Stefan Wildi

Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: Foregut, midgut, hindgut, and unknown primary

a DRK Kliniken Westend, Berlin , Germany; b UFR Bichat-Beaujon-Louis Mourier, Service de Chirurgie Digestive, Hopital Louis Mourier, Colombes , France; c Medicine and Surgery, General Surgery Section, MED/18 – General Surgery and d Department of Pathology, University of Verona, Verona , Italy; e Netherlands Cancer Centre, Amsterdam , and f Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam , The Netherlands;

Consensus guidelines for the management of patients with digestive neuroendocrine tumors - Well-differentiated jejunal-ileal tumor/carcinoma

Consensus guidelines for the management of patients with digestive neuroendocrine tumors : well-differentiated jejunal-ileal tumor/carcinoma

Well-Differentiated Pancreatic Nonfunctioning Tumors/Carcinoma

Departments of a Surgery and b Radiology, University of Verona, Verona , Italy; c Department of Internal Medicine, Charite, University of Berlin, Berlin , Germany; d Department of Nuclear Medicine, University of Rotterdam, Rotterdam , The Netherlands; e M. Korner, University of Bern, Institut fur Pathologie, Bern , Switzerland; f Department of Oncology, South Florida University, Tampa, Fla. , USA; g Department of Internal Medicine, Charite, University of Berlin, Berlin , Germany; h Department of Radiology, Charite Universitatsmedizin, Berlin , Germany; i Department of Surgery, Stadtisches Klinikum Neuss, Lukas Hospital, Neuss , Germany; j Department of Surgery, Zurich Hospital, Zurich , Switzerland; k Department of Surgery, Vivantes Humboldt Hospital, Berlin , Germany; l Department of Endocrine Oncology, University of Uppsala, Uppsala , Sweden; m Department of Pathology, University of Lyon, Lyon , France

Laparoscopic gastric bypass is superior to laparoscopic gastric banding for treatment of morbid obesity.

Objective:To define whether laparoscopic gastric banding or laparoscopic Roux-en-Y gastric bypass represents the better approach to treat patients with morbid obesity. Summary Background Data:Two techniques, laparoscopic gastric bypass or gastric banding, are currently widely used to treat morbid obesity. Since both procedures offer certain advantages, a strong controversy exists as to which operation should be proposed to these patients. Therefore, data are urgently needed to identify the best therapy. Methods:Since randomized trials are most likely not feasible because of the highly different invasiveness and irreversibility of these procedures, a matched-pair design of a large prospectively collected database appears to be the best method. Therefore, we used our prospective database including 678 bariatric procedures performed at our institution since 1995. A total of 103 consecutive patients with laparoscopic gastric bypass were randomly matched to 103 patients with laparoscopic gastric banding according to age, body mass index, and gender. Results:Both groups were comparable regarding age, gender, body mass index, excessive weight, fat mass, and comorbidites such as diabetes, heart disease, and hypertension. Feasibility and safety: All gastric banding procedures were performed laparoscopically, and one gastric bypass operation had to be converted to an open procedure. Mean operating time was 145 minutes for gastric banding and 190 minutes for gastric bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days for gastric bypass. The incidence of early postoperative complications was not significantly different, but late complications were significantly more frequent in the gastric banding group (pouch dilatation). There was no mortality in both groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m2 in the gastric banding group and from 47.8 to 31.9 kg/m2 in the gastric bypass group within 2 years of surgery. These differences became significant from the first postoperative month until the end of the follow-up (24 months). The gastric bypass procedure achieved a significantly better reduction of comorbidities. Conclusions:Laparoscopic gastric banding and laparoscopic gastric bypass are feasible and safe. Pouch dilatations after gastric banding are responsible for more late complications compared with the gastric bypass. Laparoscopic gastric bypass offers a significant advantage regarding weight loss and reduction of comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y gastric bypass appears to be the therapy of choice.

Consensus guidelines for the management of patients with digestive neuroendocrine tumours: Well-differentiated colon and rectum tumour/carcinoma

a Department of Gastroenterology, North Hampshire Hospital, Basingstoke , UK; b Stadtisches Klinikum Neuss, Lukaskrankenhaus, Chirurgische Klinik I, Neuss , Germany; c Istituto di Radiologia, Policlinco GB Rossi, Verona , Italy; d Institute for Pathology, Kantonsspital, Baden , Switzerland; e Departments of Internal Medicine and Endocrinological and Metabolic Sciences, University of Genoa, Genoa , Italy; f II. Internal Medical Department, University Hospital Martin, Martin , Slovakia; g G. Genimatas Hospital, Athens , Greece; h Erciyes University Medical School, Department of Endocrinology and Metabolism, Kayseri , Turkey; i H. Lee Moffitt Cancer Center/ University of South Florida, Tampa, Fla. , USA; j Anatomie Pathologique, Hopital Edouard Herriot, Lyon , France;

Acute gastrointestinal bleeding: detection of source and etiology with multi-detector-row CT

This study was conducted to determine the ability of multi-detector-row computed tomography (CT) to identify the source and etiology of acute gastrointestinal bleeding. Eighteen patients with acute upper (n = 10) and lower (n = 8) gastrointestinal bleeding underwent 4-detector-row CT (n = 6), 16-detector-row CT (n = 11), and 64-slice CT (n = 1) with an arterial and portal venous phase of contrast enhancement. Unenhanced scans were performed in nine patients. CT scans were reviewed to determine conspicuity of bleeding source, underlying etiology, and for potential causes of false-negative prospective interpretations. Bleeding sources were prospectively identified with CT in 15 (83%) patients, and three (17%) bleeding sources were visualized in retrospect, allowing the characterization of all sources of bleeding with CT. Contrast extravasation was demonstrated with CT in all 11 patients with severe bleeding, but only in 1 of 7 patients with mild bleeding. The etiology could not be identified on unenhanced CT scans in any patient, whereas arterial-phase and portal venous-phase CT depicted etiology in 15 (83%) patients. Underlying etiology was correctly identified in all eight patients with mild GI bleeding. Multi-detector-row CT enables the identification of bleeding source and precise etiology in patients with acute gastrointestinal bleeding.

Laparoscopic Pouch Resizing and Redo of Gastro-jejunal Anastomosis for Pouch Dilatation following Gastric Bypass

Background: With a dramatically increasing number of bariatric operations performed world-wide in the recent years, more late complications have been noticed. Proximal gastric pouch dilatation is a known late complication after laparoscopic or open restrictive surgery for morbid obesity. In the present paper, we report our experience with laparoscopic re-operation of enlarged gastric pouches after laparoscopic gastric bypass, with emphasis on technique and outcome. Methods: Data were retrieved from a prospective database of 334 patients who underwent a laparoscopic gastric bypass operation at the University Hospital of Zurich from July 2000 to December 2004. Five laparoscopic revisions for pouch dilatation after primary bypass were performed. Results: 3 female and 2 male patients with median age 40 years (range 32-55) underwent a laparoscopic pouch resizing. At the time of the re-operation, the median BMI was 32.0 kg/m2 (range 28.4-48.4). All procedures were performed laparoscopically with no conversion to open surgery. The median operating-time was 110 minutes (95-120). The median hospital stay was 6 days (range 5-14). The median BMI in the follow-up of 12 months (9-14) was 28.0 kg/m2 (25.5-45.8). Diabetes mellitus improved in 4 cases during follow-up. Conclusion: Laparoscopic pouch resizing with redo of the gastro-jejunal anastomosis was feasible, safe and effective in this small series. It led to further weight loss and improved symptoms of poor pouch emptying.

Stable Transfection of a Glypican-1 Antisense Construct Decreases Tumorigenicity in PANC-1 Pancreatic Carcinoma Cells

Glypican-1 belongs to a family of glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycans (HSPGs) that affect cell growth, invasion, and adhesion. Cell-surface HSPGs are believed to act as co-receptors for heparin-binding mitogenic growth factors. It was reported that glypican-1 is strongly expressed in human pancreatic cancer, and that it may play an essential role in regulating growth-factor responsiveness in pancreatic carcinoma cells. In this study we investigated the effects of decreased glypican-1 expression in PANC-1 pancreatic cancer cells. To this end, PANC-1 cells were stable transfected with a full-length glypican-1 antisense construct. The glypican- antisense transfected clones displayed markedly reduced glypican- protein levels and a marked attenuation of the mitogenic responses to heparin-binding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor-2 (FGF2), heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), and hepatocyte growth factor (HGF). In addition, glypican-1 antisense-expressing PANC-1 cells exhibited a significantly reduced ability to form tumors in nude mice in comparison with parental and sham-transfected PANC-1 cells. These data suggest that glypican-1 plays an important role in the responses of pancreatic cancer cells to heparin-binding growth factors, and documents for the first time that its expression may enhance tumorigenic potential in vivo.

Suppression of transforming growth factor β signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations

Background: Transforming growth factors βs (TGF-βs) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-βs modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB−/−) and transgenic mice that are heterozygous (FVB+/−) for expression of a dominant negative type II TGF-β receptor. Methods: After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. Results: The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/− mice exhibited minimal alterations in response to caerulein with attenuated neutrophil–macrophage infiltrates. Moreover, acini from FVB+/− mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. Conclusion: Our findings indicate that a functional TGF-β signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis.

Suppression of TGF-β signaling aborts caerulein-induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations

Background: Transforming growth factors βs (TGF-βs) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-βs modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB−/−) and transgenic mice that are heterozygous (FVB+/−) for expression of a dominant negative type II TGF-β receptor. Methods: After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. Results: The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/− mice exhibited minimal alterations in response to caerulein with attenuated neutrophil–macrophage infiltrates. Moreover, acini from FVB+/− mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. Conclusion: Our findings indicate that a functional TGF-β signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis.