Tim Strate

Long-term Follow-up of a Randomized Trial Comparing the Beger and Frey Procedures for Patients Suffering From Chronic Pancreatitis

Objective:To report on the long-term follow-up of a randomized clinical trial comparing pancreatic head resection according to Beger and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy according to Frey for surgical treatment of chronic pancreatitis. Summary Background Data:Resection and drainage are the 2 basic surgical principles in surgical treatment of chronic pancreatitis. They are combined to various degrees by the classic duodenum preserving pancreatic head resection (Beger) and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy (Frey). These procedures have been evaluated in a randomized controlled trial by our group. Long-term follow up has not been reported so far. Methods:Seventy-four patients suffering from chronic pancreatitis were initially allocated to DPHR (n = 38) or LE (n = 36). This postoperative follow-up included the following parameters: mortality, quality of life (QL), pain (validated pain score), and exocrine and endocrine function. Results:Median follow-up was 104 months (72-144). Seven patients were not available for follow-up (Beger = 4; Frey = 3). There was no significant difference in late mortality (31% [8/26] versus 32% [8/25]). No significant differences were found regarding QL (global QL 66.7 [0–100] versus 58.35 [0–100]), pain score (11.25 [0–75] versus 11.25 [0–99.75]), exocrine (88% versus 78%) or endocrine insufficiency (56% versus 60%). Conclusions:After almost 9 years’ long-term follow-up, there was no difference regarding mortality, quality of life, pain, or exocrine or endocrine insufficiency within the 2 groups. The decision which procedure to choose should be based on the surgeons experience.

Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience.

Objective:To evaluate surgical strategies for neuroendocrine pancreatic tumors (NEPT) in the light of the new WHO classification from 2004 and to draw conclusions for future surgical concepts. Background:The extent of surgical resection in primary and recurrent NEPT is unclear. Methods:Between 1987 and 2004, 62 patients with sporadic NEPT were treated at our institution and sections from biopsy and resection specimen were histopathologically reclassified. Clinical presentation, surgery, metastases, and pattern of recurrence were related to survival. Results:Fifteen well-differentiated tumors (WDT, 24%), 39 low-grade carcinomas (LGC, 63%), and 8 high-grade carcinomas (HGC, 13%) were identified. Median observation time was 30.5 months; 48 of 62 patients (78%) were surgically resected, and in 45 patients R0/R1 status was achieved. Overall 2- and 5-year survival in the latter group was 80% and 64%, respectively. Retrospective WHO classification revealed that organ-preserving segmental resections had been performed in 10 LGC and 1 HGC. These patients showed equal outcome as radically resected counterparts (n = 19). Liver and other organ metastases were present in 19 of 62 patients (31%), and resection was accomplished in 7 of 19 patients, which conferred better overall survival (P = 0.026, log-rank test); 21 of 45 R0/R1-resected patients (47%) suffered from recurrence, and reoperation was accomplished in 9 patients, which resulted in better overall survival (P = 0.066). Conclusion:Organ-preserving resections offer sufficient local control in LGC; therefore, radical resections do not seem to be justified. On the other hand, radical resection is indicated even in metastasized patients or in case of loco-regional recurrence. The silent and slow course of the disease facilitates long-term surgical control.

Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial.

BACKGROUND & AIMS Tailored organ-sparing procedures have been shown to alleviate pain and are potentially superior in terms of preservation of endocrine and exocrine function as compared with standard resection (Whipple) for chronic pancreatitis with inflammatory pancreatic head tumor. Long-term results comparing these 2 procedures have not been published so far. The aim of this study was to report on long-term results of a randomized trial comparing a classical resective procedure (pylorus-preserving Whipple) with an extended drainage procedure (Frey) for chronic pancreatitis. METHODS All patients who participated in a previously published randomized trial on the perioperative course comparing both procedures were contacted with a standardized, validated, quality of life and pain questionnaire. Additionally, patients were seen in the outpatient clinic to assess endocrine and exocrine pancreatic function by an oral glucose tolerance test and fecal chymotrypsin test. RESULTS There were no differences between both groups regarding quality of life, pain control, or other somatic parameters after a median of 7 years postoperatively. Correlations among continuous alcohol consumption, endocrine or exocrine pancreatic function, and pain were not found. CONCLUSIONS Both procedures provide adequate pain relief and quality of life after long-term follow-up with no differences regarding exocrine and endocrine function. However, short-term results favor the organ-sparing procedure.

Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis.

ObjectivesIn light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated. DesignRandomized, controlled intervention trial. SubjectsForty-eight minipigs of either sex. InterventionsPancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls—group 1—or to one of three treatment groups—group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study. Measurements and Main Results High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p < .05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-&agr; response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia. ConclusionsHemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid–induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.

L1 is associated with micrometastatic spread and poor outcome in colorectal cancer

L1 is a cell adhesion molecule expressed at the invasive front of colorectal tumors with an important role in metastasis. The aim of the present study was to determine L1 protein expression in a large cohort of colorectal cancer patients and its impact on early metastatic spread and survival. A total of 375 patients that underwent surgical treatment for colorectal cancer were chosen retrospectively. A tissue microarray was constructed of 576 tissue samples from these patients and analyzed by immunohistochemistry with a monoclonal antibody against human L1 (UJ127). Lymph node and bone marrow micrometastasis were assessed with monoclonal antibodies Ber-EP4 and pancytokeratin A45-B/B3, respectively. Associations between L1 expression and lymph node, bone marrow micrometastasis and survival were investigated with Fishers, log-rank test and Cox multivariate analysis. All statistical tests were two-sided. L1 was detected in a subset of 48 (13%) of 375 patients examined. Analysis of L1 expression and survival revealed a significantly worse outcome for L1-positive patients by log-rank test (P<0.05). Multivariate Cox regression analysis showed the strongest independent prognostic impact of L1 expression (P<0.05). Fishers test revealed a significant association of L1 expression and presence of disseminated tumor cells in lymph nodes and bone marrow (P<0.05). L1 is a powerful prognostic marker for patients that undergo complete surgical resection. It may have a role in early metastatic spread, as L1 is associated with micrometastases to both the lymph nodes and bone marrow. Thus, L1 should be explored further as a target for adjuvant therapy for micrometastatic disease.

Laparoscopic vs open repair of gastric perforation and abdominal lavage of associated peritonitis in pigs

AbstractBackground: Laparoscopy is increasingly used in conditions complicated by peritonitis, e.g., peptic ulcer perforation. Of some theoretical concern is the capnoperitoneum, which may aggravate peritonitis and induce septic shock due to increased intraabdominal pressure and distension of the peritoneum. This animal study was devised to analyze the effectiveness of laparoscopic versus traditional open repair of gastric perforation and abdominal lavage for associated peritonitis. Methods: To simulate gastric perforation, female Duroc pigs were subjects to standardized gastrotomy. Either 6 or 12 h after gastric perforation, the animals underwent either traditional open or laparoscopic repair of the gastric defect and peritoneal lavage. The subjects were divided into the following four groups: peritonitis for 6 h and open surgery (group I) or laparoscopic surgery (group II); peritonitis for 12 h and open surgery (group III) or laparoscopic surgery (group IV). After an observation period of 6 days, the surviving animals were killed. The main outcome criteria were survival, perioperative changes of hemodynamics suggestive for septic shock, bacteremia, and endotoxemia. Results: There were no significant differences between group I and II. Mortality was 22% in group III, as compared to 78% in group IV (p= 0.045). In group IV, the incidence of perioperative bacteremia and plasma endotoxin concentrations were significantly higher than in group III. Concomitantly, decreased mean arterial pressure and systemic vascular resistance, and increased cardiac output suggested a higher incidence of septic shock in group IV. Conclusion: Critical appraisal of laparoscopic surgery is warranted in conditions associated with severe, longstanding peritonitis.

L1 (CD171) is highly expressed in gastrointestinal stromal tumors

The treatment strategy for mesenchymal tumors of the gastrointestinal tract is based upon typing of the tumor. Especially differential diagnosis of gastrointestinal stromal tumors (GISTs) to leiomyomas is crucial for determining radicality of surgery. L1 cell adhesion molecule (CD171) plays an essential role in tumor progression. The aim of this study was to determine expression of L1 in GISTs, smooth muscle tumors, desmoid-type fibromatosis and peripheral nerve sheath tumors (PNSTs). We retrospectively analyzed a total of 129 surgically resected primary tumors or metastases of 72 GISTs, 29 smooth muscle tumors, seven PNSTs and 21 desmoid-type fibromatosis by immunohistochemistry for c-kit, CD34, smooth muscle actin, desmin, vimentin, S-100 and L1 expression. L1 expression was detected in 53 (74%) of 72 GISTs but in none of 29 smooth muscle tumors or 21 desmoid-type fibromatosis (P<0.01 by Fishers test). In all, four (57%) of seven peripheral nerve sheath tumors were L1-positive. Survival analysis of 55 surgically completely resected GISTs presenting without metastasis at initial diagnosis revealed no tumor-specific death among L1-negative patients (P=0.13 by log-rank test; median follow-up time 41 months) and one recurrence was observed (P=0.12). Interestingly high levels of L1 were seen in tumor vascular endothelial cells of smooth muscle tumors and PNSTs, but not in GISTs. Our data show that L1 is highly expressed in GISTs but not in smooth muscle tumors and desmoid-type fibromatosis being important differential diagnoses. The trend towards a reduced survival of L1-positive patients in this study has to be further evaluated in future trials with higher patient numbers.

Systemic Intravenous Infusion of Bovine Hemoglobin Significantly Reduces Microcirculatory Dysfunction in Experimentally Induced Pancreatitis in the Rat

Objective: To evaluate the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis. Summary Background Data: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue. Methods: In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0–16). Results: In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P < 0.001; 95% confidence interval for difference 17.5–45.3). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3–8.5 vs. 8–10.75, P < 0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3–8.5 vs. 6.5–10.25, P < 0.006)]. Conclusions: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.

Alveolar recruitment strategy and high positive end-expiratory pressure levels do not affect hemodynamics in morbidly obese intravascular volume-loaded patients.

We evaluated the effect of the alveolar recruitment strategy and high positive end-expiratory pressure (PEEP) on hemodynamics in 20 morbidly obese (body mass index 50 ± 9 kg/m2), intravascular volume-loaded patients undergoing laparoscopic surgery. The alveolar recruitment strategy was sequentially performed with and without capnoperitoneum and consisted of an upward PEEP trial, recruitment with 50–60 cm H2O of plateau pressure for 10 breaths, and a downward PEEP trial. Recruitment and high PEEP did not cause significant disturbances in any hemodynamic variable measured by systemic and pulmonary artery catheters. Transesophageal echocardiography revealed no differences in end-diastolic areas or evidence of segmental abnormalities in wall motion.

Extrahepatic portal hypertension in chronic pancreatitis: an old problem revisited.

ObjectiveTo evaluate the impact of concomitant nonhepatic portal hypertension in chronic pancreatitis on immediate and long-term outcome after major pancreatic surgery. MethodsA total of 154 patients (96 male, 58 female) with a history of pancreatitis of at least 12 months, severe incapacitating pain, and radiologic evidence of pancreatic head enlargement was evaluated. One hundred thirty-five patients underwent duodenum-preserving resections of the pancreatic head according to Beger or Frey, and 19 patients underwent pancreatoduodenectomy without (classical Whipple) or with pyloric preservation (PPPD) in cases of suspected malignancy. Outcome parameters included operative time and blood loss, early and late complications and death, recurrent pancreatitis, professional rehabilitation, and alterations in portal venous flow. Median follow-up in this prospective study was 51 months. ResultsPatients with portal hypertension required significantly more blood transfusions and had longer operative times than their counterparts. The overall postoperative complication rate was significantly higher in this subgroup. Restoration of postoperative portal venous blood flow was complete after Beger, Whipple, and PPPD procedures but was little affected by Frey procedures. There was no evidence of variceal hemorrhage during the observation period in all operative groups. ConclusionsConcomitant extrahepatic portal hypertension entails a substantial risk in pancreatic surgery for chronic pancreatitis. When surgery is considered in a symptomatic patient, surgical strategy is determined more by pancreatic morphology than by the intent to restore portal blood flow.