Peter Nau

NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia

Cachexia is a debilitating condition characterized by extreme skeletal muscle wasting that contributes significantly to morbidity and mortality. Efforts to elucidate the underlying mechanisms of muscle loss have predominantly focused on events intrinsic to the myofiber. In contrast, less regard has been given to potential contributory factors outside the fiber within the muscle microenvironment. In tumor-bearing mice and patients with pancreatic cancer, we found that cachexia was associated with a type of muscle damage resulting in activation of both satellite and nonsatellite muscle progenitor cells. These muscle progenitors committed to a myogenic program, but were inhibited from completing differentiation by an event linked with persistent expression of the self-renewing factor Pax7. Overexpression of Pax7 was sufficient to induce atrophy in normal muscle, while under tumor conditions, the reduction of Pax7 or exogenous addition of its downstream target, MyoD, reversed wasting by restoring cell differentiation and fusion with injured fibers. Furthermore, Pax7 was induced by serum factors from cachectic mice and patients, in an NF-κB-dependent manner, both in vitro and in vivo. Together, these results suggest that Pax7 responds to NF-κB by impairing the regenerative capacity of myogenic cells in the muscle microenvironment to drive muscle wasting in cancer.

Barbed Suture for Gastrointestinal Closure: A Randomized Control Trial

In an effort to make laparoscopic suturing more efficient, the V-Loc advanced wound closure device (Covidien, Mansfield, MA) has been produced. This device is a self-anchoring barbed suture that obviates the need for knot tying. The goal of this initial feasibility study was to investigate the use of the barbed suture in gastrointestinal enterotomy closure. A randomized study of 12 pigs comparing enterotomy closure with barbed versus a nonbarbed suture of similar tensile strength was performed. To this end, 25 mm enterotomies were made in the stomach (1 control, 1 treatment), jejunum (2 controls, 2 treatments), and descending colon (1 control, 1 treatment). Animals were killed at 3, 7, and 14 days postoperatively (4 each group) and their gastrointestinal tracts harvested; 6 of the 8 enterotomies from each pig underwent burst strength testing. The remaining 2 were fixed in formalin and sent for histological examination. All 12 pigs survived until they were killed without any major complications. Enterotomy closure with barbed suture revealed adhesion scores, burst strength pressures, and histology scores that were similar to those for the control. Jejunal closures resulted in 6 failures at 7 days (3 control, 3 barbed) and 4 failures at 14 days (2 control, 2 barbed). The barbed suture significantly reduced suturing time in the stomach, jejunum, and colon. The V-Loc wound closure device appears to offer comparable gastrointestinal closure to 3-0 Maxon while being significantly faster. Further studies with V-Loc are required to assess its use in laparoscopic surgery.

The impact of sarcopenia on survival and complications in surgical oncology: A review of the current literature

Sarcopenia is the subclinical loss of skeletal muscle and strength and has been extensively studied in both the cancer and surgical literature. Specifically, sarcopenia has gained significant recognition as an important prognostic factor for both complications and survival in cancer patients. Herein, we review the current literature to date highlighting the specific impact of sarcopenia in patients undergoing oncologic procedures. J. Surg. Oncol. 2015; 112:503–509.

A review of 130 humans enrolled in transgastric NOTES protocols at a single institution.

BackgroundThe methodology of Natural Orifice Translumenal Endoscopic Surgery (NOTES) has been validated in both human and animal models. Herein is a discussion of our experience gained from the initial 130 patients enrolled in transgastric pre-NOTES and NOTES protocols at our institution.MethodsA retrospective review of our research database was performed for all patients enrolled in NOTES protocols. The infectious risk of a gastrotomy with and without a NOTES procedure was assessed in 100 patients. Eighty patients completed a true NOTES protocol looking at staging, access, and insufflation with select patients evaluating the potential for bacterial contamination of the abdominal compartment.ResultsA total of 130 patients have completed pre-NOTES and NOTES protocols at our institution. We observed no clinically significant contamination of the abdomen secondary to transgastric procedures in 100 patients. Diagnostic transgastric endoscopic peritoneoscopy (DTEP) was completed in 20 patients with pancreatic head masses and found to have a 95% concordance with laparoscopic exploration for assessment of peritoneal metastases. Blind endoscopic gastrotomy and DTEP were evaluated in 40 patients who underwent laparoscopic Roux-en-Y gastric bypass procedures (LSRYGB) and were found to be safe, reliable, and without a clinically significant risk of contamination. Endoscopic peritoneal insufflation was successfully established and correlated with standard laparoscopic insufflation in 20 patients.ConclusionsTransgastric NOTES is a safe alternative approach to accessing the peritoneal cavity in humans. The risk of bacterial contamination secondary to peroral and transgastric access is clinically insignificant. A device for the facile closure of the gastric defect is the sole factor limiting institution of this methodology as a standalone technique.

Laparoscopic Distal Pancreatectomy with Splenic Conservation: An Operation without Increased Morbidity

Objectives. The advent of minimally invasive techniques was marked by a paradigm shift towards the use of laparoscopy for benign distal pancreatic masses. Herein we describe one centers experience with laparoscopic distal pancreatectomy. Methods. A retrospective chart review was performed for all distal pancreatectomies completed laparoscopically from 1999 to 2009. Outcomes from those cases completed with a concurrent splenectomy were compared to the spleen-preserving procedures. Results. Twenty-four patients underwent laparoscopic distal pancreatectomy. Seven had spleen-conserving operations. There was no difference in the mean estimated blood loss (316 versus 285 mL, P = .5) or operative time (179 versus 170 minutes, P = .9). The mean tumor size was not significantly different (3.1 versus 2.2 cm, P = .9). There was no difference in the average hospital stay (7.1 versus 7.0 days, P = .7). Complications in the spleen-preserving group included one iatrogenic colon injury, two pancreatic fistulas, and two cases of iatrogenic diabetes. In the splenectomy group, two developed respiratory failure, three acquired iatrogenic diabetes, and two suffered pancreatic fistulas (71% versus 41%, P = .4). Conclusions. The laparoscopic distal pancreatectomy is a safe operation with a low morbidity. Splenic conservation does not significantly increase the morbidity of the procedure.

Safe alternative transgastric peritoneal access in humans: NOTES

BACKGROUND Diagnostic transgastric endoscopic peritoneoscopy has been used to evaluate the abdomen. We present our experience with transgastric endoscopic peritoneoscopy (TEP) to access the peritoneum, direct trocar placement, and perform adhesiolysis without laparoscopic visualization in patients undergoing laparoscopic Roux-en-Y gastric bypass. METHODS Forty patients participated. There are 2 arms to the study. The initial 20 patients underwent pre-insufflation of the abdomen prior to TEP. The second 20 had no pre-insufflation. Ten patients in each arm had no surgical history. The other 10 had previous intra-abdominal procedures. TEP was performed through a gastrotomy created without laparoscopic visualization. Adhesions were visualized and taken down endoscopically prior to trocar placement. Diagnostic findings, operative times, and clinical course were recorded. RESULTS Average TEP time was 19 min. Three patients had limited visualization due to intra-abdominal adhesions (2) and omental fat (1). Three of the 20 without and 17 of 20 with a history of intra-abdominal surgery had adhesions visualized endoscopically. Endoscopic adhesiolysis was performed in 1 and 4 patients in these groups respectively. Six occult umbilical hernias, 1 inguinal hernia, and 1 hiatal hernia were noted on endoscopic exploration. There were no complications related to intubation of the stomach, accessing the peritoneum, or endoscopic exploration. CONCLUSION TEP is a safe and accurate means to access the peritoneum, visualize the abdominal wall, perform adhesiolysis, and direct trocar placement without laparoscopic guidance. Safe and reliable gastric closure remains the sole limitation to its clinical use outside of a protocol necessitating a gastrotomy.

Scheduled intravenous acetaminophen reduces postoperative narcotic analgesic demand and requirement after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND Intravenous (i.v.) acetaminophen has the potential to reduce postoperative narcotic analgesic requirement but this has not been reported in bariatric surgery. As lower dosages could reduce undesirable narcotic side effects, we investigated the opioid-sparing effect of concomitant i.v. acetaminophen in bariatric surgery. METHODS We performed a retrospective review of our electronic medical records of laparoscopic Roux-en-Y gastric bypasses (LRYGB) performed for severe obesity between 2011 and 2013. We identified 183 patients that received scheduled i.v. acetaminophen in addition to morphine sulfate (MSO4) patient-controlled analgesia (PCA). A cohort of 229 patients from the preceding 2 years who were treated with MSO4 PCA but not acetaminophen was used as a historical control. Patient demographic characteristics and narcotic use data were extracted from electronic medical records. Students t test or linear regression was used as appropriate (P< .05). RESULTS During the first 24-hour postoperative period after LRYGB, narcotic analgesic demand (total PCA demand including nondelivery of narcotic due to lock-out) was reduced by 25% with the concomitant use of i.v. acetaminophen (40.5 versus 30.9 average pushes; P<.05). During the same period, narcotic analgesic dosage requirement was cut down by 20% in the study group (average of 29.9 versus 24.1 mg of MSO4; P<.05). Linear regression analysis confirmed that these changes were independent of age, gender, and body mass index distribution, or type 2 diabetes mellitus. CONCLUSION Scheduled i.v. acetaminophen reduces the demand for and the requirement of narcotic analgesia after LRYGB. We provide new evidence in support of the routine use of multimodal analgesia that includes scheduled i.v. acetaminophen in the initial 24-hour period after bariatric surgery.

Two cases of small cell carcinoma of the gallbladder.

Small cell carcinoma of the gallbladder is a rare disease process with approximately 40 cases reported in the literature. It is most often found in elderly female population and is associated with cholelithiasis and cigarette smoking. A multidisciplinary approach to treatment with wide surgical resection and adjuvant chemotherapy is the current standard of care. Notwithstanding prompt medical intervention, it is a disease with a poor prognosis. The pathology is characterized by early metastases and extensive local invasion. Herein, we report two cases of small cell carcinoma addressed at our institution. In both cases, a radical resection was performed with subsequent referral to oncology for additional therapy.

Novel reconstruction of the extrahepatic biliary tree with a biosynthetic absorbable graft

OBJECTIVES The reference standard technique for the reconstruction of the extrahepatic biliary tree is Roux-en-Y hepaticojejunostomy. This procedure is not without complications and may not be feasible in some patients. This project sought to evaluate a novel approach for repairing common bile duct injuries with a biosynthetic graft. This allows for the reconstruction of the anatomy without necessitating an intestinal bypass. METHODS Study subjects were 11 mongrel hounds. Utilizing an open approach, the common bile duct was transected in each animal. A 1-cm graft of a synthetic bioabsorbable prosthesis was interposed over a 5-Fr pancreatic stent and sewn in place as an interposition tube graft with absorbable sutures. Intraoperative cholangiograms and monthly liver function tests were completed. Animals were killed at 6, 7, 8, 10 and 12 months. RESULTS The first five animals were killed early in the process of protocol development. One animal developed obstructive symptoms and was killed on postoperative day 14. The next five animals were longterm survivors without evidence of clinically significant graft stenosis. Mean alkaline phosphatase and total bilirubin were normal, at 140 U/l and 0.2 mg/dl, respectively. Histology showed the complete replacement of the graft with native tissue at 6 months. CONCLUSIONS   Biliary reconstruction using a synthetic bioabsorbable prosthetic as an interposition tube graft is feasible based on initial results.

Endoscopic peritoneal access and insufflation: natural orifice transluminal endoscopic surgery

BACKGROUND Diagnostic transgastric endoscopic peritoneoscopy is a safe model for exploration of the peritoneum. Endoscopic insufflation of the peritoneal cavity has not been validated in humans. We report here our experience with pneumoperitoneum established endoscopically with a laparoscopic insufflator. DESIGN Pneumoperitoneum was established with a laparoscopic insufflator through the biopsy channel of the gastroscope. Intra-abdominal pressure was measured with a transfascial Veress needle and compared with endoscopic values. The gastrotomy was used in the creation of the gastric pouch. PATIENTS Twenty patients undergoing laparoscopic Roux-en-Y gastric bypass participated in the study. Ten had undergone no previous surgery, whereas the other 10 patients had a history of abdominal procedures. INTERVENTIONS Diagnostic transgastric endoscopic peritoneoscopy was performed through a gastrotomy created endoscopically without laparoscopic visualization. MAIN OUTCOME MEASUREMENTS Diagnostic findings, operating times, and clinical course were recorded. RESULTS The average time for transgastric access was 9.6 minutes. This did not vary in patients with previous surgery (P = .3). Endoscopic insufflation was successful in all patients. The mean endoscopic and laparoscopic pressures were 9.80 and 9.75 mm Hg, respectively (P = .9). In no patients were there limitations to visualization of the abdomen. Adhesions were noted in 80% and 10% of patients with and without a history of surgery, respectively (P = .005). There were no complications related to transgastric passage of the endoscope or exploration of the peritoneal cavity. CONCLUSIONS Although limited by the small sample size in this study, we believe that transgastric access may be considered as an alternative approach to peritoneal insufflation and provides a safe alternative for exploration of the abdomen. Endoscopic insufflation through the biopsy channel by using a laparoscopic insufflator seems to be an effective and safe method for establishing pneumoperitoneum.