David W. Rattner

ASGE/SAGES Working Group on Natural Orifice Translumenal Endoscopic Surgery

The growing capabilities of therapeutic flexible endoscopy have ushered in a new era in the treatment of gastrointestinal conditions. Refinements in laparoscopic surgery have progressed to the point that complex surgical procedures, such as gastric bypass, can now be performed in a minimally invasive fashion. These trends have set the stage for the development of even less invasive methods to treat conditions in both the gut lumen and in the peritoneal cavity. It seems feasible that major intraperitoneal surgery may one day be performed without skin incisions. The natural orifices may provide the entry point for surgical interventions in the peritoneal cavity, thereby avoiding abdominal wall incisions. In the first published description, Kalloo et al. [1] demonstrated the feasibility and safety of a per-oral transgastric endoscopic approach to the peritoneal cavity with long-term survival in a porcine model. This was soon followed by other transgastric peritoneal procedures in the porcine model, including tubal ligation, [2] cholecystectomy, [3] gastrojejunostomy, [4] splenectomy, [5] and oophorectomy with tubectomy [6, 7]. Although there are no publications, Rao et al. have described transgastric appendectomy in humans (personal communication). There have been two excellent editorials on this potentially emerging field. [8, 9] To discuss this vision, 14 leaders from the American Society of Gastrointestinal Endoscopy (ASGE) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) met in New York City on July 22 and 23, 2005. The participants are listed in Table 1. All agreed that Translumenal Endoscopic Surgery could offer significant benefits to patients such as less pain, faster recovery, and better cosmesis than current laparoscopic techniques. The group identified the barriers that needed to be surmounted for the development of translumenal endoscopic intraperitoneal surgery and developed a list of next steps and guidelines to move this concept ahead.

A Better Model of Acute Pancreatitis for Evaluating Therapy

Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Débridement and closed packing for the treatment of necrotizing pancreatitis.

OBJECTIVE To evaluate the results of débridement and closed packing for necrotizing pancreatitis and to determine the optimal timing of surgical intervention based on patient outcomes. METHODS Between February 1990 and November 1996, 64 consecutive patients with necrotizing pancreatitis were treated with necrosectomy followed by closed packing of the cavity with stuffed Penrose and closed suction drains. The mean APACHE II score immediately before surgery was 9, and 31% of the patients had organ failure. Patients were stratified with an outcome score based on death and major complications; this was correlated with the timing of surgical intervention. The data were then subjected to cut-point analysis by sequential group comparison. RESULTS Patients underwent surgery a median of 31 days after diagnosis. Fifty-six percent had infected necrosis. The mortality rate was 6.2% and was no different in infected or sterile necrosis. Eleven patients required a second surgical procedure and 13 required percutaneous drainage; a single surgical procedure sufficed in 69%. Enteric fistulae occurred in 16% of patients. The mean hospital stay after surgery was 41 days, and the interval until return to regular activities was 147 days. A significant negative correlation between duration of pancreatitis and outcome scores was found, and sequential group comparison demonstrated that the change point at which significantly better outcomes were encountered was day 27. CONCLUSION Débridement of pancreatic necrosis followed by closed packing and drainage is accomplished with a low mortality rate and reduced rates of complications and second surgical procedures. Although intervention is best deferred until the demarcation of necrosis is complete, delay beyond the fourth week confers no additional advantage.

Early results of laparoscopic surgery for colorectal cancer - Retrospective analysis of 372 patients treated by clinical outcomes of Surgical Therapy (Cost) Study Group

PURPOSE: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, −4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.

Serous Cystadenoma of the Pancreas: Tumor Growth Rates and Recommendations for Treatment

Objective:To define the natural history and optimal management of serous cystadenoma of the pancreas. Summary Background Data:Serous cystadenoma of the pancreas is the most common benign pancreatic neoplasm. Diagnostic criteria, potential for growth or malignancy, and outcomes are not well defined. As a result, management for patients with serous cystadenomas varies widely in current practice. Methods:A total of 106 patients presenting with serous cystadenoma of the pancreas from 1976–2004 were identified. Hospital records were evaluated for patient and tumor characteristics, diagnostic workup, treatment, and outcome. Twenty-four patients with serial radiographic imaging were identified, and tumor growth curves calculated. Results:Mean age at presentation was 61.5 years and 75% of patients were female. The most common symptoms were abdominal pain (25%), fullness/mass (10%), and jaundice (7%); 47% were asymptomatic. Mean tumor diameter was 4.9 ± 3.1 cm, which did not vary by location. Tumors <4 cm were less likely to be symptomatic than were tumors ≥4 cm (22% vs. 72%, P < 0.001). The median growth rate in the patients who had serial radiography was 0.60 cm/y. For tumors <4 cm at presentation (n = 15), the rate was 0.12 cm/y, whereas for tumors ≥4 cm (n = 9), the rate was 1.98 cm/y (P = 0.0002). Overall, 86 patients underwent surgery, with one perioperative death. Conclusions:Large (>4 cm) serous cystadenomas are more likely to be symptomatic. Although the median growth rate for this neoplasm is only 0.6 cm/y, it is significantly greater in large tumors. Whereas expectant management is reasonable in small asymptomatic tumors, we recommend resection for large serous cystadenomas regardless of the presence or absence of symptoms.

Introduction of appendiceal CT: impact on negative appendectomy and appendiceal perforation rates.

UNLABELLED OBJECTIVE To evaluate the impact of appendiceal computed tomography (CT) availability on negative appendectomy and appendiceal perforation rates. SUMMARY BACKGROUND DATA Appendiceal CT is 98% accurate. However, its impact on negative appendectomy and appendiceal perforation rates has not been reported. METHODS The authors reviewed the medical records of 493 consecutive patients who underwent appendectomy between 1992 and 1995, 209 consecutive patients who underwent appendectomy in 1997 (59% of whom had appendiceal CT), and 206 patients who underwent appendiceal CT in 1997 without subsequent appendectomy. RESULTS Before appendiceal CT, 98/493 patients (20%) taken to surgery had a normal appendix. After CT availability, 15/209 patients (7%) taken to surgery had a normal appendix; 7 patients did not have CT, 5 patients had surgery despite a negative CT, and 3 patients had a false-positive CT. Negative appendectomy rates were lowered overall (20% to 7%), in men (11% to 5%), in women (35% to 11%), in boys (10% to 5%), and in girls (18% to 12%). Appendiceal perforation rates dropped from 22% to 14% after CT availability. CT excluded appendicitis in 206 patients in 1997 who avoided appendectomy and identified alternative diagnoses in 105 of these patients (51%). CONCLUSION The availability of appendiceal CT coincided with a drop in the negative appendectomy rate from 20% to 7% in all patients, and to only 3% in patients with a positive CT. Perforation rates decreased from 22% to 14%. Appendiceal CT can be advocated in nearly all female and many male patients.

Risk Factors for Pancreatic Cellular Injury after Cardiopulmonary Bypass

BACKGROUND Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the cause of pancreatitis after cardiopulmonary bypass remains unknown. METHODS We prospectively studied 300 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. Serum amylase, pancreatic isoamylase, and serum lipase were measured on postoperative days 1,2,3,7, and 10. Pancreatic cellular injury was defined as the presence of hyperamylasemia (greater than 123 U per liter) with an increase in either the serum level of lipase (greater than 24 U per liter) or the peak level of pancreatic isoamylase. Trypsinogen-activation peptides, which indicate intrapancreatic enzyme activation, were measured in the urine of the last 101 patients studied. RESULTS Evidence of pancreatic cellular injury was detected in 80 patients (27 percent), of whom 23 had associated abdominal signs or symptoms and 3 had severe pancreatitis (2 with pancreatic abscess and 1 with necrotizing hemorrhagic pancreatitis). Two of 19 postoperative deaths were secondary to pancreatitis. In multivariate analyses, the development of pancreatic cellular injury was significantly associated with preoperative renal insufficiency, valve surgery, postoperative hypotension, and perioperative administration of calcium chloride. The administration of more than 800 mg of calcium chloride per square meter of body-surface area was an independent predictor of pancreatic cellular injury, and the increase in risk was dose-related. No differences were found in the level of trypsinogen-activation peptides between patients who had pancreatic cellular injury and those who did not. CONCLUSIONS Pancreatic cellular injury, as indicated by hyperamylasemia of pancreatic origin, is common after cardiac surgery. The administration of large doses of calcium chloride is an independent predictor of pancreatic cellular injury and may be a cause of it.

Debridement and closed packing for sterile or infected necrotizing pancreatitis: insights into indications and outcomes in 167 patients.

Objective:To examine the surgical indications and clinical outcomes of a large cohort of patients with necrotizing pancreatitis. Summary Background Data:Mortality after debridement for necrotizing pancreatitis continues to be inordinately high. The clinical experience with patients who underwent uniform surgical treatment for necrotizing pancreatitis at the Massachusetts General Hospital over a 15-year period is described. Methods:Retrospective review of 167 patients with necrotizing pancreatitis who required intervention and were treated with single stage debridement and a closed packing technique. Particular emphasis was placed on the indication for surgery and the presence of infected necrosis. Multiple logistic regression models were used to identify predictors of mortality. Results:The primary preoperative indication for operation was infected necrosis (51%), but intraoperative cultures proved that 72% of the entire cohort was infected. The rate of reoperation was 12.6%, and 29.9% of patients required percutaneous interventional radiology drainage after initial debridement. Overall operative mortality was 11.4% (19/167), but higher in patients who were operated upon before 28 days (20.3% vs. 5.1%, P = 0.002). Other important predictors of mortality included organ failure ≥3 (OR = 2.4, P = 0.001), postoperative intensive care unit stay ≥6 days (OR = 15.9, P = 0.001), and female gender (OR = 5.41, P = 0.02). Conclusions:Open, transperitoneal debridement followed by closed packing and drainage results in the lowest reported mortality and reoperation rates, and provides a standard for comparing other methods of treatment. A negative FNA does not reliably rule out infection. The clinical status of the patients and not proof of infection should determine the need for debridement.

Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas

OBJECTIVE The purpose of the study was to determine the prevalence of activating K-ras mutations in the pancreas of patients with intraductal papillary mucinous tumors (IPMT) and to analyze their relation to the degree of site-specific histopathologic abnormality. BACKGROUND Intraductal papillary mucinous tumors of the pancreas have a biologic behavior that is significantly different from pancreatic ductal adenocarcinoma. Activating K-ras mutations, which may be important events in a multistage process of carcinogenesis, have been reported in IPMT. METHODS Forty-six different histologic specimens (comprising normal pancreatic ducts, hyperplasia, low-grade dysplasia, high-grade dysplasia-carcinoma in situ, and carcinoma) from 16 patients with IPMT and 9 specimens from patients with pancreatic ductal adenocarcinomas were designated by a pathologist. Genomic DNA was extracted from paraffin-embedded tissue sections after microdissection. The K-ras gene was amplified by polymerase chain reaction and subjected to DNA sequencing. RESULTS The K-ras mutations were detected in at least one specimen in 13 (81.2%) of 16 patients with IPMT. All mutations were found in codon 12. No codon 13 mutations were detected. The relative frequency of K-ras mutations in the different stages of IPMT was 16.7% in normal epithelium and papillary hyperplasia, 28.6% in low-grade dysplasia, and 57.1% in high-grade dysplasia-carcinoma in situ and invasive carcinoma. The K-ras mutations were detected in 6 (66%) of 9 pancreatic ductal adenocarcinomas. CONCLUSIONS The K-ras codon 12 point mutations are as frequent in IPMT as in ductal adenocarcinoma. A stepwise increase in the frequency of codon 12 mutations correlated with the stage of neoplastic evolution to cancer. This finding is consistent with an important role of K-ras gene mutations in the transformation from normal epithelium to invasive carcinoma in the majority of patients with IPMT.

Early surgical débridement of symptomatic pancreatic necrosis is beneficial irrespective of infection

In order to assess the recent trend of nonoperative management of pancreatic necrosis, we reviewed 82 variables in 73 consecutive patients with symptomatic necrotizing pancreatitis. The mortality rate for the series was 25% (18 of 73). The only preintervention variables that correlated with mortality were APACHE II score greater than 15 (p = 0.01), preintervention blood transfusion (p less than 0.001), respiratory failure (p less than 0.001), and shock (p less than 0.01). Patients who developed recurrent sepsis following the initial intervention had a significantly higher mortality rate (17 of 34) than those who did not (1 of 39) (p less than 0.001). The rate of recurrent sepsis varied widely among individual surgeons and correlated with APACHE II score. The presence of infected versus noninfected necrosis did not correlate significantly with outcome. When percutaneous radiologically guided drainage was the initial therapeutic modality (n = 6), recurrent sepsis requiring surgical drainage inevitably occurred. Patients treated with percutaneous drainage (often in combination with surgical drainage) had a longer hospital stay (82 versus 42 days, p less than 0.001), spent more days in the intensive care unit (31 versus 6 days, p less than 0.001), and required more days of total parenteral nutrition (57 versus 27 days, p less than 0.001) than those treated solely by surgical means. We conclude that aggressive initial surgical débridement should be the first step in managing symptomatic pancreatic necrosis and that the presence of infection should not be the sole determinant of intervention.