, no one has ever thought of.”

The investigators then retrospectively compared 248 critically ill patients in the ICU, of whom 116 had blood drawn with an SVT and 132 with a CVT. The two groups were well matched with respect to age (55 years vs. 57 years), admission to the emergency surgery/trauma service (63% vs. 64%), and mean APACHE II scores (14.1 vs. 12.7).

Transfusion was at the discretion of the primary team using a restrictive hemoglobin threshold of < 7.0 gm/dL, unless hemodynamic instability or active bleeding were present.

Utilizing an SVT significantly reduced daily blood loss from phlebotomy from 31.7 mL with a CVT to 22.5 mL (P < .0001) and overall phlebotomy blood loss from 299 mL to 174 mL (P < .001), Dr. Dolman reported.

This translated into a nonsignificant trend for fewer units of packed red blood cells transfused in the SVT group (mean 4.4 vs. 6.0; P = .16).

The same pattern was observed in the 158 patients admitted to the emergency surgery/trauma service, with SVT also leading to significantly fewer episodes of severe anemia (6 vs. 20; P = .01) and a trend toward shorter ICU stays (9.2 days vs. 10.6 days; P = .46), she said.

Patients with an APACHE score of at least 20, a group one would anticipate to derive greater advantage from a blood-conserving strategy, did not benefit from use of an SVT vs. a CVT, but the number of patients was very low at just 27 and 19, respectively, Dr. Dolman noted.

Anemia, however, had a profound impact on the critically ill cohort. Patients with severe anemia were significantly more likely than those with a hemoglobin level of at least 7 gm/dL to have longer ICU stays (16 days vs. 7.7 days; P < .001), longer hospital stays (23.3 days vs. 13.6 days; P < .001), and to die in the hospital (29% vs. 13%; P = .01).

Using a small-volume tube cut the number of patients with more than one episode of severe anemia from 22 to 11 (P = .01) and those with more than two episodes from 6 to 4 (P = .53).

“Anemia in the critically ill is a significant problem,” Dr. Dolman said. “Phlebotomy waste contributes to anemia and should be recorded to decrease this hidden loss.”

The impact of transfusion vs. no transfusion was less pronounced with respect to ICU stay (12 days vs. 6 days; P < .001), hospital stay (19 days vs. 11 days; P = .44), and in-hospital mortality (17% vs. 15%; P = .60), but can lead to other negative sequelae such as increased risk of infection, circulatory overload transfusion reactions, and immune modulation, she added.

Detroit Receiving Hospital continues to use conventional tubes in its ICU and other units, although a switch to small-volume tubes is expected to be considered following peer review of the full results, Dr. Dolman said.

Dr. Dolman reported having no financial disclosures.

[email protected]

On Twitter @pwendl

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

CHICAGO – Mesenteric stenting has replaced open surgery as first-line treatment for chronic mesenteric ischemia, but it is still a therapy in flux.

Controversy exists over single- versus multivessel revascularization when both the celiac artery (CA) and superior mesenteric artery (SMA) are diseased and symptoms are consistent with chronic mesenteric ischemia (CMI), Dr. Jean Panneton said at a symposium on vascular surgery sponsored by Northwestern University.

Patrice Wendling/Frontline Medical News

Some vascular specialists argue that complete revascularization provides better protection when one vessel occludes, while those favoring single-vessel revascularization contend that bypassing only the most problematic vessel avoids a longer, more complex operation in these typically fragile patients.

The data on single- versus multivessel mesenteric bypass is mixed, he said. Some studies have found that two-vessel bypass results in less symptom recurrence, improved patency, and fewer reinterventions than single-vessel bypass. Other studies, however, have found no difference in 1-year patency or freedom from symptom recurrence between the two treatments.

Regardless of the number of vessels treated, no consensus exists as to which artery responds best to stenting, Dr. Panneton, from Eastern Virginia Medical School in Norfolk, said. In their own review of 121 consecutive patients over a 7-year period, there was a major discrepancy between SMA and CA stenting in 1-year primary patency (55% vs. 18%) and 6-month clinical patency (86% vs. 67%).

“In our experience, celiac stenting had much worse ISR [in-stent restenosis] and clinical patency rates than SMA stenting, which questions its utility,” he said.

In the celiac group, stents with a diameter < 6 mm were significantly more likely than larger-caliber stents to lose primary patency, defined as peak systolic velocity < 350 cm/sec.

Interestingly, a subset analysis of patients undergoing two-vessel stenting of the CA and SMA revealed no significant differences in ISR rates or survival free from symptom recurrence, compared with single SMA stenting (J. Vasc. Surg. 2013;57:1062-6).

Surveillance after mesenteric stenting is another area in flux. Duplex ultrasound (DUS) has been validated as an accurate modality for determining native mesenteric artery stenosis, but no firm DUS criteria exist for diagnosing ISR, Dr. Panneton said. Several studies have reported that DUS velocity criteria for native mesenteric stenosis overestimates the percentage of stenosis of stented arteries.

A receiver operator curve (ROC) analysis by Dr. Panneton and his colleagues demonstrated that an SMA peak systolic velocity (PSV) of 445 cm/sec had the highest sensitivity (96%), but only 43% specificity for predicting ISR.

Further prospective validation is needed, although a similar ROC analysis reported 100% sensitivity and 95% sensitivity using a PSV of 412 cm/sec to identify SMA > 70% ISR (J. Vasc. Surg. 2012;55:730-8), he noted.

Intravascular ultrasound (IVUS) is useful as an adjunct to DUS and angiography for the detection of ISR of mesenteric arteries, but isn’t practical for routine surveillance. There is also a dearth of data on outcomes when IVUS is used with other imaging modalities, Dr. Panneton added.

What is clear is that a paradigm shift has occurred in the treatment of CMI, reflected in a threefold increase in the number of mesenteric revascularizations performed in the U.S. during the last 10 years. Still, 5-year survival rates are nearly identical between open surgery and mesenteric stenting, despite primary, secondary, and clinical patency rates seeming to favor open mesenteric bypass.

“Future technology will address the higher ISR and reintervention rates associated with mesenteric stenting and likely improve outcomes,” Dr. Panneton said.

Mesenteric stenting can still be useful, even after bypass, he said, highlighting a 78-year-old woman with a history of aortobifemoral bypass who required endovascular rescue of an SMA graft thrombosis after presenting with acute mesenteric ischemia.

“We were able with a guidewire, to get through the reversed C-loop graft that came from the iliac to the SMA and get into the distal SMA vessel,” he said. “We also used pharmacomechanical thrombectomy to really declot the graft and place a stent at the proximal anastomosis of the iliac-SMA Dacron graft.”

The team has also done mesenteric stenting using a retrograde open mesenteric stenting technique.

“It’s quite useful in acute mesenteric ischemia, but we’ve also used it more recently even in chronic mesenteric ischemia for patients who did not tolerate aortic cross-clamping or did not have any good aorta,” he said. “An example of that would be a porcelain aorta where we don’t want to clamp anything.”

Dr. Panneton is a consultant and serves on the speaker’s bureau for Medtronic.

[email protected]

CHICAGO – Mesenteric stenting has replaced open surgery as first-line treatment for chronic mesenteric ischemia, but it is still a therapy in flux.

Controversy exists over single- versus multivessel revascularization when both the celiac artery (CA) and superior mesenteric artery (SMA) are diseased and symptoms are consistent with chronic mesenteric ischemia (CMI), Dr. Jean Panneton said at a symposium on vascular surgery sponsored by Northwestern University.

Patrice Wendling/Frontline Medical News

Some vascular specialists argue that complete revascularization provides better protection when one vessel occludes, while those favoring single-vessel revascularization contend that bypassing only the most problematic vessel avoids a longer, more complex operation in these typically fragile patients.

The data on single- versus multivessel mesenteric bypass is mixed, he said. Some studies have found that two-vessel bypass results in less symptom recurrence, improved patency, and fewer reinterventions than single-vessel bypass. Other studies, however, have found no difference in 1-year patency or freedom from symptom recurrence between the two treatments.

Regardless of the number of vessels treated, no consensus exists as to which artery responds best to stenting, Dr. Panneton, from Eastern Virginia Medical School in Norfolk, said. In their own review of 121 consecutive patients over a 7-year period, there was a major discrepancy between SMA and CA stenting in 1-year primary patency (55% vs. 18%) and 6-month clinical patency (86% vs. 67%).

“In our experience, celiac stenting had much worse ISR [in-stent restenosis] and clinical patency rates than SMA stenting, which questions its utility,” he said.

In the celiac group, stents with a diameter < 6 mm were significantly more likely than larger-caliber stents to lose primary patency, defined as peak systolic velocity < 350 cm/sec.

Interestingly, a subset analysis of patients undergoing two-vessel stenting of the CA and SMA revealed no significant differences in ISR rates or survival free from symptom recurrence, compared with single SMA stenting (J. Vasc. Surg. 2013;57:1062-6).

Surveillance after mesenteric stenting is another area in flux. Duplex ultrasound (DUS) has been validated as an accurate modality for determining native mesenteric artery stenosis, but no firm DUS criteria exist for diagnosing ISR, Dr. Panneton said. Several studies have reported that DUS velocity criteria for native mesenteric stenosis overestimates the percentage of stenosis of stented arteries.

A receiver operator curve (ROC) analysis by Dr. Panneton and his colleagues demonstrated that an SMA peak systolic velocity (PSV) of 445 cm/sec had the highest sensitivity (96%), but only 43% specificity for predicting ISR.

Further prospective validation is needed, although a similar ROC analysis reported 100% sensitivity and 95% sensitivity using a PSV of 412 cm/sec to identify SMA > 70% ISR (J. Vasc. Surg. 2012;55:730-8), he noted.

Intravascular ultrasound (IVUS) is useful as an adjunct to DUS and angiography for the detection of ISR of mesenteric arteries, but isn’t practical for routine surveillance. There is also a dearth of data on outcomes when IVUS is used with other imaging modalities, Dr. Panneton added.

What is clear is that a paradigm shift has occurred in the treatment of CMI, reflected in a threefold increase in the number of mesenteric revascularizations performed in the U.S. during the last 10 years. Still, 5-year survival rates are nearly identical between open surgery and mesenteric stenting, despite primary, secondary, and clinical patency rates seeming to favor open mesenteric bypass.

“Future technology will address the higher ISR and reintervention rates associated with mesenteric stenting and likely improve outcomes,” Dr. Panneton said.

Mesenteric stenting can still be useful, even after bypass, he said, highlighting a 78-year-old woman with a history of aortobifemoral bypass who required endovascular rescue of an SMA graft thrombosis after presenting with acute mesenteric ischemia.

“We were able with a guidewire, to get through the reversed C-loop graft that came from the iliac to the SMA and get into the distal SMA vessel,” he said. “We also used pharmacomechanical thrombectomy to really declot the graft and place a stent at the proximal anastomosis of the iliac-SMA Dacron graft.”

The team has also done mesenteric stenting using a retrograde open mesenteric stenting technique.

“It’s quite useful in acute mesenteric ischemia, but we’ve also used it more recently even in chronic mesenteric ischemia for patients who did not tolerate aortic cross-clamping or did not have any good aorta,” he said. “An example of that would be a porcelain aorta where we don’t want to clamp anything.”

Dr. Panneton is a consultant and serves on the speaker’s bureau for Medtronic.

[email protected]

CHICAGO – Mesenteric stenting has replaced open surgery as first-line treatment for chronic mesenteric ischemia, but it is still a therapy in flux.

Controversy exists over single- versus multivessel revascularization when both the celiac artery (CA) and superior mesenteric artery (SMA) are diseased and symptoms are consistent with chronic mesenteric ischemia (CMI), Dr. Jean Panneton said at a symposium on vascular surgery sponsored by Northwestern University.

Patrice Wendling/Frontline Medical News

Some vascular specialists argue that complete revascularization provides better protection when one vessel occludes, while those favoring single-vessel revascularization contend that bypassing only the most problematic vessel avoids a longer, more complex operation in these typically fragile patients.

The data on single- versus multivessel mesenteric bypass is mixed, he said. Some studies have found that two-vessel bypass results in less symptom recurrence, improved patency, and fewer reinterventions than single-vessel bypass. Other studies, however, have found no difference in 1-year patency or freedom from symptom recurrence between the two treatments.

Regardless of the number of vessels treated, no consensus exists as to which artery responds best to stenting, Dr. Panneton, from Eastern Virginia Medical School in Norfolk, said. In their own review of 121 consecutive patients over a 7-year period, there was a major discrepancy between SMA and CA stenting in 1-year primary patency (55% vs. 18%) and 6-month clinical patency (86% vs. 67%).

“In our experience, celiac stenting had much worse ISR [in-stent restenosis] and clinical patency rates than SMA stenting, which questions its utility,” he said.

In the celiac group, stents with a diameter < 6 mm were significantly more likely than larger-caliber stents to lose primary patency, defined as peak systolic velocity < 350 cm/sec.

Interestingly, a subset analysis of patients undergoing two-vessel stenting of the CA and SMA revealed no significant differences in ISR rates or survival free from symptom recurrence, compared with single SMA stenting (J. Vasc. Surg. 2013;57:1062-6).

Surveillance after mesenteric stenting is another area in flux. Duplex ultrasound (DUS) has been validated as an accurate modality for determining native mesenteric artery stenosis, but no firm DUS criteria exist for diagnosing ISR, Dr. Panneton said. Several studies have reported that DUS velocity criteria for native mesenteric stenosis overestimates the percentage of stenosis of stented arteries.

A receiver operator curve (ROC) analysis by Dr. Panneton and his colleagues demonstrated that an SMA peak systolic velocity (PSV) of 445 cm/sec had the highest sensitivity (96%), but only 43% specificity for predicting ISR.

Further prospective validation is needed, although a similar ROC analysis reported 100% sensitivity and 95% sensitivity using a PSV of 412 cm/sec to identify SMA > 70% ISR (J. Vasc. Surg. 2012;55:730-8), he noted.

Intravascular ultrasound (IVUS) is useful as an adjunct to DUS and angiography for the detection of ISR of mesenteric arteries, but isn’t practical for routine surveillance. There is also a dearth of data on outcomes when IVUS is used with other imaging modalities, Dr. Panneton added.

What is clear is that a paradigm shift has occurred in the treatment of CMI, reflected in a threefold increase in the number of mesenteric revascularizations performed in the U.S. during the last 10 years. Still, 5-year survival rates are nearly identical between open surgery and mesenteric stenting, despite primary, secondary, and clinical patency rates seeming to favor open mesenteric bypass.

“Future technology will address the higher ISR and reintervention rates associated with mesenteric stenting and likely improve outcomes,” Dr. Panneton said.

Mesenteric stenting can still be useful, even after bypass, he said, highlighting a 78-year-old woman with a history of aortobifemoral bypass who required endovascular rescue of an SMA graft thrombosis after presenting with acute mesenteric ischemia.

“We were able with a guidewire, to get through the reversed C-loop graft that came from the iliac to the SMA and get into the distal SMA vessel,” he said. “We also used pharmacomechanical thrombectomy to really declot the graft and place a stent at the proximal anastomosis of the iliac-SMA Dacron graft.”

The team has also done mesenteric stenting using a retrograde open mesenteric stenting technique.

“It’s quite useful in acute mesenteric ischemia, but we’ve also used it more recently even in chronic mesenteric ischemia for patients who did not tolerate aortic cross-clamping or did not have any good aorta,” he said. “An example of that would be a porcelain aorta where we don’t want to clamp anything.”

Dr. Panneton is a consultant and serves on the speaker’s bureau for Medtronic.

[email protected]

CHICAGO – A nationwide analysis comparing straight versus hand-assisted laparoscopic colectomy appears to have resulted in a draw.

Despite being used more commonly in patients with higher body mass index and comorbidities, hand-assisted laparoscopic surgery (HALS) resulted in a significantly shorter operative time than did straight laparoscopic surgery (LAP) (171 minutes vs. 178.8 minutes; P < .001).

On the other hand, LAP was associated with a significantly shorter length of stay (5.9 days vs. 6.0 days; P < .001), fewer complications (15.9% vs. 18.2%; P = .006), fewer specifically superficial skin infections (4.1% vs. 5.4%; P = .007), and less prolonged postoperative ileus (7.5% vs. 9.1%; P = .01).

The differences were statistically significant likely because of the high volume of patients in each group, but are unlikely to be clinically significant in terms of patient care, senior study author Dr. I. Emre Gorgun said at the annual meeting of the Central Surgical Association.

Patrice Wendling/Frontline Medical News

CSA incoming president Dr. Scott A. Gruber, chief of staff at the John D. Dingell VA Medical Center in Detroit, agreed. “There were very, very small differences. I think they were trying to show that the two [approaches] are virtually equivalent,” he said in an interview. “Each has its advantages and disadvantages, but the HALS technique was used in more complex, more high-risk patients,” Dr. Gruber said.

HALS bridges the learning gap between open and straight laparoscopic surgery, which has been slow to gain adoption in colorectal surgery because it is technically demanding and has a steep learning curve, said Dr. Gorgun, a colorectal surgeon at the Cleveland Clinic. HALS allows surgeons to regain tactile sensation and manual retraction, enabling them to perform even more complex operations more effectively.

Studies also suggest that HALS reduces conversion rates and preserves the short-term benefits of LAP, though a nationwide comparison of short-term outcomes using the two techniques has been absent.

To fill this knowledge gap, the investigators used the 2012 colectomy-targeted American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP

Courtesy Applied Medical

At baseline, the HALS group was significantly older than the LAP group (61.5 years vs. 60 years), had a higher body mass index (28.6 kg/m2 vs. 28 kg/m2), was more likely to be hypertensive (49.8% vs. 45.1%), and to be American Society of Anesthesiologists class III (42% vs. 37.4%) and class IV (2.8% vs. 2.7%). Steroid use for inflammatory bowel disease was significantly higher in the LAP group (6.5% vs. 5.4%).

Mortality rates were similar in the LAP and HALS groups (0.52% vs. 0.50%; P = .94), Dr. Gorgun reported.

Multivariate logistic regression adjusted for comorbid conditions lessened the degree of differences between the two groups, but continued to favor HALS for shorter operative time (odds ratio, 0.94) and favor LAP for shorter hospital stays (OR, 1.05) and less superficial surgical site infections (OR, 1.31), less prolonged post-operative ileus (OR, 1.25), and overall morbidity (OR, 1.16).

“Both LAP and HALS approaches are used in minimally invasive colorectal surgery based on their respective contributions and complement each other,” Dr. Gorgun concluded. “Implementing the best approach to decrease postoperative complication rates and increase use of MIS [minimally invasive surgery] will play a role in improving patient care and overall quality of health care.”

Dr. Gorgun, his coauthors, and Dr. Gruber reported having no financial conflicts

[email protected]

CHICAGO – A nationwide analysis comparing straight versus hand-assisted laparoscopic colectomy appears to have resulted in a draw.

Despite being used more commonly in patients with higher body mass index and comorbidities, hand-assisted laparoscopic surgery (HALS) resulted in a significantly shorter operative time than did straight laparoscopic surgery (LAP) (171 minutes vs. 178.8 minutes; P < .001).

On the other hand, LAP was associated with a significantly shorter length of stay (5.9 days vs. 6.0 days; P < .001), fewer complications (15.9% vs. 18.2%; P = .006), fewer specifically superficial skin infections (4.1% vs. 5.4%; P = .007), and less prolonged postoperative ileus (7.5% vs. 9.1%; P = .01).

The differences were statistically significant likely because of the high volume of patients in each group, but are unlikely to be clinically significant in terms of patient care, senior study author Dr. I. Emre Gorgun said at the annual meeting of the Central Surgical Association.

Patrice Wendling/Frontline Medical News

CSA incoming president Dr. Scott A. Gruber, chief of staff at the John D. Dingell VA Medical Center in Detroit, agreed. “There were very, very small differences. I think they were trying to show that the two [approaches] are virtually equivalent,” he said in an interview. “Each has its advantages and disadvantages, but the HALS technique was used in more complex, more high-risk patients,” Dr. Gruber said.

HALS bridges the learning gap between open and straight laparoscopic surgery, which has been slow to gain adoption in colorectal surgery because it is technically demanding and has a steep learning curve, said Dr. Gorgun, a colorectal surgeon at the Cleveland Clinic. HALS allows surgeons to regain tactile sensation and manual retraction, enabling them to perform even more complex operations more effectively.

Studies also suggest that HALS reduces conversion rates and preserves the short-term benefits of LAP, though a nationwide comparison of short-term outcomes using the two techniques has been absent.

To fill this knowledge gap, the investigators used the 2012 colectomy-targeted American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP

Courtesy Applied Medical

At baseline, the HALS group was significantly older than the LAP group (61.5 years vs. 60 years), had a higher body mass index (28.6 kg/m2 vs. 28 kg/m2), was more likely to be hypertensive (49.8% vs. 45.1%), and to be American Society of Anesthesiologists class III (42% vs. 37.4%) and class IV (2.8% vs. 2.7%). Steroid use for inflammatory bowel disease was significantly higher in the LAP group (6.5% vs. 5.4%).

Mortality rates were similar in the LAP and HALS groups (0.52% vs. 0.50%; P = .94), Dr. Gorgun reported.

Multivariate logistic regression adjusted for comorbid conditions lessened the degree of differences between the two groups, but continued to favor HALS for shorter operative time (odds ratio, 0.94) and favor LAP for shorter hospital stays (OR, 1.05) and less superficial surgical site infections (OR, 1.31), less prolonged post-operative ileus (OR, 1.25), and overall morbidity (OR, 1.16).

“Both LAP and HALS approaches are used in minimally invasive colorectal surgery based on their respective contributions and complement each other,” Dr. Gorgun concluded. “Implementing the best approach to decrease postoperative complication rates and increase use of MIS [minimally invasive surgery] will play a role in improving patient care and overall quality of health care.”

Dr. Gorgun, his coauthors, and Dr. Gruber reported having no financial conflicts

[email protected]

CHICAGO – A nationwide analysis comparing straight versus hand-assisted laparoscopic colectomy appears to have resulted in a draw.

Despite being used more commonly in patients with higher body mass index and comorbidities, hand-assisted laparoscopic surgery (HALS) resulted in a significantly shorter operative time than did straight laparoscopic surgery (LAP) (171 minutes vs. 178.8 minutes; P < .001).

On the other hand, LAP was associated with a significantly shorter length of stay (5.9 days vs. 6.0 days; P < .001), fewer complications (15.9% vs. 18.2%; P = .006), fewer specifically superficial skin infections (4.1% vs. 5.4%; P = .007), and less prolonged postoperative ileus (7.5% vs. 9.1%; P = .01).

The differences were statistically significant likely because of the high volume of patients in each group, but are unlikely to be clinically significant in terms of patient care, senior study author Dr. I. Emre Gorgun said at the annual meeting of the Central Surgical Association.

Patrice Wendling/Frontline Medical News

CSA incoming president Dr. Scott A. Gruber, chief of staff at the John D. Dingell VA Medical Center in Detroit, agreed. “There were very, very small differences. I think they were trying to show that the two [approaches] are virtually equivalent,” he said in an interview. “Each has its advantages and disadvantages, but the HALS technique was used in more complex, more high-risk patients,” Dr. Gruber said.

HALS bridges the learning gap between open and straight laparoscopic surgery, which has been slow to gain adoption in colorectal surgery because it is technically demanding and has a steep learning curve, said Dr. Gorgun, a colorectal surgeon at the Cleveland Clinic. HALS allows surgeons to regain tactile sensation and manual retraction, enabling them to perform even more complex operations more effectively.

Studies also suggest that HALS reduces conversion rates and preserves the short-term benefits of LAP, though a nationwide comparison of short-term outcomes using the two techniques has been absent.

To fill this knowledge gap, the investigators used the 2012 colectomy-targeted American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP

Courtesy Applied Medical

At baseline, the HALS group was significantly older than the LAP group (61.5 years vs. 60 years), had a higher body mass index (28.6 kg/m2 vs. 28 kg/m2), was more likely to be hypertensive (49.8% vs. 45.1%), and to be American Society of Anesthesiologists class III (42% vs. 37.4%) and class IV (2.8% vs. 2.7%). Steroid use for inflammatory bowel disease was significantly higher in the LAP group (6.5% vs. 5.4%).

Mortality rates were similar in the LAP and HALS groups (0.52% vs. 0.50%; P = .94), Dr. Gorgun reported.

Multivariate logistic regression adjusted for comorbid conditions lessened the degree of differences between the two groups, but continued to favor HALS for shorter operative time (odds ratio, 0.94) and favor LAP for shorter hospital stays (OR, 1.05) and less superficial surgical site infections (OR, 1.31), less prolonged post-operative ileus (OR, 1.25), and overall morbidity (OR, 1.16).

“Both LAP and HALS approaches are used in minimally invasive colorectal surgery based on their respective contributions and complement each other,” Dr. Gorgun concluded. “Implementing the best approach to decrease postoperative complication rates and increase use of MIS [minimally invasive surgery] will play a role in improving patient care and overall quality of health care.”

Dr. Gorgun, his coauthors, and Dr. Gruber reported having no financial conflicts

[email protected]

CHICAGO – Combining hiatal hernia repair with bariatric surgery is feasible and safe, with no intraoperative complications or deaths reported in a series of 83 patients.

“Concomitant repair of hiatal hernia during these operations can be technically challenging but is a more efficient way of handling this pathology than undergoing separate procedures,” study author Dr. John Rodriguez, from the Cleveland Clinic, said at the annual meeting of the Central Surgical Association.

Patrice Wendling/Frontline Medical News

The presence of a hiatal hernia can play an important role when sizing a pouch or performing a dissection and can make it difficult to have consistent outcomes or gastric sleeves if the complete stomach can’t be visualized, he explained. Hernias can prevent weight gain but also prevent resolution of reflux symptoms.

Prospectively collected data from 83 patients who underwent concomitant hernia repair and bariatric surgery were retrospectively, compared with 83 historic controls who underwent bariatric surgery alone. The two groups were well-matched with regard to age (57.2 years vs. 56.2 years), weight (118.4 kg vs. 119.9 kg), and body mass index (BMI) (44.5 kg/m²vs. 44.6 kg/m²), although diabetes was significantly more common in controls (13.2% vs. 38.5%).

In the study group, hernias were classified as Type I in 47 patients, Type II in 5, Type III in 28, and Type IV in 3. Primary hernia repair was performed in all patients, using anterior reconstruction in 45, posterior reconstruction in 21, posterior reconstruction plus mesh in 7, and an unspecified approach in 10.

Operative time was slightly longer with the addition of hernia repair, but the difference did not reach statistical significance (164.4 minutes vs. 147.5 minutes; P = .07), Dr. Rodriguez said. Average hospital length of stay was nearly identical at 3.5 vs. 3.4 days (P = .09).

In all, 24 patients undergoing concomitant surgery described having early postoperative symptoms such as nausea, dysphagia, abdominal pain, reflux, and dehydration, compared with 15 controls. But, again the difference was not significant (33.7% vs. 18%; P = .09), he said.

Three study patients had late postoperative complications after 1 year requiring esophagogastroduodenoscopy caused by one each of stenosis, hernia recurrence, and marginal ulcer. Among controls, there were four late marginal ulcers and two stenoses (P = .3).

Notably, hiatal hernia was diagnosed intraoperatively in a full 61.4% of the study group. Obesity is an established risk factor for hiatal hernia, although many patients who present for bariatric surgery are asymptomatic, Dr. Rodriguez observed.

At 12 months, patients undergoing bariatric surgery with and without concomitant hernia repair had similar weight loss (80.7 kg vs. 87.4 kg; P = .1) and final BMI (30 kg/m² vs. 32.5 kg/m²; P = .06).

Use of antireflux medication, however, was significantly higher in those without concomitant surgery (38.5% vs. 43.7%; P = .01), he said. Gastroesophageal reflux disease (GERD) symptoms were present in 84.3% of study patients and 77% of controls at baseline.

Antireflux medication use declined in 66% of patients undergoing laparoscopic Roux en-Y gastric bypass vs. 50% undergoing only laparoscopic sleeve gastrectomy. Surgical approach did not affect weight loss (59.7 kg vs. 51.8 kg) or final BMI (30.3 kg/m² vs. 32.4 kg/m²).

“The true incidence of hiatal hernia in the obese is likely underestimated,” Dr. Rodriguez said. “Concomitant repair is safe and may prevent further symptoms.”

Limitations of the study were the small, retrospective cohort, a lack of standardized GERD symptom scoring and objective GERD testing, and no uniform hiatal hernia repair. Standardized approaches may improve outcomes during combined procedures, he said.

During a discussion of the results, Dr. Peter T. Hallowell, an audience member from the University of Virginia, Charlottesville, rose to say this is “information we urgently need in bariatric surgery.”

Dr. Rodriguez and his coauthors reported having no financial conflicts.

[email protected]

CHICAGO – Combining hiatal hernia repair with bariatric surgery is feasible and safe, with no intraoperative complications or deaths reported in a series of 83 patients.

“Concomitant repair of hiatal hernia during these operations can be technically challenging but is a more efficient way of handling this pathology than undergoing separate procedures,” study author Dr. John Rodriguez, from the Cleveland Clinic, said at the annual meeting of the Central Surgical Association.

Patrice Wendling/Frontline Medical News

The presence of a hiatal hernia can play an important role when sizing a pouch or performing a dissection and can make it difficult to have consistent outcomes or gastric sleeves if the complete stomach can’t be visualized, he explained. Hernias can prevent weight gain but also prevent resolution of reflux symptoms.

Prospectively collected data from 83 patients who underwent concomitant hernia repair and bariatric surgery were retrospectively, compared with 83 historic controls who underwent bariatric surgery alone. The two groups were well-matched with regard to age (57.2 years vs. 56.2 years), weight (118.4 kg vs. 119.9 kg), and body mass index (BMI) (44.5 kg/m²vs. 44.6 kg/m²), although diabetes was significantly more common in controls (13.2% vs. 38.5%).

In the study group, hernias were classified as Type I in 47 patients, Type II in 5, Type III in 28, and Type IV in 3. Primary hernia repair was performed in all patients, using anterior reconstruction in 45, posterior reconstruction in 21, posterior reconstruction plus mesh in 7, and an unspecified approach in 10.

Operative time was slightly longer with the addition of hernia repair, but the difference did not reach statistical significance (164.4 minutes vs. 147.5 minutes; P = .07), Dr. Rodriguez said. Average hospital length of stay was nearly identical at 3.5 vs. 3.4 days (P = .09).

In all, 24 patients undergoing concomitant surgery described having early postoperative symptoms such as nausea, dysphagia, abdominal pain, reflux, and dehydration, compared with 15 controls. But, again the difference was not significant (33.7% vs. 18%; P = .09), he said.

Three study patients had late postoperative complications after 1 year requiring esophagogastroduodenoscopy caused by one each of stenosis, hernia recurrence, and marginal ulcer. Among controls, there were four late marginal ulcers and two stenoses (P = .3).

Notably, hiatal hernia was diagnosed intraoperatively in a full 61.4% of the study group. Obesity is an established risk factor for hiatal hernia, although many patients who present for bariatric surgery are asymptomatic, Dr. Rodriguez observed.

At 12 months, patients undergoing bariatric surgery with and without concomitant hernia repair had similar weight loss (80.7 kg vs. 87.4 kg; P = .1) and final BMI (30 kg/m² vs. 32.5 kg/m²; P = .06).

Use of antireflux medication, however, was significantly higher in those without concomitant surgery (38.5% vs. 43.7%; P = .01), he said. Gastroesophageal reflux disease (GERD) symptoms were present in 84.3% of study patients and 77% of controls at baseline.

Antireflux medication use declined in 66% of patients undergoing laparoscopic Roux en-Y gastric bypass vs. 50% undergoing only laparoscopic sleeve gastrectomy. Surgical approach did not affect weight loss (59.7 kg vs. 51.8 kg) or final BMI (30.3 kg/m² vs. 32.4 kg/m²).

“The true incidence of hiatal hernia in the obese is likely underestimated,” Dr. Rodriguez said. “Concomitant repair is safe and may prevent further symptoms.”

Limitations of the study were the small, retrospective cohort, a lack of standardized GERD symptom scoring and objective GERD testing, and no uniform hiatal hernia repair. Standardized approaches may improve outcomes during combined procedures, he said.

During a discussion of the results, Dr. Peter T. Hallowell, an audience member from the University of Virginia, Charlottesville, rose to say this is “information we urgently need in bariatric surgery.”

Dr. Rodriguez and his coauthors reported having no financial conflicts.

[email protected]

CHICAGO – Combining hiatal hernia repair with bariatric surgery is feasible and safe, with no intraoperative complications or deaths reported in a series of 83 patients.

“Concomitant repair of hiatal hernia during these operations can be technically challenging but is a more efficient way of handling this pathology than undergoing separate procedures,” study author Dr. John Rodriguez, from the Cleveland Clinic, said at the annual meeting of the Central Surgical Association.

Patrice Wendling/Frontline Medical News

The presence of a hiatal hernia can play an important role when sizing a pouch or performing a dissection and can make it difficult to have consistent outcomes or gastric sleeves if the complete stomach can’t be visualized, he explained. Hernias can prevent weight gain but also prevent resolution of reflux symptoms.

Prospectively collected data from 83 patients who underwent concomitant hernia repair and bariatric surgery were retrospectively, compared with 83 historic controls who underwent bariatric surgery alone. The two groups were well-matched with regard to age (57.2 years vs. 56.2 years), weight (118.4 kg vs. 119.9 kg), and body mass index (BMI) (44.5 kg/m²vs. 44.6 kg/m²), although diabetes was significantly more common in controls (13.2% vs. 38.5%).

In the study group, hernias were classified as Type I in 47 patients, Type II in 5, Type III in 28, and Type IV in 3. Primary hernia repair was performed in all patients, using anterior reconstruction in 45, posterior reconstruction in 21, posterior reconstruction plus mesh in 7, and an unspecified approach in 10.

Operative time was slightly longer with the addition of hernia repair, but the difference did not reach statistical significance (164.4 minutes vs. 147.5 minutes; P = .07), Dr. Rodriguez said. Average hospital length of stay was nearly identical at 3.5 vs. 3.4 days (P = .09).

In all, 24 patients undergoing concomitant surgery described having early postoperative symptoms such as nausea, dysphagia, abdominal pain, reflux, and dehydration, compared with 15 controls. But, again the difference was not significant (33.7% vs. 18%; P = .09), he said.

Three study patients had late postoperative complications after 1 year requiring esophagogastroduodenoscopy caused by one each of stenosis, hernia recurrence, and marginal ulcer. Among controls, there were four late marginal ulcers and two stenoses (P = .3).

Notably, hiatal hernia was diagnosed intraoperatively in a full 61.4% of the study group. Obesity is an established risk factor for hiatal hernia, although many patients who present for bariatric surgery are asymptomatic, Dr. Rodriguez observed.

At 12 months, patients undergoing bariatric surgery with and without concomitant hernia repair had similar weight loss (80.7 kg vs. 87.4 kg; P = .1) and final BMI (30 kg/m² vs. 32.5 kg/m²; P = .06).

Use of antireflux medication, however, was significantly higher in those without concomitant surgery (38.5% vs. 43.7%; P = .01), he said. Gastroesophageal reflux disease (GERD) symptoms were present in 84.3% of study patients and 77% of controls at baseline.

Antireflux medication use declined in 66% of patients undergoing laparoscopic Roux en-Y gastric bypass vs. 50% undergoing only laparoscopic sleeve gastrectomy. Surgical approach did not affect weight loss (59.7 kg vs. 51.8 kg) or final BMI (30.3 kg/m² vs. 32.4 kg/m²).

“The true incidence of hiatal hernia in the obese is likely underestimated,” Dr. Rodriguez said. “Concomitant repair is safe and may prevent further symptoms.”

Limitations of the study were the small, retrospective cohort, a lack of standardized GERD symptom scoring and objective GERD testing, and no uniform hiatal hernia repair. Standardized approaches may improve outcomes during combined procedures, he said.

During a discussion of the results, Dr. Peter T. Hallowell, an audience member from the University of Virginia, Charlottesville, rose to say this is “information we urgently need in bariatric surgery.”

Dr. Rodriguez and his coauthors reported having no financial conflicts.

[email protected]

CHICAGO – Surgical outcomes of acute, complicated diverticulitis are equivalent regardless of whether a colorectal or general surgeon wields the scalpel, a multicenter study showed.

There was no difference between the colorectal surgery (CRS) and general surgery groups for the primary outcomes of 90-day morbidity (26% vs 28%; P = .76), readmission (32% vs. 25%; P = .48), and length of stay (both median 9 days; P = .82).

Patrice Wendling/Frontline Medical News

Surgeon specialization was not associated with any of the outcomes in multivariate regression that accounted for patient demographics, surgeon type, and disease characteristics, study author Capt. G. Paul Wright, U.S. Army Reserve Medical Corps, reported at the annual meeting of the Central Surgical Association.

The authors tackled the controversial issue in light of recent data suggesting improved acute, complicated diverticulitis surgery outcomes in the hands of specialized surgeons. A 2014 study reported that colorectal surgeons were less likely than general surgeons to use a Hartmann’s procedure and had reduced LOS and time to stoma reversal (J. Am. Coll. Surg. 2014;218:1156-61).

The current analysis involved 115 consecutive patients with acute, complicated diverticulitis who underwent emergent surgery with either a colorectal surgeon (n = 62) or general surgeon (n = 53) at two university-affiliated hospitals from 2006 to 2013. Age, Charlson Comorbidity Index, and American Society of Anesthesiologists class were similar between groups.

The colorectal surgeon group (CRS), however, was significantly more likely to have had previous episodes of diverticulitis (58% vs. 25%; P < .001), likely representing a referral bias or preexisting relationship with their surgeon, Dr. Wright said.

The general surgeon (GS) group had a significantly higher number of Systemic Inflammatory Response Syndrome criteria (P = .009 for all groups), higher rates of Hinchey class 3 disease (59% vs. 32%: P = .02), and ICU admissions (25% vs. 7%; P = .006).

The most common procedure among general surgeons was a Hartmann’s procedure (64% vs. 34%; P < .001), whereas colorectal surgeons favored primary anastomosis with diverting ileostomy (45% vs. 0%; P < .001), Dr. Wright, from Grand Rapids Medical Education Partners and Michigan State University, both in Grand Rapids, reported.

General surgeons were more likely to close the skin (85% vs. 50%), while in the CRS group the skin was left partially or completely open in 50% of patients. Operative time at the index admission was an average of 36 minutes longer in the CRS group (mean 164 minutes vs. 128 minutes; P = .005).

The CRS group had a higher rate of stoma reversal (78% vs 65%) and shorter time to stoma reversal (4 months vs. 4.7 months), but the difference was not statistically significant. The CRS group had a significantly shorter stoma reversal OR duration (mean 106 minutes vs. 182 minutes; P = .0010) and stoma reversal length of stay (mean 4 days vs. 7 days; P < .001).

“As general surgeons will no doubt continue to care for acute diverticulitis, increased use of primary anastomosis with proximal diversion when appropriate may be warranted due to the secondary benefits seen in stoma reversal,” Dr. Wright said.

Mortality was low and similar, at just one death in the CRS and two in the GS group.

Invited discussant William Cirocco, from Ohio State University in Columbus, said the type of surgical intervention is just one aspect in the management of patients with diverticulitis.

“An additional nonoperative approach may lead to conversion of an emergent to a nonemergent single-stage dissection. These critical decisions require experience and training,” Dr. Cirocco said. “For patients who require emergent operation for diffuse peritonitis, I believe that background and experience of the individual surgeon trumps the presence or absence of specialty training.”

Dr. Wright and his coauthors reported having no financial conflicts.

[email protected]

CHICAGO – Surgical outcomes of acute, complicated diverticulitis are equivalent regardless of whether a colorectal or general surgeon wields the scalpel, a multicenter study showed.

There was no difference between the colorectal surgery (CRS) and general surgery groups for the primary outcomes of 90-day morbidity (26% vs 28%; P = .76), readmission (32% vs. 25%; P = .48), and length of stay (both median 9 days; P = .82).

Patrice Wendling/Frontline Medical News

Surgeon specialization was not associated with any of the outcomes in multivariate regression that accounted for patient demographics, surgeon type, and disease characteristics, study author Capt. G. Paul Wright, U.S. Army Reserve Medical Corps, reported at the annual meeting of the Central Surgical Association.

The authors tackled the controversial issue in light of recent data suggesting improved acute, complicated diverticulitis surgery outcomes in the hands of specialized surgeons. A 2014 study reported that colorectal surgeons were less likely than general surgeons to use a Hartmann’s procedure and had reduced LOS and time to stoma reversal (J. Am. Coll. Surg. 2014;218:1156-61).

The current analysis involved 115 consecutive patients with acute, complicated diverticulitis who underwent emergent surgery with either a colorectal surgeon (n = 62) or general surgeon (n = 53) at two university-affiliated hospitals from 2006 to 2013. Age, Charlson Comorbidity Index, and American Society of Anesthesiologists class were similar between groups.

The colorectal surgeon group (CRS), however, was significantly more likely to have had previous episodes of diverticulitis (58% vs. 25%; P < .001), likely representing a referral bias or preexisting relationship with their surgeon, Dr. Wright said.

The general surgeon (GS) group had a significantly higher number of Systemic Inflammatory Response Syndrome criteria (P = .009 for all groups), higher rates of Hinchey class 3 disease (59% vs. 32%: P = .02), and ICU admissions (25% vs. 7%; P = .006).

The most common procedure among general surgeons was a Hartmann’s procedure (64% vs. 34%; P < .001), whereas colorectal surgeons favored primary anastomosis with diverting ileostomy (45% vs. 0%; P < .001), Dr. Wright, from Grand Rapids Medical Education Partners and Michigan State University, both in Grand Rapids, reported.

General surgeons were more likely to close the skin (85% vs. 50%), while in the CRS group the skin was left partially or completely open in 50% of patients. Operative time at the index admission was an average of 36 minutes longer in the CRS group (mean 164 minutes vs. 128 minutes; P = .005).

The CRS group had a higher rate of stoma reversal (78% vs 65%) and shorter time to stoma reversal (4 months vs. 4.7 months), but the difference was not statistically significant. The CRS group had a significantly shorter stoma reversal OR duration (mean 106 minutes vs. 182 minutes; P = .0010) and stoma reversal length of stay (mean 4 days vs. 7 days; P < .001).

“As general surgeons will no doubt continue to care for acute diverticulitis, increased use of primary anastomosis with proximal diversion when appropriate may be warranted due to the secondary benefits seen in stoma reversal,” Dr. Wright said.

Mortality was low and similar, at just one death in the CRS and two in the GS group.

Invited discussant William Cirocco, from Ohio State University in Columbus, said the type of surgical intervention is just one aspect in the management of patients with diverticulitis.

“An additional nonoperative approach may lead to conversion of an emergent to a nonemergent single-stage dissection. These critical decisions require experience and training,” Dr. Cirocco said. “For patients who require emergent operation for diffuse peritonitis, I believe that background and experience of the individual surgeon trumps the presence or absence of specialty training.”

Dr. Wright and his coauthors reported having no financial conflicts.

[email protected]

CHICAGO – Surgical outcomes of acute, complicated diverticulitis are equivalent regardless of whether a colorectal or general surgeon wields the scalpel, a multicenter study showed.

There was no difference between the colorectal surgery (CRS) and general surgery groups for the primary outcomes of 90-day morbidity (26% vs 28%; P = .76), readmission (32% vs. 25%; P = .48), and length of stay (both median 9 days; P = .82).

Patrice Wendling/Frontline Medical News

Surgeon specialization was not associated with any of the outcomes in multivariate regression that accounted for patient demographics, surgeon type, and disease characteristics, study author Capt. G. Paul Wright, U.S. Army Reserve Medical Corps, reported at the annual meeting of the Central Surgical Association.

The authors tackled the controversial issue in light of recent data suggesting improved acute, complicated diverticulitis surgery outcomes in the hands of specialized surgeons. A 2014 study reported that colorectal surgeons were less likely than general surgeons to use a Hartmann’s procedure and had reduced LOS and time to stoma reversal (J. Am. Coll. Surg. 2014;218:1156-61).

The current analysis involved 115 consecutive patients with acute, complicated diverticulitis who underwent emergent surgery with either a colorectal surgeon (n = 62) or general surgeon (n = 53) at two university-affiliated hospitals from 2006 to 2013. Age, Charlson Comorbidity Index, and American Society of Anesthesiologists class were similar between groups.

The colorectal surgeon group (CRS), however, was significantly more likely to have had previous episodes of diverticulitis (58% vs. 25%; P < .001), likely representing a referral bias or preexisting relationship with their surgeon, Dr. Wright said.

The general surgeon (GS) group had a significantly higher number of Systemic Inflammatory Response Syndrome criteria (P = .009 for all groups), higher rates of Hinchey class 3 disease (59% vs. 32%: P = .02), and ICU admissions (25% vs. 7%; P = .006).

The most common procedure among general surgeons was a Hartmann’s procedure (64% vs. 34%; P < .001), whereas colorectal surgeons favored primary anastomosis with diverting ileostomy (45% vs. 0%; P < .001), Dr. Wright, from Grand Rapids Medical Education Partners and Michigan State University, both in Grand Rapids, reported.

General surgeons were more likely to close the skin (85% vs. 50%), while in the CRS group the skin was left partially or completely open in 50% of patients. Operative time at the index admission was an average of 36 minutes longer in the CRS group (mean 164 minutes vs. 128 minutes; P = .005).

The CRS group had a higher rate of stoma reversal (78% vs 65%) and shorter time to stoma reversal (4 months vs. 4.7 months), but the difference was not statistically significant. The CRS group had a significantly shorter stoma reversal OR duration (mean 106 minutes vs. 182 minutes; P = .0010) and stoma reversal length of stay (mean 4 days vs. 7 days; P < .001).

“As general surgeons will no doubt continue to care for acute diverticulitis, increased use of primary anastomosis with proximal diversion when appropriate may be warranted due to the secondary benefits seen in stoma reversal,” Dr. Wright said.

Mortality was low and similar, at just one death in the CRS and two in the GS group.

Invited discussant William Cirocco, from Ohio State University in Columbus, said the type of surgical intervention is just one aspect in the management of patients with diverticulitis.

“An additional nonoperative approach may lead to conversion of an emergent to a nonemergent single-stage dissection. These critical decisions require experience and training,” Dr. Cirocco said. “For patients who require emergent operation for diffuse peritonitis, I believe that background and experience of the individual surgeon trumps the presence or absence of specialty training.”

Dr. Wright and his coauthors reported having no financial conflicts.

[email protected]