Management and outcomes following pancreaticoduodenectomy for ampullary adenocarcinoma.

INTRODUCTION: The purpose of this study was to evaluate outcomes following pancreaticoduodenectomy(PD) for ampullary adenocarcinoma(AAC). METHODS: We evaluated patients having undergone PD for AAC and the impact of clinical/histopathologic factors and adjuvant therapy(AT) on survival. RESULTS: 52 patients underwent potentially curative PD. Perineural and lymphovascular invasion were associated with decreased survival. There was no difference in survival between patients treated with PD vs. PD+AT, however, AT was more often administered to patients with N1 vs. N0 and stage II/III vs. I disease. Among patients receiving AT, we observed a trend towards improved survival when radiation was included. Recurrence occurred in 7/18(39%) stage I patients, only 2(7%) of which received AT. CONCLUSION: AT did not improve survival, however was more commonly administered in advanced disease. Stage I patients had high recurrence rates but rarely received AT. Prospective evaluation of appropriate AT regimens and use in early stage patients should be considered.

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression.

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells-all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13-HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13-HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13-HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC.

Incidence of Helicobacter pylori in operatively managed acute nonvariceal upper gastrointestinal bleeding.

Helicobacter pylori is a known contributor to ulcerogenesis and nonvariceal acute upper gastrointestinal hemorrhage. Its incidence in operatively managed patients with upper gastrointestinal hemorrhage is ill defined. Patients undergoing surgery for upper gastrointestinal hemorrhage secondary to gastroduodenal ulceration between 1993 and 1998 at the University of Tennessee were retrospectively reviewed. Factors examined included age, nonsteroidal drug use, endoscopic intervention, urgency of operation, and H. pylori status confirmed by histologic examination. Forty-two patients had surgery with three excluded because of a lack of histologic evaluation. The site of bleeding was gastric in 23 and duodenal in 14. H. pylori infection was present in nine (39.1%) gastric and 11 (68.7%) duodenal ulcers. The incidence of H. pylori infection was reduced in those over 60 years of age (28.6%). Endoscopy was performed in all patients, but only two had biopsies for assessment of H. pylori. Operative morbidity was 17.9% and mortality was 5.1%. No patient had rebleeding following surgery. The incidence of H. pylori in this population is less than that reported in uncomplicated ulcer disease. Those older than 60 tended to be H. pylori negative. Endoscopic assessment for H. pylori was infrequent. Traditional indications for surgical intervention in ulcer hemorrhage should not be altered based on H. pylori status.

Gastric outlet obstruction resulting from peptic ulcer disease requiring surgical intervention is infrequently associated with Helicobacter pylori infection.

BACKGROUND: Gastric outlet obstruction (GOO) secondary to peptic ulcer disease requiring therapeutic intervention remains a common problem. The incidence of Helicobacter pylori infection in this cohort has not been well defined. Pneumatic dilatation (PD) has been proposed as first-line therapy before surgical intervention. If H pylori infection in patients with GOO is infrequent, PD may not offer permanent control without the need for longterm antacid therapy. STUDY DESIGN: The purpose of this study was to examine the incidence of H pylori infection and surgical outcomes in patients undergoing resection for GOO. The records of all patients having resection (vagotomy and antrectomy) for benign disease from 1993 to 1998 for GOO at the University of Tennessee affiliated hospitals were reviewed retrospectively. Smoking history, NSAID use, weight loss, previous ulcer treatment, previous treatment for H pylori, and previous attempts at PD were among the factors examined. H pylori infection was documented by Steiner stain from either preoperative biopsy or, in most patients, final surgical specimens. Surgical complications and patient satisfaction were ascertained from inpatient records, postoperative clinical notes, and, where possible, followup telephone surveys. RESULTS: Twenty-four patients underwent surgical resection during the study period. There were 16 men and 8 women, with a mean age of 61 years (range 40 to 87 years). Weight loss was documented in 58% and averaged 27 lb. Five of 24 patients had previous attempts at PD, 3 of whom were H pylori negative. All five had further weight loss after these failed attempts. Of the 24 patients reviewed, only 8 (33%) were H pylori positive. There were no procedure-related deaths. Longterm clinical followup was possible in 16 of 24 patients, and all but one demonstrated dramatic clinical improvement by Visick score. CONCLUSIONS: We conclude the following: 1) In this cohort, H pylori infection was present in a minority; 2) previous attempts at PD were unsuccessful, which may be related to the H pylori-negative status of the patients; 3) mortality related to the operation was zero; and 4) patient satisfaction was positive by the Visick scale. Patients with H pylori-negative GOO resulting from peptic ulcer disease should be strongly considered for an early, definitive, acid-reducing surgical procedure.

Breakdown of intestinal repair after laparotomy for trauma: incidence, risk factors, and strategies for prevention.

BACKGROUND: Breakdown of intestinal repair and enteric leakage after trauma laparotomy can have dire consequences. Factors contributing to these failures when stratified according to location of intestinal injury and method of repair were examined. METHODS: We retrospectively reviewed all intestinal injuries occurring in a recent 2-year time span in adult patients surviving for more than 48 hours at a Level I trauma center. Data included Injury Severity Score, Abdominal Trauma Index score, site (stomach, duodenum, small and large intestine), and type of repair (enterorrhaphy vs. resection and anastomosis). Physiologic parameters within 48 hours of repair were assessed. Nonparametric analysis was used with significance assessed at the 95% confidence interval. RESULTS: Two hundred twenty-two intestinal repairs in 171 patients were evaluated. All repairs but one were performed at the initial surgery. Eleven (5%) of these failed in 11 patients (6.4%)--four duodenum, four small bowel, and three colon--and were not recognized for an average of 15 days. Breakdown of repair occurred in patients with higher Injury Severity Scores and Abdominal Trauma Index scores (30 vs. 21 and 29 vs. 14, respectively; p < 0.001) and higher intraoperative blood and fluid administration (8.8 vs. 2.2 U and 11.5 vs. 5.1 L, respectively; p < 0.05). This was associated with longer intensive care unit and hospital stays (15.1 vs. 1.9 and 68.4 vs. 10.4 days, respectively; p < 0.001). All small bowel leaks occurred after resection and anastomosis versus enterorrhaphy (p < 0.05). All anastomotic breakdowns (four small bowel, one colon) occurred in the setting of massive blood and fluid administration versus those that did not leak (12.5 vs. 1.7 U and 12.7 vs. 5.8 L, respectively; p < 0.05). Four of 12 duodenal enterorrhaphies failed. All were associated with pancreatic injury versus none without (p < 0.05). The abdominal compartment syndrome occurred in three patients. In each case, breakdown of a small bowel anastomosis occurred. CONCLUSIONS: (1) Stomach repair and small bowel and large-bowel enterorrhaphy may be safely accomplished in any setting. (2) Associated pancreatic injury is a risk factor for disruption of duodenorrhaphy. (3) In patients with massive blood and fluid administration, delay of bowel anastomoses should be considered. (4) Disruption of small bowel anastomoses is associated with abdominal compartment syndrome.

Pancreatic pseudocysts following acute pancreatitis.

BACKGROUND: Pancreatic pseudocysts (PP) following acute pancreatitis have traditionally been approached by observation to allow cyst maturation. However, recent evidence suggests a selective approach toward management is indicated. METHODS: We retrospectively reviewed the presentation, operative management, and outcome of patients developing PP following acute pancreatitis since 1988. PP related to chronic pancreatitis were excluded. RESULTS: Twenty-seven patients were identified, 17 with giant PP (> 10 cm) and 10 with PP less than 10 cm. Groups were not different with respect to age and etiology of pancreatitis, predominantly biliary. Patients with giant PP had a significantly greater number of Ranson criteria at presentation and underwent drainage procedures earlier following their initial presentation. With respect to giant PP, 7 patients underwent internal drainage all via cystogastrostomy with 5 complications. Nine of 10 patients underwent urgent operation via external drainage. There were 3 pancreatic fistulas in this group. The morbidity and mortality rates for giant PP were 65% and 18% respectively. With respect to smaller PP, 8 underwent internal drainage with 1 death (mortality rate 10%). External drainage was performed in 2 patients with 1 pancreatic fistula (morbidity 10%). CONCLUSIONS: Patients with PP and a high Ranson score following acute pancreatitis are at significant risk for giant PP formation. Expectant management of giant PP is associated with higher morbidity and mortality than small PP suggesting that earlier external drainage, before clinical deterioration, may be beneficial. To be accurate, comparisons of outcomes for various treatment modalities must take into consideration PP size.

Laparoscopic cholecystectomy in the geriatric population.

Although the role of laparoscopic cholecystectomy (LC) as a safe and cost effective procedure has been ascertained, its role in the geriatric population, the majority of whom present with coexistent diseases, has yet to be defined. We retrospectively reviewed outcome parameters of 144 consecutive patients over age 65 undergoing LC, for both acute cholecystitis and symptomatic cholelithiasis. These results were compared with 72 patients having open cholecystectomy (OC) during the same time period and in the year preceding the introduction of LC. Groups were well matched with respect to age, age distribution indication for surgery, and underlying comorbid illnesses. Of those with symptomatic cholelithiasis, LC did not prolong operative time when compared with OC, but resulted in significantly earlier discharge (1.8 +/- 2.9 vs. 6.7 +/- 5.7 days (P < 0.0001)), with comparable hospital costs and with no increase in postoperative complications. With respect to acute cholecystitis, LC significantly prolonged operative time (105.8 +/- 40.8 vs. 78.1 +/- 28.5 minutes (P < 0.05)), but when successful, significantly reduced postoperative stay (4.2 +/- 3.8 vs. 7.5 +/- 2.3 days (P < 0.05)). There was no increase in postoperative complications in those having LC, and hospital costs were comparable with OC. Seven patients were converted from LC to OC; 4 of these (16%) were for acute cholecystitis versus a 2.5 per cent incidence of conversion for symptomatic cholelithiasis, and these resulted in prolonged hospital stays and costs. There was no incidence of hypotension/hypercarbia, despite a 64 per cent incidence of cardiopulmonary cardiopulmonary diseases in those having LC. There was a 14 per cent incidence of cardiopulmonary complications in those having LC in contrast to a 43 per cent incidence in OC. LC in the geriatric population is a safe procedure for symptomatic cholelithiasis. The procedure should be undertaken with caution in those with acute cholecystitis with a low threshold for either early conversion or primary OC. Finally, our results suggest that extensive hemodynamic monitoring is not indicated.

The effect of growth hormone on nutritional markers in enterally fed immobilized trauma patients.

BACKGROUND: Earlier clinical studies have demonstrated improved nitrogen balance in nonstressed patients receiving hypocaloric feedings and growth hormone (GH). This study investigates the effect of GH on nitrogen balance, on serum protein concentrations, and on other indices of nutrition when combined with enteral feeding in immobilized patients after closed-head injury or spinal cord injury. METHODS: Sixteen patients who tolerated enteral feedings and remained nonseptic were randomized to receive either placebo or 0.2 mg/kg recombinant human GH for 7 to 13 days. Nitrogen balances were collected daily, and serum proteins were measured at study entrance and exit. RESULTS: GH treatment resulted in higher GH and insulin-like growth factor-1 concentrations but did not improve nitrogen balance. GH treatment also resulted in increased transferrin and serum albumin levels and total lymphocyte count during the study period. CONCLUSIONS: Adjuvant recombinant human GH has no effect on nitrogen balance in highly stressed, totally immobilized patients after head or spinal cord injury, but it significantly enhances constitutive serum protein concentrations and other indices of nutritional repletion.

Microcirculatory flow changes after initial resuscitation of hemorrhagic shock with 7.5% hypertonic saline/6% dextran 70.

In rabbits, laser Doppler flow probes were placed in the jejunum and on the renal cortex. Pulsed Doppler probes were implanted on the abdominal aorta and superior mesenteric and femoral arteries for measuring blood flow velocity. Cardiac output was measured by thermal dilution. Either 30% or 40% of the calculated blood volume was withdrawn through a carotid catheter. After 30 or 60 minutes, an initial bolus of either lactated Ringer's (LR, 16 ml/kg) or 7.5% hypertonic saline/6% dextran 70 (HSD; 4 ml/kg) IV was followed by unlimited IV LR (administered as rapidly as possible) to restore systemic arterial blood pressure to the prehemorrhage levels. With HSD, arterial pressure corrected more rapidly (p less than 0.05), and the initial hemodilution was greater (p less than 0.05), but there were no differences by two hours. With HSD, cardiac output (90%-100% vs. 130%-160% of control; p less than 0.05), plasma Na+ (139-140 mM vs. 146-148 mM; p less than 0.05) and plasma osmolarity (292-295 mOsm vs. 308-310 mOsm; p less than 0.05) were all significantly higher than the values with LR, but there was no effect on blood flow velocities through the infrarenal aorta, femoral artery, or superior mesenteric artery. Renal cortical perfusion (56% vs. 97% of control; p less than 0.05) and jejunal mucosal perfusion (83% vs. 162% of control; p less than 0.05) were significantly higher with HSD. HSD had no detectable effect on bacterial translocation at 24 hours. Thus: 1) HSD restores blood flow more rapidly to the gut mucosal and kidney microcirculations than initial resuscitation with LR; 2) the mechanism could be associated with a transient hemodilution and persistent increases in plasma Na and osmolarity, which reduce hemorrhage-induced cell swelling and blood viscosity changes; and 3) laser Doppler analysis could aid in the diagnosis of reperfusion injury after shock.

Improved outcome with femur fractures: early vs. delayed fixation.

Prior studies documented that early fixation of femur fractures results in a decreased incidence of adult respiratory distress syndrome (ARDS), fat embolism syndrome, and pneumonia. This study evaluates the impact of magnitude of injury on pulmonary complications and length of ICU and hospital stays in 339 trauma patients with femur fracture undergoing early (n = 121) vs. late (n = 218) operative fixation. Groups were similar with respect to transfusions, hypotension, and associated injuries, but more patients over age 50 years underwent early fixation. Patients were categorized according to Injury Severity Score (ISS): 1) less than 15 (n = 202), 2) 16-35 (n = 104), and 3) greater than 36 (n = 33). Delayed fixation significantly increased the incidence of pulmonary shunt in ISS (3) patients and of pneumonia in patients older than 50. Late fixation resulted in significantly longer hospital stays in all groups and more ICU days in the ISS (3) group. We believe that early femur fixation should be performed on all patients. Pulmonary complications were decreased and health care costs reduced.