Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology.

BACKGROUND: The management of sub-totally resected sporadic vestibular schwannoma (VS) may include observation, re-resection or irradiation. Identifying the optimal choice can be difficult due to the disease's variable progression rate. We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression. METHODS: We used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or non-progressing VS. RESULTS: Rapidly progressing VS was distinctly enriched in CD4+, CD8+, CD20+, and CD68+ immune cells. RNA data indicated the upregulation of anti-viral innate immune response and T-cell senescence. K - Top Scoring Pair analysis identified 6 pairs of immunosenescence-related genes (CD38-KDR, CD22-STAT5A, APCS-CXCR6, MADCAM1-MPL, IL6-NFATC3, and CXCL2-TLR6) that had high sensitivity (100%) and specificity (78%) for identifying rapid VS progression. CONCLUSION: Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS.

Advances in understanding cancer-associated neurogenesis and its implications on the neuroimmune axis in cancer.

Nerves and immunologic mediators play pivotal roles in body homeostasis by interacting with each other through diverse mechanisms. The spread of nerves in the tumor microenvironment increases tumor cell proliferation and disease progression, and this correlates with poor patient outcomes. The effects of sympathetic and parasympathetic nerves on cancer regulation are being investigated. Recent findings demonstrate the possibility of developing therapeutic strategies that target the tumor microenvironment and its components such as immune cells, neurotransmitters, and extracellular vesicles. Therefore, examining and understanding the mechanisms and pathways associated with the sympathetic and parasympathetic nervous systems, neurotransmitters, cancer-derived mediators and their interactions with the immune system in the tumor microenvironment may lead to the development of new cancer treatments. This review discusses the effects of nerve cells, immune cells, and cancer cells have on each other that regulate neurogenesis, cancer progression, and dissemination.

A new approach in bowel preparation before colonoscopy in patients with constipation: A prospective, randomized, investigator-blinded trial.

OBJECTIVE: Enema administration in the morning of routine colonoscopy is known to be useless. However, the potential bowel cleansing effects of distal colon emptying with enema prior to purgatives are not known. The aim of this study is to investigate the effects of enema use before purgatives in preparation for colonoscopy. MATERIAL AND METHODS: Two hundred twenty-seven patients were randomly assigned into three groups; enema before purgative use, enema after purgative use, and no enema. Patients were compared in terms of age, sex, BMI, Rome III constipation criteria, history of abdominal surgery, tolerance to the preparation procedure, complications during preparation such as nausea, vomiting, headache and dizziness, cecal insertion time, total duration of colonoscopy, polyp determination rate and colonic cleansing based on the Boston Bowel Preparation Scale. RESULTS: One hundred two (44.9%) patients were male and 125 (55.1%) female. The mean age and BMI was 55.4±11.8 years and 28.8±4.7, respectively. No difference was observed between the groups in terms of sex, age, or BMI. The number of fulfilled Rome criteria and of previous abdominal surgeries were significantly higher in females than in men. Right colon Boston Bowel Preparation Scale score was higher in the group using enemas before purgatives than the scores of other groups. This improvement was statistically significant in the female patient group with higher constipation rate. CONCLUSIONS: Use of enemas before purgatives in patients with constipation significantly improves adequacy of right colon cleansing.

Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells.

Therapy resistance and poor outcome in prostate cancer is associated with increased expression of cyclin D1. Androgens promote DNA double-strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclin D1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of γH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1 dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance.

Giant colon lipoma.

Colon lipomas are rare, non-epithelial tumors. They are generally smaller than two centimeters and asymptomatic, they are incidentally diagnosed and do not require treatment. Large and symptomatic colon lipomas are rather rare. Its differential diagnosis is generally made by histopathological examination of the resected specimen. A fifty-year-old female patient presented with the symptoms of abdominal pain, swelling in the abdomen and loss of weight. During colonoscopy, there was a submucosal mass of 8×6 cm, which almost completely obstructed the lumen in the hepatic flexure and was covered by a mucosa that was sporadically ulcerated and necrotic in nature. In magnetic resonance imaging, an ovoid mass with a diameter of 8.5 cm at its widest dimension was detected, which had signal intensity similar to that of adipose tissue. Since the patient was symptomatic and differential diagnosis could not be made, she underwent laparoscopic right hemicolectomy. A submucosal lipoma was detected on histopathological examination of the specimen. The patient was discharged without any problems on post-operative day 7. Definite diagnosis of lipomas before surgery is challenging; they may be mistaken for malignancy, especially if the lesion is large and ulcerated. For large and symptomatic colon lipomas, surgery is required to both prevent complications and rule out malignancy.

[Primary Pelvic Cystic Echinococcosis]. / Primer Pelvik Kistik Ekinokokkoz .

Cystic echinococcosis caused by Echinococcus granulosus is still an important health problem in endemic areas. Cystic echinococcosis may involve different organs or areas with the most common sites being the liver and the lungs. Pelvic involvement has previously been reported and was mainly accepted as secondary to cystic echinococcosis in other organs, isolated pelvic involvement is very rare. In this case report, we aimed to present the case with pelvic cystic mass that was finally diagnosed with isolated pelvic cystic echinococcosis in and after the operation, and we would like to draw attention to include "cystic echinococcosis" in the differential diagnosis of pelvic masses.

Ligation under vision in the management of symptomatic hemorrhoids: A preliminary experience.

AIM: To evaluate the surgical outcomes of 47 patients who underwent hemorrhoidal arterial ligation under vision (LUV) for symptomatic Grade II and Grade III hemorrhoids. METHODS: A total of 47 patients who underwent LUV between May 2005 and February 2009 were analyzed retrospectively. The patients were evaluated with regard to demographic data, grade of the disease, symptoms, medical and/or surgical treatment previously received, operation time, pain scores, analgesic requirement, length of hospital stay, and complications related to the procedure. RESULTS: The study population (n = 47) included 31 (65.9%) men and 16 (34.1%) women with a median age of 37.4 ± 11.7 (range, 19-63) years. Of these 47 patients, 18 (38.3%) patients had Grade II hemorrhoidal disease (HD) and 29 (61.7%) patients had Grade III HD. On average, six ligatures (range, 3-8) were used. The mean operation time was 27 ± 4.8 (range, 15-35) minutes. No major complication that required surgical intervention occurred in the early postoperative period for any of the patients except for two patients with rectal submucosal hematoma. The mean hospital stay was 1.2 ± 0.65 (range, 1-4) days. The median follow-up period was 21.5 ± 7.7 (range, 12-44) months. At the last follow-up, 38 (80.8%) patients remained asymptomatic; two (4.2%) patients with Grade II HD and four (8.5%) patients with Grade III HD were still suffering from bleeding but with a reduction in the frequency; prolapsed hemorrhoids were detected only in three (6.3%) patients. CONCLUSION: LUV is a safe and easily applied alternative technique with low postoperative complications for the surgical treatment of symptomatic Grade II and III HD.

Sirt1-deficient mice have hypogonadotropic hypogonadism due to defective GnRH neuronal migration.

Hypogonadatropic hypogonadism (HH) can be acquired through energy restriction or may be inherited as congenital hypogonadotropic hypogonadism and its anosmia-associated form, Kallmann's syndrome. Congenital hypogonadotropic hypogonadism is associated with mutations in a group of genes that impact fibroblast growth factor 8 (FGF8) function. The Sirt1 gene encodes a nicotinamide adenine dinucleotide-dependent histone deacetylase that links intracellular metabolic stress to gene expression. Herein Sirt1(-/-) mice are shown to have HH due to failed GnRH neuronal migration. Sirtuin-1 (Sirt1) catalytic function induces GnRH neuronal migration via binding and deacetylating cortactin. Sirt1 colocalized with cortactin in GnRH neurons in vitro. Sirt1 colocalization with cortactin was regulated in an FGF8/fibroblast growth factor receptor-1 dependent manner. The profound effect of Sirt1 on the hormonal status of Sirt1(-/-) mice, mediated via defective GnRH neuronal migration, links energy metabolism directly to the hypogonadal state. Sirt1-cortactin may serve as the distal transducer of neuronal migration mediated by the FGF8 synexpression group of genes that govern HH.

Symptomatic duodenal lipoma with endoscopic snare polypectomy.

Duodenal lipomas are extremely rare benign tumors. 90% arise from the submucosa and is usually localized in the second portion. They are usually asymptomatic and are detected incidentally during endoscopy or surgery. Appearance of symptoms are related to lesion size, those greater than four centimeters frequently may cause intussusception, obstruction or bleeding. A 59- year-old woman presented with complaints of abdominal fullness in the upper quadrants after meals, and heartburn symptoms. She had been under treatment for iron deficiency anemia during the last five months. The upper gastrointestinal endoscopy revealed a mobile, 4×2 cm polypoid mass extending from the second portion of the duodenum to the third portion, with a regular mucosa and wide pedicle. Saline and epinephrine was injected to polyp base and "snare" polypectomy was performed. Patient's complaint of fullness in the upper part of the abdomen declined after polypectomy and the treatment of anemia was discontinued after a month, with normal blood count values in the fourth month.

Effects of resveratrol on incisional wound healing in rats.

PURPOSE: The objective of this study was to investigate the effect of resveratrol on the healing process after midline laparotomy in rats. METHODS: The study was performed on adult female Wistar-Albino rats. The study group was orally administered 0.5 mg/kg resveratrol once a day for 7 days before the operation until 12 h before surgery and then the treatment was maintained throughout the study. Each rat was anesthetized, and a 4-cm midline laparotomy was performed. Ten animals in each group were sacrificed on postoperative days 7, and 14. A tensile strength analysis was performed, hydroxyproline levels were measured, and the abdominal incision wounds were examined histologically. RESULTS: Resveratrol administration significantly increased the tensile strength of the abdominal fascia, and increased the hydroxyproline levels on postoperative day 14. The acute inflammation scores, collagen deposition scores and the neovascularization scores on postoperative days 7 and 14 were found to be significantly higher in the resveratrol treatment group compared to the control group. The amount of granulation tissue and the fibroblast maturation scores were found to be significantly higher only on postoperative day 14 in the treatment group compared to the control group. CONCLUSION: Our findings show that resveratrol may have a beneficial effect on incisional wound healing.

Acute abdomen and hemorrhagic shock caused by spontaneous rupture of renal cyst in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is an important cause of end stage renal failure. Rarely, these patients may present with hemorrhagic shock caused by rupture of the renal cyst. The aim of this study was to report a rare case of a patient who arrived at the emergency department with autosomal dominant polycystic kidney disease presenting with acute abdominal pain and hemorrhagic shock. A 58-year-old male with chronic renal failure was admitted to the emergency department with acute abdominal pain and hemorrhagic shock. The patient was admitted to the Department of Surgery with diagnosis of acute abdomen and perirenal hematoma. Although the patient was on conservative treatment, his symptoms did not improve and the patient was operated emergently. During exploration, there was bleeding from the right polycystic kidney, which was 30×20 cm in dimension. The patient underwent nephrectomy and drainage of the hematoma, and was discharged on the fifth postoperative day without any problems. Bleeding due to rupture of a cyst in autosomal dominant polycystic kidney disease occurs rarely but it may be life threatening. Although conservative methods are often preferable in treatment, surgery can be life saving for patients in whom the clinical situation does not improve.

Simvastatin improves incisional wound healing in a rat model: an experimental study.

UNLABELLED:  This study investigated the effect of simvastatin on the heal- ing process of abdominal wall wounds in rats. METHODS: The study was performed with adult female Wistar-Albino rats. Control group (n = 20) rats were fed standard laboratory diet until 12 hours before sur- gery. Study group (n = 20) rats received oral simvastatin therapy with an orogastric tube (10 mg/kg once a day) for 7 days until 12 hours before surgery. Each rat was anesthetized, and a 4 cm-long midline laparotomy was performed. Ten animals from each group were killed at postoperative days (PODs) 7 and 14. Breaking strength analysis was measured, and the abdominal incision wounds were examined histolog- ically. RESULTS: Hydroxyproline levels and tensile strength of abdominal fascia were significantly higher in the study group on PODs 7 and 14 compared to the control group. The granulation tissue fibroblast matu- ration scores on POD 7, and both collagen deposition scores and neo- vascularization scores on PODs 7 and 14, were found to be statistically significantly higher in the simvastatin treatment group compared to the control group, based on the results of the histologic tissue examina- tions. CONCLUSION: Simvastatin can be used as a supporting therapy in wound healing. .

Prognostic Factors of Patients With Transmural Advanced Gastric Carcinoma.

BACKGROUND: The purpose of this study is to evaluate perioperative morbidity, mortality and the prognostic factors that influence survival of the patients with transmural advanced gastric carcinoma after curative surgical therapy. METHODS: Fifty patients with transmural advanced gastric adenocarcinoma underwent curative resection in our clinic. The records of the patients were reviewed and the prognostic factors such as age, gender, location and size of the tumor, type of surgery, blood transfusion, depth of tumor invasion, lymph node metastases, stage of the disease, grading, vascular invasion, lymph vessel invasion, characteristics of the tumor according to Lauren's classification, and lymph node ratio were evaluated by using statistical methods. RESULTS: In a total of 12 patients (24%) major morbidities developed, and five patients (10%) died. The overall survival rate was 48% at 1 year, 31% at 3 years, and 19% at 5 years. Lymph node metastases (P = 0.03), lymph vessel invasion (P = 0.001), blood transfusion (P = 0.021), and lymph node ratio (P = 0.006) were the prognostic features identified by univariate analysis. Among the multiple significant prognostic factors in the univariate analysis only one factor, lymph node ratio, proved to be independently significant in the multivariate analysis (RR: 4.47). CONCLUSIONS: Our data showed that we can expect a good survival for patients with a lymph node ratio less than 0.2.

Surgical treatment of hepatic injury: morbidity and mortality analysis of 109 cases.

BACKGROUND/AIMS: We aimed to determine the factors that affect morbidity and mortality in patients that underwent surgery for hepatic injury. METHODOLOGY: Records of 109 blunt or penetrating hepatic trauma patients that underwent surgery in the Third Surgical Clinic of Izmir Atattürk Training and Research Hospital between 1994 and 2004 were reviewed retrospectively. Evaluated parameters were: age, gender, cause of injury, diagnostic procedures, preoperative blood pressure (BP), hemoglobin (Hb) level, amount of intraabdominal blood, associated injuries, the number of involved hepatic segments and anatomic distribution, severity of injury, abdominal trauma index (ATI), amount of blood transfusions, type of surgery, hospital stay, and rates of morbidity and mortality. RESULTS: Median age of the patients was 29 years. The injury was penetrating in 53.2% of the patients and blunt in 46.8%. Abdominal blood was 500cc or less in 70 (64.2%) patients. Isolated hepatic injury was encountered in 29 (26.6%) cases. 22.9% of the patients had major injuries. Hemostasis was achieved by electrocautery, sponge-gel, primary suturing, hepatic resection or perihepatic packing. Morbidity and mortality rates were 40.4% and 14.6% respectively. CONCLUSIONS: Age, type of the injury, BP and Hb levels, amount of intraabdominal blood, degree of injury, ATI, and accompanying organ injuries significantly affect morbidity and/or mortality.

Survival analysis after surgical treatment of gastric cancer: review of 121 cases.

BACKGROUND/AIMS: This study was performed to evaluate major morbidity, early mortality and to analyze survival in our patients that underwent surgical treatment for gastric cancer. METHODOLOGY: Records of 121 patients with gastric adenocarcinoma that underwent surgery between 1997 and 2004 were reviewed retrospectively. Age, gender, tumor site, presence of local invasion, depth of tumor invasion, lymph node metastases, stage of the disease, distant metastases, histological differentiation, type of surgery, and blood transfusions were evaluated in relation to survival. Survival curves were estimated using the Kaplan-Meier method and the differences in survival were compared by the log-rank test. RESULTS: Forty-two cases (34.7%) underwent total gastrectomy, 34 (28.1%) had subtotal gastrectomy, and 45 (37.2%) received palliative surgery. The majority of the patients (61.2%) had stage IV gastric cancer. Total morbidity and mortality were 26.4% and 17.3%, respectively. The factors that influence survival were type of surgery, adjacent organ invasion, existence of metastases, lymph node status, blood transfusions, and stage of the disease in this study. Among the significant prognostic factors in the univariate analysis, only one factor, R0 resection proved to be independently significant in the multivariate analysis. CONCLUSIONS: R0 resection was found to have a significant favorable effect on survival in our study.

Palliative surgery for advanced stage (stage IV) gastric adenocarcinoma.

BACKGROUND/AIMS: The factors that effect resectability, major morbidity, early mortality, and survival in advanced stage gastric adenocarcinoma patients are evaluated. METHODOLOGY: Records of 74 patients that underwent surgery for stage IV gastric adenocarcinoma in the Third Surgical Clinic of Izmir Atatürk Training Hospital between January 1997 and January 2004 were reviewed retrospectively. Two groups (the patients with resectable disease and those with unresectable disease) were compared with regard to age, gender, primary complaint, symptoms, site of the tumor, involvement of adjacent organs, lymph node involvement, distant metastases, differentiation of tumor, surgical procedure, perioperative blood transfusions, and postoperative hospital stay. RESULTS: Mean age of the 74 patients was 58.4 years. Forty-five cases (60.8%) were considered as unresectable and 29 (39.2%) patients underwent a palliative resection. There was a significant relation between resectability and site of the tumor, and severity of invasion. As the number of perioperative blood transfusions increased, morbidity and mortality increased significantly. Although early mortality was high in the palliative resection group, survival (mean 10.4 months, longest 25 months) was better compared to that of the unresectable gastric cancer group (mean 3.5 months, longest eight months). CONCLUSIONS: A palliative gastric surgery may be applied to improve prognosis of advanced gastric cancer patients, even at the presence of peritoneal dissemination, hepatic metastases, N3 lymph node involvement, adjacent organ invasion, or poor differentiation of the tumor.