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Mesh wrapping hepatorrhaphy is an established method to control severe hepatic bleeding after trauma. Besides the multiple advantages of this technique, only a few complications are described in literature. We report a patient with severe liver trauma showing ischemia of the liver caused by post-traumatic edema and compression of the liver after mesh wrapping hepatorraphy to control the bleeding. To avoid this complication, early and frequent control of liver enzymes is highly recommended and, in case of elevation, laparotomy and decompression should be performed. [ABSTRACT FROM AUTHOR]

Background: The concept of balloon laparoscopy (B-LSC) pursues the simplification of conventional diagnostic laparoscopy (LSC). The pneumoperitoneum is replaced by a transparent balloon, which is positioned in front of the optical system. It shall be shown that with this arrangement diagnostic LSC can be performed outside of the operating room without requiring general anesthesia., Methods: An inflatable balloon was developed for a 30 degrees /3.5-mm rod lens. Intra-abdominally the balloon was expanded to a diameter of 30 mm by air insufflation, and B-LSC was performed. Twelve patients were examined in general anesthesia before laparoscopic surgery. Twelve patients were subjected to B-LSC fully awake or with sedation (midazolam or propofol/S-ketamine) as a "second-look" procedure by way of a flexible trocar (port) left in the abdominal wall at the end of previous operation. Eight patients have been first provided with a trocar under sedation (midazolam or propofol/S-ketamine) combined with local anesthesia, and B-LSC was performed before laparoscopic surgery., Results: On a scale of 1-5, the general impression was rated 1.9, the navigability to the different abdominal organs 2.5, the resolution 1.5, the stability of the system optic/trocar 2.1, the suitability of the balloon format 1.9, and the stability of the balloon against lateral shear forces 2.4. The degree of painfulness of the examination was rated 2.8, the tolerance of the port 1.4, and the degree of painfulness of trocar placement at 2.5. On a scale of 1 to 3, the strain of the abdominal musculature was rated 1.4 and the obstruction by adhesions 1.7., Discussion: B-LSC is technically practicable with good imaging qualities and without requiring pneumoperitoneum. It is tolerated in great extent under slight sedation and particularly well under deep sedation. The procedure is suitable for diagnostics of unclear abdominal conditions, as a second-look LSC and also as a staging LSC.

Background: Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation., Methods: Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study., Results: We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues., Conclusion: We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate.

Background: Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-alpha (IFN-alpha) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution., Patients and Methods: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n=7) or periampullary (n=4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-FU 200 mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-IFN-alpha was administered on three days weekly during Week one to five of the radiotherapy course as subcutanous injections with 3*3 Mio. I.U. weekly., Results: The four-year overall survival rate for all patients was 55%. In the neoadjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemoradioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed., Conclusion: Our data strengthens the hypothesis of concomitant chemoradioimmunotherapy with 5-FU, IFN-alpha and cisplatin as a possible new treatment of pancreatic cancer in resected patients.

Background and Aims: Isolated tumor cells (ITCs) in cancer patients are retrieved mostly using immunohistochemistry with antibodies directed against antiepithelial antigens (for example Ber-EP4), which are supposed not to be present in metastatic-free tissue. To date, there has been ongoing controversy whether those cells have biologic significance and are linked with tumor progression and impaired patient's prognosis. Therefore, the aim of this study was to further characterize Ber-EP4-positive cells in various tissues, with special emphasis on their tumorigenic origin., Materials and Methods: The frequency and prognostic impact of ITCs in lymph nodes displayed by means of monoclonal antibody Ber-EP4 were evaluated in retrospective (n = 292) and prospective (n = 100) collectives of various gastrointestinal carcinomas free of metastatic disease in conventional histopathology (pN0). Furthermore, the frequency of ITCs in the peritoneal cavity and bone marrow was analyzed in case of absence of overt distant metastasis (pM0) in the prospective collective. Ber-EP4-immunoreactive cells were further characterized for tumorigenic origin using morphological criteria and immunohistochemical double staining for Ber-EP4 and p53., Results: Ber-EP4-positive cells could be revealed in lymph nodes in 44.3% of pN0-gastrointestinal carcinomas, in the peritoneal cavity in 19%, and in the bone marrow in 10%. In lymph nodes, BerEP4-immunoreactive cells exhibited a metastatic-atypical morphology in 59%; however, it was always typical for true tumor cells in the peritoneal cavity or bone marrow. The cumulative 5-year survival rate was adversely affected by Ber-EP4-immunoreactive cells in uni- and multivariate analysis, irrespective of the underlying cell morphology (68% for Ber-EP4 negative, 41% for Ber-EP4 positive with atypical and typical morphology each). In the case of a p53-positive primary tumor, 70% of the corresponding ITCs also overexpressed p53, while the remainder was deemed p53 negative (p = 0.002)., Conclusion: ITCs detected by the antiepithelial antibody Ber-EP4 are present in a substantial proportion of apparently tumor-free lymph nodes. These cells impair patients' prognoses, irrespective of the underlying cell morphology. As approximately one third of Ber-EP4-positive cells in p53-positive primary tumors do not overexpress p53; their true tumorigenic origin needs to be further investigated.

Introduction: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results., Methods: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination., Results: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN., Conclusions: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.

The intestinal epithelium has one of the greatest regenerative capacities in the body; however, neither stem nor progenitor cells have been successfully cultivated from the intestine. In this study, we applied an "artificial niche" of mouse embryonic fibroblasts to derive multipotent cells from the intestinal epithelium. Cocultivation of adult mouse and human intestinal epithelium with fibroblast feeder cells led to the generation of a novel type of nestin-positive cells (intestinal epithelium-derived nestin-positive cells [INPs]). Transcriptome analyses demonstrated that mouse embryonic fibroblasts expressed relatively high levels of Wnt/bone morphogenetic protein (BMP) transcripts, and the formation of INPs was specifically associated with an increase in Lef1, Wnt4, Wnt5a, and Wnt/BMP-responsive factors, but a decrease of BMP4 transcript abundance. In vitro, INPs showed a high but finite proliferative capacity and readily differentiated into cells expressing neural, pancreatic, and hepatic transcripts and proteins; however, these derivatives did not show functional properties. In vivo, INPs failed to form chimeras following injection into mouse blastocysts but integrated into hippocampal brain slice cultures in situ. We conclude that the use of embryonic fibroblasts seems to reprogram adult intestinal epithelial cells by modulation of Wnt/BMP signaling to a cell type with a more primitive embryonic-like stage of development that has a high degree of flexibility and plasticity.

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in 10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1 differed significantly from all other groups, no differences in OS between the other TRG groups were seen. Patients with complete tumor regression after neoadjuvant RCT showed a much better survival than patients with tumors that responded less to induction therapy. Further qualitative subdivision of tumor regression could not identify patient groups with significant differences in prognosis. After comparing our data with the literature, it is reasonable to consider classifying all patients into 'Complete tumor regression' and 'Incomplete tumor regression'.

Background: The aim of this study was to determine the accuracy of prediction of the surgeon's 'gut-feeling' in estimating postoperative outcome., Methods: A prospective series of 1077 consecutive patients undergoing major hepatobiliary or gastrointestinal surgery were studied. Patients having elective (n = 827) and emergency (n = 250) procedures were included. The surgeon predicted the development of postoperative complications immediately after completion of surgery on a scale from 0 to 100 percent. These predictions were compared with the actual outcome and with predictions made using the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM). The Portsmouth predictor equation (P-POSSUM) was applied for the estimation of mortality., Results: The observed morbidity and mortality rates were 29.5 and 3.4 percent respectively. POSSUM predicted a morbidity rate of 46.4 percent and P-POSSUM a mortality rate of 6.9 percent. The surgeon's gut-feeling was more accurate in the prediction of morbidity at 32.1 percent. On the basis of gut-feeling, surgeons overpredicted morbidity in elective surgery, but underestimated the risk of complications in the emergency setting. The (P)-POSSUM scoring system overpredicted morbidity and mortality for elective and emergency operations., Conclusion: The surgeon's gut-feeling is a good predictor of postoperative outcome, especially after elective surgery. (P)-POSSUM overpredicted morbidity and mortality in this series of major gastrointestinal and hepatobiliary operations.

Purpose: To determine the frequency and prognostic impact of isolated tumor cells (ITC) in regional lymph nodes judged to be tumor free in conventional histopathology among gastric cancer patients., Methods: Among 161 patients who underwent gastrectomy and D2-lymphadenectomy, 56 were staged pN0(35%). Archival paraffin blocks of 1148 resected regional lymph nodes of those pN0 patients were reevaluated for ITC using monoclonal antibody Ber-EP4. Patients with and without ITC were compared with regard to the distribution of various clinicopathological factors. Prognostic impact of ITC was tested in uni- and multivariate analysis., Results: Of 56 pN0 patients, 33 (59%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of ITC was not dependent on other clinicopathological factors. ITC impaired patients' prognoses significantly in uni- as well as multivariate analyses [estimated 5-year survival rate: 82% for pN0((i-))vs 58% for pN0((i+))(p = 0.059) and 15% for pN1/2 (p = 0.0005 and p < 0.0001, respectively)]., Conclusion: ITC are a frequent event in apparently tumor-free lymph nodes of gastric cancer patients and are overlooked by conventional histopathology. They are encountered even in limited stages of disease and impair patients' prognoses. This should be borne in mind when advocating local resection for early gastric cancer.

Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9-3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer., (Copyright 2004 Wiley-Liss, Inc.)

Objectives: Delayed gastric emptying (DGE) has been specifically attributed to pylorus-preserving pancreaticoduodenectomy (PPPD). As PPPD has been shown to be comparable with the classic Kausch-Whipple pancreaticoduodenectomy (KWPD) in terms of oncological radicality, DGE has advanced to be the leading argument for hemigastrectomy in PD., Methods: A prospective, nonrandomized comparison of patients undergoing PPPD (n = 113), KWPD (n = 19), and duodenum-preserving, pancreatic head resection (DPPHR, n = 18) for various diseases was performed. First, groups were analyzed with regard to structural similarity; then, they were compared with special emphasis on DGE and other postoperative complications. Finally, further prognostic factors were sought that had an impact on DGE., Results: The PPPD group was comparable with the KWPD group, but not to the DPPHR population. The in-clinic course after DPPHR compared favorably with PPPD as well as KWPD, and, here, no DGE occurred. The overall morbidity rates of PPPD and KWPD were comparable; 1 patient died in hospital (mortality rate, 0.7%). The gastric tube after PPPD and KWPD could be withdrawn at a median of 2 and 3 days, respectively, a liquid diet was started after 4 and 5 days, respectively, and a full diet was tolerated after 10 days each (n.s.). DGE was distributed evenly among PPPD (12%) and KWPD patients (21%, n.s.), and it was noted almost exclusively when other postoperative complications were present (P < 0.0001). No further prognostic factors influencing DGE could be identified., Conclusion: Pylorus preservation does not increase the frequency of DGE. DGE almost exclusively occurs as a consequence of other postoperative complications. Therefore, DGE should not be used as an argument to advocate hemigastrectomy in PPPD.

Background: A single centre study was conducted to examine the frequency of cholecystectomies, both open and laparoscopic, up to 2 years prior to the diagnosis of pancreatic cancer. In particular, it was of interest to investigate whether there is a diagnostic delay in a significant number of pancreatic cancer patients and if these patients already have symptoms or findings at the time of cholecystectomy that might have been indicative of the underlying malignant disease., Methods: It is demonstrated that 17 out of 186 pancreatic cancer patients (9%) underwent a cholecystectomy within the 2 years prior to cancer diagnosis., Results: A significant number of these patients showed a considerable weight loss at the time of the cholecystectomy. It is hypothesized that symptoms which led to cholecystectomies in these patients were most likely related to the pancreatic cancer. Owing to the resulting delay of pancreatic cancer diagnosis the resection rate with curative intent decreases to 35% from 44% in the whole series., Conclusion: Patients suffering from cholecystolithiasis and showing atypical symptoms or other notable findings such as considerable weight loss might be assessed in more detail pre- as well as postoperatively in order to minimize the diagnostic delay in pancreatic cancer and to avoid unnecessary operations.

The aim of this study was to define the value of MRI of the pancreas for preoperative local staging of patients with a suspected pancreatic mass. Ninety-four patients (41 women, 53 men; age range 32-87 years) with a suspected pancreatic tumor underwent preoperative staging with MRI on a 1.5-T system. The MRI protocol included breath-hold MR cholangiopancreatography in turbo spin-echo technique, biphasic contrast-enhanced 3D MR angiography, and MRI of the upper abdomen with breath-hold T2-weighted half-Fourier acquired single-shot turbo spin-echo and T1-weighted fast-low-angle-shot (pre- and postcontrast) sequences. Data were collected prospectively and analyzed by two radiologists in agreement modality. Evaluation criteria were vascular involvement, resectability, and a characterization benign vs malignant. Results were compared to histopathology in 78 patients. Sixteen patients were followed-up. In 74 of 94 patients a solid tumor or an inflammation of the pancreas ( n=62) or the papilla ( n=12) was detected. In this group, MRI had a sensitivity of 98%, a specificity of 92%, and an accuracy of 96% in the characterization of malignant tumors. Regarding only the solid tumors, the positive predictive value of MRI was 87% with respect to resectability. Other pathologic findings included adenoma or inflammation of the duodenum ( n=5), carcinoma or benign stenosis of the choledochus duct ( n=7) and carcinoma of the gall bladder ( n=2). In 6 patients MRI did not depict any pathologic findings, and follow-up confirmed this interpretation. Magnetic resonance imaging allows a local preoperative staging in patients with suspected pancreatic tumor. Limitations, however, concern to the diagnostics of peritoneal and/or liver metastases.

Background: The effectiveness of laparoscopic Nissen fundoplication (LNF) was assessed in patients with chronic gastroesophageal reflux disease (GERD) using pH study and different quality-of-life indexes. We correlated both types of data and hypothesised that improvement in quality of life following LNF does not necessarily correlate with improvement in pH values., Methods: Seventy patients presenting with typical symptoms of GERD (14 with Barrett's esophagus) underwent LNF between May 1997 and December 2000. All patients were evaluated both prior to and 3 months after surgery using 24-h pH study, endoscopy, and a validated quality-of-life questionnaire., Results: Following LNF, reflux was reduced to normal in all but six patients. Howevers despite persistent reflux, the Gastrointestinal Quality of Life Index (GQLI), of these six patients improved postoperatively from 79.5 +/- 12.2 to 111.7 +/- 8.3. These results correlate with those of patients who had normal postoperative pH studies-namely, 88.5 +/- 19.3 to 112 +/- 16.7. There was no difference in quality-of-life improvement between patients with Barrett's esophagus and those without it., Conclusion: There is only a weak correlation between quality-of-life assessment and pH study. Because the patient's quality of life is likely to improve following LNF, an objective means parameter of assessing the effectiveness of antireflux surgery, such as pH study or endoscopy, is recommended.

Background: The most frequent complication following gastroenterostomy (GE) for gastric outlet obstruction is delayed gastric emptying (DGE), which occurs in roughly 20% of patients. There is evidence that DGE may be linked to the longitudinal incision of the jejunum and that a transverse incision (cross-section GE) may decrease the incidence of DGE following GE., Patients and Methods: In contrast to the orthodox GE, the jejunum is severed transversely up to a margin of 1.5 cm at the mesenteric border and the anastomosis is created with a single running suture. A Braun anastomosis is added 20-30 cm distally to the GE. Patients were followed prospectively with special regard to the occurrence of DGE., Results: Between 1 August 1994 and 1 August 1998, 25 patients underwent cross-section GE, mostly because of an irresectable periampullary carcinoma. Eight patients exhibited clinical signs of gastric outlet obstruction preoperatively, while in 17 the GE was performed on a prophylactic basis. A biliary bypass was added in 15 patients. There was no disruption of the GE, but one patient died in hospital (4%). The nasogastric tube was withdrawn on the first postoperative day (range 0-6 days), a liquid diet was started on the fifth day (range 2-7 days) and a full regular diet was tolerated at a median of 9 days (6-14 days).The incidence of DGE was 4%: only the single patient who died fulfilled the formal criteria for DGE., Discussion: In contrast to orthodox GE, DGE seems to be of minor clinical importance following cross-section GE. As the technique is easy to perform, is free of specific complications and leads to a low incidence of DGE, it should be considered as an alternative to conventional GE.

Background & Aims: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade., Methods: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection., Results: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001)., Conclusions: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Background: Ingestion of food has been shown to modulate the lower-oesophageal-sphincter pressure (LESP). Fat is especially effective in decreasing the postprandial LESP. As there is good evidence that neurotensin (NT) is able to decrease the LESP, we conducted the present trial to determine whether NT could possibly be a mediator of the fat-induced decrease of the LESP., Methods: Six half-breed dogs were fitted for cervical side-to-side oesophagostomy to allow repeated oesophageal intubation; plasma NT immunoactivity was recorded during infusion of NT and after intragastric instillation of 200 ml of a fat solution. Experiments were repeated, with the specific NT antibody GN25 administered intravenously., Results: The optimal dose of NT required to simulate a postprandial situation was 50 pmol/kg/h. Infusion of this NT dose led to a statistically significant decrease of the LESP. Simultaneous administration of the NT antibody (immunoneutralisation) significantly inhibited this effect. Intragastric fat decreased the LESP and increased plasma NT. Immunoneutralisation of endogenously released NT led to an earlier restoration of baseline LESP, but this effect was not statistically significant., Conclusions: NT and intragastric fat modulate the LESP. NT appears to mediate the postprandial, fat-induced decrease of the LESP. Research with specific NT-receptor antagonists is necessary to determine the exact role of NT and other regulatory peptides in this context.

Background: Delayed gastric emptying (DGE) is the most frequent postoperative complication after pylorus-preserving pancreaticoduodenectomy (PPPD). This prospective, non-randomized study was undertaken to determine whether the incidence of DGE may be reduced by modifying the original reconstructive anatomy with a retrocolic duodenojejunostomy towards an antecolic duodenojejunostomy., Patients and Methods: The study was comprised of 51 patients who underwent PPPD between August 1994 and November 1997. The operation was carried out as originally described but was modified by performing the duodenojejunostomy antecolically. Clinical data were recorded prospectively, with special regard to DGE., Results: After PPPD, the nasogastric tube could be removed at a median of 2 days (range 1-22 days) postoperatively; in two patients, the nasogastric tube was reinserted because of vomiting and nausea. A liquid diet was started at a median of 5 days (3-11 days); the patients were able to tolerate a full, regular diet at a median of 10 days (7-28 days). The overall incidence of DGE was 12% (n=6). No postoperative complications other than DGE were exhibited by 36 patients (71%). In this group, DGE was only seen in one patient (3%). In the second group, where postoperative complications other than DGE occurred (n=15), five patients (30%) exhibited DGE (P=0.002)., Conclusions: DGE after PPPD seems to be of minor clinical importance following uncomplicated surgery. When taking the results into consideration, it can be said that, despite the lack of a control group, antecolic duodenojejunostomy might be the key to a low incidence of DGE after PPPD. In our experience, DGE is linked to the occurrence of other postoperative complications rather than to pylorus preservation.

The contribution of gastrin-releasing peptide (GRP) in the physiologic pancreatic response to a meal is unknown. We therefore investigated whether immunoneutralization of GRP could influence the exocrine pancreatic response to a meal as well as plasma concentrations of the peptide hormones neurotensin (NT) and cholecystokinin (CCK). Modified Herrera fistulas were implanted in five mongrel dogs. After a standard meal, we analyzed plasma NT, CCK, and GRP, and protein and enzyme (amylase, lipase, trypsin) content of exocrine pancreatic juice. An unspecific rabbit immunoglobulin solution was administered intravenously as a control. This experiment was repeated with a specific anti-GRP-immunoglobulin. The i.v. administration of the anti-GRP-antibody significantly inhibited meal-stimulated pancreatic secretion. Integrated protein output decreased from 58.4 to 36.8 g/180 min (p < 0.05), as did amylase (2,102 to 1,145 KU/180 min; p < 0.05), lipase (2,258 to 1,172 KU/180 min; p < 0.05), and trypsin (5,321 to 4,990 U/180 min). Postprandially released NT decreased from 8,271 to 5,825 pmol/180 min (p < 0.05). In contrast, integrated amounts of CCK remained relatively stable with 473 to 611 pmol/180 min. The neuropeptide GRP is one of the biologically important regulatory factors influencing meal-stimulated pancreatic secretion, as well as the postprandial plasma level of the peptide hormone NT in the dog. These mentioned effects of postprandially released GRP seem not to be mediated by CCK in an endocrine manner.

A stimulatory effect on exocrine pancreas secretion could be demonstrated with high concentrations of the 25-amino-acid peptide xenin in non-anesthetized dogs. This peptide has been isolated from gastric mucosa and it is part of a structural coat protein. It has close structural similarities to neurotensin. The longer C-terminal fragments xenin-(13--25) and xenin-(18--25) are essential for the stimulation of exocrine pancreas secretion in vivo. The smaller peptide fragments xenin-(21--25) and xenin-(22--25) failed to stimulate the pancreas as well as the N-terminal peptide fragment xenin-(1--23). The stimulatory effects of xenin may be mediated via neural neurotensin pathways, because neurotensin receptor blockade abolished the stimulatory effect on pancreatic secretion. Cholinergic pathways are not involved, because atropine had no inhibiting effect.

This report concerns a case of a Cushing's syndrome 10 years after first diagnosis of a Zollinger-Ellison syndrome within the same patient. In a 69-year-old female patient symptoms of hypergastrinaemia have been successfully treated with a proton pump inhibitor. Cushing's syndrome was the result of ectopic adrenocorticotropic hormone production by a large cystic gastrin-producing tumour of the pancreatic tail. After resection by subtotal pancreatectomy serum adrenocorticotropic hormone, cortisol, gastrin levels and secretin infusion test returned to normal. In contrast to all other previously published cases of ectopic adrenocorticotropic hormone syndrome associated with Zollinger-Ellison syndrome, this tumour had not metastasized into the liver and did not show local invasive growth.

DNA aneuploidy, as determined by flow cytometry, was detected in 36 out of 59 adenocarcinomas of the esophagogastric junction (61.0%). DNA aneuploidy was more frequent in tumors with infiltrative growth pattern and in high pT categories. No correlation was found with pN category, grading and Laurén's classification. In contrast to clinicopathological parameters, DNA ploidy has no impact on patients survival in univariate survival analysis.

Objective: To compare the results of transhiatal oesophagectomy with those of transthoracic resection with systematic two field en bloc lymphadenectomy in the treatment of carcinoma of the oesophagus., Design: Prospective open (non-random) study., Setting: University hospital, Germany., Subjects: 87 patients with carcinoma of the oesophagus of whom 46 underwent transhiatal, and 41 transthoracic resection., Main Outcome Measures: Morbidity and short and long term mortality., Results: The type of operation was chosen on clinical grounds, and the groups were comparable except for site and type of tumour, and nodal stage. The hospital mortality was 7/46 (15%) in the transhiatal group and 4/41 (10%) in the transthoracic group. The most common complication was anastomotic leak (23/46, 50%, compared with 10/41, 24%, p = 0.014), followed by major pulmonary complications (16/46, 35%, compared with 12/41, 29%), and cardiac complications (12/46, 26% compared with 11/41, 27%). Median survival was 350 days in the transhiatal group and 378 days in the transthoracic group. The percentage survival after one, two, and three years in the two groups was 48 and 55, 26 and 18, and 21 and 17, respectively. There were no significant differences in short or long term mortality., Conclusion: We have been unable to show that the oncologically more radical procedure (transthoracic resection with systematic two field en bloc lymphadenectomy) results in longer survival, but we have shown that it can be done with similar morbidity and short term mortality. Because it is possible to stage the disease exactly with a transthoracic resection, and because published reports from other centres have hinted at improved prognosis after it, we shall continue to do the operation for suitable patients.

The prognostic influence of blood-vessel invasion (BVI), lymphatic-vessel invasion (LVI) and neural invasion (NI) was evaluated retrospectively in a series of 161 patients with squamous cell carcinoma (SCC) of the esophagus who underwent esophageal resection. Evidence of BVI, LVI and NI was found in 32.9%, 48.5% and 26.1%, respectively. Incidence of BVI, LVI and NI was significantly higher in high pT categories (pT3 and pT4) than in low pT categories (pT1 and pT2) and in patients with distant metastases than in patients without distant metastases. Incidence of LVI and NI in lymph-node-positive patients was significantly higher than in lymph-node-negative patients. The 5-year survival rate was significantly lower in patients with BVI or LVI than in patients without BVI or LVI. Patients with evidence of NI showed no significant differences in 5-year survival from patients without evidence of NI. By stepwise multivariate Cox regression analysis, BVI and LVI were shown to be independent prognostic factors. A search for vascular invasion may therefore provide additional prognostic precision in SCC of the esophagus.

Background: The p53 gene product is known to regulate cell growth and proliferation. Whereas the wild-type p53 protein suppresses cell growth, the mutated p53 protein acts as an oncogene. Mutations in the p53 gene usually result in p53 protein stabilization and accumulation; so that the gene product can be detected by immunohistochemistry. Recently, the immunohistochemical detection of the p53 protein was associated with prognosis in breast, colorectal, and other types of cancer. However, its prognostic role in esophageal cancer remains to be elucidated., Methods: p53 expression in formalin fixed, paraffin embedded samples of 204 patients with primary squamous cell carcinoma of the esophagus, who underwent esophageal resection, were analyzed immunohistochemically with DO-1, a monoclonal antibody that detects wild-type and mutant forms of p53. The relationship between p53 immunoreactivity and prognostic factors was determined by the Chi-square test, and the prognostic impact of p53 protein expression was analyzed using univariate and multivariate survival analyses., Results: In 137 of 204 tumors (67.2%), nuclear immunoreactivity for the p53 protein was detected. There was no correlation with sex, age, pathologic tumor (pT) category, pathologic lymph node (pN) category, metastasis (M) category, residual cancer (R) category, histologic grade, or preoperative radiation therapy. In contrast to clinicopathologic parameters, p53 expression was not correlated with prognosis in univariate and multivariate survival analyses., Conclusions: The p53 protein can be detected by immunohistochemistry in a high percentage of squamous cell carcinomas of the esophagus. However, the overexpression of the p53 gene product has no impact on the prognosis.