M. Alexander Otto

BOSTON– Imagine being able to biopsy a tumor and grow it in a lab.
 

The implications are nearly endless. To start, chemotherapy and radiation options could be screened in vitro, much like culture and sensitivity testing of bacteria, to find a patient’s best option. Tumor cultures could be banked for mass screening of new cytotoxic candidates.

It’s already beginning to happen in a few research labs around the world, and it might foretell a breakthrough in cancer treatment.

After decades of failure, the trick to growing tumor cells in culture has finally been figured out. When stem cells are fished out of healthy tissue – from the crypts of the gastrointestinal lining, for instance – and put into a three-dimensional matrix culture with growth factors, they grow into little replications of the organs they came from, called “organoids;” when stem cells are pulled from cancers, they replicate the primary tumor, growing into “tumoroids” ready to be tested against cytotoxic drugs and radiation.

Philip B. Paty, MD, FACS, a colorectal surgeon and organoid researcher at Memorial Sloan Kettering Cancer Center, New York, said he is certain that the person who led the team that figured out the right culture condition – Hans Clevers, MD, PhD, a molecular genetics professor at the University of Utrecht (the Netherlands) – is destined for a Nobel Prize.

Dr. Paty took a few minutes at the annual clinical congress of the American College of Surgeons to explain in an interview why, and what ‘organoid technology’ will likely mean for cancer treatment in a few years.

“The ability to grow and sustain cancer means that we now can start doing real science on human tissues. We could never do this before. We’ve been treating cancer without being able to grow tumors and study them.” The breakthrough opens the door to “clinical trials in a dish,” and will likely take personalized cancer treatment to a new level, he said.

“It remains to be proven that “organoid technology “can change outcomes for patients, but those studies are likely coming,” said Dr. Paty, who investigates tumoroid response to radiation in his own lab work.

[email protected]

BOSTON– Imagine being able to biopsy a tumor and grow it in a lab.
 

The implications are nearly endless. To start, chemotherapy and radiation options could be screened in vitro, much like culture and sensitivity testing of bacteria, to find a patient’s best option. Tumor cultures could be banked for mass screening of new cytotoxic candidates.

It’s already beginning to happen in a few research labs around the world, and it might foretell a breakthrough in cancer treatment.

After decades of failure, the trick to growing tumor cells in culture has finally been figured out. When stem cells are fished out of healthy tissue – from the crypts of the gastrointestinal lining, for instance – and put into a three-dimensional matrix culture with growth factors, they grow into little replications of the organs they came from, called “organoids;” when stem cells are pulled from cancers, they replicate the primary tumor, growing into “tumoroids” ready to be tested against cytotoxic drugs and radiation.

Philip B. Paty, MD, FACS, a colorectal surgeon and organoid researcher at Memorial Sloan Kettering Cancer Center, New York, said he is certain that the person who led the team that figured out the right culture condition – Hans Clevers, MD, PhD, a molecular genetics professor at the University of Utrecht (the Netherlands) – is destined for a Nobel Prize.

Dr. Paty took a few minutes at the annual clinical congress of the American College of Surgeons to explain in an interview why, and what ‘organoid technology’ will likely mean for cancer treatment in a few years.

“The ability to grow and sustain cancer means that we now can start doing real science on human tissues. We could never do this before. We’ve been treating cancer without being able to grow tumors and study them.” The breakthrough opens the door to “clinical trials in a dish,” and will likely take personalized cancer treatment to a new level, he said.

“It remains to be proven that “organoid technology “can change outcomes for patients, but those studies are likely coming,” said Dr. Paty, who investigates tumoroid response to radiation in his own lab work.

[email protected]

BOSTON– Imagine being able to biopsy a tumor and grow it in a lab.
 

The implications are nearly endless. To start, chemotherapy and radiation options could be screened in vitro, much like culture and sensitivity testing of bacteria, to find a patient’s best option. Tumor cultures could be banked for mass screening of new cytotoxic candidates.

It’s already beginning to happen in a few research labs around the world, and it might foretell a breakthrough in cancer treatment.

After decades of failure, the trick to growing tumor cells in culture has finally been figured out. When stem cells are fished out of healthy tissue – from the crypts of the gastrointestinal lining, for instance – and put into a three-dimensional matrix culture with growth factors, they grow into little replications of the organs they came from, called “organoids;” when stem cells are pulled from cancers, they replicate the primary tumor, growing into “tumoroids” ready to be tested against cytotoxic drugs and radiation.

Philip B. Paty, MD, FACS, a colorectal surgeon and organoid researcher at Memorial Sloan Kettering Cancer Center, New York, said he is certain that the person who led the team that figured out the right culture condition – Hans Clevers, MD, PhD, a molecular genetics professor at the University of Utrecht (the Netherlands) – is destined for a Nobel Prize.

Dr. Paty took a few minutes at the annual clinical congress of the American College of Surgeons to explain in an interview why, and what ‘organoid technology’ will likely mean for cancer treatment in a few years.

“The ability to grow and sustain cancer means that we now can start doing real science on human tissues. We could never do this before. We’ve been treating cancer without being able to grow tumors and study them.” The breakthrough opens the door to “clinical trials in a dish,” and will likely take personalized cancer treatment to a new level, he said.

“It remains to be proven that “organoid technology “can change outcomes for patients, but those studies are likely coming,” said Dr. Paty, who investigates tumoroid response to radiation in his own lab work.

[email protected]

BOSTON – Chemotherapy and radiation cure 70%-80% of patients with low rectal cancer.

It’s for them that the watch-and-wait paradigm was established over a decade ago, and widely adopted since then. The idea is to hold off on surgery after a complete response to chemotherapy and radiation, to see if the patient really needs it.

While most do not, tumors regrow in 20%-30%, and when they come back, they tend to be aggressive, with poor outcomes. Patients in those situations would have been better off with upfront surgery.

The problem right now is that there’s no way to predict who will be cured by neoadjuvant therapy and whose tumor will come back, said Philip Paty, MD. FACS, a colorectal surgeon at Memorial Sloan Kettering Cancer Center, New York.

“There are some who are probably harmed by the watch-and-wait paradigm. The risk of local regrowth is hardbaked into [the model]; we haven’t been able to eliminate it,” he said at the annual clinical congress of the American College of Surgeons..

Dr. Paty is one of many investigators working to identify those at risk. In the meantime, watch-and-wait patients need to be followed closely, particularly in the first 2 years. Surgery is the best option at the first sign of regrowth. Dr. Paty explained his follow-up protocol, as well as the current state of watch and wait for low rectal cancer, in an interview at the meeting.

He also talked about overcoming hurdles. The risk of surgery, including permanent bowel and sexual dysfunction, is so great “that many patients latch onto watch and wait and won’t let go. They don’t come back for follow-up, or resist the idea of surgery even if it’s needed,” he said.

[email protected]

BOSTON – Chemotherapy and radiation cure 70%-80% of patients with low rectal cancer.

It’s for them that the watch-and-wait paradigm was established over a decade ago, and widely adopted since then. The idea is to hold off on surgery after a complete response to chemotherapy and radiation, to see if the patient really needs it.

While most do not, tumors regrow in 20%-30%, and when they come back, they tend to be aggressive, with poor outcomes. Patients in those situations would have been better off with upfront surgery.

The problem right now is that there’s no way to predict who will be cured by neoadjuvant therapy and whose tumor will come back, said Philip Paty, MD. FACS, a colorectal surgeon at Memorial Sloan Kettering Cancer Center, New York.

“There are some who are probably harmed by the watch-and-wait paradigm. The risk of local regrowth is hardbaked into [the model]; we haven’t been able to eliminate it,” he said at the annual clinical congress of the American College of Surgeons..

Dr. Paty is one of many investigators working to identify those at risk. In the meantime, watch-and-wait patients need to be followed closely, particularly in the first 2 years. Surgery is the best option at the first sign of regrowth. Dr. Paty explained his follow-up protocol, as well as the current state of watch and wait for low rectal cancer, in an interview at the meeting.

He also talked about overcoming hurdles. The risk of surgery, including permanent bowel and sexual dysfunction, is so great “that many patients latch onto watch and wait and won’t let go. They don’t come back for follow-up, or resist the idea of surgery even if it’s needed,” he said.

[email protected]

BOSTON – Chemotherapy and radiation cure 70%-80% of patients with low rectal cancer.

It’s for them that the watch-and-wait paradigm was established over a decade ago, and widely adopted since then. The idea is to hold off on surgery after a complete response to chemotherapy and radiation, to see if the patient really needs it.

While most do not, tumors regrow in 20%-30%, and when they come back, they tend to be aggressive, with poor outcomes. Patients in those situations would have been better off with upfront surgery.

The problem right now is that there’s no way to predict who will be cured by neoadjuvant therapy and whose tumor will come back, said Philip Paty, MD. FACS, a colorectal surgeon at Memorial Sloan Kettering Cancer Center, New York.

“There are some who are probably harmed by the watch-and-wait paradigm. The risk of local regrowth is hardbaked into [the model]; we haven’t been able to eliminate it,” he said at the annual clinical congress of the American College of Surgeons..

Dr. Paty is one of many investigators working to identify those at risk. In the meantime, watch-and-wait patients need to be followed closely, particularly in the first 2 years. Surgery is the best option at the first sign of regrowth. Dr. Paty explained his follow-up protocol, as well as the current state of watch and wait for low rectal cancer, in an interview at the meeting.

He also talked about overcoming hurdles. The risk of surgery, including permanent bowel and sexual dysfunction, is so great “that many patients latch onto watch and wait and won’t let go. They don’t come back for follow-up, or resist the idea of surgery even if it’s needed,” he said.

[email protected]

BOSTON – A quality improvement project conducted at the Cleveland Clinic dropped the 30-day colorectal surgery infection rate from 11.8% to 6.6%, driven mostly by a reduction in deep organ space infections from 5.5% to 1.7%.

It was a remarkable finding that got the attention of attendees at the annual clinical congress of the American College of Surgeons. The Cleveland Clinic had been an outlier, in the wrong direction, compared with other centers, and administrators wanted a solution.

I. Emre Gorgun, MD, FACS, a colorectal surgeon and quality improvement officer at Cleveland Clinic, led the search for evidence-based interventions. Eventually, big changes were made to perioperative antibiotics, mechanical bowel prep, preop shower routines, and intraoperative procedures. The efforts paid off (Dis Colon Rectum. 2018 Jan;61[1]:89-98).

To help surgeons lower their own infection rates, Dr. Gorgun agreed to an interview at the meeting to explain exactly what was done.

There was resistance at first from surgeons who wanted to stick with their routines, but they came around once they were shown the data backing the changes. Eventually, “everyone was on board. We believe in this,” Dr. Gorgun said.

[email protected]

BOSTON – A quality improvement project conducted at the Cleveland Clinic dropped the 30-day colorectal surgery infection rate from 11.8% to 6.6%, driven mostly by a reduction in deep organ space infections from 5.5% to 1.7%.

It was a remarkable finding that got the attention of attendees at the annual clinical congress of the American College of Surgeons. The Cleveland Clinic had been an outlier, in the wrong direction, compared with other centers, and administrators wanted a solution.

I. Emre Gorgun, MD, FACS, a colorectal surgeon and quality improvement officer at Cleveland Clinic, led the search for evidence-based interventions. Eventually, big changes were made to perioperative antibiotics, mechanical bowel prep, preop shower routines, and intraoperative procedures. The efforts paid off (Dis Colon Rectum. 2018 Jan;61[1]:89-98).

To help surgeons lower their own infection rates, Dr. Gorgun agreed to an interview at the meeting to explain exactly what was done.

There was resistance at first from surgeons who wanted to stick with their routines, but they came around once they were shown the data backing the changes. Eventually, “everyone was on board. We believe in this,” Dr. Gorgun said.

[email protected]

BOSTON – A quality improvement project conducted at the Cleveland Clinic dropped the 30-day colorectal surgery infection rate from 11.8% to 6.6%, driven mostly by a reduction in deep organ space infections from 5.5% to 1.7%.

It was a remarkable finding that got the attention of attendees at the annual clinical congress of the American College of Surgeons. The Cleveland Clinic had been an outlier, in the wrong direction, compared with other centers, and administrators wanted a solution.

I. Emre Gorgun, MD, FACS, a colorectal surgeon and quality improvement officer at Cleveland Clinic, led the search for evidence-based interventions. Eventually, big changes were made to perioperative antibiotics, mechanical bowel prep, preop shower routines, and intraoperative procedures. The efforts paid off (Dis Colon Rectum. 2018 Jan;61[1]:89-98).

To help surgeons lower their own infection rates, Dr. Gorgun agreed to an interview at the meeting to explain exactly what was done.

There was resistance at first from surgeons who wanted to stick with their routines, but they came around once they were shown the data backing the changes. Eventually, “everyone was on board. We believe in this,” Dr. Gorgun said.

[email protected]

BOSTON – Fat grafting has taken off in recent years, especially for breast reconstruction, but it’s become clear that it also has a role in scar treatment, according to Benjamin Levi, MD, director of the burn/wound and regenerative medicine laboratory at the University of Michigan, Ann Arbor.

Some corners of the Internet tout it as “some sort of magic stem cell surgery,” Dr. Levi said, but in reality, for scar surgeons, it’s just another useful tool in the armamentarium, one that excels at filling skin depressions due to underlying tissue loss, whether from burns, trauma, or surgery. Unlike hyaluronic acid and other options, fat grafts last; about half of injected adipocytes remain indefinitely. Fat grafting might also help soften scars, he said.

To get the most out of the procedure, of course, it has to be done correctly, so Dr. Levi took a few minutes at the annual clinical congress of the American College of Surgeons to share his tips on harvesting and spinning down fat grafts, injecting adipocytes, and other matters. Although the concepts of fat grafting are straightforward, the techniques are a bit tricky. Dr. Levi hoped his treatment pearls would help other physicians, especially those considering adding fat grafting to their practice.
 

[email protected]

BOSTON – Fat grafting has taken off in recent years, especially for breast reconstruction, but it’s become clear that it also has a role in scar treatment, according to Benjamin Levi, MD, director of the burn/wound and regenerative medicine laboratory at the University of Michigan, Ann Arbor.

Some corners of the Internet tout it as “some sort of magic stem cell surgery,” Dr. Levi said, but in reality, for scar surgeons, it’s just another useful tool in the armamentarium, one that excels at filling skin depressions due to underlying tissue loss, whether from burns, trauma, or surgery. Unlike hyaluronic acid and other options, fat grafts last; about half of injected adipocytes remain indefinitely. Fat grafting might also help soften scars, he said.

To get the most out of the procedure, of course, it has to be done correctly, so Dr. Levi took a few minutes at the annual clinical congress of the American College of Surgeons to share his tips on harvesting and spinning down fat grafts, injecting adipocytes, and other matters. Although the concepts of fat grafting are straightforward, the techniques are a bit tricky. Dr. Levi hoped his treatment pearls would help other physicians, especially those considering adding fat grafting to their practice.
 

[email protected]

BOSTON – Fat grafting has taken off in recent years, especially for breast reconstruction, but it’s become clear that it also has a role in scar treatment, according to Benjamin Levi, MD, director of the burn/wound and regenerative medicine laboratory at the University of Michigan, Ann Arbor.

Some corners of the Internet tout it as “some sort of magic stem cell surgery,” Dr. Levi said, but in reality, for scar surgeons, it’s just another useful tool in the armamentarium, one that excels at filling skin depressions due to underlying tissue loss, whether from burns, trauma, or surgery. Unlike hyaluronic acid and other options, fat grafts last; about half of injected adipocytes remain indefinitely. Fat grafting might also help soften scars, he said.

To get the most out of the procedure, of course, it has to be done correctly, so Dr. Levi took a few minutes at the annual clinical congress of the American College of Surgeons to share his tips on harvesting and spinning down fat grafts, injecting adipocytes, and other matters. Although the concepts of fat grafting are straightforward, the techniques are a bit tricky. Dr. Levi hoped his treatment pearls would help other physicians, especially those considering adding fat grafting to their practice.
 

[email protected]

BOSTON – Deep surgical site infections after retrorectus ventral hernia repair do not necessarily require mesh excision, according to Cleveland Clinic investigators.

When infected mesh is removed, however, there’s a novel approach that avoids the pitfalls of both immediate and staged abdominal wall reconstruction, according to a second team from the Georgetown University, Washington.

The two approaches were offered at the annual clinical congress of the American College of Surgery as alternatives to usual care. Infected ventral hernia mesh is a well-known headache for general surgeons, and management isn’t standardized. Surgeons are keenly alert for new approaches to improve outcomes; the presenters said they hoped their talks would help.

The work “is really pushing this forward, and giving us new data to manage a really vexing problem,” said an audience member.
 

Almost 80% salvageable

Infected meshes are usually removed, but the Cleveland Clinic investigators found that that’s often not necessary.

They reviewed 905 elective ventral hernia repairs at the clinic with synthetic sublay mesh in the retrorectus space. The median hernia width was about 15 cm, and the implanted mesh – usually medium- or heavy-weight polypropylene – had a mean area of 900 cm², “so these were big hernias with a lot of mesh. [Patients] often come to us as a last resort because they’ve been told no elsewhere,” said lead investigator Dominykas Burneikis, MD.

Twenty-four patients (2.7%) developed deep surgical site infections below the anterior rectus fascia. Instead of returning to the OR for new mesh, the team opened, drained, and debrided the wounds, and patients received antibiotics plus negative pressure wound therapy.

Those measures were enough for all but one patient. Mesh was generally found to be granulating well into surrounding tissue, so it was left completely intact in 19 cases (79%), and just trimmed a bit in four others. One man had an excision after his skin flap died and the hernia recurred. At 8 months, 11 patients were completely healed, and 12 had granulating wounds with no visible mesh. There were no cutaneous fistulas.

In short, “we had an 80% mesh salvage rate at 8 months, [which] led us to conclude that most synthetic mesh infections after retrorectus sublay repair do not require explanation,” Dr. Burneikis said.


 

A hybrid approach

When infected mesh does need to come out, abdominal wall reconstruction is either done in the same procedure or months later. Immediate reconstruction generally means operating in a contaminated field, with subsequent rates of wound infection of up to 48%. Delayed closure, meanwhile, means long-term wound care and temporary hernia recurrence, among other problems.

The Georgetown team reported good outcomes with a hybrid approach that combines the benefits of both procedures while avoiding their pitfalls. In the first step, mesh is removed, the abdominal wall debrided, fistulas taken down, and cultures obtained, explained lead investigator and surgery resident Kieranjeet Nijhar, MD.

The wound is temporarily closed with a sterile plastic liner under negative pressure, and patients are taken to the floor for IV antibiotics based on culture results. Three days later, after the infection has been knocked down, the patient is returned to the OR for debridement to healthy tissue and definitive reconstruction with biologic mesh. It’s all done during the same hospitalization.

Dr. Nijhar reviewed 53 cases at Georgetown since 2009. Patients were a mean age of 58 years, with an average body mass index of 35.1 kg/m². Infected mesh was most commonly underlain or retrorectus; mean defect size was 206 cm². Patients spent an average of 11 days in the hospital.

During a mean follow-up of about 9 months, 17 patients (32%) had surgical site problems – infection, dehiscence, hematoma, or seroma – and hernia recurred in six (11.3%); the results compare favorably with especially immediate reconstruction. As in prior studies, higher age and bridge repair were associated with recurrence and methicillin-resistant Staphylococcus aureus (MRSA) infection with surgical site problems.

“We propose this as a potential alternative for” repairs of ventral hernias with infected mesh, Dr. Nijhar said.

Dr. Nijhar and Dr. Burneikis had no relevant disclosures. There was no external funding for the work.
 

[email protected]

BOSTON – Deep surgical site infections after retrorectus ventral hernia repair do not necessarily require mesh excision, according to Cleveland Clinic investigators.

When infected mesh is removed, however, there’s a novel approach that avoids the pitfalls of both immediate and staged abdominal wall reconstruction, according to a second team from the Georgetown University, Washington.

The two approaches were offered at the annual clinical congress of the American College of Surgery as alternatives to usual care. Infected ventral hernia mesh is a well-known headache for general surgeons, and management isn’t standardized. Surgeons are keenly alert for new approaches to improve outcomes; the presenters said they hoped their talks would help.

The work “is really pushing this forward, and giving us new data to manage a really vexing problem,” said an audience member.
 

Almost 80% salvageable

Infected meshes are usually removed, but the Cleveland Clinic investigators found that that’s often not necessary.

They reviewed 905 elective ventral hernia repairs at the clinic with synthetic sublay mesh in the retrorectus space. The median hernia width was about 15 cm, and the implanted mesh – usually medium- or heavy-weight polypropylene – had a mean area of 900 cm², “so these were big hernias with a lot of mesh. [Patients] often come to us as a last resort because they’ve been told no elsewhere,” said lead investigator Dominykas Burneikis, MD.

Twenty-four patients (2.7%) developed deep surgical site infections below the anterior rectus fascia. Instead of returning to the OR for new mesh, the team opened, drained, and debrided the wounds, and patients received antibiotics plus negative pressure wound therapy.

Those measures were enough for all but one patient. Mesh was generally found to be granulating well into surrounding tissue, so it was left completely intact in 19 cases (79%), and just trimmed a bit in four others. One man had an excision after his skin flap died and the hernia recurred. At 8 months, 11 patients were completely healed, and 12 had granulating wounds with no visible mesh. There were no cutaneous fistulas.

In short, “we had an 80% mesh salvage rate at 8 months, [which] led us to conclude that most synthetic mesh infections after retrorectus sublay repair do not require explanation,” Dr. Burneikis said.


 

A hybrid approach

When infected mesh does need to come out, abdominal wall reconstruction is either done in the same procedure or months later. Immediate reconstruction generally means operating in a contaminated field, with subsequent rates of wound infection of up to 48%. Delayed closure, meanwhile, means long-term wound care and temporary hernia recurrence, among other problems.

The Georgetown team reported good outcomes with a hybrid approach that combines the benefits of both procedures while avoiding their pitfalls. In the first step, mesh is removed, the abdominal wall debrided, fistulas taken down, and cultures obtained, explained lead investigator and surgery resident Kieranjeet Nijhar, MD.

The wound is temporarily closed with a sterile plastic liner under negative pressure, and patients are taken to the floor for IV antibiotics based on culture results. Three days later, after the infection has been knocked down, the patient is returned to the OR for debridement to healthy tissue and definitive reconstruction with biologic mesh. It’s all done during the same hospitalization.

Dr. Nijhar reviewed 53 cases at Georgetown since 2009. Patients were a mean age of 58 years, with an average body mass index of 35.1 kg/m². Infected mesh was most commonly underlain or retrorectus; mean defect size was 206 cm². Patients spent an average of 11 days in the hospital.

During a mean follow-up of about 9 months, 17 patients (32%) had surgical site problems – infection, dehiscence, hematoma, or seroma – and hernia recurred in six (11.3%); the results compare favorably with especially immediate reconstruction. As in prior studies, higher age and bridge repair were associated with recurrence and methicillin-resistant Staphylococcus aureus (MRSA) infection with surgical site problems.

“We propose this as a potential alternative for” repairs of ventral hernias with infected mesh, Dr. Nijhar said.

Dr. Nijhar and Dr. Burneikis had no relevant disclosures. There was no external funding for the work.
 

[email protected]

BOSTON – Deep surgical site infections after retrorectus ventral hernia repair do not necessarily require mesh excision, according to Cleveland Clinic investigators.

When infected mesh is removed, however, there’s a novel approach that avoids the pitfalls of both immediate and staged abdominal wall reconstruction, according to a second team from the Georgetown University, Washington.

The two approaches were offered at the annual clinical congress of the American College of Surgery as alternatives to usual care. Infected ventral hernia mesh is a well-known headache for general surgeons, and management isn’t standardized. Surgeons are keenly alert for new approaches to improve outcomes; the presenters said they hoped their talks would help.

The work “is really pushing this forward, and giving us new data to manage a really vexing problem,” said an audience member.
 

Almost 80% salvageable

Infected meshes are usually removed, but the Cleveland Clinic investigators found that that’s often not necessary.

They reviewed 905 elective ventral hernia repairs at the clinic with synthetic sublay mesh in the retrorectus space. The median hernia width was about 15 cm, and the implanted mesh – usually medium- or heavy-weight polypropylene – had a mean area of 900 cm², “so these were big hernias with a lot of mesh. [Patients] often come to us as a last resort because they’ve been told no elsewhere,” said lead investigator Dominykas Burneikis, MD.

Twenty-four patients (2.7%) developed deep surgical site infections below the anterior rectus fascia. Instead of returning to the OR for new mesh, the team opened, drained, and debrided the wounds, and patients received antibiotics plus negative pressure wound therapy.

Those measures were enough for all but one patient. Mesh was generally found to be granulating well into surrounding tissue, so it was left completely intact in 19 cases (79%), and just trimmed a bit in four others. One man had an excision after his skin flap died and the hernia recurred. At 8 months, 11 patients were completely healed, and 12 had granulating wounds with no visible mesh. There were no cutaneous fistulas.

In short, “we had an 80% mesh salvage rate at 8 months, [which] led us to conclude that most synthetic mesh infections after retrorectus sublay repair do not require explanation,” Dr. Burneikis said.


 

A hybrid approach

When infected mesh does need to come out, abdominal wall reconstruction is either done in the same procedure or months later. Immediate reconstruction generally means operating in a contaminated field, with subsequent rates of wound infection of up to 48%. Delayed closure, meanwhile, means long-term wound care and temporary hernia recurrence, among other problems.

The Georgetown team reported good outcomes with a hybrid approach that combines the benefits of both procedures while avoiding their pitfalls. In the first step, mesh is removed, the abdominal wall debrided, fistulas taken down, and cultures obtained, explained lead investigator and surgery resident Kieranjeet Nijhar, MD.

The wound is temporarily closed with a sterile plastic liner under negative pressure, and patients are taken to the floor for IV antibiotics based on culture results. Three days later, after the infection has been knocked down, the patient is returned to the OR for debridement to healthy tissue and definitive reconstruction with biologic mesh. It’s all done during the same hospitalization.

Dr. Nijhar reviewed 53 cases at Georgetown since 2009. Patients were a mean age of 58 years, with an average body mass index of 35.1 kg/m². Infected mesh was most commonly underlain or retrorectus; mean defect size was 206 cm². Patients spent an average of 11 days in the hospital.

During a mean follow-up of about 9 months, 17 patients (32%) had surgical site problems – infection, dehiscence, hematoma, or seroma – and hernia recurred in six (11.3%); the results compare favorably with especially immediate reconstruction. As in prior studies, higher age and bridge repair were associated with recurrence and methicillin-resistant Staphylococcus aureus (MRSA) infection with surgical site problems.

“We propose this as a potential alternative for” repairs of ventral hernias with infected mesh, Dr. Nijhar said.

Dr. Nijhar and Dr. Burneikis had no relevant disclosures. There was no external funding for the work.
 

[email protected]

BOSTON – When surgeon Wendy R. Greene, MD, FACS, director of acute and critical care surgery at Emory University, Atlanta, asked a room of about 300 general surgeons at the annual clinical congress of the American College of Surgeons how many use needle aspiration first for breast abscesses, and how many use a scalpel, it was about a 50-50 split.

M. Alexander Otto/MDedge News

This divided response is why Dr. Greene addressed in her presentation the right approach to the problem of breast abscesses. In short, “for run-of-the-mill abscesses less than 5 cm, don’t get out the scalpel; get out the needle first,” she said.

Breast abscesses make women feel terrible. They have flulike symptoms, plus a warm, red, and tender bump on their breast. New mothers over age 30 years are most at risk, especially if they are past 40 weeks’ gestation.

There certainly are indications for the scalpel first. If the skin overlaying the abscess is dead, shiny, sloughing off, or leaking pus, or if the abscess is larger than 5 cm on ultrasound, a small stab incision is in order, and it should be made at the maximum point of fluctuation, after numbing the surrounding tissue. Put a wipe in place to catch the pus, debride as necessary, and “irrigate, irrigate, irrigate,” Dr. Greene said.

She uses suction to make sure all the pus is out, then injects a lidocaine into the cavity for pain control and lets it rest a few minutes before another round of suction.

Septic, deteriorating patients, and the immunocompromised, need a larger incision and drainage, with IV antibiotics in the hospital, but even in those cases, “avoid placing percutaneous drains; there’s rarely a role for them in modern management of breast abscesses.” Women will have poorer results and poorer cosmesis, Dr. Greene said.

Aggressive drainage isn’t necessary most of the time, and it can destroy healthy tissue and leave new mothers with breastfeeding problems and milk fistulas. There’s also a risk for scarring, deformity, and loss of the ability to lactate.

An 18-21 gauge needle with local anesthetic is usually enough. The lesion should be obvious on ultrasound, and it’s useful to guide the needle and ensure the cavity collapses on aspiration.

Dr. Greene said it also is important to culture milk in new mothers, and culture her infant’s nose and mouth, because cracked skin on the breast can let germs from nursing into the milk ducts.

Women are sent home after aspiration with antibiotics for 7-10 days, ones that are safe for nursing infants. They might be back with another abscess in a few weeks, so it’s important to be patient and ready for ongoing treatment.

The ultimate worry with recurrent cases is that a breast mass is blocking a milk duct, so mammography is often in order for repeat patients, especially with a family history of breast cancer. Wait until the acute infection has died down; a mammograph can be too painful otherwise, Dr. Greene said.

In the meantime, let infants nurse. They “are a great way to help drain the breast,” she said.

Dr. Greene had no relevant disclosures.

[email protected]

BOSTON – When surgeon Wendy R. Greene, MD, FACS, director of acute and critical care surgery at Emory University, Atlanta, asked a room of about 300 general surgeons at the annual clinical congress of the American College of Surgeons how many use needle aspiration first for breast abscesses, and how many use a scalpel, it was about a 50-50 split.

M. Alexander Otto/MDedge News

This divided response is why Dr. Greene addressed in her presentation the right approach to the problem of breast abscesses. In short, “for run-of-the-mill abscesses less than 5 cm, don’t get out the scalpel; get out the needle first,” she said.

Breast abscesses make women feel terrible. They have flulike symptoms, plus a warm, red, and tender bump on their breast. New mothers over age 30 years are most at risk, especially if they are past 40 weeks’ gestation.

There certainly are indications for the scalpel first. If the skin overlaying the abscess is dead, shiny, sloughing off, or leaking pus, or if the abscess is larger than 5 cm on ultrasound, a small stab incision is in order, and it should be made at the maximum point of fluctuation, after numbing the surrounding tissue. Put a wipe in place to catch the pus, debride as necessary, and “irrigate, irrigate, irrigate,” Dr. Greene said.

She uses suction to make sure all the pus is out, then injects a lidocaine into the cavity for pain control and lets it rest a few minutes before another round of suction.

Septic, deteriorating patients, and the immunocompromised, need a larger incision and drainage, with IV antibiotics in the hospital, but even in those cases, “avoid placing percutaneous drains; there’s rarely a role for them in modern management of breast abscesses.” Women will have poorer results and poorer cosmesis, Dr. Greene said.

Aggressive drainage isn’t necessary most of the time, and it can destroy healthy tissue and leave new mothers with breastfeeding problems and milk fistulas. There’s also a risk for scarring, deformity, and loss of the ability to lactate.

An 18-21 gauge needle with local anesthetic is usually enough. The lesion should be obvious on ultrasound, and it’s useful to guide the needle and ensure the cavity collapses on aspiration.

Dr. Greene said it also is important to culture milk in new mothers, and culture her infant’s nose and mouth, because cracked skin on the breast can let germs from nursing into the milk ducts.

Women are sent home after aspiration with antibiotics for 7-10 days, ones that are safe for nursing infants. They might be back with another abscess in a few weeks, so it’s important to be patient and ready for ongoing treatment.

The ultimate worry with recurrent cases is that a breast mass is blocking a milk duct, so mammography is often in order for repeat patients, especially with a family history of breast cancer. Wait until the acute infection has died down; a mammograph can be too painful otherwise, Dr. Greene said.

In the meantime, let infants nurse. They “are a great way to help drain the breast,” she said.

Dr. Greene had no relevant disclosures.

[email protected]

BOSTON – When surgeon Wendy R. Greene, MD, FACS, director of acute and critical care surgery at Emory University, Atlanta, asked a room of about 300 general surgeons at the annual clinical congress of the American College of Surgeons how many use needle aspiration first for breast abscesses, and how many use a scalpel, it was about a 50-50 split.

M. Alexander Otto/MDedge News

This divided response is why Dr. Greene addressed in her presentation the right approach to the problem of breast abscesses. In short, “for run-of-the-mill abscesses less than 5 cm, don’t get out the scalpel; get out the needle first,” she said.

Breast abscesses make women feel terrible. They have flulike symptoms, plus a warm, red, and tender bump on their breast. New mothers over age 30 years are most at risk, especially if they are past 40 weeks’ gestation.

There certainly are indications for the scalpel first. If the skin overlaying the abscess is dead, shiny, sloughing off, or leaking pus, or if the abscess is larger than 5 cm on ultrasound, a small stab incision is in order, and it should be made at the maximum point of fluctuation, after numbing the surrounding tissue. Put a wipe in place to catch the pus, debride as necessary, and “irrigate, irrigate, irrigate,” Dr. Greene said.

She uses suction to make sure all the pus is out, then injects a lidocaine into the cavity for pain control and lets it rest a few minutes before another round of suction.

Septic, deteriorating patients, and the immunocompromised, need a larger incision and drainage, with IV antibiotics in the hospital, but even in those cases, “avoid placing percutaneous drains; there’s rarely a role for them in modern management of breast abscesses.” Women will have poorer results and poorer cosmesis, Dr. Greene said.

Aggressive drainage isn’t necessary most of the time, and it can destroy healthy tissue and leave new mothers with breastfeeding problems and milk fistulas. There’s also a risk for scarring, deformity, and loss of the ability to lactate.

An 18-21 gauge needle with local anesthetic is usually enough. The lesion should be obvious on ultrasound, and it’s useful to guide the needle and ensure the cavity collapses on aspiration.

Dr. Greene said it also is important to culture milk in new mothers, and culture her infant’s nose and mouth, because cracked skin on the breast can let germs from nursing into the milk ducts.

Women are sent home after aspiration with antibiotics for 7-10 days, ones that are safe for nursing infants. They might be back with another abscess in a few weeks, so it’s important to be patient and ready for ongoing treatment.

The ultimate worry with recurrent cases is that a breast mass is blocking a milk duct, so mammography is often in order for repeat patients, especially with a family history of breast cancer. Wait until the acute infection has died down; a mammograph can be too painful otherwise, Dr. Greene said.

In the meantime, let infants nurse. They “are a great way to help drain the breast,” she said.

Dr. Greene had no relevant disclosures.

[email protected]

SAN DIEGO – Denervation of the main renal arteries with ultrasound is more effective than radiofrequency (RF) ablation at lowering blood pressure in patients with resistant hypertension, according to a single-center, randomized trial from Germany.

M. Alexander Otto/MDedge News

Dubbed RADIOSOUND–HTN, it was the first time the two emerging technologies have been pitted against each other. At 3-month follow-up, the 42 patients randomized to ultrasound ablation with the Paradise catheter (ReCor Medical) had a mean systolic daytime blood pressure reduction of 13.2 mm Hg on ambulatory monitoring, vs. 6.5 mm Hg among 39 patients randomized to RF ablation with Medtronic’s Symplicity Spyral catheter (P = .043).
 

Meanwhile, 39 patients randomized to both main artery and side branch ablation with the Spyral had a mean reduction of 8.3 mm Hg, slightly better than RF ablation of the main renal arteries alone, but the difference was not statistically significant, and “no definite conclusion on the value of an additional side branch ablation can be drawn,” said senior investigator Philipp Lurz , MD, PhD, a cardiologist at the University of Leipzig, Germany, and his colleagues (Circulation. 2018 Sep 25. doi: 10.1161/circulationaha.118.037654).

Denervation was probably more complete with the Paradise catheter, which might explain the results. Ultrasound energy penetrates about 6-7 mm from the lumen, reaching up to 90% of sympathetic nerve fibers, while RF energy penetrates 3-4 mm; indeed, the idea of going into the branches with RF ablation is because nerve fibers are closer to the lumen surface, Dr. Lurz said at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, where he presented the study, which was simultaneously published in Circulation.

Also, the Paradise catheter – an endovascular balloon device inflated to fit the lumen – delivers fully circumferential, ringlike ablations with each application, while the Spyral catheter delivers four ablations simultaneously in a spiral pattern, and requires more ablations to create a similar effect, according to Dr. Lurz.

About two-thirds of patients in all three arms responded to treatment, meaning at least a 5 mm Hg drop in systolic blood pressure. Among the nonresponders, it’s possible that their hypertension wasn’t caused by sympathetic overdrive. “Future trials should focus on identifying these patients to avoid futile” procedures, and define “specific anatomic predictors associated with a more effective” renal denervation, Dr. Lurz and his team said in their study report.

The researchers noted that “the present study included patients with larger renal arteries” – at least one renal artery 5.5 mm or greater in diameter – “based on the assumption that sympathetic fibers are in greater distance from the lumen than in smaller arteries, and therefore ... higher penetration depth would be more relevant ... Results might have differed in a cohort of patients with smaller renal artery diameters.”

Both Paradise and Spyral are in pivotal trials for Food and Drug Administration approval.

The subjects were an average of 64 years. The majority were men, and there were no significant differences in baseline characteristics between the arms. The mean baseline daytime blood pressure was 153/86 mm Hg despite treatment with three or more classes of antihypertensives dosed to at least 50% of their maximum. There was no drug testing to confirm patients were taking their medications, but their general practitioners vouched for their adherence.

One patient in the ultrasound arm group developed a pseudoaneurysm treated successfully by compression. One of the RF subjects developed a postprocedural intracapsular and retroperitoneal hematoma that resolved spontaneously. No renal vascular complications or stenoses were detected at follow-up.

There was no industry funding for the work. Dr. Lurz is a speaker and consultant for both ReCor Medical and Medtronic.
 

[email protected]

SOURCE: Fengler K et al. TCT 2018, Abstract.

SAN DIEGO – Denervation of the main renal arteries with ultrasound is more effective than radiofrequency (RF) ablation at lowering blood pressure in patients with resistant hypertension, according to a single-center, randomized trial from Germany.

M. Alexander Otto/MDedge News

Dubbed RADIOSOUND–HTN, it was the first time the two emerging technologies have been pitted against each other. At 3-month follow-up, the 42 patients randomized to ultrasound ablation with the Paradise catheter (ReCor Medical) had a mean systolic daytime blood pressure reduction of 13.2 mm Hg on ambulatory monitoring, vs. 6.5 mm Hg among 39 patients randomized to RF ablation with Medtronic’s Symplicity Spyral catheter (P = .043).
 

Meanwhile, 39 patients randomized to both main artery and side branch ablation with the Spyral had a mean reduction of 8.3 mm Hg, slightly better than RF ablation of the main renal arteries alone, but the difference was not statistically significant, and “no definite conclusion on the value of an additional side branch ablation can be drawn,” said senior investigator Philipp Lurz , MD, PhD, a cardiologist at the University of Leipzig, Germany, and his colleagues (Circulation. 2018 Sep 25. doi: 10.1161/circulationaha.118.037654).

Denervation was probably more complete with the Paradise catheter, which might explain the results. Ultrasound energy penetrates about 6-7 mm from the lumen, reaching up to 90% of sympathetic nerve fibers, while RF energy penetrates 3-4 mm; indeed, the idea of going into the branches with RF ablation is because nerve fibers are closer to the lumen surface, Dr. Lurz said at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, where he presented the study, which was simultaneously published in Circulation.

Also, the Paradise catheter – an endovascular balloon device inflated to fit the lumen – delivers fully circumferential, ringlike ablations with each application, while the Spyral catheter delivers four ablations simultaneously in a spiral pattern, and requires more ablations to create a similar effect, according to Dr. Lurz.

About two-thirds of patients in all three arms responded to treatment, meaning at least a 5 mm Hg drop in systolic blood pressure. Among the nonresponders, it’s possible that their hypertension wasn’t caused by sympathetic overdrive. “Future trials should focus on identifying these patients to avoid futile” procedures, and define “specific anatomic predictors associated with a more effective” renal denervation, Dr. Lurz and his team said in their study report.

The researchers noted that “the present study included patients with larger renal arteries” – at least one renal artery 5.5 mm or greater in diameter – “based on the assumption that sympathetic fibers are in greater distance from the lumen than in smaller arteries, and therefore ... higher penetration depth would be more relevant ... Results might have differed in a cohort of patients with smaller renal artery diameters.”

Both Paradise and Spyral are in pivotal trials for Food and Drug Administration approval.

The subjects were an average of 64 years. The majority were men, and there were no significant differences in baseline characteristics between the arms. The mean baseline daytime blood pressure was 153/86 mm Hg despite treatment with three or more classes of antihypertensives dosed to at least 50% of their maximum. There was no drug testing to confirm patients were taking their medications, but their general practitioners vouched for their adherence.

One patient in the ultrasound arm group developed a pseudoaneurysm treated successfully by compression. One of the RF subjects developed a postprocedural intracapsular and retroperitoneal hematoma that resolved spontaneously. No renal vascular complications or stenoses were detected at follow-up.

There was no industry funding for the work. Dr. Lurz is a speaker and consultant for both ReCor Medical and Medtronic.
 

[email protected]

SOURCE: Fengler K et al. TCT 2018, Abstract.

SAN DIEGO – Denervation of the main renal arteries with ultrasound is more effective than radiofrequency (RF) ablation at lowering blood pressure in patients with resistant hypertension, according to a single-center, randomized trial from Germany.

M. Alexander Otto/MDedge News

Dubbed RADIOSOUND–HTN, it was the first time the two emerging technologies have been pitted against each other. At 3-month follow-up, the 42 patients randomized to ultrasound ablation with the Paradise catheter (ReCor Medical) had a mean systolic daytime blood pressure reduction of 13.2 mm Hg on ambulatory monitoring, vs. 6.5 mm Hg among 39 patients randomized to RF ablation with Medtronic’s Symplicity Spyral catheter (P = .043).
 

Meanwhile, 39 patients randomized to both main artery and side branch ablation with the Spyral had a mean reduction of 8.3 mm Hg, slightly better than RF ablation of the main renal arteries alone, but the difference was not statistically significant, and “no definite conclusion on the value of an additional side branch ablation can be drawn,” said senior investigator Philipp Lurz , MD, PhD, a cardiologist at the University of Leipzig, Germany, and his colleagues (Circulation. 2018 Sep 25. doi: 10.1161/circulationaha.118.037654).

Denervation was probably more complete with the Paradise catheter, which might explain the results. Ultrasound energy penetrates about 6-7 mm from the lumen, reaching up to 90% of sympathetic nerve fibers, while RF energy penetrates 3-4 mm; indeed, the idea of going into the branches with RF ablation is because nerve fibers are closer to the lumen surface, Dr. Lurz said at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, where he presented the study, which was simultaneously published in Circulation.

Also, the Paradise catheter – an endovascular balloon device inflated to fit the lumen – delivers fully circumferential, ringlike ablations with each application, while the Spyral catheter delivers four ablations simultaneously in a spiral pattern, and requires more ablations to create a similar effect, according to Dr. Lurz.

About two-thirds of patients in all three arms responded to treatment, meaning at least a 5 mm Hg drop in systolic blood pressure. Among the nonresponders, it’s possible that their hypertension wasn’t caused by sympathetic overdrive. “Future trials should focus on identifying these patients to avoid futile” procedures, and define “specific anatomic predictors associated with a more effective” renal denervation, Dr. Lurz and his team said in their study report.

The researchers noted that “the present study included patients with larger renal arteries” – at least one renal artery 5.5 mm or greater in diameter – “based on the assumption that sympathetic fibers are in greater distance from the lumen than in smaller arteries, and therefore ... higher penetration depth would be more relevant ... Results might have differed in a cohort of patients with smaller renal artery diameters.”

Both Paradise and Spyral are in pivotal trials for Food and Drug Administration approval.

The subjects were an average of 64 years. The majority were men, and there were no significant differences in baseline characteristics between the arms. The mean baseline daytime blood pressure was 153/86 mm Hg despite treatment with three or more classes of antihypertensives dosed to at least 50% of their maximum. There was no drug testing to confirm patients were taking their medications, but their general practitioners vouched for their adherence.

One patient in the ultrasound arm group developed a pseudoaneurysm treated successfully by compression. One of the RF subjects developed a postprocedural intracapsular and retroperitoneal hematoma that resolved spontaneously. No renal vascular complications or stenoses were detected at follow-up.

There was no industry funding for the work. Dr. Lurz is a speaker and consultant for both ReCor Medical and Medtronic.
 

[email protected]

SOURCE: Fengler K et al. TCT 2018, Abstract.

BOSTON – A new surgical option for stage IV colon cancer with isolated liver metastases is beginning to attract attention: the liver-first approach.

It’s an alternative to usual care, meaning simultaneous bowel and liver resection or bowel resection with liver surgery later on.

Systemic chemotherapy comes first, followed by liver resection. If margins are microscopically negative, the patient gets another round of chemotherapy. If no additional lesions emerge, the primary tumor is taken out. The entire process can take up to a year.

The approach was developed in the Netherlands for rectal cancer with advanced liver metastases. The idea was to get the liver lesions out before they became unresectable, then remove the primary tumor later on. It’s gaining traction now for colon cancer, and beginning to trickle into the United States at a few academic medical centers.

It comes down to what’s more dangerous, the metastases or the primary tumor? Tumor science hasn’t answered that question yet. There’s general agreement that metastases are what kill people with cancer, but it’s not known if they come mostly from previous metastases or from the primary tumor. The liver-first approach assumes the former.

M. Alexander Otto/MDedge News

Liver-first is “extremely controversial. For older surgeons who are not in tertiary care centers, liver-first doesn’t make sense, and it doesn’t seem to make sense to patients. They wonder why you would go after the liver when they were diagnosed with a colon tumor,” said Janice Rafferty, MD, FACS, professor of surgery at the University of Cincinnati, at the annual clinical congress of the American College of Surgeons.

“Well, it’s because the primary tumor doesn’t limit your life,” she continued. “The life-limiting disease is in the liver, not the colon. If you explain it to them that way, it makes sense. If we cannot get an R0 resection on the liver, it doesn’t make sense to go after the primary, unless it’s symptomatic with obstruction, bleeding, or fistula.”

There have been about 10 attempts at a randomized trial of this approach versus usual care, but they were not successful because of the difficulty of recruiting patients. Patients – and no doubt, some surgeons – may have some resistance to the logic of going after metastases first.

Dr. Rafferty moderated a review of research from Yale University, New Haven, Conn., that attempted to plug the evidence gap. The Yale investigators “presented really interesting data that shows that liver-first has improved survival,” she said.

The Yale team used the National Cancer Database to compare 2010-2015 outcomes from liver-first patients with patients who had simultaneous or bowel-first resections, followed by later liver resections. The database didn’t allow them to tease out simultaneous from bowel-first cases, so they lumped them together as usual care. To avoid confounding, rectal carcinomas and metastases to the lung, brain, and other organs were excluded.

Median survival was 34 months among 358 liver-first patients versus 24 months among 18,042 usual care patients in an intention-to-treat analysis. Among patients who completed their resections, median survival was 57 months among 140 liver-first patients versus 36 months with usual care in 3,988.

The benefit held after adjustment for patient and tumor characteristics (hazard ratio for death 0.77 in favor of liver first). When further adjusted for chemotherapy timing, there was a strong trend for liver-first but it was not statistically significant, suggesting that up-front chemotherapy contributed to the results (HR, 0.88; 95% confidence interval, 0.75-1.01; P = .09).

There were many caveats. The liver-first patients were younger, with over half under the age of 60 years versus just over 40% in usual care. They were also healthier based on Charlson comorbidity scores and more likely to have upfront chemotherapy and be treated at an academic center.

So, what should surgeons make of these findings? Lead investigator Vadim Kurbatov, MD, a Yale surgery resident, argued that, at the very least, they suggest that liver-first is a viable option for stage IV colon cancer with isolated liver metastases. Going further, they suggest that liver first may be the right way to go for younger, healthier patients at academic centers.

For sicker stage IV patients, however, the role of liver-first is unclear. “We really do need a randomized trial,” he said.

Dr. Kurbatov and Dr. Rafferty had no relevant disclosures to report. The work was funded in part by the National Institutes of Health.

[email protected]

BOSTON – A new surgical option for stage IV colon cancer with isolated liver metastases is beginning to attract attention: the liver-first approach.

It’s an alternative to usual care, meaning simultaneous bowel and liver resection or bowel resection with liver surgery later on.

Systemic chemotherapy comes first, followed by liver resection. If margins are microscopically negative, the patient gets another round of chemotherapy. If no additional lesions emerge, the primary tumor is taken out. The entire process can take up to a year.

The approach was developed in the Netherlands for rectal cancer with advanced liver metastases. The idea was to get the liver lesions out before they became unresectable, then remove the primary tumor later on. It’s gaining traction now for colon cancer, and beginning to trickle into the United States at a few academic medical centers.

It comes down to what’s more dangerous, the metastases or the primary tumor? Tumor science hasn’t answered that question yet. There’s general agreement that metastases are what kill people with cancer, but it’s not known if they come mostly from previous metastases or from the primary tumor. The liver-first approach assumes the former.

M. Alexander Otto/MDedge News

Liver-first is “extremely controversial. For older surgeons who are not in tertiary care centers, liver-first doesn’t make sense, and it doesn’t seem to make sense to patients. They wonder why you would go after the liver when they were diagnosed with a colon tumor,” said Janice Rafferty, MD, FACS, professor of surgery at the University of Cincinnati, at the annual clinical congress of the American College of Surgeons.

“Well, it’s because the primary tumor doesn’t limit your life,” she continued. “The life-limiting disease is in the liver, not the colon. If you explain it to them that way, it makes sense. If we cannot get an R0 resection on the liver, it doesn’t make sense to go after the primary, unless it’s symptomatic with obstruction, bleeding, or fistula.”

There have been about 10 attempts at a randomized trial of this approach versus usual care, but they were not successful because of the difficulty of recruiting patients. Patients – and no doubt, some surgeons – may have some resistance to the logic of going after metastases first.

Dr. Rafferty moderated a review of research from Yale University, New Haven, Conn., that attempted to plug the evidence gap. The Yale investigators “presented really interesting data that shows that liver-first has improved survival,” she said.

The Yale team used the National Cancer Database to compare 2010-2015 outcomes from liver-first patients with patients who had simultaneous or bowel-first resections, followed by later liver resections. The database didn’t allow them to tease out simultaneous from bowel-first cases, so they lumped them together as usual care. To avoid confounding, rectal carcinomas and metastases to the lung, brain, and other organs were excluded.

Median survival was 34 months among 358 liver-first patients versus 24 months among 18,042 usual care patients in an intention-to-treat analysis. Among patients who completed their resections, median survival was 57 months among 140 liver-first patients versus 36 months with usual care in 3,988.

The benefit held after adjustment for patient and tumor characteristics (hazard ratio for death 0.77 in favor of liver first). When further adjusted for chemotherapy timing, there was a strong trend for liver-first but it was not statistically significant, suggesting that up-front chemotherapy contributed to the results (HR, 0.88; 95% confidence interval, 0.75-1.01; P = .09).

There were many caveats. The liver-first patients were younger, with over half under the age of 60 years versus just over 40% in usual care. They were also healthier based on Charlson comorbidity scores and more likely to have upfront chemotherapy and be treated at an academic center.

So, what should surgeons make of these findings? Lead investigator Vadim Kurbatov, MD, a Yale surgery resident, argued that, at the very least, they suggest that liver-first is a viable option for stage IV colon cancer with isolated liver metastases. Going further, they suggest that liver first may be the right way to go for younger, healthier patients at academic centers.

For sicker stage IV patients, however, the role of liver-first is unclear. “We really do need a randomized trial,” he said.

Dr. Kurbatov and Dr. Rafferty had no relevant disclosures to report. The work was funded in part by the National Institutes of Health.

[email protected]

BOSTON – A new surgical option for stage IV colon cancer with isolated liver metastases is beginning to attract attention: the liver-first approach.

It’s an alternative to usual care, meaning simultaneous bowel and liver resection or bowel resection with liver surgery later on.

Systemic chemotherapy comes first, followed by liver resection. If margins are microscopically negative, the patient gets another round of chemotherapy. If no additional lesions emerge, the primary tumor is taken out. The entire process can take up to a year.

The approach was developed in the Netherlands for rectal cancer with advanced liver metastases. The idea was to get the liver lesions out before they became unresectable, then remove the primary tumor later on. It’s gaining traction now for colon cancer, and beginning to trickle into the United States at a few academic medical centers.

It comes down to what’s more dangerous, the metastases or the primary tumor? Tumor science hasn’t answered that question yet. There’s general agreement that metastases are what kill people with cancer, but it’s not known if they come mostly from previous metastases or from the primary tumor. The liver-first approach assumes the former.

M. Alexander Otto/MDedge News

Liver-first is “extremely controversial. For older surgeons who are not in tertiary care centers, liver-first doesn’t make sense, and it doesn’t seem to make sense to patients. They wonder why you would go after the liver when they were diagnosed with a colon tumor,” said Janice Rafferty, MD, FACS, professor of surgery at the University of Cincinnati, at the annual clinical congress of the American College of Surgeons.

“Well, it’s because the primary tumor doesn’t limit your life,” she continued. “The life-limiting disease is in the liver, not the colon. If you explain it to them that way, it makes sense. If we cannot get an R0 resection on the liver, it doesn’t make sense to go after the primary, unless it’s symptomatic with obstruction, bleeding, or fistula.”

There have been about 10 attempts at a randomized trial of this approach versus usual care, but they were not successful because of the difficulty of recruiting patients. Patients – and no doubt, some surgeons – may have some resistance to the logic of going after metastases first.

Dr. Rafferty moderated a review of research from Yale University, New Haven, Conn., that attempted to plug the evidence gap. The Yale investigators “presented really interesting data that shows that liver-first has improved survival,” she said.

The Yale team used the National Cancer Database to compare 2010-2015 outcomes from liver-first patients with patients who had simultaneous or bowel-first resections, followed by later liver resections. The database didn’t allow them to tease out simultaneous from bowel-first cases, so they lumped them together as usual care. To avoid confounding, rectal carcinomas and metastases to the lung, brain, and other organs were excluded.

Median survival was 34 months among 358 liver-first patients versus 24 months among 18,042 usual care patients in an intention-to-treat analysis. Among patients who completed their resections, median survival was 57 months among 140 liver-first patients versus 36 months with usual care in 3,988.

The benefit held after adjustment for patient and tumor characteristics (hazard ratio for death 0.77 in favor of liver first). When further adjusted for chemotherapy timing, there was a strong trend for liver-first but it was not statistically significant, suggesting that up-front chemotherapy contributed to the results (HR, 0.88; 95% confidence interval, 0.75-1.01; P = .09).

There were many caveats. The liver-first patients were younger, with over half under the age of 60 years versus just over 40% in usual care. They were also healthier based on Charlson comorbidity scores and more likely to have upfront chemotherapy and be treated at an academic center.

So, what should surgeons make of these findings? Lead investigator Vadim Kurbatov, MD, a Yale surgery resident, argued that, at the very least, they suggest that liver-first is a viable option for stage IV colon cancer with isolated liver metastases. Going further, they suggest that liver first may be the right way to go for younger, healthier patients at academic centers.

For sicker stage IV patients, however, the role of liver-first is unclear. “We really do need a randomized trial,” he said.

Dr. Kurbatov and Dr. Rafferty had no relevant disclosures to report. The work was funded in part by the National Institutes of Health.

[email protected]

BOSTON – When pancreatitis symptoms don’t resolve within a month, patients need some sort of surgical intervention, according to Steven Hughes, MD, FACS, professor and chief of surgical oncology at the University of Florida, Gainesville.

Pancreatitis management has been evolving in recent years. Prophylactic antibiotics and total parenteral nutrition are out; tube feeds are in, and there’s compelling evidence to take the gallbladder out, regardless of etiology, he said at the annual clinical congress of the American College of Surgeons.

However, too many patients get drains placed in the first 2 weeks; it’s the wrong move because it consigns to surgery a lot of patients who otherwise would have recovered on their own. “In the first 2 weeks, please do not place drains. Once you place the drain, you have committed the patient to a very different clinical course,” Dr. Hughes said.

Surgery generally comes a month or more after the initial presentation. Infection is inevitable at that point; the delay gives the lesion time to consolidate and wall itself off, making for a cleaner, safer operation.

Transgastric necrosectomy is the go-to when pancreatic lesions are toward the midline. It’s Dr. Hughes’s favored approach when the anatomy is appropriate; he shared his thoughts at the meeting.

Transgastric necrosectomy provides “single-stop shopping. You can get a thorough debridement in a single procedure,” and durable internal drainage. “Most importantly, from a patient’s perspective, it leaves them without external drains. You can transition a patient who’s been percutaneously drained to no external drainage at the time of this operation,” he said.

Additional pluses include cholecystectomy either before or after necrosectomy and the ability to place enteric feeding systems. “I like to use a combination G-J tube that allows drainage of the emptying stomach along with distal tube feeds,” he said.

Laparoscopic and endoscopic approaches are possible, but Dr. Hughes favors an open procedure “because the finger is the best debriding tool I have found.” There’s an anterior and then posterior gastric incision to dig out the necroma. The anterior incision is closed, but the posterior cut is sealed open to the necroma with a running hemostatic suture to allow for a “large cavity between the cavity and the stomach” for ongoing drainage.

“I have ultrasound on the field, but typically finding the necroma is like falling out of a canoe and finding water.” Even so, “I like to bring a 10-mm straight scope for direct viewing onto the field to explore the necrotic cavity and ensure I’ve done an adequate necrosectomy,” he said.

“I do think that this operation can be performed in patients who have some retrocolic extension even over into the pancreatic head and down the right paracolic gutter, but certainly if the collection extends down towards the pelvis, the notion that this is going to be adequate in and of itself requires further investigation,” he said.

In a cohort of 18 patients he and his colleagues followed for at least 2 years, “I was impressed that this operation is rather durable,” with rapid resolution of disease, Dr. Hughes said. Just a couple people needed additional operations. “The majority created persistent fistulas between the pancreatic body tail and the stomach.”

He cautioned that the procedure “is not for the faint of heart. The splenic vein and the splenic artery as well the celiac axis and portal vein are at risk during this procedure, and if you get into them, you have got a wolf by both ears. I would encourage you to consider referral for these patients.”

Dr. Hughes strongly encouraged surgeons to “ make sure your interventional radiologists and advanced endoscopists are on board, whether for the postop pseudoaneurysm bleeding or recurrent sepsis.”

Dr. Hughes had no relevant disclosures to report.

[email protected]

BOSTON – When pancreatitis symptoms don’t resolve within a month, patients need some sort of surgical intervention, according to Steven Hughes, MD, FACS, professor and chief of surgical oncology at the University of Florida, Gainesville.

Pancreatitis management has been evolving in recent years. Prophylactic antibiotics and total parenteral nutrition are out; tube feeds are in, and there’s compelling evidence to take the gallbladder out, regardless of etiology, he said at the annual clinical congress of the American College of Surgeons.

However, too many patients get drains placed in the first 2 weeks; it’s the wrong move because it consigns to surgery a lot of patients who otherwise would have recovered on their own. “In the first 2 weeks, please do not place drains. Once you place the drain, you have committed the patient to a very different clinical course,” Dr. Hughes said.

Surgery generally comes a month or more after the initial presentation. Infection is inevitable at that point; the delay gives the lesion time to consolidate and wall itself off, making for a cleaner, safer operation.

Transgastric necrosectomy is the go-to when pancreatic lesions are toward the midline. It’s Dr. Hughes’s favored approach when the anatomy is appropriate; he shared his thoughts at the meeting.

Transgastric necrosectomy provides “single-stop shopping. You can get a thorough debridement in a single procedure,” and durable internal drainage. “Most importantly, from a patient’s perspective, it leaves them without external drains. You can transition a patient who’s been percutaneously drained to no external drainage at the time of this operation,” he said.

Additional pluses include cholecystectomy either before or after necrosectomy and the ability to place enteric feeding systems. “I like to use a combination G-J tube that allows drainage of the emptying stomach along with distal tube feeds,” he said.

Laparoscopic and endoscopic approaches are possible, but Dr. Hughes favors an open procedure “because the finger is the best debriding tool I have found.” There’s an anterior and then posterior gastric incision to dig out the necroma. The anterior incision is closed, but the posterior cut is sealed open to the necroma with a running hemostatic suture to allow for a “large cavity between the cavity and the stomach” for ongoing drainage.

“I have ultrasound on the field, but typically finding the necroma is like falling out of a canoe and finding water.” Even so, “I like to bring a 10-mm straight scope for direct viewing onto the field to explore the necrotic cavity and ensure I’ve done an adequate necrosectomy,” he said.

“I do think that this operation can be performed in patients who have some retrocolic extension even over into the pancreatic head and down the right paracolic gutter, but certainly if the collection extends down towards the pelvis, the notion that this is going to be adequate in and of itself requires further investigation,” he said.

In a cohort of 18 patients he and his colleagues followed for at least 2 years, “I was impressed that this operation is rather durable,” with rapid resolution of disease, Dr. Hughes said. Just a couple people needed additional operations. “The majority created persistent fistulas between the pancreatic body tail and the stomach.”

He cautioned that the procedure “is not for the faint of heart. The splenic vein and the splenic artery as well the celiac axis and portal vein are at risk during this procedure, and if you get into them, you have got a wolf by both ears. I would encourage you to consider referral for these patients.”

Dr. Hughes strongly encouraged surgeons to “ make sure your interventional radiologists and advanced endoscopists are on board, whether for the postop pseudoaneurysm bleeding or recurrent sepsis.”

Dr. Hughes had no relevant disclosures to report.

[email protected]

BOSTON – When pancreatitis symptoms don’t resolve within a month, patients need some sort of surgical intervention, according to Steven Hughes, MD, FACS, professor and chief of surgical oncology at the University of Florida, Gainesville.

Pancreatitis management has been evolving in recent years. Prophylactic antibiotics and total parenteral nutrition are out; tube feeds are in, and there’s compelling evidence to take the gallbladder out, regardless of etiology, he said at the annual clinical congress of the American College of Surgeons.

However, too many patients get drains placed in the first 2 weeks; it’s the wrong move because it consigns to surgery a lot of patients who otherwise would have recovered on their own. “In the first 2 weeks, please do not place drains. Once you place the drain, you have committed the patient to a very different clinical course,” Dr. Hughes said.

Surgery generally comes a month or more after the initial presentation. Infection is inevitable at that point; the delay gives the lesion time to consolidate and wall itself off, making for a cleaner, safer operation.

Transgastric necrosectomy is the go-to when pancreatic lesions are toward the midline. It’s Dr. Hughes’s favored approach when the anatomy is appropriate; he shared his thoughts at the meeting.

Transgastric necrosectomy provides “single-stop shopping. You can get a thorough debridement in a single procedure,” and durable internal drainage. “Most importantly, from a patient’s perspective, it leaves them without external drains. You can transition a patient who’s been percutaneously drained to no external drainage at the time of this operation,” he said.

Additional pluses include cholecystectomy either before or after necrosectomy and the ability to place enteric feeding systems. “I like to use a combination G-J tube that allows drainage of the emptying stomach along with distal tube feeds,” he said.

Laparoscopic and endoscopic approaches are possible, but Dr. Hughes favors an open procedure “because the finger is the best debriding tool I have found.” There’s an anterior and then posterior gastric incision to dig out the necroma. The anterior incision is closed, but the posterior cut is sealed open to the necroma with a running hemostatic suture to allow for a “large cavity between the cavity and the stomach” for ongoing drainage.

“I have ultrasound on the field, but typically finding the necroma is like falling out of a canoe and finding water.” Even so, “I like to bring a 10-mm straight scope for direct viewing onto the field to explore the necrotic cavity and ensure I’ve done an adequate necrosectomy,” he said.

“I do think that this operation can be performed in patients who have some retrocolic extension even over into the pancreatic head and down the right paracolic gutter, but certainly if the collection extends down towards the pelvis, the notion that this is going to be adequate in and of itself requires further investigation,” he said.

In a cohort of 18 patients he and his colleagues followed for at least 2 years, “I was impressed that this operation is rather durable,” with rapid resolution of disease, Dr. Hughes said. Just a couple people needed additional operations. “The majority created persistent fistulas between the pancreatic body tail and the stomach.”

He cautioned that the procedure “is not for the faint of heart. The splenic vein and the splenic artery as well the celiac axis and portal vein are at risk during this procedure, and if you get into them, you have got a wolf by both ears. I would encourage you to consider referral for these patients.”

Dr. Hughes strongly encouraged surgeons to “ make sure your interventional radiologists and advanced endoscopists are on board, whether for the postop pseudoaneurysm bleeding or recurrent sepsis.”

Dr. Hughes had no relevant disclosures to report.

[email protected]

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3