OBJECTIVE: Patients with proximal malignant jaundices are often diagnosed in an advanced stage and need biliary decompression treatments, such as percutaneous transhepatic biliary drainage (PTBD) and bare metal stenting (BMS), to improve the hepatic function. Whether it is better to perform those two procedures together or in a separate time, it is not well understood. The aim of this study was to investigate the effectiveness and cost-benefit of a combined "one-stage" PTBD/BMS procedure in patients with malignant jaundices. PATIENTS AND METHODS: Forty-five patients with malignant jaundice treated with "one stage" PTBD/BMS were retrospectively enrolled to evaluate technical success, complications, survival, and length of hospitalization. RESULTS: A full technical success of the procedures was reported for all patients, with only one major complication among 45 treated patients. A better performance in terms of hospitalization rate was achieved by the one-stage procedure compared to the two-stage, also resulting in global saving of costs. A high survival rate was observed at the 3rd and 6th month (97.7% and 86.6%, respectively), with a median overall survival time of 271,58 days. CONCLUSIONS: Our study shows that performing PTBD/BMS as a "one-stage" procedure is useful, safe, and cost-effective with a high percentage of technical success and a similar occurrence of complications compared to the two-stage procedure.

Background: The use of Primary Resection-Anastomosis with or without protective ileostomy (PRA) or Hartmann’s Procedure (HP) in the surgery of complicated acute diverticulitis is still an open question. The latest published meta-analyses were limited to the most severe stages (Hinchey III and IV). Our systematic review aimed to compare PRA with the HP in all non-elective surgical patients with complicated acute diverticulitis (perforation or obstruction). Methods: A computerized literature search was performed on Medline databases until July 2014. The studies included in the meta-analysis were 24 with a total of 4,062 patients. Study outcomes included postoperative surgical complications, reintervention, 30-day mortality, overall mortality as well as the length of stay as secondary outcome. The pooled effects were estimated using a fixed effect model or random effect model based on the heterogeneity test. Results were expressed as odds ratio (OR) and 95% confidence interval (CI) for dichotomous outcomes and as mean difference (MD) with 95% CI for continuous outcomes. Subgroup analyses by study type were performed. Results: The PRA group had a lower rate of postoperative surgical complications (OR=0.525, 95% CI 0.387-0.713), reintervention (OR=0.688, 95% CI 0.525-0.902), 30-day mortality (OR=0.389, 95% CI 0.259-0.586), overall mortality (OR=0.467, 95% CI 0.272-0.803) and length of stay (MD=9.129, 95% CI 2.391-15.867) compared to the HP group. Conclusion: Our meta-analysis shows that the PRA technique is better than HP for all considered outcomes. Due to the high variability of the included studies, further randomized controlled trials would be required to confirm these results.

Background Differences in the actions of enteric neurotransmitters on colonic circular and longitudinal muscle layers have not been clearly determined, nor the possible existence of intrinsic myogenic phenotypes that might contribute to regional differences in human colon motor activity. The aim of this study was to analyze the direct pharmaco-mechanical coupling of carbachol (CCh) and vasoactive intestinal polypeptide (VIP) on human colonic smooth muscle strips and cells. Methods Circular and longitudinal muscle strips and cells were obtained from 15 human specimens of ascending and sigmoid colon. Both isometric tension on muscle strips and contraction and relaxation on cells were measured in response to increasing CCh and VIP concentrations. Key Results Circular muscle strips of ascending colon were more sensitive to the effect of CCh than that of sigmoid colon, EC50 values being, respectively, 4.15 mu mol L-1 and 8.47 mu mol L-1 (P < 0.05), although there were no differences in maximal responses. No regional differences were observed in longitudinal muscle strips or in smooth muscle cells. Maximal responses to CCh were higher on circular than longitudinal muscle strips and cells throughout the colon. A greater sensitivity to VIP was observed in ascending colon compared with sigmoid colon, both in circular (EC50: 0.041 and 0.15 mu mol L-1, respectively, P < 0.01) and longitudinal (EC50: 0.043 and 0.09 mu mol L-1, respectively, P < 0.05) strips, and similar differences were observed in longitudinal smooth muscle cells (EC50: 44.85 and 75.24 nmol L-1, respectively, P < 0.05). Conclusions & Inferences Regional myogenic differences in pharmaco-mechanical coupling between the enteric neurotransmitters and smooth muscle contribute to the complex regional motor patterns of human colon.

Objectives: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. Materials and Methods: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. Results: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. Conclusion: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms.

We have investigated the presence of oestrogen receptor-related (ERR) mRNA in human colorectal tumour tissues and adjacent normal mucosa by reverse transcriptase and nested-polymerase chain reaction. ERRα was found in 100% of the patients and ERRγ in approximately 30% while ERRβ was not detected at all. The multiplex PCR analysis showed elevated levels of ERRα mRNA in tumour tissue compartment as compared to normal mucosa, whereas ERRγ mRNA was found in lower levels but in both tissue compartments. In contrast, oestrogen receptor (ERα and ERβ) mRNA levels were shown to be decreased in tumour tissues. A positive correlation was observed between ERα and ERβ and between ERα and ERRα, respectively, in normal mucosa but not in tumour tissue. ERRα expression in tumour tissues significantly increased from TNM stages II to IV, whereas both ERs progressively declined. These findings suggest that ERRα, as well as the two ERs, might play a critical role in the progression of the colorectal cancer.

BACKGROUND:Little is known about the pathophysiology of diverticular disease. AIM:To compare passive and active stress and the response to carbachol of colonic smooth muscle specimens from patients with diverticular disease and patients with colon cancer. The effect of the NK2 receptor antagonist, SR48968, on electrically evoked contractions of circular muscle was also investigated. PATIENTS:Sigmoid colon segments were obtained from 16 patients (51-83 years) undergoing elective sigmoid resection for diverticular disease and 39 patients (50-88 years) undergoing left hemicolectomy for non-obstructive sigmoid colon cancer. METHODS:Isometric tension was measured on circular or longitudinal taenial muscle. Strips were stretched gradually to Lo (length allowing the development of optimal active tension with carbachol) and were also exposed to increasing carbachol concentrations. The effects of atropine, tetrodotoxin and SR48968 on electrically evoked (supramaximal strength, 0.3 ms, 0.1-10 Hz) contractions of circular strips from 8 patients with diverticular disease and 19 patients with colon cancer were also studied. RESULTS:Both passive and active stress in circular muscle strips obtained from patients with diverticular disease was higher than in patients with colon cancer (P < 0.05). Electrically evoked contractions were significantly reduced by atropine in all preparations and were virtually suppressed by combined SR48968 and atropine. Tetrodotoxin suppressed electrically evoked contractions only in patients with colon cancer, whereas a tetrodotoxin-resistant component was identified in patients with diverticular disease. CONCLUSIONS:The changes in both passive and active stress in specimens from patients with diverticular disease may reflect circular smooth muscle dysfunction. Acetylcholine and tachykinins are the main excitatory neurotransmitters mediating electrically evoked contractions in human sigmoid colon circular muscle.

A distinct genetic pathway may be involved in the development of polypoid and flat colorectal cancers, two morphologically different cancer subtypes. The present study was undertaken to clarify whether different combinations of some genetic alterations commonly involved (such as K-ras and p53 gene mutations) may exist between polypoid and flat types. In addition, to investigate any different proliferative behavior between the two distinct types of colorectal cancer, we tested the enzymatic activity of ornithine decarboxylase (ODC). A total of 29 polypoid type and 21 flat type colorectal cancers were selected for this study. We investigated K-ras and p53 mutations by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and single strand conformational polymorphism (PCR-SSCP) analysis, respectively. A radiometric method was used to evaluate ODC activity. K-ras and p53 gene mutations were present in 30 and 48% of cases, respectively. A significant association between the p53 mutation and the flat type of colorectal cancer was detected; on the contrary, no significant difference in frequency of K-ras mutation between polypoid and flat type colorectal cancer was found. A statistically significant difference in ODC activity levels was observed between polypoid and flat types. Moreover, we found that ODC activity was significantly higher in neoplastic tissue than in surrounding normal mucosa in polypoid type colorectal cancer. Different mutation patterns and proliferative behavior were observed in polypoid and flat colorectal malignant tumors. Further studies will be required to ascertain whether the distinct growth appearance of colorectal cancer can affect the outcome and prognosis of patients with this type of malignant disease.

BACKGROUNDMany patients with gallstone disease continue to report gastrointestinal symptoms after cholecystectomy, but the predictive value of preoperative factors is not well understood. We aimed to investigate whether psychological symptoms can be associated with poor outcome after cholecystectomy in patients with gallstones and dyspepsia.METHODSA sample of 52 consecutive patients with uncomplicated gallstone disease and dyspepsia (conceived in a broader sense to include symptoms of the whole digestive tract) were assessed for psychological (revised 90-item Hopkins Symptom Checklist) and gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale). One year after laparoscopic cholecystectomy, patients rated their gastrointestinal symptoms and were divided into improved and unimproved on the basis of the change in symptoms.RESULTSTwenty-one (40.4%) patients did not improve after surgery. Improved and unimproved patients did not differ in terms of sex, age, education or illness duration. Unimproved patients showed significantly higher psychological and dyspeptic symptoms than improved patients before surgery. Logistic regression showed that psychological factors were significantly associated with unimprovement after surgery.CONCLUSIONSPatients with gallstone disease and dyspeptic symptoms are unlikely to improve 1 year after surgery if they show psychological distress before surgery. Psychological symptoms were strongly associated with poor post-cholecystectomy outcome, thus highlighting the clinical relevance of joint assessment of psychological and gastrointestinal symptoms before surgery.

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic neoplasm of unknown etiology, occurring most commonly in young women. It is a neoplasm with a low malignancy and a good prognosis after surgical removal. For this reason it is important to distinguish this tumor from other pancreatic tumors and, in particular, from the more frequent carcinomas. Two cases of SPTP are presented with a review of the literature. The first case was of a 67-year-old woman with a 2 cm mass in the head of the pancreas and the second was of a 44-year-old woman with a 6 cm mass in the head of the pancreas. In both cases the pancreatic lesions were shown by ultrasonography and a computed tomography scan. The biopsy performed under ultrasound guidance did not allow a certain pre-operative diagnosis and, for this reason, the two patients underwent a pancreaticoduodenectomy as in cancer of the pancreas. Only histological examination permitted a definite diagnosis of SPTP. In the second case a histopathological pattern indicated a low malignant potential, while in the first case the neoplasm showed an infiltrative growth into the surrounding pancreatic parenchyma, suggestive of high malignant potential. Some authors consider this latter neoplasm as a subgroup of SPTP which distinguishes itself through its higher malignant potential. Our experience suggests that aggressive surgery must be chosen in all cases where a pre-operative certain diagnosis is unavailable.

BACKGROUND The enzyme farnesyltransferase has emerged as an important target for anti-cancer therapies. Farnesyltransferase inhibitors have been introduced in clinical trials of subjects with colorectal cancer. We investigated Farnesyltransferase activity, beta-subunit Farnesyltransferase protein expression and its mRNA in patients with colorectal cancer and its relationship with clinicopathological features and K-ras mutation. METHODS Farnesyltransferase activity was determined by Farnesyltransferase [3H] SPA enzyme assay. Beta-subunit Farnesyltransferase protein expression was investigated by Western blotting and its mRNA by reverse transcriptase-polymerase chain reaction. K-ras mutation was detected by polymerase chain reaction amplification and restriction enzyme analysis. Multiple linear regression analysis was used to analyse relationships among age, sex, site of tumour, Dukes' stage, histological differentiation, K-ras mutation and Farnesyltransferase activity in normal mucosa and cancer. RESULTS The levels of Farnesyltransferase activity and beta-subunit Farnesyltransferase protein expression were significantly higher in cancer than in normal mucosa. Moreover, tumours located on the right side, with mucinous histological differentiation and with K-ras mutation showed higher levels of Farnesyltransferase activity. CONCLUSIONS Our findings suggest that Farnesyltransferase activity may be a potential marker of tumourigenicity. The differences in Farnesyltransferase activity in relation to histological grading, tumour location and K-ras mutation described here may constitute a starting point for investigating the causes of this variation within the large bowel.

Cholecystokinin is the most important stimulant of postprandial gallbladder contraction, and a regulator of gallbladder fasting tone. The aim of this study was to evaluate the effect of dexloxiglumide on isolated human gallbladder contraction induced by cholecystokinin–octapeptide and to compare this effect to that of lorglumide and amiglumide, two glutaramic acid analogs of dexloxiglumide. The negative logarithms of the antagonist dissociation constant (pKB) values were 7.00 ± 0.14, 6.95 ± 0.11, and 6.71 ± 0.10 for lorglumide, dexloxiglumide, and amiglumide, respectively. Dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin–octapeptide curve, without affecting its maximal response. A similar effect was obtained both with lorglumide and amiglumide. Moreover, the slopes for the three antagonists did not differ significantly from unity. These data show that the three molecules have a potent antagonistic effect, of a competitive nature, on gallbladder cholecystokinin type 1 receptors. It may be concluded that dexloxiglumide, lorglumide, and amiglumide exhibit a promising therapeutic profile for biliary colic and other gastrointestinal disorders in which CCK1 receptors play important physiological roles.

BACKGROUND:The relationship between bile reflux and gastric cancer is not defined. In order to verify whether a relationship exists, we evaluated the duodenogastric reflux and the mucosal polyamines concentration, polycation compounds actively involved in cell proliferation, in the non-operated stomach and in gastric remnant after Billroth II gastric resection, a precancerous condition.MATERIALS AND METHODS:The study was performed on three groups of subjects: A) 43 subjects with slight dispeptic symptoms, never operated on; B) 54 cholecystectomized subjects; C) 38 subjects operated on Billroth II gastric resection for duodenal ulcer. Duodenogastric reflux was assessed by measuring the concentration of bile acids in gastric juice and expressed as Fasting Bile Reflux in micromol/hour. Gastric mucosal polyamine concentration was assessed by High Performance Liquid Chromatography and expressed in nmol/mg of proteins.RESULTS:The lowest levels of Fasting Bile Reflux (7.95 micromol/hour) and polyamines (7.09 nmol/mg proteins) were observed in subjects never operated on. The middle values were present after cholecystectomy (Fasting Bile Reflux = 18 micromol/hour; polyamines = 8.14 nmol/mg proteins). The highest values were observed after Billroth II gastric resection (Fasting Bile Reflux = 830 micromol/hour; polyamines 11.74 nmol/mg proteins) (Kruskal-Wallis test, p = 0.0001). There was a positive correlation between Fasting Bile Reflux and polyamines (Spearman's rank = 0.33; p = 0.0008).CONCLUSIONS:High levels of duodenogastric reflux observed after Billroth II gastric resection are associated with high polyamine concentration in the gastric mucosa. Bile reflux can be considered an important causal factor of the increased risk of gastric stump cancer after Billroth II gastric resection.

In vivo studies have demonstrated that somatostatin induces human gallbladder relaxation. To determine whether this polypeptide acts directly on the gallbladder muscle, its effect on strips of human gallbladder was studied in vitro. Strips of gallbladder were set up isometrically in an organ bath containing oxygenated Krebs' solution. Dose-response curves to cholecystokinin-octapeptide and carbachol were first established. The ability of somatostatin to cause relaxation under basal conditions and during 50% maximal stimulation by cholecystokinin-octapeptide (7.2 x 10(-8) M) and carbachol (3.5 x 10(-6) M) was assessed in 32 strips at 4.3 x 10(-6) M concentration which mimics the plasma concentrations found in patients with somatostatinoma and in 12 additional strips at 4.3 x 10(-8) M concentration. Somatostatin action on the intrinsic innervation by using electrical field stimulation (EFS) (200 mA 5 msec in duration, 30 Hz; 400 mA, 1 msec in duration, 10 Hz) was also evaluated in 39 strips. Somatostatin had no effect on the basal or carbachol-generated tensions. On the contrary, somatostatin (4.3 x 10(-6) M) reduced cholecystokinin-octapeptide-generated tensions by 8% (P < 0.001) and reduced EFS-generated tensions at 30 Hz by 7.7% (P < 0.01) and those at 10 Hz by 41.2% (P < 0.01). All responses to cholecystokinin-octapeptide and carbachol were abolished by dibutyryl-guanosine 3', 5'-cyclic monophosphate (5 x 10(-3) M) and atropine (10(-5) M), respectively (P < 0.0002 and P < 0.0002). All responses to electrical field stimulation were reduced or abolished by tetrodotoxin (2 x 10(-6) M) (P < 0.001 and P < 0.0001, respectively). Our findings show that somatostatin exerts its inhibitory action on the response to cholecystokinin-octapeptide and on the intrinsic innervation of the gallbladder smooth muscle. The probable neurotransmitter is the acetylcholine.

BACKGROUND:Videolaparocholecystectomy is now regarded as the elective surgical technique for the treatment of cholelithiasis.AIMS:In order to evaluate the feasibility and risks of videolaparocholecystectomy in patients with previous upper abdominal surgery the authors performed a retrospective case-control study in a group of 15 patients with cholelithiasis who had previously undergone gastrectomy for peptic ulcer (group A) and a control group of 15 patients with cholelithiasis who had not undergone upper abdominal surgery (group B).METHODS:The control group was matched with the case group for age, sex, surgeon, indications for cholecystectomy (simple cholelithiasis, acute cholecystitis). The following parameters were compared in both groups: laparotomic conversion rate (33% in group A vs 20% in group B; p = 0.317), postoperative complications (0% in group A vs 13% in group B, p = 0.157), reoperations (0% in group A vs 13% in group B, p = 0.157), duration of surgery (median of 78 minutes in group A vs 80 minutes in group B; p = 1.000), duration of postoperative hospital stay (mean of 3 days in group A vs 3.5 days in group B, p = 0.507).RESULTS:None of the differences between the variables examined was statistically significant.CONCLUSIONS:The authors, conclude that videolaparocholecystectomy can be regarded as a safe and effective surgical technique for the treatment of cholelithiasis also in patients who have undergone previous upper abdominal surgery.

To investigate the effects of cholecystectomy on gastric motor function, 13 patients with symptomatic gallstones were studied before and 8-12 months after surgery. Twelve healthy subjects entered the study as control group. The cutaneous electrogastrography and ultrasound examination of gastric emptying were simultaneously performed at pre- and post-prandial states. The dominant gastric frequency and its coefficient of variation were not affected by surgery. After cholecystectomy, an increase in normal 3 cpm wave percentage and a decrease in power ratio were found (P < 0.05 and P < 0.01, respectively). Gastric emptying recorded after cholecystectomy was faster than before surgery (306.9 +/- 15.9 min vs 336.9 +/- 11.8 min, respectively; P < 0.05). Such changes were associated with the relief of symptoms, and the comparison between patients and controls showed a normalization of the gastric electrical activity and gastric emptying after surgery. In conclusion, in symptomatic patients, gallstones are associated with motor dysfunctions, and cholecystectomy seems to induce a normalization of gastrointestinal motility.

To evaluate how the introduction of H2-receptor antagonists has modified the epidemiology of surgical management of peptic ulcer, we examined data records of patients operated on for gastric or duodenal ulcer in our Institute. Patients were divided into two groups: a) patients operated from 1970 to 1979 and b) patients operated from 1980 to 1992. The comparison between the two groups showed the following variations: decrease in male/female ratio from 8 to 4.4:1 (p = 0.0009); decrease in duodenal/ gastric ulcer ratio from 5 to 3.5:1 (p = 0.02); decrease in elective/emergency surgery ratio from 16 to 6.4:1 (p = 0.00006); increase in mean age of patients undergoing emergency operations from 51 to 58 years (p = 0.05); decrease in elective/emergency surgery ratio for gastric ulcer from 17.5 to 5.3:1 (p = 0.03), above all for the increase in emergency operations for hemorrhage; decrease in the prevalence of operations for refractory duodenal ulcer from 49% to 36% (p = 0.00009). Our findings show that H2-receptor antagonists have greatly modified the epidemiology of surgical treatment of peptic ulcer with a clear decrease in elective surgery for refractory duodenal ulcer in men and an increase in emergency surgery for gastric ulcer.