Moritz N. Wente

Incidence, Risk Factors, and Prevention of Biliary Tract Injuries during Laparoscopic Cholecystectomy in Switzerland

Abstract. Bile duct injury (BDI) during laparoscopic cholecystectomy (LC) which may result in patient disability or death are reported to occur more frequently when compared to open surgery. The aim of this nationwide prospective study beyond the laparoscopic learning curve was to analyze the incidence, risk factors, and management of major BDI. During a 3-year period (1995–1997) 130 items of all LC data were collected on a central computer system from 84 surgical institutions in Switzerland by the Swiss Association of Laparoscopic and Thoracoscopic Surgery and evaluated for major BDIs. Simple biliary leakage was excluded from analysis. There were 12,111 patients with a mean age of 55 years (3–98 years) enrolled in the study. The overall BDI incidence was 0.3%, 0.18% for symptomatic gallstones, and 0.36% for acute cholecystitis. In cases of severe chronic cholecystitis with shrunken gallbladder, the incidence was as high as 3%. Morbidity and mortality rates were significantly increased in BDIs. BDI was recognized intraoperatively in 80.6%, in 64% of cases by help of intraoperative cholangiography. Immediate surgical repair was performed laparoscopically (suture or T-drainage) in 21%; in 79%, open repair (34% simple suture, 66% Roux-en-Y reconstruction) was needed. The BDI incidence did not decrease during the last 7 years. In 47%, BDIs were caused by experienced laparoscopic surgeons, perhaps because they tend to operate on more difficult patients. In conclusion, the incidence of major BDIs remains constant in Switzerland at a level of 0.3%, which is still higher when compared to open surgery. However, most cases are now detected intraoperatively and immediately repaired which ensures a good long-term outcome. For preventing such injuries, exact anatomical knowledge with its variants and a meticulous surgical dissecting technique especially in case of acute inflammation or shrunken gallbladder are mandatory.

Middle Segmental Pancreatic Resection: An Option to Treat Benign Pancreatic Body Lesions

Objective:To clarify whether middle segmental pancreatic resection can be performed with comparable morbidity and mortality to classic pancreatic resections for lesions in the mid-portion of the pancreas. Summary Background Data:Pancreaticoduodenectomies or distal pancreatectomy, traditionally used to treat lesions of the pancreatic body, sacrifice a significant amount of normal pancreatic tissue. Middle segmental pancreatic resection has therefore been introduced to minimize loss of functioning pancreatic tissue. Patients and Methods:In a prospective 4-year single-center study, 40 consecutive patients with lesions of the neck or the body of the pancreas underwent a middle segmental pancreatic resection. A matched-pairs analysis comparing middle segmental pancreatic resection with pp-Whipple and distal pancreatectomy was included. Results:Seventeen patients had neoplastic lesions (4 solid malignancies, 9 cystic lesions, 4 neuroendocrine tumors) and 23 patients had focal chronic pancreatitis. Postoperative surgical morbidity was 27.5% and mortality 2.5%. The reoperation rate was 5.0%. Three patients (7.5%) developed pancreatic fistula. Median postoperative hospital stay was 11 days (range, 6–62 days). After a median follow-up of 29 months, 97.4% (38 patients) of the patients were satisfied with the operation. The mean quality of life status (EORTC QLQ-C30) was comparable to a normal control population. Matched-pairs analysis revealed no differences of perioperative parameters (except operation time), morbidity, and mortality. However, endocrine pancreatic function was better preserved (P < 0.05) in patients with middle segmental pancreatic resection. Conclusions:Middle segmental pancreatic resection is an appropriate procedure for selected patients with tumorous lesions in the mid-portion of the pancreas. It preserves pancreatic parenchyma and function and has a mortality and morbidity rate comparable to other pancreatic resection procedures.

The neurotrophic factor artemin promotes pancreatic cancer invasion

Objective:To analyze the role of Artemin in pancreatic ductal adenocarcinoma (PDAC) in terms of expression, influence on cancer cell behavior, and pain correlation. Summary Background Data:PDAC is characterized by prominent local nerve alterations and perineural invasion, which frequently affects the extrapancreatic nerve plexus, causing severe pain and precluding curative resection. Artemin, a neurotrophic protein controlling growth, regeneration, and survival of neurons was analyzed to highlight the neuro-cancer interactions in PDAC. Methods:Artemin and its receptors (GFRα3/RET) were studied in PDAC tissues and normal pancreas by Western blot analysis and immunohistochemistry. RNA expression was analyzed in pancreatic tissues (normal, cancer) and pancreatic cancer cell lines by QRT-PCR. To evaluate whether Artemin influences cancer cell proliferation and invasion, MTT-growth and Matrigel-invasion assays were used. In addition, the tissue expression of Artemin was correlated with pain in PDAC. Results:Artemin and GFRα3/RET were both detected at enhanced levels in PDAC compared with normal pancreas, localizing predominantly in hypertrophic nerves and arterial walls, as well as in cancer cells of primary and metastatic lesions. The levels of Artemin and GFRα3 did not correlate with pain in PDAC patients. However, Artemin promoted pancreatic cancer cell invasion up to 5-fold, without affecting cancer cell proliferation. Conclusion:Artemin expression was not associated with pain in PDAC. However by increasing cancer cell invasion, Artemin seems to influence neural invasion and thereby contribute to cancer cell spreading along pancreatic nerves.

Osteonectin Influences Growth and Invasion of Pancreatic Cancer Cells

Objective:We sought to examine the expression and functional role of osteonectin in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Background:The glycoprotein osteonectin plays a vital role in cell–matrix interactions and is involved in various biologic processes. Overexpression of osteonectin is present in malignant tumors and correlates with disease progression and poor prognosis. Methods:Expression of osteonectin was analyzed by quantitative polymerase chain reaction and immunohistochemistry in pancreatic tissues and by enzyme-linked immunosorbent assay in the serum of patients and donors. Recombinant osteonectin and specific antisense oligonucleotides were used to examine the effects of osteonectin on induction of target genes, and on proliferation and invasiveness of pancreatic cancer cells. Results:There was a 31-fold increase in osteonectin mRNA levels in PDAC and a 16-fold increase in chronic pancreatitis as compared with the normal pancreas (P < 0.01). By immunohistochemistry, faint immunoreactivity was detected in the normal pancreas. In contrast, strong staining of the cancer cells was observed in addition to extensive osteonectin immunoreactivity in surrounding fibroblasts and in the extracellular matrix. In metastatic tissues, strong immunoreactivity was observed in fibroblasts and in extracellular matrix surrounding metastatic cancer cells, whereas the signal was absent in most tumor cells. In vitro studies showed that osteonectin was able to inhibit cancer cell growth while promoting invasiveness of pancreatic tumor cells. Conclusion:Osteonectin is markedly overexpressed in pancreatic cancer and has the potential to increase the invasiveness of pancreatic cancer cells.

Chirurgisch-klinische Studien in der praktischen Durchführung

Abstract. The employment of the optimal therapeutic option according to the best current knowledge is called evidence-based medicine (EBM). Moreover, considering the cost explosion in public health systems, EBM should contribute towards economical and targeted use of the restricted resources and towards quality assurance in medicine. Obviously, this is applicable to the operative specialties and can be termed as evidence-based surgery. Surgeons have to do their “homework“ about this subject and to perform randomized controlled trials (the gold standard with the greatest evidence) on a large scale, in order to come up to this expectation in future. Evidence-based therapy is essential for the preservation and especially for the further development and evolution of high-quality surgery with, at the same time, quality assurance in the new millenium. This article presents the definition of EBM and its implication in the operative fields. Fundamental principles for the practical conduct of clinical randomized controlled trials are defined and the specific problems in surgery are discussed.Zusammenfassung. Die Anwendung der besten Therapieoption nach dem derzeitigen Stand des Wissens wird als Evidenz-basierte Medizin (EBM) bezeichnet. Angesichts der Kostenexplosion im Gesundheitswesen soll die EBM darüber hinaus ihre speziellen Beiträge zum gezielten und ökonomischen Einsatz der knapper werdenden Ressourcen und zur Qualitätssicherung in der Medizin leisten. Dies gilt selbstverständlich auch für die operativen Fächer und kann hier als Evidenz-basierte Chirurgie bezeichnet werden. Chirurgen müssen in dieser Richtung verstärkt ihre „Hausaufgaben“ machen und in besonderem Maße randomisierte kontrollierte klinische Studien (Goldstandard mit der höchsten klinischen Evidenz) durchführen, um diesen Ansprüchen in der Zukunft gerecht zu werden. Diese Evidenz-basierte Therapie ist wichtig für den Erhalt und insbesondere für die Fort- und Weiterentwicklung einer hochqualifizierten und zugleich qualitätsgesicherten Chirurgie im neuen Millennium. Der vorliegende Artikel definiert EBM und deren Bedeutung für die Chirurgie. Darüber hinaus werden wesentliche Grundlagen bei der praktischen Durchführung von klinisch randomisierten kontrollierten Studien und deren spezifische Probleme in der Chirurgie diskutiert.

Molecular characterisation of pancreatic ductal adenocarcinoma in patients under 40

Background: Pancreatic ductal adenocarcinoma (PDAC) rarely affects people under 40. Objectives: To determine whether the clinical, pathomorphological and genetic features of PDAC occurring in young patients (⩽40 years) differ from those in elderly patients. Methods: Clinical and pathomorphological data were obtained from seven patients presenting with PDAC, with age ranging from 35 to 40 years of age (mean 38 years). All tumours were characterised by using immunohistochemistry and molecular genetics. Results: All seven patients were women and lacked an association to cancer-predisposing genetic syndromes. Four patients were smokers and one had non-hereditary chronic pancreatitis. Pathomorphologically, tumours in three patients displayed moderate differentiation and four showed poor differentiation including one adenosquamous carcinoma. All tumours showed overexpression of transforming growth factor β1 and loss or significant reduction of Smad4. Accumulation of p53 and overexpression of epidermal growth factor receptor (EGFR) were seen in five and four patients, respectively. No expression of p16, oestrogen hormone receptor or progesterone receptor was found. Mismatch repair gene products (MutL homologue 1 (MLH1), MSH2 and MSH6) were expressed in all tumours. Mutational analyses showed K-ras mutations in only three of the seven tumours. Conclusion: A large clinical, pathomorphological and genetic overlap of PDAC in young patients aged under 40 is seen with that in elderly patients. The existence of yet undefined initiating events of pancreatic carcinogenesis is suggested by the low rate of K-ras mutations, in at least a subgroup of young patients.

Left ventricular end-diastolic area is a measure of cardiac preload in patients with early septic shock.

Background and objective Central venous pressure, intrathoracic blood volume, and left ventricular end-diastolic area are reliable measures of cardiac preload under stable clinical conditions. The purpose of this study was to compare different preload parameters over 24 h under conditions of multiple, frequently changing treatments in early septic shock. Methods In 28 mechanically ventilated patients within 6 h of the onset of septic shock, left ventricular end-diastolic area was measured using transoesophageal echocardiography. Intrathoracic blood volume, stroke volume variation, and central venous pressure were analysed as preload parameters. The relation between parameter changes and changes in therapy was examined with respect to cardiac index and stroke volume index. Results Regarding preload variables, linear regression analyses revealed a significant correlation between left ventricular end-diastolic area and stroke volume index (r2 = 0.59, P < 0.001) and cardiac index (r2 = 0.41, P < 0.001), respectively. Changes in left ventricular end-diastolic index and intrathoracic blood volume index reflected changes in the stroke volume index, whereas central venous pressure did not. Myocardial responsiveness also failed to predict changes in the stroke volume index. Conclusion Only the left ventricular end-diastolic area index may help predict preload in ventilated patients with early septic shock.

Review of the clinical experience with a modified release form of tacrolimus [FK506E (MR4)] in transplantation

Abstract:u2002 Non‐compliance in solid transplantation recipients is a major factor in acute graft rejection, which influences patient survival. Nowadays, tacrolimus is one of the most widely used immunosuppressant agents together with cyclosporine following kidney and liver transplantation with a standardized twice‐daily dosing regimen. To improve the patients’ compliance to the prescribed immunosuppressive therapy, FK506E (MR4), a modified release (MR) oral dosage form of tacrolimus has been developed for a once‐daily dosing regimen. This report reviews the most recent results of clinical trials with MR tacrolimus after kidney and liver transplantation.

Gastrointestinale Stromatumoren (GIST)

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. GIST occur predominantly in the stomach and less frequently in the extraduodenal small bowel, the colon, and the rectum; rarely, GIST can be found in the esophagus and the duodenum. Due to their biological behavior, the primary treatment goal for localized primary GIST is complete resection, without the need for lymphadenectomy or wide resection margins. Thus, gastric wedge resections and segmental resections of the small bowel are the most common surgical procedures for treating primary GIST. Surgical therapy of extensive primary tumors or of metastatic or recurrent GIST should be integrated into a multimodal therapeutic concept that includes targeted therapy with tyrosine kinase inhibitors, such as imatinib.ZusammenfassungGastrointestinale Stromatumoren (GIST) sind die häufigsten mesenchymalen Tumoren des tubulären Gastrointestinaltraktes. Sie kommen insbesondere im Magen vor, in geringerer Häufigkeit im extraduodenalen Dünndarm, Kolon und Rektum und nur in Einzelfällen im Ösophagus und Duodenum. Primärziel der Therapie eines lokalisierten primären GIST ist die komplette Resektion, wobei aufgrund der Biologie dieser Tumorentität in der Regel keine Lymphadenektomie oder Resektion mit weitem Sicherheitsabstand erforderlich ist. Daher sind Wedge-Resektionen des Magens oder Segmentresektionen des Dünndarms die häufigsten Eingriffe zur Therapie eines primären GIST. Insbesondere die chirurgische Therapie von primär ausgedehnten Tumoren, von GIST-Metastasen und -Rezidiven sollte in ein multimodales Therapiekonzept unter Anwendung von Tyrosinkinaseinhibitoren, wie z.xa0B. Imatinib, integriert werden.AbstractGastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. GIST occur predominantly in the stomach and less frequently in the extraduodenal small bowel, the colon, and the rectum; rarely, GIST can be found in the esophagus and the duodenum. Due to their biological behavior, the primary treatment goal for localized primary GIST is complete resection, without the need for lymphadenectomy or wide resection margins. Thus, gastric wedge resections and segmental resections of the small bowel are the most common surgical procedures for treating primary GIST. Surgical therapy of extensive primary tumors or of metastatic or recurrent GIST should be integrated into a multimodal therapeutic concept that includes targeted therapy with tyrosine kinase inhibitors, such as imatinib.

Soluble iC3b as an early marker for pancreatic adenocarcinoma is superior to CA19.9 and radiology.

Pancreatic adenocarcinoma as an aggressive tumor still lacks specific markers. Resection offers the only potential cure, and earlier diagnosis could benefit many patients. Here, we analyzed siC3b as a potential diagnostic marker. Soluble iC3b is generated in the fluid phase after binding of autoantibodies to tumor cells and subsequent inactivation of the complement cascade by interaction with complement regulatory proteins. Two hundred thirty-two plasma samples from patients with adjuvant treatment after resection, from healthy volunteers, and from vulnerable patients were collected prospectively and analyzed for siC3b. Every 3 months, the patients underwent imaging and the results from siC3b enzyme-linked immunosorbent assay were categorized according to radiologically defined recurrence within 4 months after blood withdrawal. Furthermore, the regulatory factors of the complement system were analyzed in tumor cells and in urine. The most important finding was that up to 4 months before radiologically defined recurrence, siC3b plasma level is increased with a sensitivity and specificity resulting in an area under the curve of 0.85, which could be further increased by combining it with CA19.9 (area under the curve=0.92). Complement regulatory proteins are highly expressed in pancreatic carcinoma cells and detectable in the patients urine. In summary, screening for siC3b in patients with an increased risk for pancreatic ductal adenocarcinoma (patients with chronic pancreatitis, hereditary pancreatitis, after curative resection, and patients with a variety of familial cancer syndromes) allows for early detection with high sensitivity, as siC3b plasma levels are increased up to 4 months before radiologic evidence. Sensitivity could be further increased by combining this approach with CA19.9.