Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population.

OBJECTIVE: Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT. METHODS: Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients. RESULTS: We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.

Primary thyroid lymphoma.

Primary thyroid lymphoma is an uncommon thyroid malignancy. The treatment modalities significantly differ from other thyroid malignancies. Frequently it is accompanied by Hashimoto's thyroiditis, and it may be difficult to differentiate the two entities histologically. Patients typically present with suddenly growing mass in the thyroid gland. Discrimination between primary and secondary lymphoma is important due to variations in diagnostic tools, treatment modalities and prognosis. Surgery, chemotherapy, radiotherapy or combinations of these modalities may be applied in treatment. In this report, three cases with primary thyroid lymphoma in which three different treatment modalities have been applied are presented.

Can heat shock protein 32 be used for the early diagnosis of acute mesenteric ischemia?

OBJECTIVE: Acute mesenteric ischemia is a challenging and fatal disease. The aim of this study was to detect the heat shock protein 32 (HSP32) response in intestinal tissue and systemic blood to intestinal ischemia and ischemia/reperfusion to define a tool for the early diagnosis of acute mesenteric ischemia. MATERIAL AND METHODS: Thirty female Wistar albino rats were equally divided into 3 groups. Group 1 rats underwent simple laparotomy and closure (control). In Group 2 rats, 1-hour intestinal ischemia followed by 5-hour reperfusion was performed, and Group 3 rats were subjected to 6-hour intestinal ischemia. The experiment was repeated with a 24-hour waiting period. At the end of the waiting period, blood was withdrawn from the tail veins of the rats and the rats were sacrificed via cardiac puncture. Re-laparotomy was subsequently performed and intestinal tissue and luminal samples were obtained for biochemical and pathological investigations. The HSP32 levels of intestinal tissues, luminal contents and blood levels were compared among the groups. RESULTS: At the end of the 24-hour waiting period, the median tissue HSP32 levels were 0.43 (0-6.6) ng/mL for Group 1, 9.51 (2.5-49.9) ng/mL for Group 2 and 43.13 (6.3-121.3) ng/mL for Group 3 (p=0.001). The median blood HSP32 levels were 0.11 (0.1-1.4) ng/mL for Group 1, 0.42 (0.1-0.7) ng/mL for Group 2, and 0.25 (0.1-1.2) ng/mL for Group 3 (p=0.047). The HSP levels in the luminal contents were undetectable. CONCLUSION: Both ischemia and ischemia/reperfusion significantly raised intestinal tissue HSP32 levels in comparison with the control group. However, this change was not reflected in the circulating blood or luminal contents.

Coexistence of gastric multiple neuroendocrine tumors with unusual morphological features and gastric signet-ring cell carcinoma.

The coexistence of signet-ring cell carcinoma and neuroendocrine tumors is very rare. We report a 57-year-old man who presented with a history of weight loss and nausea. Gastric mucosal biopsies obtained during gastrointestinal endoscopy revealed a gastric signet-ring cell carcinoma. The patient underwent a total gastrectomy with a standard D2 lymph node dissection. Ten individual tumors were detected in the resected specimen. Based on the histopathological and immunohistochemical findings, the final diagnosis was co-existing signet-ring cell carcinoma and neuroendocrine tumor. Spindle-shaped cells and extracytoplasmic mucin were noted in some tumor cells forming the neuroendocrine component. This case is a rare synchronous tumor because of its unusual neuroendocrine component.

Routine Use of Prophylactic Antibiotics during Laparoscopic Cholecystectomy Does Not Reduce the Risk of Surgical Site Infections.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard for the treatment of symptomatic gallbladder stones. As infections are rare in uncomplicated LC, it is widely accepted that prophylactic antibiotics need not be administered, and guidelines do not support routine antibiotic prophylaxis during elective LC. However, routine antibiotic prophylaxis for elective LC is still popular in many clinical settings. We investigated this situation in our department. METHOD: This randomized double-blind controlled study included 570 patients who underwent LC between March 2007 and February 2010. The exclusion criteria were antibiotic intake before surgery, steroid treatment, and the presence of pancreatitis, cholangitis, obstructive jaundice, cephalosporin allergy, or pregnancy. The patients were randomized into three groups. Group 1 (n = 193) received physiologic saline as placebo, Group 2 (n = 191) received a first-generation cephalosporin (cefazolin; 1 g), and Group 3 (n = 186) received a second-generation cephalosporin (cefuroksim aksetil; 750 mg). Bile and epigastric and umbilical port tissue samples were harvested for culture. All patients were observed until the end of the fourth week after surgery. Patient age, sex, weight, American Society of Anesthesiologists (ASA) score, diabetes mellitus, smoking history, history of biliary colic in the past month, length of the hospital stay before the operation, operational findings (acute or chronic cholecystitis), operation duration, use of drainage, type of prophylaxis administered if any, culture results, surgical site infection (SSI) development, and time to SSI development along with associated treatments were evaluated. RESULTS: There was no statistically significant difference between the groups with respect to any of the demographic and clinical features analyzed in this study. The SSI rate was 1.2% in total, and in Groups 1, 2, and 3, it was 1.5%, 1.04%, and 1.07%, respectively. There was no statistical difference regarding SSI among the groups (p = 1.00). Superficial SSI was observed in all groups, and in all patients, the site of infection was the entrance to the epigastric port through which the gallbladder had been removed. CONCLUSIONS: Surgical site infection is rare after LC, and antibiotic prophylaxis does not appear to affect the outcome significantly. Moreover, factors such as positive bile cultures, history of biliary attack, ASA score, diabetes, obesity, and smoking do not have any effect on SSI development. Thus, we conclude that antibiotic prophylaxis is not needed for elective LC.

Can Parathormon Levels after Ipsilateral Lobectomy Predict Postoperative Hypocalcemia in Patients Undergoing Total Thyroidectomy?

The purpose of this study was to investigate the relationship between the serum parathormone (PTH) levels measured after completion of hemithyroidectomy on the first side during total thyroidectomy and the postoperative hypocalcemia. The patients were divided into two groups, as those who demonstrated a decrease in PTH levels measured after completion of hemithyroidectomy of the first side (Group 1, n = 43) and those who did not demonstrate a decrease in PTH levels (Group 2, n = 24). The serum PTH levels were measured just before the incision (PTHi), when the hemithyroidectomy stage had been completed (PTHht), at the end of the operation (PTHtt), and at the postoperative 24th hour (PTH24hr). The serum total calcium (Ca2+) levels were also measured. The median percentage differences in PTHtt levels based on basal PTHi levels of Groups 1 and 2 were -60.6 and -15.7 per cent, respectively, P = 0.001. The frequency of postoperative biochemical hypocalcemia was higher in Group 1, P < 0.05. It was determined that a 10 per cent or higher decrease in PTHht levels in Group 1 could predict biochemical hypocalcemia at the postoperative 24th hour. In conclusions, postoperative hypocalcemia is seen more frequent in patients with a decrease of PTHht during total thyroidectomy. A decrease of 10 per cent in PTHht levels measured after ipsilateral lobectomy and a 62 per cent or higher decrease in PTHtt levels measured in the end of the total thyroidectomy could be helpful for prediction of postoperative hypocalcemia in these patients.

Immunohistochemical expression of CDX2, CK7, HER2 and HER4 in periampullary adenocarcinoma : implications for clinicopathology and patient outcomes.

Background: Periampullary carcinomas originate from the pancreatic head, the ampulla, the distal bile duct, or the duodenum. The expression of CK7 and CDX2 has been used in the classification of periampullary carcinomas. There is prognostic value of human epidermal growth factor receptor (HER) 2 and HER 4, which have been linked to poor prognosis in several types of tumors, such as breast and gastric carcinomas. We aimed to evaluate the expression and prognostic value of CDX2, CK7, HER 2, and HER4 in periampullary adenocarcinoma. Patients and Methods: We retrospectively selected 98 patients who had undergone pancreatoduodenectomy for periampullary adenocarcinoma at our pathology department. The tumor location, pathological subtype, involvement of vessels and lymph nodes, perineural invasion, clinical follow-up, and tumorstage were noted. Immunohistochemistry was performed for CK7, CDX2, HER2, and HER4. Results: CDX2 staining was predictive of perineural invasion. Additionally, there was a significant association between the overexpression of HER2 and HER4 and the presence of perineural invasion. HER4 was significantly positive in patients with the pancreatobiliary subtype compared with patients with the intestinal subtype. Patients with the pancreatobiliary subtype, lymph node involvement, and advanced pT and UICC stages had significantly lower median survival. Conclusion: Our findings suggest that only pancreatobiliary subtype, lymph node involvement and advanced pT and UICC stages were independent predictors of short survival, but the ampulla tumor location predicted a significantly better survival time. The immunohistochemical expression of CDX2, CK7, HER4, and HER2, vessel involvement, and perineural invasion were not associated with the survival of patients with periampullary adenocarcinoma.

Gender does not affect the prognosis of Fournier's gangrene: a case-matched study.

BACKGROUND: Female gender is accepted as a poor prognostic factor for Fournier's gangrene (FG). However, there is a paucity of data in the literature regarding this matter. This case-matched study was designed to investigate the impact of gender on outcomes of FG. METHODS: Study patient data were retrieved from 120-patient, prospectively maintained database. Thirty-two female patients with FG were case-matched to 32 male patients based on symptom duration (days), FG severity index score, patient age, etiology, and presence of diabetes mellitus (DM) terms. Outcomes of FG were compared between the 2 groups. RESULTS: Median age was 57 years (range: 22-80 years), and 35 (54.7%) patients had DM. Patients underwent average of 3 debridement procedures (range: 1-9 debridements), and 15 (23.4%) received diverting stoma. Overall mortality rate was 28.1% (18 of 64 patients). Female gender was associated with widespread disease (p=0.009), increased need for consecutive debridements (p=0.005), prolonged length of intensive care unit stay (p=0.035), and increased requirement for split-thickness skin graft reconstruction (p=0.040). However, mortality rates were comparable between genders (p=0.264). CONCLUSION: FG is often more extensive in females and seems to be associated with anatomical features of female pelvis. However, female gender is not a factor affecting prognosis of patients with FG.

Retrospective analysis of clinicopathological features of solid pseudopapillary neoplasm of the pancreas.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that accounts for 2-3% of all primary pancreatic neoplasms. This study aimed to characterize clinicopathological features associated with SPNs and to retrospectively evaluate the relationship of these features with predictive parameters associated with aggressive behavior. We reviewed 16 cases of SPN of the pancreas that had been diagnosed between 2005 and 2014 at our pathology department. A total of 16 cases, 15 female and one male, were evaluated in this study. The patient age ranged from 13 years to 63 years with a median of 35.70 years. The mean tumor diameter ranged from 2 cm to 18 cm with a mean diameter of 5.90 cm. We identified a significant association between the presence of clear cells and perineural invasion (p=0.019), which was considered to be a predictive factor for aggressive behavior. Other features (i.e., localization, nuclear grooves, central hyalinization, myxoid stroma, eosinophilic bodies, foamy histiocyte aggregates, multinucleated cells, and calcification) were not significantly associated with predictive factors for aggressive behavior. One patient died as a result of a pancreatic fistula that developed as a postoperative complication. The remaining 15 patients are alive and have not demonstrated any signs of recurrence or metastasis. The current study suggested that the presence of clear cells might serve as a possible prognostic indicator of perineural invasion, which is a predictive parameter associated with aggressive behavior in SPN.

miR-216b Targets FGFR1 and Confers Sensitivity to Radiotherapy in Pancreatic Ductal Adenocarcinoma Patients Without EGFR or KRAS Mutation.

OBJECTIVES: The success of gemcitabine plus radiotherapy is dependent on the mutation status of pancreatic ductal adenocarcinoma (PDAC) tumors in the EGFR and KRAS genes; however, radiotherapy resistance may also be modulated epigenetically by microRNA (miRNA) regulation. In this study, we examined the potential effect of miRNAs on the resistance to radiotherapy in cases without EGFR or KRAS mutation. METHODS: The association of EGFR and KRAS mutation status and different expression patterns of 6 selected miRNAs related to the EGFR/KRAS signaling pathway were evaluated in the tumors of 42 patients with PDAC. RESULTS: Reduced miR-216b and miR-217 expression was associated with aggressive tumor characteristics and shortened disease-free survival. In addition, miR-216b expression was reduced 2.7-fold in the cases that did not benefit from therapy, although they did not demonstrate EGFR or KRAS expression (P = 0.0316). A negative correlation between FGFR1 and miR-216b expression (r = -0.355) was found in the tumors of these cases. CONCLUSIONS: Further studies and validations are required; in the tumors of patients with PDAC without activating mutations and induced expression of EGFR/KRAS genes, down-regulated miR-216b expression may be associated with a poor response to radiotherapy via deregulation of another signaling pathway related to FGFR1 signaling.

Is stoma care effective in terms of morbidity in complicated ileostomies?

BACKGROUND: Performing transient or permanent ileostomy is one of the common procedures involved in colorectal surgery. Complication rates up to 40% have been reported in ileostomies. In this report, the effect of specific stoma care unit on ileostomy and its complications were investigated. METHODS: A total of 141 patients, who were operated and underwent ileostomy, due to different causes, at Department of General Surgery, Uludag University, Bursa, Turkey, between 2003 and 2006, were examined, retrospectively. Patient records were examined in terms of age, sex, surgery indications, urgent/elective state, benign/malign origin, ileostomy type, complications and stoma care, and education. χ(2) test was used to compare the categorical data. RESULTS: Among the patients, 95 (67%) were male and 46 (33%) were female. The mean age was 47 years (17-67). Some of the subjects (49%) were operated urgently and some (51%) were under elective conditions. The ileostomy types used included the following: end ileostomy (43%), loop ileostomy (46%), and double-barrel ileostomy (11%). Permanent ileostomy was performed in 23 patients and transient ileostomy was performed in 118 patients. The patients were operated because of either benign (48%) or malign (52%) causes. Complications developed in 37 (26%) patients. The rate of development of complication was markedly higher in ileostomies performed under urgent conditions (61% vs 39%) (P<0.001). The complications included mucocutaneous separation (12 patients), maceration in the peristomal skin (ten patients), retraction (five patients), necrosis (three patients), prolapsus (three patients), and other metabolic complications (four patients). The complications were treated with care (68%) and surgical revision (32%). CONCLUSION: The rate of ileostomy was found to be higher in the male patients compared to female patients. The risk of development of complications was found to be higher in ileostomies performed under urgent conditions. The most common complication observed was mucocutaneous separation. Ileostomy complications can be treated conservatively with professional care and education.

Factors Affecting Surgical Site Infection Rates in Hepatobiliary Surgery.

BACKGROUND: There are several studies regarding risk factors affecting surgical site infections (SSIs); nevertheless, there are an insufficient number of studies focusing on risk factors for SSI in hepatobiliary (HPB) surgery. In this study, we aimed to determine risk factors related to HPB surgery. METHODS: A total of 1,418 patients were included in this study, all of whom underwent hepatobiliary system surgery in a five-year period between January 2005 and December 2009. Demographic data, patient- and surgery-related risk factors, and laboratory parameters were analyzed retrospectively from a database maintained prospectively. RESULTS: The overall incidence of SSI was 3.94% for HPB surgery. In multivariable analysis, blood transfusion (OR: 20.9), the presence of surgical drains (OR: 10.7), a pre-operative hospital stay of more than eight days (OR: 8.1), diabetes mellitus (OR: 6.2), chronic obstructive pulmonary disease (OR: 6.127), inappropriate antimicrobial prophylaxis (OR: 6), obesity (OR: 3.2), the presence of an external-internal biliary drainage catheter (OR: 2), and a direct bilirubin concentrations more than 15 mg/dL (OR: 1.4) were determined as independent risk factors related to SSI. E.coli and Enterococcus spp. were the pathogens isolated most commonly in SSIs. CONCLUSIONS: Most of the independent risk factors for hepatobiliary system surgery are similar to those for other general abdominal surgical procedures. The presence of an external-internal biliary drainage catheter and direct bilirubin concentrations higher than 15 mg/dL were found to be specific risk factors for HPB surgery.

Jejunoduodenal intussusception caused by a solitary polyp in a woman with Peutz-Jeghers syndrome: a case report.

INTRODUCTION: Peutz-Jeghers syndrome is a rare autosomal dominant disorder characterized by hamartomatous polyps and characteristic mucocutaneous pigmentation. The hamartomatous polyps of Peutz-Jeghers syndrome can cause intestinal occlusion, especially in the small intestine. Intussusception is seen frequently in children, but rarely in adults. CASE PRESENTATION: We present the case of a 21-year-old female patient who was admitted to our emergency service with symptoms of ileus as a result of intussusception due to duodenal polyps. Radiological and endoscopic findings determined a jejunoduedonal intussusception. After an unsuccessful endoscopic attempt, a laparotomy was performed that revealed a polypoid mass originating from the fourth part of her duodenum, with intussusception of her proximal jejunum. CONCLUSION: Intussusception caused by Peutz-Jeghers syndrome is a rare diagnosis and is mostly jejunojejunal or jejunoileal. Despite the fact that a few duodenojejunal cases have been reported, this is to the best of our knowledge the first case of jejunoduedonal intussusception in a patient with Peutz-Jeghers syndrome to be described in the literature.

Gallbladder polyps: factors affecting surgical decision.

AIM: To determine the factors affecting the decision to perform surgery, and the efficiency of ultrasonography (USG) in detecting gallbladder polyps (GP). METHODS: Data for 138 patients who underwent cholecystectomy between 1996 and 2012 in our clinic with a diagnosis of GP were retrospectively analyzed. Demographic data, clinical presentation, principal symptoms, ultrasonographic and histopathological findings were evaluated. Patients were evaluated in individual groups according to the age of the patients (older or younger than 50 years old) and polyp size (bigger or smaller than 10 mm) and characteristics of the polyps (pseudopolyp or real polyps). χ(2) tests were used for the statistical evaluation of the data. RESULTS: The median age was 50 (26-85) years and 91 of patients were female. Of 138 patients who underwent cholecystectomy with GP diagnosis, only 99 had a histopathologically defined polyp; 77 of them had pseudopolyps and 22 had true polyps. Twenty-one patients had adenocarcinoma. Of these 21 patients, 11 were male, their median age was 61 (40-85) years and all malignant polyps had diameters > 10 mm (P < 0.0001). Of 138 patients in whom surgery were performed, 112 had ultrasonographic polyps with diameters < 10 mm. Of the other 26 patients who also had polyps with diameters > 10 mm, 22 had true polyps. The sensitivity of USG was 84.6% for polyps with diameters > 10 mm (P < 0.0001); however it was only 66% in polyps with diameters < 10 mm. CONCLUSION: The risk of malignancy was high in the patients over 50 years old who had single polyps with diameters > 10 mm.