Theodore N. Pappas

Mechanisms of major biliary injury during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has become the procedure of choice for surgical removal of the gallbladder. The most significant complication of this new technique is injury to the bile duct. Twelve cases of bile duct injury during laparoscopic cholecystectomy were reviewed. Eight injuries were of a classic type: misidentification of the common duct for the cystic duct, resection of part of the common and hepatic ducts, and associated right hepatic arterial injury. Another injury was similar: clip ligation of the distal common duct with proximal ligation and division of the cystic duct, resulting in biliary obstruction and leakage. Three complications arose from excessive use of cautery or laser in the region of the common duct, resulting in biliary strictures. Evaluation of persistent diffuse abdominal pain led to the recognition of ductal injury in most patients. Ultimately, 10 patients required a Roux-en-Y hepaticojejunostomy to provide adequate biliary drainage. One patient had a successful direct common duct repair, and the remaining patient underwent endoscopic dilatation.

Outcomes after esophagectomy: a ten-year prospective cohort

BACKGROUND The Department of Veterans Affairs National Surgical Quality Improvement Program is a unique resource to prospectively analyze surgical outcomes from a cross-section of surgical services nationally. We used this database to assess risk factors for morbidity and mortality after esophagectomy in Veterans Affairs Medical Centers from 1991 to 2001. METHODS A total of 1,777 patients underwent an esophagectomy at 109 Veterans Affairs hospitals with complete in-hospital and 30-day outcomes recorded. Bivariate and multivariable analyses were completed. RESULTS Thirty-day mortality was 9.8% (174/1,777) and the incidence of one or more of 20 predefined complications was 49.5% (880/1,777). The most frequent postoperative complications were pneumonia in 21% (380/1,777), respiratory failure in 16% (288/1,777), and ventilator support more than 48 hours in 22% (387/1,777). Preoperative predictors of mortality based on multivariable analysis included neoadjuvant therapy, blood urea nitrogen level of more than 40 mg/dL, alkaline phosphatase level of more than 125 U/L, diabetes mellitus, alcohol abuse, decreased functional status, ascites, and increasing age. Preoperative factors impacting morbidity were increasing age, dyspnea, diabetes mellitus, chronic obstructive pulmonary disease, alkaline phosphatase level of more than 125 U/L, lower serum albumin concentration, increased complexity score, and decreased functional status. Intraoperative risk factors for mortality included the need for transfusion; intraoperative risk factors for morbidity included the need for transfusion and longer operative time. CONCLUSIONS These data constitute the largest prospective outcomes cohort in the literature and document a near 50% morbidity rate and 10% mortality rate after esophagectomy. Data from this study can be used to better stratify patients before esophagectomy.

Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA.

BACKGROUND Studies have suggested an increased risk of peritoneal seeding in patients with pancreatic cancer diagnosed by percutaneous FNA. EUS-FNA is an alternate method of diagnosis. The aim of this study was to compare the frequency of peritoneal carcinomatosis as a treatment failure pattern in patients with pancreatic cancer diagnosed by EUS-FNA vs. percutaneous FNA. METHODS Retrospective review of patients with non-metastatic pancreatic cancer identified 46 patients in whom the diagnosis was made by EUS-FNA and 43 with the diagnosis established by percutaneous FNA. All had neoadjuvant chemoradiation. Patients underwent restaging CT after completion of therapy, followed by attempted surgical resection if there was no evidence of disease progression. RESULTS There were no significant differences in tumor characteristics between the two study groups. In the EUS-FNA group, one patient had developed peritoneal carcinomatosis compared with 7 in the percutaneous FNA group (2.2% vs. 16.3%; p<0.025). No patient with a potentially resectable tumor in the EUS-FNA group had developed peritoneal carcinomatosis. CONCLUSIONS Peritoneal carcinomatosis may occur more frequently in patients who undergo percutaneous FNA compared with those who have EUS-FNA for the diagnosis of pancreatic cancer. A concern for peritoneal seeding of pancreatic cancer via percutaneous FNA is warranted. EUS-guided FNA is recommended as the method of choice for diagnosis in patients with potentially resectable pancreatic cancer.

Laparoscopic ventral and incisional hernioplasty

Abstract.Background: While the first laparoscopic ventral hernia repair was reported in 1992, there have been no studies comparing laparoscopic to conventional ventral herniorrhaphy. Methods: Twenty-one ventral hernias repaired laparoscopically are compared to a similar group of 16 patients undergoing traditional open repair during a 2-year period. Operative and hospital courses along with outcomes and cost analysis are analyzed. Results: There was no statistical difference between groups in number of previous abdominal operations, prior hernia repairs, and comorbidities. Patients undergoing open repair were older with larger fascial defects. Open repairs had a shorter operative time as compared to the laparoscopic group, but statistically longer postoperative stays and costs. Postoperative complications occurred in 31% of the open group and 23% of the laparoscopic group. There were two recurrences in each group. Conclusions: Laparoscopic herniorrhaphy is as safe and effective as the traditional open technique with shorter length of stay and decreased hospital costs.

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

AbstractBackground: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT. Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.

Clinical application of porcine small intestinal submucosa in the management of infected or potentially contaminated abdominal defects

The repair of abdominal wall defects in potentially contaminated or grossly infected fields presents a difficult clinical problem. Polypropylene mesh is relatively contraindicated in these settings because of the potential for chronic infection. The alternatives to polypropylene include polyglactin mesh, which is not associated with chronic infection but is associated with a 100% recurrence of hernia. The ideal prosthetic for this patient group should be resistant to infection and ensure a low rate of hernia recurrence. We studied the use of small intestinal submucosa, which has been reported to be resistant to infection and incorporates into the fascia over 3 to 6 months, in 20 patients with ventral or inguinal hernias (18 ventral, 2 inguinal hernia) in the setting of bacterial contamination. The early postoperative complication rate was 50%. One patient with fasciitis had degradation of the small intestinal submucosa and loss of the bioprosthesis within 7 days. Other early complications included seroma (n = 2), ileus (n = 1), and wound infection (n = 8). No patient experienced chronic infection. Mean follow up was 15.7 months and the rate of recurrence documented by CT or physical examination was 30%. We concluded the following: (1) small intestinal submucosa is an effective alternative bioprosthesis in the management of ventral/inguinal hernia when there is associated bacterial contamination; (2) human vs. pig immune response has not been seen in this patient population; (3) early graft failure due to overwhelming fascial infection was noted in one patient and may be a limitation of this technology in a minority of patients; and (4) early hernia recurrence is relatively low but long-term follow-up has not been completed.

Peptide YY release by fatty acids is sufficient to inhibit gastric emptying in dogs

Peptide YY is a candidate enterogastrone localized to endocrine cells of the ileocolonic mucosa. The purpose of the present study was to determine if blood levels of peptide YY observed after perfusion of the intestine with fatty acids are capable of slowing gastric emptying. Gastric emptying of a 300-ml saline meal was monitored during intravenous infusion of normal saline or graded doses of peptide YY. Gastric emptying was significantly inhibited by infusion of peptide YY in doses of 200 and 400 pmol/kg X h. During the saline control study, 229 +/- 12 ml of the 300-ml saline meal emptied by 10 min. This figure was reduced (p less than 0.01) to 110 +/- 28 ml by the infusion of peptide YY at a dose of 200 pmol/kg X h. This dose of peptide YY produced plasma concentrations (delta PYY = 239 +/- 50 pM) that were lower than those seen in response to intestinal perfusion of oleic acid (delta PYY = 395 +/- 55 pM) in the same animals. We conclude that perfusion of the intestine with oleic acid releases peptide YY in amounts sufficient to slow gastric emptying.

Differential expression of substance P receptors in patients with Crohn's disease and ulcerative colitis

BACKGROUND & AIMS Although clinical and pathological differences exist between Crohns disease (CD) and ulcerative colitis (UC), distinguishing features are often absent, making diagnosis and treatment problematic. This study evaluated the differences in the expression of substance P (SP) receptors in patients with CD or UC. METHODS Tissue samples from patients with inflammatory bowel disease or control patients were obtained at surgery, processed for 125I-SP binding, and analyzed by quantitative autoradiography. RESULTS Patients with CD showed a massive increase in SP receptors in lymphoid aggregates, small blood vessels, and enteric neurons of the small and large bowel relative to controls. Six of 16 CD specimens had no pathological evidence of CD yet continued to express high concentrations of SP receptors. Pathologically positive patients with UC showed high concentrations of SP receptors on colonic lymphoid aggregates and small blood vessels but not enteric neurons. No increased SP binding was evident in clinically and pathologically quiescent UC colons and normal UC ileostomy samples. CONCLUSIONS The increased expression of SP receptors on the enteric neurons of patients with CD distinguishes CD from UC. The persistent increased SP binding in pathologically normal CD tissue may indicate a subclinical disease state. SP receptor expression may have important diagnostic, etiologic, and therapeutic usefulness in inflammatory bowel disease.

Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience.

ObjectiveTo examine clinical outcomes in patients receiving neoadjuvant chemoradiation for locally advanced rectal adenocarcinoma. Summary Background DataPreoperative radiation therapy, either alone or in combination with 5-fluorouracil-based chemotherapy, has proven both safe and effective in the treatment of rectal cancer. However, data are lacking regarding which subgroups of patients benefit from the therapy in terms of decreased local recurrence and increased survival rates. MethodsA retrospective chart review was performed on 141 consecutive patients who received neoadjuvant chemoradiation (5-fluorouracil ± cisplatin and 4,500–5,040 cGy) for biopsy-proven locally advanced adenocarcinoma of the rectum. Surgery was performed 4 to 8 weeks after completion of chemoradiation. Standard statistical methods were used to analyze recurrence and survival. ResultsMedian follow-up was 27 months, and mean age was 59 years (range 28–81). Mean tumor distance from the anal verge was 6 cm (range 1–15). Of those staged before surgery with endorectal ultrasound or magnetic resonance imaging, 57% of stage II patients and 82% of stage III patients were downstaged. The chemotherapeutic regimens were well tolerated, and resections were performed on 140 patients. The percentage of sphincter-sparing procedures increased from 20% before 1996 to 76% after 1996. On pathologic analysis, 24% of specimens were T0. However, postoperative pathologic T stage had no effect on either recurrence or survival. Positive lymph node status predicted increased local recurrence and decreased survival. ConclusionsNeoadjuvant chemoradiation is safe, effective, and well tolerated. Postoperative lymph node status is the only independent predictor of recurrence and survival.

Increased Toxicity With Gefitinib, Capecitabine, and Radiation Therapy in Pancreatic and Rectal Cancer: Phase I Trial Results

PURPOSE Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. PATIENTS AND METHODS Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. RESULTS Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. CONCLUSION The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.