Lipomatous pancreas facilitates late onset of renal cell carcinoma metastases.

BACKGROUND: Late metastasizing into pancreatic tissue is a special hallmark of renal cell carcinomas (RCC). A very low prevalence leads to scarce data about therapy, prognosis and spreading pathways. The aim of the study was to analyze whether a high fat content in the pancreas facilitates RCC metastases formation. A model for density measurement of pancreatic tissue has been developed and evaluated. Pancreatic fat content was measured comparing Hounsfield units (HU) of CT scans. METHODS: In a consecutive single centre retrospective database of 3600 patients with pancreatic resections, only 12 patients (0.3%) cases of RCC metastases in the pancreas were found. HU were measured in 3 pancreatic regions: head, body and tail in patients' CT scans. HU values were compared to a control population and results aligned with recent literature. RESULTS: We revealed a prevalence of pancreatic metastases of RCC in 0.3% of cases. The formation of RCC in the pancreas occurred within 14 ± 5.6 years after initial diagnosis of RCC. 83.3% of the patients were alive after a follow-up period of up to 48 months. Clinical data analysis revealed an affinity for metastatic formation to lipomatous pancreas. This could be objectivized by HU analysis in CT scans. CONCLUSION: Pancreatic metastases occur late after the first diagnosis of renal carcinoma and show an affinity for lipomatous pancreatic tissues. Due to its rarity in occurrence, multicentric studies are highly recommended to further analyze this correlation between fatty pancreas and RCC.

Impact of drains on nausea and vomiting after thyroid and parathyroid surgery: a randomized controlled trial.

OBJECTIVE: Nausea and vomiting are common side effects following thyroid and parathyroid surgery. In a prospective controlled randomized trial, postoperative nausea and vomiting (PONV) and the number of episodes of vomiting were defined as two primary endpoints. We analysed whether the placement of drains after thyroid or parathyroid surgery enhances PONV and/or influences vomiting. PATIENTS AND METHODS: From November 2007 to January 2012, 136 consecutive patients were included for thyroid or parathyroid surgery and were randomly assigned to group A (drain, n = 69) or group B (no drain, n = 67). PONV was assessed with visual analogue scale (VAS; range 0 to 10) measurements. Furthermore, episodes of vomiting as well as analgetic and antiemetic therapies were recorded. Difference in neck circumference was compared pre- and postoperatively. RESULTS: Patients' characteristics did not differ between group A and B. Postoperative VAS values for pain were 2.4 ± 0.3 (group A) and 2.6 ± 0.2 (group B) (p = 0.62), and for nausea 1.4 ± 0.2 (group A) and 1.1 ± 0.2 (group B) (p = 0.57). The relative occurrences of episodes for postoperative vomiting were equal in both groups 0.3 ± 0.1 (p = 1.0). Antiemetic drugs were administered 37 times (group A) and 18 times (group B) (p = 0.099). The total number of treatments of patients with antiemetic drugs was 23 (33.3%) in group A vs. 13 (19.4%) in group B (p = 0.081). The neck circumference postoperatively was significantly larger in group B (p = 0.0025). CONCLUSIONS: Drains after surgery do not enhance postoperative pain, nausea and vomiting. The placement of drains in thyroid surgery is recommended to avoid relevant fluid collection. Drains however may influence the amount of antiemetic drug requirements. TRIAL REGISTRATION: CLINICALTRIALS. GOV IDENTIFIER: NCT01679418.

Subtotal colectomy for malignant left-sided colon obstruction is associated with a lower anastomotic leak rate than segmental colectomy.

AIM: To compare subtotal colectomy to segmental colectomy for malignant left-sided colonic obstruction. PATIENTS AND METHODS: Obstruction was defined by failure to trespass a colonic stenosis during endoscopy, by truncation of the contrast column during contrast enema, by severe colonic dilatation (cecum >10 cm, transverse colon >8 cm, descending colon >6 cm) or by serosal tears. From 53 consecutive patients treated for malignant left-sided colon obstruction at our surgical department from July 2002 to July 2010, 19 patients had subtotal colectomy and 30 patients had segmental colectomy. Four patients were excluded: two of them had non-colorectal primary cancer and the other two had a two-stage procedure. RESULTS: The rate of severe colonic dilatation and serosal tears, the physiological severity score and the expected morbidity were higher in the group with subtotal colectomy than in the group of segmental colectomy (p<0.05). However, the anastomotic leak rate was lower in the group with subtotal colectomy (0/19) than in the group with segmental colectomy (6/30) (p=0.042). Overall, there were no statistically significant differences regarding mortality or morbidity between the two groups. CONCLUSION: Despite worse preoperative conditions, patients who underwent subtotal colectomy for left-sided obstructing colonic cancer had a significantly lower anastomotic leak rate than those who underwent segmental colectomy. This fact supports the concept of subtotal colectomy for this entity. However, perioperative mortality seems to be independent of the presence or absence of an anastomotic leak.

An audit of outcomes of a series of periampullary carcinomas.

BACKGROUND: Non-pancreatic periampullary carcinoma such as ampullary carcinoma (AmpCA), distal cholangiocellular carcinoma (CholCA) and duodenal carcinoma (DuoCA) have a better prognosis than pancreatic head adenocarcinoma (PanCA). This study describes the outcome and parameters, which predict survival of non-pancreatic periampullary carcinoma after resection. METHODS AND PATIENTS: Data from 148 consecutive patients with non-pancreatic periampullary carcinomas were recorded prospectively between 1993 and 2005 and analyzed using univariate and multivariate models. RESULTS: One hundred thirty-three of 148 (90%) patients were resected for histologically proven non-pancreatic periampullary carcinomas. R0 resection was achieved for 92% of AmpCA, for 88% of CholCA and for all the DuoCA. The lowest recurrence rate was seen in DuoCA with 18%, followed by AmpCA with 21% and CholCA with 46%. The mean survival time was 60.9 months for AmpCA patients, 42.9 months for CholCA and 45.4 months for DuoCA patients. Five-year survival was 50.5%, 29.9% and 24.5% for AmpCA, CholCA and DuoCA, respectively. Multivariate analysis identified low bilirubin levels (<100 micromol/l), R0 resections and absence of surgical complications to be strong independent predictors of survival (p<0.05). In AmpCA low tumor stages are also an independent predictor of long-term survival (p<0.01). For T1/T2 AmpCA the 5-year survival rate was 61%, whereas none of the patients with a T3/T4 tumor survived 5 years. CONCLUSION: Only T1/T2 ampullary carcinomas have a good prognosis, whereas T3/T4 ampullary tumors show aggressiveness similar to that of pancreatic head adenocarcinomas. Absence of surgical complications determines long-term outcome. Therefore, the combination of a complication-free and radical resection is essential for long-term survival.

Helicobacter pylori infection stimulates plasminogen activator inhibitor 1 production by gastric epithelial cells.

Chronic infection with the gastric pathogen Helicobacter pylori significantly increases the risk of developing atrophic gastritis, peptic ulcer disease, and gastric adenocarcinoma. H. pylori strains that possess the cag pathogenicity island, which translocates CagA into the host cells, augment these risks. The aim of this study was to determine the molecular mechanisms through which H. pylori upregulates the expression of plasminogen activator inhibitor 1 (PAI-1), a member of the urokinase activator system that is involved in tumor metastasis and angiogenesis. Levels of PAI-1 mRNA and protein were examined in tissues from H. pylori-infected patients and in vitro using AGS gastric epithelial cells. In vitro, cells were infected with toxigenic cag-positive or nontoxigenic cag-negative strains of H. pylori or isogenic mutants. The amount of PAI-1 secretion was measured by enzyme-linked immunosorbent assay, and mRNA levels were determined using real-time PCR. The regulation of PAI-1 was examined using the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor and small interfering RNA. Analysis of human biopsy samples revealed an increase in both PAI-1 mRNA and protein levels in patients with H. pylori gastritis compared to those of uninfected controls. Infection of AGS cells with H. pylori significantly increased PAI-1 mRNA expression and the secretion of PAI-1 protein. Moreover, PAI-1 mRNA and protein production was more pronounced when AGS cells were infected by H. pylori strains carrying a functional cag secretion system than when cells were infected by strains lacking this system. PAI-1 secretion was also reduced when cells were infected with either cagE-negative or cagA-negative mutants. The ectopic overexpression of CagA significantly increased the levels of PAI-1 mRNA and protein, whereas blockade of the ERK1/2 pathway inhibited H. pylori-mediated PAI-1 upregulation. These findings suggest that the upregulation of PAI-1 in H. pylori-infected gastric epithelial cells may contribute to the carcinogenic process.

Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases.

BACKGROUND: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. OBJECTIVE: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. METHODS: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany (n = 638), Netherlands (n = 136), and Switzerland (n = 106), and in healthy (n = 1409) and alcoholic (n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. RESULTS: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. CONCLUSIONS: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.

Treatment of pancreatic cancer: the role of surgery.

Pancreatic cancer shows an aggressive growth behavior which results in an extremely poor prognosis. It is presently the 4th to 5th leading cause of cancer-related deaths in Western countries with an incidence of 8-10 new cases per 100,000 inhabitants. Since current conservative oncological therapies fail to influence the long-term outcome, curative resection remains the only possibility with a potential for cure. During the past decades, a considerable decrease in postoperative mortality after pancreatic resection and a significant increase in the resection rate have been achieved. Although several types of pancreatic resection have evolved, standard procedures are the classical Whipple resection for cancers of the pancreatic head and left resection for cancers of pancreatic body and tail. Since the pylorus-preserving Whipple resection and extended Whipple resection are still debated as better alternatives to the classical Whipple procedure, large, controlled clinical trials in patients need to be conducted to reach reliable conclusions. However, there is mounting evidence that the pylorus-preserving Whipple procedure offers a better postoperative outcome than the classical Whipple operation without compromising radicality and thereby the long-term prognosis. Despite the progress in surgical treatment of pancreatic cancer, the overall prognosis following resection remains unsatisfactory to date. It is hoped that progress in multimodality treatment and modern therapies, resulting from both clinical and advanced basic research, can improve the prognosis of this malignancy in the near future.

Controlled release of vancomycin from poloxamer 407 gels.

The purpose of this study was to investigate Poloxamer 407 25% (w/w) formulations aimed at prolonging the residence time of vancomycin, a time-dependent antibiotic, in a body site with a high infectious risk. Reversible thermal gelation of the formulations permitted their local injection in liquid form and in situ gelation as they warmed to body temperature. Neither the rheological properties of the Poloxamer matrices nor the antibacterial activity of vancomycin was altered by their combination. In vitro, the dispersed form exhibited prolonged release, with a lower diffusion coefficient of vancomycin compared to the solubilized form (4.7x10(-8) vs 2. 1x10(-7) cm(2) s(-1)131 mg l(-1) for the solubilized form), followed by lower but effective antibacterial levels for at least 8 days. Controlled-release profiles, good preservation of vancomycin activity, good tolerability in rats, and ease of administration suggest that Poloxamer 407 may be useful as a vancomycin delivery vehicle for local prophylaxis of infections, especially in prosthetic surgery.