Louis G. Britt

Results of pancreas transplantation with portal venous and enteric drainage.

PURPOSE The standard method for pancreatic transplantation involves drainage of exocrine secretions into the urinary bladder with venous outflow into the systemic circulation. Despite the high success rate associated with this approach, it often leads to complications, including chemical cystitis, reflux pancreatitis, metabolic acidosis, and hyperinsulinemia. The authors developed a new technique of pancreatic transplantation with portal drainage of endocrine secretions and enteric drainage of exocrine secretions (PE), which theoretically should be more physiologic. PROCEDURES All patients were insulin-dependent diabetics with end-stage renal disease who underwent combined kidney-pancreas transplantation. Between 1990 and 1994, 19 patients have been transplanted using intraperitoneal placement of the pancreas allograft with exocrine drainage into a Roux-en Y loop and venous drainage into the portal circulations (PE). A comparison group of all patients undergoing standard systemic-bladder (SB) transplantation between April 1989 and March 1993 (n = 28) also was studied. Patient follow-up ranges from 6 months to 5 years for the SB patients (mean = 2.5 years) and 6 months to 4 years for the PE patients (mean = 1.6 years). Routine follow-up includes documentation of the clinical course and detailed endocrine studies. FINDINGS Patient and graft actuarial survival at 1 and 3 years is no different for SB and PE patients. Urinary tract infections occurred in 89.3% of the SB patients (2.8/patient) versus 26.3% of the PE patients (0.25/patient, p < or = 0.0001). None of the PE patients experienced hematuria compared with 53.6% of the SB patients (p < or = 0.0001); however, two PE patients had melanotic episodes. The incidence of urinary retention and reflux pancreatitis was 32.1% versus 5.3% (p < or = 0.028) for SB and PE groups, respectively. Patients in the SB group required sodium bicarbonate therapy (mean = 55 mEq/day) although no PE patient required routine therapy; despite this, SB patients experienced more episodes of acidosis (44 vs. 5). Endocrine studies indicate no difference in glycosylated hemoglobin or fasting and stimulated glucose values throughout the follow-up period. In contrast, hyperinsulinemia was evident in both fasting and stimulated tests for the SB patients, with values consistently two- to fivefold higher than those of the PE group. CONCLUSIONS These results indicate that PE and SB pancreas transplantation are equivalent in terms of patient and graft survival and suggest that the PE approach is associated with a decreased incidence of metabolic and bladder-related complications. In addition, the PE approach eliminates the state of peripheral hyperinsulinemia that characterizes the SB procedure. Continued follow-up will be necessary to determine if long-term outcomes will differ for patients with PE and SB grafts.

Progress in the operative management of sporadic primary hyperparathyroidism over 34 years.

Background:Progress in the diagnosis, localization of abnormal parathyroids, and intraoperative management of primary hyperparathyroidism has been observed over the past 34 years. The goal of this study is to report the outcome of patients undergoing 2 different operative approaches in a single institution, showing the evolution of surgical management of sporadic primary hyperparathyroidism (SPHPT). Methods:Parathyroidectomy was performed in 890 (827 initial, 63 reoperative) patients with SPHPT using 2 different approaches: traditional bilateral neck exploration (BNE, n = 396) or limited parathyroidectomy guided by parathormone dynamics (LPX, n = 494). Seven hundred eighteen patients (335 BNE, 383 LPX) followed ≥ 6 months or identified as operative failures were studied. Operative failure is defined as hypercalcemia and high intact (1–84) parathyroid hormone molecule (iPTH) within 6 months after operation. Successful parathyroidectomy is normocalcemia for 6 months; hypercalcemia and elevated iPTH after this time is recurrent hyperparathyroidism. Results:There were 20 (6%) of 335 operative failures in the BNE group and 11 (3%) of 383 failures in the LPX group (P = 0.04). The incidence of multiglandular disease (MGD) determined by gland size (10%) versus hormone hypersecretion (3%) was statistically different (P < 0.001). Since most of the recurrences occurred later than 30 months, the incidence of recurrent hyperparathyroidism in patients followed for longer than 2.5 years was 4% (11/287) in the BNE group (average, 11.5 years) and 3% (5/183) in the LPX group (average, 4.2 years). Conclusion:LPX, with its reported advantages of minimal dissection, shorter operative time, and use in ambulatory settings, compares favorably with the traditional BNE. Parathyroidectomy guided by parathormone dynamics has an improved success rate and should be considered as a standard operative approach in SPHPT.

Primary repair of colon wounds. A prospective trial in nonselected patients.

102 patients with penetrating intraperitoneal colon injuries were entered into a prospective study. Colon wound management was undertaken without regard to associated injuries or amount of fecal contamination. Primary repair was performed in 83 patients, segmental resection with anastomosis in 12, and resection with end colostomy in 7. There were no suture line failures in the primary repair group, and one suture line failure in the anastomosis group. The one failure was in a patient who underwent repeated explorations for bleeding before the leak occurred. The septic complication rate was 33% of the entire series and was unrelated to primary repair. Logistic regression analysis to identify risk factors for sepsis included transfusion greater than or equal to 4 units (p less than 0.02), more than two associated injuries (p less than 0.04), significant contamination (p less than 0.05), and increasing colon injury severity scores (p less than 0.02). The method of colon wound management, location and mode of injury, presence of hypotension (BP less than 90), and age did not significantly contribute to sepsis. We conclude that nearly all penetrating colon wounds can be repaired primarily or with resection and anastomosis, regardless of risk factors.

A prospective study of 91 patients undergoing both computed tomography and peritoneal lavage following blunt abdominal trauma.

Recent reports comparing computed tomography of the abdomen (CTA) and diagnostic peritoneal lavage (DPL) following trauma have been contradictory. A 10-month prospective study was conducted at our trauma center comparing both methods. Criteria for entry into the study included suspected blunt abdominal trauma without indication for immediate laparotomy, with either equivocal abdominal examination, diminished sensorium, or neurologic deficit. Ninety-one patients meeting these criteria underwent CTA followed by DPL. CTA was performed using both oral and intravenous contrast; DPL was performed by the open technique with RBC greater than 100,000 mm3 or WBC greater than 500 mm3 as criteria for a positive examination. CTA was interpreted initially by available radiology staff and residents and retrospectively reviewed by an experienced tomographer blind to DPL and surgical results. Twenty patients in whom either test was positive underwent laparotomy; all others were admitted for observation and/or extra-abdominal surgery. Laparotomy revealed 26 organs injured in the 20 patients explored at admission; none of the observed patients required delayed laparotomy. The results of CTA and DPL were compared to the findings at laparotomy or the clinical course of those not explored. The sensitivity, specificity, and accuracy for initial CTA were 60%, 100%, and 91%; for review CTA 85%, 100%, and 97%; for DPL 90%, 100%, and 98%. We conclude that: even with experienced examiners, CTA offers no diagnostic advantage over DPL in blunt trauma; because of relative costs, we do not recommend the routine application of CTA; CTA is a reliable alternative when circumstances prevent the performance of DPL.

Superiority of closed suction drainage for pancreatic trauma. A randomized, prospective study.

During a 42-month period, 65 patients sustaining pancreatic injuries were treated. They were randomized on alternate days (two separate trauma teams) to receive sump (S) or closed suction (CS) drainage. Twenty-eight patients were randomized to S and 37 to CS; there were six early deaths, which precluded drainage analysis, leaving 24 evaluable S patients and 35 CS patients. Penetrating wounds occurred in 71% and blunt in 29%. No significant differences appeared between the groups with respect to age, Penetrating Abdominal Trauma Index (PATI), Injury Severity Score (ISS), or grade of pancreatic injury. Twelve patients in each group required resection and drainage for grade III injuries, with the remaining patients receiving external drainage alone. Five of twenty-four S patients versus one of thirty-five CS patients developed intra-abdominal abscesses (p less than 0.04). We conclude that septic complications after pancreatic injury are significantly reduced by CS drainage. Bacterial contamination via sump catheters is a major source for intra-abdominal infections after pancreatic trauma.

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.

Pancreas divisum: is it a surgical disease?

Six patients with the congenital anomaly, pancreas divisum, and recurrent acute pancreatitis were treated surgically. The diagnostic triad of multiple episodes of abdominal pain with elevated serum amylase and identification of the anomaly by ERCP was present uniformly. Sphincteroplasty of the ampulla of Vater and ductoplasty of the accessory papilla were performed in five patients. One patient had sphincteroplasty only due to failure to identify the accessory duct. Two patients eventually required major pancreatic resection for pain relief. Three additional patients were identified and managed nonopera-tively. Data of 44 patients with surgically treated pancreas divisum have been collected from the literature. Review of these patients indicates that dual sphincteroplasty or dorsal ductoplasty are the two most frequently employed procedures and appear to give good results.

Acute pancreatitis induces cytokine production in endotoxin-resistant mice.

OBJECTIVE The purpose of this study was to determine whether pathologic progression and cytokine responses in acute pancreatitis (AP) are altered in the absence of endotoxemia. SUMMARY BACKGROUND DATA Previous studies have demonstrated that AP is characterized by rapid production and release of inflammatory cytokines, which play a major role in the local pancreatic and systemic complications of this disease. Infection and endotoxemia have been implicated as a major source of morbidity and death in AP and as possible stimuli for the overwhelming cytokine response seen in this disease. METHODS AP was induced by a choline-deficient and ethionine-supplemented diet for 4 days in normal C57BL/6J mice (controls, n = 23) and in CD14 knockout mice (CD14KO, n = 23), which cannot produce circulating cytokines in response to endotoxin. Control and endotoxin-resistant mice were killed at time 0, then at 24, 48, 72, and 96 hours after the start of the diet. At each time point serum was collected for amylase, glucose, and cytokine measurements (tumor necrosis factor-alpha [TNFalpha] and interleukin-1beta [IL1beta]), and the pancreas was removed for histologic examination. TNFalpha was measured with a bioassay using WEHI-2F cells and IL1beta with a bioassay using D10.G4.1 cells. RESULTS CD14KO mice developed biochemical manifestations of AP with alterations in amylase levels, hypoglycemia, weight loss, and histologic changes of pancreatitis similar to the pattern seen in control mice. TNFalpha and IL1beta production had similar kinetics in both groups, with significant peak TNFalpha serum levels at 72 hours and a progressive rise of IL1beta levels throughout the study period. Histologic changes appeared earlier and were more pronounced in the control versus the CD14KO mice. However, the mortality rate was identical (20% at 96 hours) for both groups. CONCLUSIONS These results demonstrate that the progression of AP, the cytokine response associated with the disease, and early death are independent of endotoxin action. These findings, which suggest that an uncharacterized stimulus is responsible for triggering the cytokine cascade in this disease, may have significant implications for the management of patients with AP.

Case Report: Long-Term Remission of Parathyroid Cancer: Possible Relation to Vitamin D and Calcitriol Therapy

Recurrence of surgically treated parathyroid cancer occurs in 30% to 65% of patients and has a poor prognosis; only 1 of 29 cases remained normocalcemic more than 2 years later. No medical attempts to prevent recurrence have been reported. A 24-year-old pregnant woman whose mother died of parathyroid cancer underwent apparently successful surgery for parathyroid cancer. Serum Ca and parathyroid hormone (PTH) returned to normal levels but 3 months after surgery, although normocalcemic, the serum PTH level was elevated. The administration of vitamin D 200,000 U/month or calcitriol 0.5 microgram daily and 1 g of Ca supplementation daily, resulted in the normalization of PTH during 81 months of follow-up. On three occasions, when vitamin D or calcitriol were omitted, serum intact, C-terminal, or mid-molecule PTH levels rose. Ionized and total serum Ca, creatinine, calcitriol and calcidiol levels were normal, and multiple ultrasounds of the neck remained negative after surgery. This observation suggests that serum PTH could be an early marker for the detection of recurrence in parathyroid cancer with normal serum Ca, and that suppression of PTH secretion by vitamin D or calcitriol could avert or delay the progression of recurrence. Additional trials with calcitriol in operated normocalcemic parathyroid cancer with an elevated serum PTH level is recommended.

The Southern Solution to Our Current Malaise

I have lived a life of great good fortune in health, faith, family, and profession. Emblematic of that good fortune is my membership in this society, its encouragement, inspiration, fellowship, and the occasional worthy golf partner. My gratitude for the privilege of this podium is beyond my means of expression, but despite my perceived lack of eloquence, it is no less heartfelt.