Role of Notch, IL-1 and leptin expression in colorectal cancer.

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1ß, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?

BACKGROUND: This study compared the predictive accuracy of four scoring systems, namely Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), and Mortality in Emergency Department (MEDS), for estimating prognosis in patients with necrotizing fasciitis. METHODS: Seventy-four patients who presented with necrotizing fasciitis were retrospectively examined. The ability of the scoring systems to predict mortality was assessed by comparing the estimated mortality rates in mortality groups (survivors/non-survivors), and mortality rates among survivors and non-survivors with an estimated mortality of >10%, 30%, and 50% in the scoring systems were compared in pairs. RESULTS: Estimated mortality rates in the survivor and non-survivor groups were different for all the scoring systems. The estimated mortality rates of APACHE II and SAPS II were much closer to the actual mortality rates than the other two scoring systems. When the predicted mortality rates were analyzed as limits for a mortality risk, the predicted mortality rate by APACHE II was superior to that by SAPS II. CONCLUSION: The studied scoring systems had significantly higher predicted mortality rates in non-survivors than in survivors; however, they all underestimated the mortality rate. APACHE II and SAPS II were relatively superior for estimating mortality in patients with necrotizing fasciitis. APACHE II rather than the other scoring systems should be currently used.

Factors affecting breast cancer treatment delay in Turkey: a study from Turkish Federation of Breast Diseases Societies.

BACKGROUND: One of the most important factors in breast cancer (BC) mortality is treatment delay. The primary goal of this survey was to identify factors affecting the total delay time (TDT) in Turkish BC patients. METHODS: A total of 1031 patients with BC were surveyed using a uniform questionnaire. The time between discovering the first symptom and signing up for the first medical visit (patient delay time; PDT) and the time between the first medical visit and the start of therapy (system delay time; SDT) were modelled separately with multilevel regression. RESULTS: The mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks, respectively. In all, 42% of the patients had a TDT >12 weeks. Longer PDT was significantly correlated with disregarding symptoms and having age of between 30 and 39 years. Shorter PDT was characteristic of patients who: had stronger self-examination habits, received more support from family and friends and had at least secondary education. Predictors of longer SDT included disregard of symptoms, distrust in success of therapy and medical system and having PDT in excess of 4 weeks. Shorter SDT was linked to the age of >60 years. Patients who were diagnosed during a periodic check-up or opportunistic mammography displayed shorter SDT compared with those who had symptomatic BC and their first medical examination was by a surgeon. CONCLUSION: TDT in Turkey is long and remains a major problem. Delays can be reduced by increasing BC awareness, implementing organized population-based screening programmes and founding cancer centres.

Pneumomediastinum and subcutaneous emphysema caused by sigmoid diverticulum perforation secondary to blunt abdominal trauma: report of a case.

Pneumomediastinum and subcutaneous emphysema are very rare reported signs of colonic perforation most often associated with diverticulitis, toxic megacolon and colonoscopy. We report a case of a 60-year-old man with subcutaneous emphysema and pneumomediastinum, which developed three days after a car accident without pneumothorax. A computed tomography scan demonstrated perforation of a sigmoid diverticulum in conjunction with air. A laparotomy was performed and revealed a perforated sigmoid diverticulum, fistulized into the retroperitoneal cavity. We suspect that this diverticular perforation was caused by the deterioration of the sigmoid mesocolon secondary to the blunt abdominal trauma. To our knowledge, this is the first report in the literature about pneumomediastinum and subcutaneous emphysema caused by sigmoid diverticular rupture following mesosigmoid trauma.

Effects of doxycycline on renal ischemia reperfusion injury induced by abdominal compartment syndrome.

BACKGROUND: The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS: Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1ß, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS: Creatinine, MDA, IL-1ß, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1ß, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION: Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.

Perforated mixed carcinoid-adenocarcinoma in transverse colon and at gastroenterostomy site: case report.

Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.

Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model.

BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and ß-cell lymphoma 2 (ßcl-2) expression were assessed immunohistochemically. RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1ß, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of ßcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.

Colonic perforation during barium enema in a patient without known colonic disease: a case report.

The barium enema is a safe and accurate diagnostic study of the colon but, in rare cases, causes complications, such as colonic perforation. A colon weakened by iatrogenic trauma due to the enema tip and/or retention balloon, or by disease is more likely to perforate during an enema than is a normal healthy bowel. Rarely the colon may burst due to excessive transmural pressure alone. We report a case of colonic perforation during barium enema in a 72-year-old female patient, due to excessive barium applied into the rectum.

Esophagectomy in esophageal lipoma: report of a case.

Lipoma is an uncommon benign tumor of the alimentary tract and its overall incidence is 4.1%, but that of the esophagus is extremely rare, with an incidence of only 0.4%. We present a case of esophageal lipoma. A 55-year-old man had a two-year history of dysphagia and odynophagia. Upper gastrointestinal system endoscopy showed a mass in the wall of the esophagus, occupying the lumen, and causing obstruction. Computed tomography and abdominal ultrasonography were performed because of endoscopic suspicion of submucosal tumor, and the mass was confirmed to be a lipoma in the wall of the esophagus. It was removed surgically by a thoracic approach. His symptoms resolved after the operation. Surgical excision by enucleation of the tumor is the preferred treatment of esophageal lipoma, but opening of the esophageal mucosa during this procedure is a rare cause for esophageal resection.

Fatal isoflurane hepatotoxicity without re-exposure.

Isoflurane is less hepatotoxic than its predecessors, halothane and enflurane. We present a 68-year-old man who developed fulminant and fatal hepatic necrosis two days after open cholecystectomy done under isoflurane anesthesia. Laboratory findings included grossly elevated transaminases and bilirubin and prolonged prothrombin time. Serological studies were negative for viral hepatitis. Postmortem examination demonstrated centrilobular necrosis of liver.

Effectiveness of bombesin and Saccharomyces boulardii against the translocation of Candida albicans in the digestive tract in immunosuppressed rats.

PURPOSE: We investigated the effects of bombesin on disseminated candidiasis, and compared the effectiveness of bombesin with Saccharomyces boulardii against Candida albicans translocation from the gastrointestinal tract in immunosuppressed rats. METHODS: Sixty rats were divided into five groups of 12. Group 1 was given only a laboratory pellet diet and water during the experiments; the other four groups were orally inoculated with C. albicans; and groups 3, 4, and 5 were also given prednisolone intraperitoneally. The treatment groups consisted of group 4, given S. boulardii orally, and group 5, given bombesin subcutaneously. The rats were killed after 10 days, and the large bowel, liver, spleen, and kidneys were removed for microbiological and histopathological examination. Blood samples were taken to measure tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) levels, and the results were compared. RESULTS: The number of translocated C. albicans colonies from the gastrointestinal tract and the serum TNF-alpha and IL-beta levels were significantly lower in groups 4 and 5 than in group 3 (P < 0.05). Histological analysis revealed that the bombesin-treated group (group 5) had significantly less mucosal ulceration and submucosal inflammation in the large bowel, less inflammation and necrosis in the liver, and less inflammation of the Bowman capsules in the kidney than the S. boulardii-treated group (group 4) (P < 0.05). CONCLUSIONS: These findings show that both S. boulardii and bombesin inhibit the translocation of C. albicans from the gastrointestinal tract, although mucosal ulceration, submucosal inflammation in the large bowel, and dissemination in the liver and kidneys were significantly less severe in the bombesin-treated immunosuppressed rats.

Small cell carcinoma of rectum: a case report.

We present a case of a 40-year-old woman with small-cell carcinoma (SCC) of the rectum. She had profuse bleeding in rectum for 5 d. By colonoscopy, polyps were determined in the rectum and biopsies were carried out. Histopathologically, the polyps were adenomatous. Because of the profuse bleeding in rectum, she underwent low anterior resection. After the diagnosis of SCC, she received intravenous chemotherapy with standard doses of siklofosfamid, adriamycin, and vepesid. Nevertheless, intracranial metastases were revealed and she died 6 mo after the operation.

Ectopic thyroid in the gallbladder: report of a case.

Ectopic thyroid is a rare developmental anomaly. We describe an unusual case of ectopic thyroid tissue found in the gallbladder wall of a 68-year-old man who underwent cholecystectomy for acute cholecystitis. Pathological findings were compatible with ectopic thyroid tissue in the gallbladder wall. This very rare pathology is discussed with a review of the relevant literature.