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Background: Due to the organ shortage, marginal donors are increasingly used in liver transplantation (OLT). These grafts may be safely used in less critical recipients but, the real influence of extended donor criteria (EDC) remains uncertain when graft-recipient matching is not applied. Our study analyzed the impact of EDC on initial graft function within the Eurotransplant patient-driven allocation system. Patients and methods: We reviewed 70 OLT performed between 2004 and 2006. The impact of the following EDC were analyzed: age > 60; intensive care unit (ICU) stay > 4 days; peak serum Na+ > 160 mEq/L; body mass index (BMI) > 30; cardiac arrest with cardiopulmonary resuscitation, and high doses of vasopressors. Early graft function, as defined according to peak transaminase level and spontaneous prothrombin time within the first 5 posttransplant days, was compared between the donors with none or one criterion (group A = 39) and those with >1 criterion (group B = 31). Results: The most frequent EDC were high vasopressor use, ICU stay > 4 days and BMI > 30, were present in respectively 44%, 27%, and 16% of the donors. No EDC were present in 13 donors, one in 26, three in eight, and four in three. Demographics and origin and severity of the liver disease were similar in both groups. We failed to observe significant differences in initial graft function. Conclusion: The presence of EDC did not significantly affect early graft function in a population where donor and recipient were not matched. While this observation must be confirmed in a multicenter analysis, it tends to support the use of marginal liver grafts, even in patient-driven allocation systems. © 2007 Elsevier Inc. All rights reserved.

Laparoscopic Toupet fundoplication (TF) is reported to be as effective as Nissen (NF), but to be associated with fewer unfavorable postoperative side-effects. This study evaluates the one- and three-year clinical outcome of 140 randomized patients after a laparoscopic NF or TF. Inclusion criteria included patients over 16 years old with complications of gastro-oesophageal reflux disease (GORD) and persistence or recurrence of symptoms after three months of treatment. Subjects with a previous history of gastric surgery or repeated fundoplication, brachy-oesophagus or severe abnormal manometry results were excluded. Seventy-seven NF and 63 TF were performed. The severity of symptoms was assessed before and after the procedure. One hundred and twenty-one of the 140 patients after one year, and 118 after three years, were evaluated and no statistically significant clinical difference was observed. The level of satisfaction concerning the outcome of the operation remained high after one or three years regardless of the type of fundoplication performed. Functional complications after NF are not avoided with TF.

La chirurgie de l’obesite est, actuellement, la seule option therapeutique permettant une perte de poids durable chez des patients presentant une obesite morbide. L’objectif de cet article est de definir l’approche multidisciplinaire permettant l’evaluation et la selection des patients ainsi que la technique chirurgicale la mieux adaptee au profil dietetique et psychologique de chaque patient.

The aim of this case report is to outline the challenge and the feasibility of laparoscopic gastric bypass in a patient with situs inversus totalis. Situs inversus totalis does not seem to be a contraindication for laparoscopic surgery.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the industrialized world. Despite progress in the understanding of the molecular and genetic basis of this disease, the 5-year survival rate has remained low and usually does not exceed 5%. Only 20%-25% of patients present with potentially resectable disease and surgery represents the only chance for a cure. After decades of gemcitabine hegemony and limited therapeutic options, more active chemotherapies are emerging in advanced PDAC, like 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin and nab-paclitaxel plus gemcitabine, that have profoundly impacted therapeutic possibilities. PDAC is considered a systemic disease because of the high rate of relapse after curative surgery in patients with resectable disease at diagnosis. Neoadjuvant strategies in resectable, borderline resectable, or locally advanced pancreatic cancer may improve outcomes. Incorporation of tissue biomarker testing and imaging techniques into preoperative strategies should allow clinicians to identify patients who may ultimately achieve curative benefit from surgery. This review summarizes current knowledge of adjuvant and neoadjuvant treatment for PDAC and discusses the rationale for moving from adjuvant to preoperative and perioperative therapeutic strategies in the current era of more active chemotherapies and personalized medicine. We also discuss the integration of good specimen collection, tissue biomarkers, and imaging tools into newly designed preoperative and perioperative strategies., SCOPUS: re.j, info:eu-repo/semantics/published

A new technical tool was developed and introduced into the therapeutic field of videoscopic surgery—robotic telemanipulation surgery. The aim of this study is to investigate in a prospective randomized trial the feasibility of the Nissen procedure using the da Vinci and to evaluate the benefits and the costs of this new technique compared with the conventional laparoscopic approach. Twenty patients with gastro-esophageal reflux disease (GERD) were randomized into laparoscopic Nissen versus robot-assisted Nissen fundoplication. All the patients signed an informed consent document. The time data of the procedure, the efficacy of the instruments, the intra-operative incidents, postoperative morbidity, and cost minimization are presented. Nine patients were assigned to the robot, and 11 to the laparoscopic procedure. Both groups were similar in age, male/female ratio, and body mass index. The robot procedure time was significantly longer. The hospital stay and the alimentation day were similar. The number of postoperative complaints was similar after the 1st, 6th, and 12th postoperative months. However, on the 3rd postoperative month, the number of complaints was significantly higher in the robot group. The robot procedure was more expensive with regard to the instrumentation and reusable material, the nursing costs, the investment costs, and the maintenance costs. No clear advantage of using robotics in the Nissen procedure was observed. The procedure seems to be feasible and safe. The technique is limited because of unadapted instruments. The disadvantages are the high costs and prolonged operative time.

Background Acute pancreatitis with pancreatic-duct rupture and fluid collections is a rare complication after Silastic ring vertical gastroplasty. It can be attributed to pancreatic trauma occurring during surgery. Methods Endoscopic therapy with transmural drainage of collections was performed in 4 patients who had undergone Silastic ring vertical gastroplasty and who had presented with acute pancreatitis with main pancreatic-duct rupture at the body of the pancreas. Observations All patients had successful transmural drainage with cystogastrostomy, followed by stent insertion. Only one patient had a late recurrence because of stent migration. The major difficulty was related to positioning of the endoscope and the possible need of pneumatic dilation of the outlet channel to reach the puncture site. Conclusions Endoscopic therapy is useful in acute pancreatitis with pancreatic-duct rupture after Silastic-ring vertical gastroplasty and, although technically difficult, could be considered as a first-line approach in the management of these patients.

Background: Among the different techniques of surgical treatment for morbid obesity, silastic ring vertical gastroplasty (SRVG) is an alternative, effective and easily reproducible technique. The aim of this study is to evaluate a cohort of patients >6 years after SRVG for morbid obesity. Methods: From 1991 to 1996, 273 consecutive patients were eligible for SRVG. The evaluation criteria included weight loss, evolution of co-morbidities, long-term morbidities, satisfaction of patients and quality of life. Results: Among these 273 patients, 1 patient died in the postoperative period (0.4%). Postoperative morbidities occured in 27 patients (10%). The long-term follow-up involved 213 patients (78%). Late postoperative complications consisted of outlet stoma stenosis (14%), staple-line dehiscence (5.6%) and incisional hernia (8.5%). 23 patients (10%) needed a re-do operation. Co-morbidities drastically improved. BMI fell from 45.3 to 30.7. Failure of SRVG was statistically associated with male gender and super-obese patients. 69% of the patients were satisfied, and 73% would recommend this operation. Conclusion: SRVG is very effective in a selected group of morbidly obese patients.

The study was conducted to develop a sensitive and specific radioimmunoassay (RIA) for the measurement of pepsinogen in porcine serum, and to use this test for the determination of pepsinogen concentrations in serum samples from fetuses and pigs of different ages. Compared to a previously described RIA, major improvements were made concerning the use of specific polyclonal antibodies and the use of an appropriate buffer. The assay was able to detect pepsinogen concentrations of/=0.2 ng/mL. The recovery of pepsinogen was close to 95%. The intra-assay coefficients of variations ranged between 3.9 and 7.5% whereas the interassay ranged between 8.8 and 11.9%. These percentages correspond to a satisfactory accuracy and reproducibility of the assay. No cross-reactions were observed with the main commercially available products of the aspartic proteases family except porcine pepsin cross-reacted over 62.5 microg/mL. Pepsinogen concentrations increased steadily with increasing age of the fetuses and the pigs (P0.05). Pepsinogen concentrations (+/-SE) in fetuses of 90-100 (n=24) and 100-110 days of pregnancy (n=36) were 0.5+/-0.1 and 5.3+/-1.3 ng/mL, respectively. In pigs of 21, 98, and 213 days of age, the pepsinogen concentrations were 290.6+/-10.8, 343.1+/-17.9 and 383.5+/-15.3 ng/mL, respectively. The results demonstrate that RIA is accurate and can be used easily to assess pepsinogen concentrations in pig sera. The test may constitute a valuable tool in epidemiological surveys and in studies related to gastric diseases in pigs.

Insulin-like growth factor-I (IGF -I) is likely to be an indicator of somatotropin (ST) administration in the horse. To investigate the different ways ST administration may be detected, the following aspects of IGF -I concentrations in plasma were studied: (i) the daily variation; (ii) variation following a treadmill test; (iii) concentrations at rest and after exercise; and (iv) concentrations in plasma from two young horses and two adults treated with methionyl equine somatotropin (e ST). In the population of horses at rest, IGF -I mean concentration (SEM) was 261 (104) ng ml(-1). In post race samples, IGF -I mean concentration was 187 (100) ng ml(-1). All of these data indicate that exercise does not modify IGF -I concentration in plasma. The magnitude of the increase in IGF -I following administration of e ST differed according to the age of the horses. The critical value of 700 ng ml(-1)was exceeded for 1 day in adult horses and for at least 11 days in young horses. These results show that IGF -I has potential as an indirect marker of ST administration in horses.

Insulin-like Growth Factor I is a marker of Somatotropin administration. In order to quantify this peptide in horse plasma samples, a high performance liquid chromatography/electrospray mass spectrometry method using R3 Insulin-like Growth Factor I as internal standard was developed. The extraction procedure involves an acid ethanol extraction and an immunoaffinity purification. Quantification is made possible by using deconvolution software and by measuring the insulin like growth factor-I/internal standard ratio. Comparison between high performance liquid chromatography/electrospray mass spectrometry and two immunological methods indicated agreement between methods even though more samples are needed to confirm this finding.

Background: Nissen fundoplication (NF) is recognized as the surgical treatment of the gastro-oesophageal reflux disease (GERD). NF can be achieved either by open surgery or by laparoscopic approach. Methods: From 1987 to 1997, 210 patients were treated for GERD by NF: 61 by open and 149 by laparoscopic approach. All the patients were followed more than 1 year and were scored by clinical assessment (Visick scale adaptation). In case of Visick score > 1, Gl-endoscopy, X-ray series or 24-hour pH-study complete the evaluation. Results: The operative time was comparable between both groups. The postoperative recovery was statistically faster in the laparoscopic group (p = 0.0001). The mean time of follow-up was 6 years after open NF and 4 years after laparoscopic NF. After open NF or laparoscopic NF, 72% and 67% of the patients are respectively scored Visick 1,13% and 21% -Visick 2,6.8% and 6% -Visick 3 and 8,.2% and 6% -Visick 4 (NS). Patients with recurrence of GERD were scored Visick 4, so failure of the surgical treatment is observed in 5 patients after open NF and 9 patients after laparoscopic NF. The occurrence of incisional hernia was significantly higher in the open group (p = 0.0001). Conclusion: NF remains a safe procedure for surgical treatment of GERD and can be achieved by laparoscopic approach with comparable results to those by open laparotomy. In our experience, the advantages of the laparoscopic approach is a faster postoperative recovery and a lower risk of incisional hernia.

The purpose of our study was to determine prospectively the value of helical CT and of various signs of ischemia in the context of acute bowel obstruction.All patients seen over a 3-year period with a CT diagnosis of small-bowel obstruction were included. There were 144 examinations in 142 patients. Images were interpreted prospectively with consensus by a fellow and an experienced gastrointestinal radiologist. Attention was focused on the presence of the following signs of strangulation and ischemia: reduced enhancement of the small-bowel wall, mural thickening, mesenteric fluid, congestion of small mesenteric veins, and ascites. A diagnosis of ischemia was made if enhancement of the bowel wall was reduced or if at least two of the other signs were found. Results were correlated with surgical findings in 73 cases and clinical follow-up in 71 cases.A diagnosis of ischemia was made at surgery in 24 patients. CT diagnosis was correct in 23 patients (96% sensitivity). There were nine false-positive diagnoses (93% specificity). The negative predictive value of CT was 99%. Reduced enhancement of the bowel wall had a sensitivity of 48% and specificity of 100%, mural thickening had a sensitivity of 38% and specificity of 78%, mesenteric fluid had a sensitivity of 88% and specificity of 90%, congestion of mesenteric veins had a sensitivity of 58% and specificity of 79%, and ascites had a sensitivity of 75% and specificity of 76%.Helical CT is a highly sensitive method to diagnose or rule out intestinal ischemia in the context of acute small-bowel obstruction.

We have cloned a novel complementary DNA whose expression was decreased in rat Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a protein of 570 amino acids and shares 92% homology with the human MAGE-D protein. In contrast to other MAGE genes (A, B, or C), we have shown that MAGE-D expression was ubiquitous in healthy rat tissues. In the seminiferous tubules, the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression has been shown to be restricted to germ cells. Interestingly, MAGE-D was also detected for the first time in the female gonad by Northern blotting. In MLTC-1 cells (mouse Leydig tumor cell line-1), LH and PRL stimulated MAGE-D expression. Using hypophysectomized rats, it was confirmed that FSH decreased MAGE-D expression, whereas LH and PRL increased MAGE-D messenger RNA level in the whole testis most probably through a direct action on Leydig cells. As MAGE-D ...

Objective To isolate new cDNAs corresponding to genes whose expression is increased during castration-induced rat prostate apoptosis. Materials and methods Differential display of mRNAs from 3-day castrated and normal rat ventral prostates was used to identify differentially expressed clones. Northern blots were hybridized to confirm the positive regulation of the candidates and to follow the change in their expression in the involuting rat prostate, and in thymocytes of dexamethazone-treated rats. Results Five cDNAs were cloned: one encoding ribosomal protein L7, one coding for the insulin-like growth factor binding protein-3 (IGFBP-3), and three whose products are unknown. After castration, all five genes had expression kinetics that closely paralleled the proportion of prostatic epithelial cells undergoing apoptosis. The gene encoding L7 and two of the unknown genes were also upregulated in glucocorticoid-induced programmed death in thymocytes. In addition to the IGFBP-3 gene, those coding for proteins IGFBP-4, -5 and -6 were also overexpressed in the involuting prostate of androgen-deprived rats. Conclusion Five new genes were identified that are up-regulated during castration-induced rat prostate apoptosis, three of which are potentially involved in the common intracellular pathway leading to programmed cell death.

BACKGROUND Although essential, androgens alone are not sufficient to induce normal growth and functionality of the prostate. Nonandrogenic hormones must also be involved in the proliferation of the prostate cancer cells which do not respond to antiandrogenic therapy and which thus become androgen-independent. Prolactin, but also growth hormone and luteinizing hormone, are potentially able to act on both normal and abnormal prostatic cells. METHODS In this review we summarize data from the literature concerning the physiological and pathological implications of prolactin, growth hormone, and luteinizing hormone on the prostate. RESULTS In rodent prostates, prolactin and growth hormone can induce a variety of effects independently of androgens (e.g., transactivation of certain genes, or synthesis of the major secretion products). Moreover, hyperprolactinemia is responsible for inflammation and dysplasia of the gland, while growth hormone promotes the development of prostate tumors in vivo in the mouse and rat. Growth hormone acts on the gland directly, through prostatic growth hormone receptors, and/or indirectly via the stimulation of insulin-like growth factor-I (IGF-I) synthesis in the liver. Luteinizing hormone receptor is expressed in rat and human prostates. Luteinizing hormone increases the amount of various transcripts in the rat prostate through an androgen-independent pathway. CONCLUSIONS Prolactin, growth hormone, and luteinizing hormone, alone or synergistically with androgens, play physiologically significant roles in the normal prostate. The involvement of these hormones in the development of benign prostatic hyperplasia and prostatic carcinoma is an issue that needs to be addressed. Prostate 38:159–165, 1999. © 1999 Wiley-Liss, Inc.

Gas-producing bacteria are known to selectively colonize a variety of abdominal viscera, but gas-producing infection limited to the spleen until now has not been reported. A gas-producing (emphysematous) infection of the spleen was diagnosed in a supersuper- obese diabetic patient with abdominal pain and signs of sepsis. The patient presented a serious diagnostic challenge because massive abdominal obesity did not enable her to pass through the aperture of a standard computerized tomography unit. Therapeutic options were limited because computerized tomography- guided drainage or splenectomy were technically not feasible or were considered too risky.

Background In adhesive small bowel obstruction, the early recognition of complications such as strangulation or volvulus is essential to choose between surgical or conservative initial treatment. The objective of this study was to determine prospectively the contribution of computed tomography (CT) to decision making in the management of these patients. Methods Patients with suspected adhesive small bowel obstruction had CT at admission. Patients with CT signs of volvulus or strangulation and/or clinical signs of peritoneal irritation underwent urgent surgery; other patients had conservative initial treatment. Results Fifty-four patients were evaluated. CT demonstrated signs of strangulation or volvulus in 19 patients, including three with signs of peritoneal irritation. Within this group, urgent laparotomy was performed in 17 patients and confirmed the CT diagnosis in 16. Thirty-seven patients without clinical or CT signs of complications had initial conservative treatment; among them, seven of 12 with a distal obstruction determined by CT required a delayed operation for persisting obstruction, compared with two of 25 patients with a proximal obstruction (P Conclusion CT is useful for the evaluation of adhesive small bowel obstruction, to detect accurately patients with complications who require urgent operation and to determine the location of the adhesion, which represents a significant prognostic factor for success of conservative treatment.

We investigated the feasibility, safety, and efficacy of laparoscopic antireflux surgery (LARS) after failure of Enteryx injection in the lower esophageal sphincter for the treatment of gastroesophageal reflux disease (GERD). Four patients underwent LARS after failure of Enteryx injection. Particular care was taken during the procedure to identify unusual material or fibrosis. All patients underwent LARS successfully. In three patients, tight adhesions with fibrous tissues and black foreign material were observed around the esophagus. No complications occurred during the procedures. The postoperative period was uneventful and functional results were excellent. LARS following Enteryx injection is feasible. Careful dissection is mandatory to avoid operative complications. Both techniques may be considered as options for treating GERD.

Laparoscopic cholecystectomy (LC) seems to be associated with an increased risk of biliary or vascular injuries. Hepatic artery pseudoaneurysms (HAP) are rare complications of LC. HAP can occur in the early or late postoperative period. Patients with HAP present with abdominal pain, hemobilia, and liver function test (LFT) alterations. We report the case of a patient who was affected with a cystic duct stump leak associated with a right HAP and was treated by endoscopic biliary drainage and angiographic coil embolization.

In this study, we investigated the involvement of GH in rat prostate function. First, we demonstrated that specific transcripts corresponding to the GH receptor (4.5 kilobases) and to the GH-binding protein (1.2 kilobases) were expressed in the normal rat prostate, but also in all prostatic carcinoma cell lines tested (LNCaP, PC-3, MAT-Lu, MAT-LyLu, and Pif-1). Moreover, these transcripts were much more abundant in the human and rat carcinoma cells than in the normal tissue. One-year-old dwarf rats were supplemented for 7 days with saline (group DR1) or highly purified rat GH (group DR2). Northern blotting and quantitation of prostatic messenger RNAs (mRNAs) revealed that GH increases the steady state levels of transcripts coding for androgen receptor (2.4-fold), type I and II 5 alpha-reductases (2.6- and 2.2-fold), and several androgen-dependent proteins [prostatein C3 subunit (3.6-fold), probasin (11.0-fold), and R. W. B. (Royal Winnipeg Ballet) (12.5-fold)]. This suggests that GH might either potentiate the action of androgens on the prostate or act directly on this gland by a mechanism that does not depend on testicular androgens. To address this question, we supplemented hypophysectomized and castrated adult rats for 7 days with saline (group HC1), rat GH (group HC2), testosterone propionate (group HC3), or GH plus testosterone (group HC4), starting 3 days after castration. In this animal model, the abundance of C3 mRNA increased in all hormone-treated rats; the stimulation factors were 3.5 (group HC2), 25.5 (group HC3), and 9.5 (group HC4) compared to group HC1. Analysis of prostatein synthesis by Western blotting confirmed these results at the protein level. The same trend was observed for probasin and RWB mRNA levels. Probasin mRNA increased 4.5-fold in group HC2 and 12-fold in group HC3, but did not increase in group HC4 (both hormones combined); enhancement of RWB mRNA was, respectively, 5.0-, 28.0-, and 15.0-fold in groups HC2, HC3, and HC4. GH did not affect the abundance of androgen receptor mRNA. As described previously, the level of this mRNA dropped significantly in group HC3. GH alone did not significantly alter the level of either 5 alpha-reductase mRNA, whereas testosterone, alone or with GH, produced a 2-fold increase in type II 5 alpha-reductase mRNA (groups HC3 and HC4). Type I isoenzyme mRNA reached 1.6 times the control level (group HC1) in groups HC3 and HC4.(ABSTRACT TRUNCATED AT 400 WORDS)

Intussusception in adults is rare. The authors report 18 cases and illustrate the pathological and clinical findings. Intussusception is usually secondary to a benign small bowel lesion or to a malign

To investigate the clinicopathological features of intraductal papillary mucinous neoplasms and evaluate the prognosis between histopathological groups.Retrospective review of 55 consecutive patients operated between 1991 and 2006, analysis of clinicopathological features and survival.Group I comprised of 9 mild and 14 moderate dysplasias, group II of 11 carcinomas in situ and group III of 21 invasive cancers. Age, diabetes, anorexia and jaundice were significantly more frequent in group III. Thirty-two patients (58.2%) presented main duct type which was more frequently associated with invasive carcinoma. Mean tumoral size progress from group I to group III (26.1mm vs. 27.4mm vs. 32.0mm p=0.015) as the mean size of the pancreatic duct (6.7mm vs. 7.9mm vs. 11.5mm p=0.008). Median follow-up was 154 months with 5-year survival rate of 60.7 %. For group I, II and III it was 76.3 %, 100 % and 25.8 % respectively (p=0.00007). Lymph node positivity was associated with poor outcome: 44.1% vs. 0% (N0 vs. N+) (p=0.0019).The prognosis of non-invasive intraductal papillary mucinous neoplasms of the pancreas is favourable. For patients with invasive cancer, nodal invasion is a factor of worst prognosis.

A new ultrasensitive chemiluminoenzyme immunoassay (CLEIA) using digoxigenin-labeled bradykinin (BK) as a tracer is proposed to quantify kinins in tissue samples. Rabbit polyclonal IgGs anti-BK directed against the C- terminal end were used for the immunoconcentration step along with dioxetane derivative for the revelation step. The sensitivity of the assay for BK was 0.1 fmol/ml with ED 50 of 0.78 pmol/ml. This method was applied on extracts of normal and carrageenan-inflamed tissues. The edema produced by the injection of carrageenan in rat hindpaws was associated with a sevenfold increase of immunoreactive kinins in the inflamed paw extract ( from 0.021 ± 0.007 to 0.141 ± 0.021 pmol/g tissue ; p ), the immunoreactivity corresponded to BK, kallidin, and T-kinin after HPLC separation. When a mixture of inhibitors of kininase I (mergepta) and kininase II (captopril) was coinjected with carrageenan, the carrageenan-induced edema was unaffected but the kinin tissue content was significantly enhanced ( 0.207 ± 0.003 pmol/g tissue ; p ). However, the kinin tissue content and the edema response were unaltered by inhibitors given separately. Hence, this highly sensitive assay provides a biochemical evidence that kinins may act as proinflammatory mediators, and highlights a compensatory increase of kininase I and II activities in inflamed tissues.

Thyroid transcription factor 1 (TTF-1) plays a key role in morphogenesis of the lungs and is expressed in up to 90% of pulmonary small cell carcinomas. This explains why this marker is frequently used in the search for the primary origin of metastatic endocrine tumours. Here we report on a TTF-1 expressing mixed endocrine-exocrine carcinoma of the common bile duct in a patient with pulmonary nodules that did not appear to be neoplastic. TTF-1 positivity in pulmonary and extrapulmonary neuroendocrine tumours is reviewed, and we conclude that TTF-1 expression in neuroendocrine tumours of the small-cell type are not uncommon at extrapulmonary locations. Therefore, immunohistochemistry for TTF-1 in such tumours should be interpreted with caution., Journal Article, info:eu-repo/semantics/published

Background & Aims Patients who undergo surgery for pancreatic ductal adenocarcinoma (PDAC) frequently receive adjuvant gemcitabine chemotherapy. Key determinants of gemcitabine cytotoxicity include the activities of the human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit 1 (RRM1). We investigated whether tumor levels of these proteins were associated with efficacy of gemcitabine therapy following surgery. Methods Sequential samples of resected PDACs were retrospectively collected from 434 patients at 5 centers; 142 patients did not receive adjuvant treatment (33%), 243 received adjuvant gemcitabine-based regimens (56%), and 49 received nongemcitabine regimens (11%). We measured protein levels of hENT1, dCK, and RRM1 by semiquantitative immunohistochemistry with tissue microarrays and investigated their relationship with patients' overall survival time. Results The median overall survival time of patients was 32.0 months. Among patients who did not receive adjuvant treatment, levels of hENT1, RRM1, and dCK were not associated with survival time. Among patients who received gemcitabine, high levels of hENT1 and dCK were significantly associated with longer survival time (hazard ratios of 0.34 [ P P = .012], respectively). Interaction tests for gemcitabine administration and hENT1 and dCK status were statistically significant ( P = .0007 and P = .016, respectively). On multivariate analysis of this population, hENT1 and dCK retained independent predictive values, and those patients with high levels of each protein had the longest survival times following adjuvant therapy with gemcitabine. Conclusions High levels of hENT1 and dCK in PDAC predict longer survival times in patients treated with adjuvant gemcitabine.

Laparoscopic cholecystectomy is considered nowadays as the standard management of acute cholecystitis (AC). However, results from multicentric studies in the general surgical community are still lacking.A prospective multicenter survey of surgical management of AC patients was conducted over a 2-year period in Belgium. Operative features and patients' clinical outcome were recorded. The impact of independent predictive factors on the choice of surgical approach, the risk of conversion, and the occurrence of postoperative complications was studied by multivariate logistic regression analysis.Fifty-three surgeons consecutively and anonymously included 1,089 patients in this prospective study. A primary open approach was chosen in 74 patients (6.8%), whereas a laparoscopic approach was the first option in 1,015 patients (93.2%). Independent predictive factors for a primary open approach were previous history of upper abdominal surgery [odds ratio (OR) 4.13, p0.001], patient age greater than 70 years (OR 2.41, p0.05), surgeon with more than 10 years' experience (OR 2.08, p = 0.005), and gangrenous cholecystitis (OR 1.71, p0.05). In the laparoscopy group, 116 patients (11.4%) required conversion to laparotomy. Overall, 38 patients (3.5%) presented biliary complications and 49 had other local complications (4.5%). Incidence of bile duct injury was 1.2% in the whole series, 2.7% in the open group, and 1.1% in the laparoscopy group. Sixty patients had general complications (5.5%). The overall mortality rate was 0.8%. All patients who died were in poor general condition [American Society of Anesthesiologists (ASA) III or IV].Although laparoscopic cholecystectomy is currently considered as the standard treatment for acute cholecystitis, an open approach is still a valid option in more advanced disease. However, overall mortality and incidence of bile duct injury remain high.

During the years 1978-1990, 401 patients with esophageal cancer were evaluated for curative resection. A retrospective study was undertaken to estimate the efficacy of surgery and select criteria for long-term survival. After investigation, 187 patients (47%) underwent surgery. To evaluate the long-term results, 101 curative esophageal resections classified into stage I (11 patients), II (24 patients), and III, pathological TNM (66 patients), with at least 2 years' follow-up, were considered. Esophagogastrectomy was performed in 91% of the cases and gastric transposition was achieved in 96% of the patients. The anastomoses were intrathoracic (98%) and at the apex of the right thorax for tumors of the middle third of the esophagus. Staplers were used in 76% of sutures. Postoperative hospital mortality was 5.9%. Specific morbidity included strictures 11%, esophagitis 12%, and anastomotic leak 2%. Actuarial 5-year survival was 90.9% in stage I, 52.3% in stage II, and 17.7% in stage III. The overall 5-year survival rate was 34.2%, 64.8% for the N0 patients, and decreased to 17.7% when node involvement was observed. Five- to 8-year survival is also considered. It is concluded from this study that esophagectomy is actually the appropriate treatment in patients with nonmetastatic resectable carcinoma with an overall 34.2% 5-year survival. The operation can be performed with a low morbidity and mortality rate if done in experienced centers.

In 2006, a TNM system for foregut neuroendocrine tumors has been proposed. Our study aimed to present the management of neuroendocrine tumors of pancreas according to this classification and to highlight some of its limitations.Clinical, biochemical, radiological, surgical and pathological data were retrospectively collected on 22 consecutives patients, who underwent surgery for neuroendocrine tumors of pancreas between November, 1991 and September, 2005. These data were used to set the TNM.After excluding 5 patients, the remaining 17 patients were analyzed. In 9 patients, with a mean age of 39 years, tumors were benign with a mean size of 1.8 cm, classed at stage I-IIa, whereas for 8 patients with a mean age of 57 years, tumors were malignant with a mean size of 6cm and were classed at stage IIb-IV. There were 3 deaths in stage IIb-IV, and none in stage I-IIa.TNM may be considered as a useful tool for prognostic stratification, but true benign tumors need to be excluded in order to improve the classification. Size and age appeared as variables affecting malignant behavior and the prognosis.

In this study we investigated the involvement of several different pituitary hormones on rat prostate development. 22-day-old Wistar rats, hypophysectomized (hypox) at 19 days of age were supplemented with highly purified human prolactin (hPRL), human luteinizing hormone (hLH), porcine follicle-stimulating hormone (pFSH), and bovine growth hormone (bGH) or with saline. Quantitative analysis of RNAs shows that treatment with either PRL or GH increases significantly steady-state mRNAs levels of the following genes in the prostate: androgen receptor (AR) (respectively 3.5- and 4.8-fold above hypox controls), IGF-I (5- and 2.7-fold), and IGF-I receptor (2.9- and 2.3-fold). LH and FSH, by contrast, have negative effects on these parameters. To test whether the enhancing effect of PRL and GH on AR-mRNA abundance was followed by increased content in the protein itself, binding assays were performed with the androgen agonist [3H]R1881 (131 and 153 fmol/mg protein while hypox controls contained 110 fmol/mg protein). In addition to the well-documented presence of prolactin receptors in prostatic tissues, we have further demonstrated, by means of nuclease S1 protection assays plus dot- and Northern-blot analyses, that a GH receptor mRNA is produced in the immature rat prostate. Moreover, we observed not only strong lactogenic but also purely somatogenic binding to be occurring in the immature prostates. Finally, we have studied IGF-I mRNA content in separated epithelial/stromal cell fractions and have concluded that IGF-I expression is principally located in the prostatic stroma. Taken together, these results suggest that PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. In this context IGF-I appears as a paracrine factor playing a role in epithelium/stroma interactions during prostatic development.

We have studied dose-dependent effects of highly purified human PRL (39 IU/mg) on the testis of immature (22-day-old) hypophysectomized rats daily supplemented for 7 days with 2, 10, or 30 micrograms hormone. Dose-dependent stimulation was observed for all parameters: testis weight (1.6- and 2-fold above control for 10 and 30 micrograms PRL), basal and hCG-stimulated testosterone (14- and 21-fold), intratesticular testosterone (7- and 21-fold) and estradiol (1.2- and 1.5-fold), LH receptor concentration (1.8- and 2.5-fold), in vitro pregnenolone production by cholesterol side-chain cleavage enzyme (3-, 5- and 7-fold), and aromatase activity (2.1- and 2.4-fold). The number of Leydig cells exhibiting immunoreactivity toward anti-P450scc, anti-P450(17 alpha), and anti-3 beta-hydroxysteroid dehydrogenase antibodies also underwent a dose-dependent increase (under conditions revealing many immunopositive cells in hypox control animals). The respective increases were 8- to 14-fold for anti-P450scc and P450(17 alpha) and 1.5- to 2-fold for anti-3 beta-hydroxysteroid dehydrogenase. The number of germ cells and the percentage of tubular sections containing late pachytene spermatocytes as most advanced stages of spermatogenesis were subject to similar dose-dependent effects. These results suggest that during puberty PRL stimulates testicular function by promoting multiplication and differentiation of Leydig cells (acting at various steps of steroidogenesis and on tissue responsiveness to LH) and germ cells.

In most diseases, the clinical need for serum/plasma markers has never been so crucial, not only for diagnosis, but also for the selection of the most efficient therapies, as well as exclusion of ineffective or toxic treatment. Due to the high sample complexity, prefractionation is essential for exploring the deep proteome and finding specific markers. In this study, three different sample preparation methods (i.e., highly abundant protein precipitation, restricted access materials (RAM) combined with IMAC chromatography and peptide ligand affinity beads) were investigated in order to select the best fractionation step for further differential proteomic experiments focusing on the LMW proteome (MW inferior to 40,000 Da). Indeed, the aim was not to cover the entire plasma/serum proteome, but to enrich potentially interesting tissue leakage proteins. These three methods were evaluated on their reproducibility, on the SELDI-TOF-MS peptide/protein peaks generated after fractionation and on the information supplied. The studied methods appeared to give complementary information and presented good reproducibility (below 20%). Peptide ligand affinity beads were found to provide efficient depletion of HMW proteins and peak enrichment in protein/peptide profiles.

Insulinoma is the most common functioning endocrine tumor of the pancreas responsible for fasting hypoglycemia resulting from autonomous insulin hypersecretion. Most insulinomas are small and difficult to localize with conventional imaging. We successfully localized a small insulinoma in our patient using diffusion-weighted magnetic resonance imaging before surgery.We report the case of a female patient with a clinical suspicion of insulinoma. A preoperative MR with diffusion-weighted imaging was performed and localized a small nodule in the pancreatic tail. Treatment consisted of surgical enucleation. Histologic examination identified a neuroendocrine tumor compatible with an insulinoma.Diffusion-weighted imaging can be useful in detecting and localizing small insulinomas, especially for those with no hypervascular pattern.

Transoral gastroplasty (TOGA) has been offered as an investigational alternative restrictive procedure in our hospital for the last 3 years. Since laparoscopic Roux-en-Y gastric bypass (LRYGBP) can be performed as a revisional surgery after failure of a restrictive surgery, this study reports on the feasibility of conversion of TOGA into a LRYGBP in case of failure of the endoscopic procedure.Since 2006, 71 TOGA procedures were performed in morbidly obese patients. Four patients underwent an LRYGBP after TOGA procedure for unsatisfactory results after 1-year observation. All of them had undergone a second procedure in which additional TOGA restrictions were placed to attempt to tighten the pouch before being referred for LRYGBP. The surgical outcome of these patients was analysed.All four patients were easily converted to a LRYGBP with no major complication and no mortality. The operative results (operating time, morbidities, follow-up) of all LRYGBP post TOGA were similar to primary LRYGBP performed by the same operator.LRYGBP post-TOGA apparently can be done without any trouble. The performance of TOGA does not seem to interfere with the short-term results of the LRYGBP.

A 67000 Mr bovine pregnancy-associated glycoprotein (bPAG) has been isolated from fetal cotyledons and purified to homogeneity by HPLC. The purification was monitored by a double immunodiffusion test and by RIA in conjunction with an antiserum raised against a crude fraction of placenta-specific antigens. The molecular weight of bPAG was estimated to be 67000 by SDS-PAGE. The isoelectric points (pI) of the four isoforms, determined by high-resolution analytical electrofocusing in polyacrylamide gel, were 4.4, 4.6, 5.2, and 5.4. The carbohydrate content of the bPAG consisted of approximately 10.02 +/- 1.09% neutral sugar and variant amounts of sialic acid (from 0.29 +/- 0.06% in the most basic isoform to 2.1 +/- 0.31% in the most acidic isoform). A specific antiserum was raised against the purified bPAG. A specific RIA showed that the bPAG was antigenically unrelated to BSA, alphafetoprotein (AFP), and human schwangerschafts-spezifischen (pregnancy-specific) beta 1 glycoprotein (SP1). According to some characteristics (e.g. the molecular weight), the purified bPAG may correspond to a form of the pregnancy-specific protein B previously described by Sasser and colleagues (Biol Reprod 1986; 35:936-942).

The postoperative morbidity following pancreaticoduodenectomy (PD) remains very high. Somatostatin or octreotide are indicated in the prevention of pancreatic stump-related complications. The aim of this study is to compare the efficacy of somatostatin and octreotide after PD.Between November 2000 and December 2003 we collected prospectively clinical and biological data from patients with a benign or malignant pancreatic tumor requiring a PD. Fifty patients were randomized into two groups, 25 treated with somatostatin (group S) and 25 with octreotide (group O).There was no postoperative death. Complications occurred in 20 patients (40%), 11 in group S, 9 in group O (NS). General complications occurred in 7 patients in group S, and 5 patients in group O. Local complications related to the pancreatic stump were found in 4 patients in both groups. At the end of the period of administration of the two study drugs, 2 patients (8%) had a pancreatic fistula in group S and 3 in group O (12%) (p=0.52). A trend of more rapid decreased level of amylase and lipase concentrations in surgical drainage was observed in group S but it is not statistically significant (p=0.29).In patients requiring PD for pancreatic tumor, somatostatin and octreotide seem to behave similarly in the postoperative period.

Splenic cysts are rarely observed in young patients. We report three cases of splenic cysts. The management and the surgical procedure, if needed, are discussed. If the splenic cyst is symptomatic or if its size reaches a diameter of 4-6cm, it requires surgical management. This treatment would be performed by laparoscopic approach and is intended to spare splenic tissue as much as possible. A prophylactic anti-pneumococcal vaccination is recommended before surgical treatment.

To evaluate the safety and feasibility in human subjects of a new transoral restrictive procedure for the treatment of obesity. The protocol was approved by the institutional review boards (IRBs) of both centers involved, and all patients gave informed consent. Patients met established inclusion criteria for bariatric surgery. The TOGa system (Satiety Inc., Palo Alto, CA), a set of transoral endoscopically guided staplers, was used to create a stapled restrictive pouch along the lesser curve of the stomach. Patients were hospitalized overnight for observation and underwent barium upper gastrointestinal (UGI) the next morning. Post procedure, all patients were placed on a liquid diet for 1 month and asked to begin an exercise program. Follow-up was carried out at 1 week and 1, 3, 4, 5, and 6 months. Twenty one patients were enrolled [17 female, age 43.7 (22–57) years, BMI 43.3 (35–53) kg/m2]. Device introduction was completed safely in all patients. There were no serious adverse events (AEs). The most commonly reported procedure or device related adverse events were vomiting, pain, nausea, and transient dysphagia. At 6 month endoscopy, all patients had persistent full or partial stapled sleeves. Gaps in the staple line were evident in 13 patients. Patients lost an average 17.6 pounds at 1 month, 24.5 pounds at three months, and 26.5 pounds at 6 months post-treatment [excess weight loss (EWL) of 16.2%, 22.6%, and 24.4%, respectively]. There is great interest in new procedures for morbid obesity that could offer lower morbidity than current options. Early experience with the TOGa procedure indicates that this transoral approach may be safe and feasible. Further experience with the device and technique should improve anatomic and functional outcomes in the future. Additional studies are underway.

To report a new CT sign of small bowel strangulation. Two cases of small bowel obstruction evaluated by spiral CT with intravenous contrast injection. In both cases we observed an absence of parietal enhancement of the diseased bowel loop, visible on early scans only. This feature was accompanied by signs of bowel obstruction. The two patients had a segment of necrotic ileum resected. Delayed enhancement of a bowel loop in cases of small bowel obstruction should suggest the diagnosis of strangulation and lead to rapid surgical treatment. 8 refs., 2 figs.

Post-operative pancreatic fistulae represent a challenge for all the actors in gastroenterology: for surgeons, because they want to prevent and treat conservatively this complication since re-operation is associated with high morbidity and mortality rates; for radiologists, because they have to provide the best staging and informations without any additional risk; and for endoscopists, because endoluminal treatment is emerging as a safe and effective procedure provided it is performed in highly experienced tertiary centres in the setting of a multidisciplinary approach. Herein, we review the definitions, the causes, the staging and the possible options to prevent or treat post-operative pancreatic fistulae. Special attention is paid to the endoscopic management of this complication: including the relief of ductal obstructions, the stenting of leakages and the drainage of bulging or non-bulging fluid collections. Practical problems and issues are clearly outlined as well as the need for future improvements in staging and management of the patients having such complications.

Purpose: To evaluate the feasibility and tolerance of a postoperative course of gemcitabine (GEM) combined with continuous radiation after curative resection of pancreatic adenocarcinoma. Methods and Materials: Thirty patients (median age, 61 years; performance status, 0 to 1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. Gemcitabine 1000 mg/m 2 (3 out of 4 weeks, two cycles) was given within 8 weeks of surgery and followed by GEM 300 mg/m 2 weekly combined with continuous radiation (45 Gy in 25 fractions, 1.8 Gy per fraction). Results: For GEM alone, all patients received the two courses with dose reductions in 14 of 30 patients (46%). All but 3 patients completed full chemoradiation; 1 stopped radiation because of subocclusion of a gastroenterostomy, and 2 did not start owing to disease progression. Reduction in GEM during radiation was necessary in 12 of 30 patients (40%). No toxic death was noted; World Health Organization Grade 3/4 hematologic and nonhematologic toxicities were seen in 10 of 30 patients (33%) and 3 of 30 patients (10%), respectively. After a median follow-up of 19 months, no late toxicity was reported. Eleven patients died from progressive disease; median disease-free survival and overall survival were 14.5 and 19 months, respectively. Conclusion: This adjuvant combination is well tolerated and can be safely administered after curative surgery for pancreatic cancer. Further evaluation of this regimen is ongoing.

Prostate cancer develops from clones that are already present as early as thirty-five years of age, when circulating concentrations of androgens are high. The progression of the disease is low and the cancer is diagnosed at a more advanced age. Prostate cancer evolves from an androgen dependant stage to stage where it escapes from all anti-androgenic treatments. The patient usually dies within two years following the diagnosis of advanced cancer. Therefore, it is of great interest to develop new therapies for androgen independent prostate cancer. The androgen independent evolution of prostate cancer is a complex phenomenon at the cellular and molecular levels. It includes an increased sensitivity to growth factors, the control of proliferation pathways, apoptotic and survival pathways as well as the control of angiogenesis. Epidemiological studies have also suggested that certain vitamins or phyto-oestrogens could protect against prostate cancer development. The present review attempts to present an overview of the fundamental research in cellular signalling which could be interesting as target for the treatment of androgen independent prostate cancer. Also the potential interest of non-androgenic steroids was reviewed for the same goal.

Background Increasing numbers of cases and organ shortage justify reconsidering the global therapeutic approach for hepatocelluar carcinoma in cirrhotic patients. Methods Recent literature was reviewed, focused on new therapeutic technologies such as radiofrequency. Results For small tumors, liver transplantation offers theoretically the best chance for cure. However, organ shortage may eliminate this advantage, because of tumor progression while waiting for a graft. For small tumors, arising on compensated cirrhosis, resection or radiofrequency ablation may provide efficient local tumor control without precluding subsequent transplantation in case of tumor recurrence and/or cirrhosis decompensation. Conclusions For small tumors and compensated cirrhosis, resection or radiofrequency could represent acceptable first line treatments. In addition to permit safe and immediate tumor control, this strategy would allow a preferential redistribution of grafts to patients with decompensated cirrhosis in whom transplantation is the only possibility. J. Surg. Oncol. 2003;84:36–44. © 2003 Wiley-Liss, Inc.

With pylorus-preserving pancreatoduodenectomy (PPPD) the goal is to reduce long-term morbidities such as gastric dumping, marginal ulceration or bile-reflux gastritis. Compared with te classical Whipple procedure, PPPD is affected by an equal postoperative morbidity but is known to induce delayed gastric emptying (DGE). It is difficult to evaluate the true incidence of DGE after PPPD (from 5 to 50% according to the literature). Early and low doses of erythromycin in the postoperative period could prevent the onset of DGE and the administration of cisapride 15 mg/day improves gastric emptying up to 6 months after PPPD.

Enteryx (ethylene vinyl alcohol copolymer) was developed as a bulking agent to be injected endoscopically at the lower oesophageal sphincter (LOS) to increase the competency of the gastro-oesophageal barrier in patients suffering from gastro-oesophageal reflux disease (GORD). Preliminary clinical studies have shown that Enteryx implantation is a fast, minimally invasive and safe procedure. In prospective multicentre studies, significant improvement in reflux symptoms, reduction in the use of proton pump inhibitors (PPIs), and objective improvement in acid oesophageal exposure time were observed after 6 months of follow-up. Improvement of GORD symptoms seems to be correlated with the persistence of the implant. Preliminary data suggest a lengthening and an increase in the LOS relaxation pressure as mechanisms of action of this injection technique. Longer follow-up and controlled sham studies are needed to confirm the efficacy of this technique before it can be proposed as a routine alternative to medical or surgical therapies for GORD.

Prostatic cancer is a heterogeneous disease. This applies both to its causes and to the mechanisms that facilitate its progression. Several molecular changes occur during this progression, giving the cancer cells a selective advantage over normal cells. Although tumor progression occurs in the context of androgen independence, the changes occurring in the tumor are only partially independent from the signaling pathways involving the androgen receptor. In subjects who have congenital 5α-reductase deficiency and who no longer synthesize DHT (dihydrotestosterone), the prostate no longer develops. Androgen depletion induces massive apoptosis of prostatic cells. This cell death affects the epithelial cells more than it does the cells of the fibromuscular stroma. Administration of testosterone to castrated animals causes an increase in the mitotic activity of the prostatic epithelial cells and restores the function of the gland. Castration early in life prevents the development of prostatic cancer and hyperplasia during ageing.