Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor.

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART. METHOD: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded. RESULTS: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro). CONCLUSION: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population.

Polycystic ovary syndrome (PCOS) is a frequent complex disorder with an ill-defined etiology. Genetic factors seem rather effective at the occurrence of the disease, however, the evidence of established various studies results are unsatisfied. We aimed to make a contribution to the genetic baseline of the disease by investigating melanocortin 3 receptor gene polymorphism in affected patients. 101 PCOS patients and 162 age-matched healthy volunteered control subjects recruited to the study. PCOS patients classified according to their BMI class and insulin resistance situation. Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed. Although no significant difference was observed in rs3827103 polymorphism between PCOS patients and controls; rs3746619 polymorphism was determined associated with PCOS in the heritage of dominant (AA + AC) and co-dominant (AA) genotypes. Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease.

Basal Serum Neurokinin B Levels in Differentiating Idiopathic Central Precocious Puberty from Premature Thelarche.

OBJECTIVE: To find out the diagnostic role of kisspeptin and neurokinin B in idiopathic central precocious puberty (ICPP) and premature thelarche (PT). METHODS: The girls who presented with early breast development before the age of 8 years were evaluated. Patients with intracranial pathologies were excluded. Basal and stimulated follicle-stimulating hormone/luteinizing hormone (LH) levels and basal neurokinin B/kisspeptin levels were measured. Patients who had peak value of LH >5 mIU/mL and a bone age (BA)/chronological age (CA) ratio >1.1 were diagnosed as central precocious puberty (CPP), while cases who did not meet these criteria were diagnosed as PT. Healthy age-matched prepubertal girls were included as the control group. RESULTS: The study group contained 25 girls with ICPP (7±0.8 years), 35 girls with PT (6.8±0.7 years), and 30 controls (6.7±0.7 years). Basal serum kisspeptin and neurokinin B levels were 2.36±0.47 ng/mL and 2.61±0.32 ng/mL, respectively in the ICPP group, 2.23±0.43 ng/mL and 2.24±0.23 ng/mL, respectively in the PT group, and 1.92±0.33 ng/mL and 2.03±0.24 ng/mL, respectively in the controls. Both kisspeptin and neurokinin B levels were higher in the ICPP and PT groups compared to controls (p<0.05). Moreover, basal neurokinin B level was different between ICPP and PT groups (p<0.01). A serum neurokinin B level of 2.42 ng/mL provided the most appropriate level to differentiate ICPP from PT, with a sensitivity of 84% and specificity of 77.1%. CONCLUSION: Differentiation of CPP from PT is sometime difficult, and there is a need for a simple method for the differential diagnosis. Our results suggest that basal serum neurokinin B level can be used as an adjunctive parameter to differentiate ICCP from PT.

A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycemic infant.

Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent hypoglycemia in the neonatal and infancy periods. Mutations in the ABCC8 and KCNJ11 genes, which encode subunits of the ATP-sensitive potassium channel in the pancreatic beta cell, are identified in approximately 50% of these patients. The first-line drug in the treatment of HH is diazoxide. Octreotide and glucagon can be used in patients who show no response to diazoxide. Nifedipine, a calcium-channel blocker, has been shown to be an effective treatment in a small number of patients with diazoxide-unresponsive HH. We report a HH patient with a homozygous ABCC8 mutation (p.W1339X) who underwent a near-total pancreatectomy at 2 months of age due to a lack of response to diazoxide and octreotide treatment. Severe hypoglycemic attacks continued following surgery, while the patient was being treated with octreotide. These attacks resolved when nifedipine was introduced. Whilst our patient responded well to nifedipine, the dosage could not be increased to 0.75 mg/kg/day due to development of hypotension, a reported side effect of this drug. Currently, our patient, now aged 4 years, is receiving a combination of nifedipine and octreotide treatment. He is under good control and shows no side effects. In conclusion, nifedipine treatment can be started in patients with HH who show a poor response to diazoxide and octreotide treatment.

Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report.

Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.

Metastatic lymph node ratio is an independent prognostic factor in gastric cancer.

BACKGROUND/AIMS: The metastatic status of the regional lymph node is the most significant prognostic factor for gastric cancer. However, diverse prognoses are evident even among the same N classifications of the current tumor-node-metastasis system. The aim of this study is to evaluate the prognostic significance of the ratio of metastatic to examined lymph nodes (N ratio) for identifying a high-risk subgroup of patients with gastric cancer. METHODOLOGY: The postoperative survival of 264 consecutive patients with operable gastric cancer was analyzed with regard to its N ratio and current N classification. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: The lymph node ratio was classified as follows N ratio 1, 1 to 10, N ratio 2, 11 to 25; and N ratio 3, >25. The 5-year survival rates stratified by N ratio were N ratio 1, 81%; N ratio 2, 49%; N ratio 3, 25%. The rates of survival were significantly different according to the N ratio in pN1 and pN2 classification of the UICC/TNM classification (p<0.05). Cox regression analysis revealed that N ratio was sensitive prognostic factor in these surgically treated patients, which were also significantly correlated with extent of lymph node dissection and pathologic tumor stage (p<0.05). CONCLUSIONS: N ratio can be recommended as an applicable parameter for lymph node involvement of gastric cancer. It is a more effective and precise indicator for prognostic stratification of patients with lymph node positive gastric cancer than the current N classification of the tumor-node-metastasis system.

Impact of laparoscopic surgery on bladder and sexual function after total mesorectal excision for rectal cancer.

BACKGROUND: Bladder and sexual dysfunction are well-documented complications of rectal cancer surgery. This study aimed to determine whether laparoscopy can improve the outcome of these dysfunctions or not. METHODS: The study included 63 of the 116 patients who underwent surgery for rectal cancer between 2002 and 2006. Bladder and male sexual function were studied by means of a questionnaire on the basis of the International Prostatic Symptom Score (IPSS) and International Index of Erectile Function (IIEF). In addition, bladder function was determined by means of postvoid residual urine measurement and uroflowmetry. Postoperative functions were compared with the preoperative data to detect subjective functional deterioration. Outcomes were compared between patients who underwent open (group 1, n = 29) and laparoscopic (group 2, n = 34) total mesorectal excision. RESULTS: Only minor disturbances of bladder function were reported for one patient (3%) in group 1 and three patients (9%) in group 2 (p > 0.05). Impotency after surgery was experienced by 6 of 17 preoperatively sexually active males (29%) in group 1 and 1 of 18 males (5%) in group 2 (p = 0.04). Similarly, 5 of 10 women (50 %) in group 1 and 1 of 14 women (7%) in group 2 felt that their overall level of sexual function had decreased as a result of surgery (p = 0.03). CONCLUSIONS: Open rectal cancer resection is associated with a higher rate of sexual dysfunction, but not bladder dysfunction, compared with laparoscopic surgery. Laparoscopic rectal cancer surgery offers a significant advantage with regard to preservation of postoperative sexual function and constitutes a true advance in rectal cancer surgery compared with the open technique. The proposed advantages can be attributed to improvement in visibility by the magnification feature of laparoscopic surgery.

Histopathological comparison of topical therapy modalities for acute radiation proctitis in an experimental rat model.

AIM: To evaluate the prevalent topical therapeutic modalities available for the treatment of acute radiation proctitis compared to formalin. METHODS: A total of 120 rats were used. Four groups (n = 30) were analyzed with one group for each of the following applied therapy modalities: control, mesalazine, formalin, betamethasone, and misoprostol. A single fraction of 17.5 Gy was delivered to each rat. The rats in control group rats were given saline, and the rats in the other three groups received appropriate enemas twice a day beginning on the first day after the irradiation until the day of euthanasia. On d 5, 10, and 15, ten rats from each group were euthanized and a pathologist who was unaware of treatment assignment examined the rectums using a scoring system. RESULTS: The histopathologic scores for surface epithelium, glands (crypts) and lamina propria stroma of the rectums reached their maximum level on d 10. The control and formalin groups had the highest and mesalazine had the lowest, respectively on d 10. On the 15th d, mesalazine, betamethasone, and misoprostol had the lowest scores of betamethasone. CONCLUSION: Mesalazine, betamethasone, and misoprostol are the best topical agents for radiation proctitis and formalin has an inflammatory effect and should not be used.

Malignant phyllode tumor metastatic to the duodenum.

Phyllode tumor (PT) is extremely rare tumor of the breast. Distant metastasis occurs in 10%-20% of patients with malignant phyllode tumor. The most common sites of metastases are the lungs and bones. Although theoretically any organ may have metastasis, an isolated duodenum metastasis has not been documented as yet in the English-language literature. We report herein a case with a isolated duodenal metastasis from PT of breast in a 31 year-old-woman who underwent right mastectomy 4 years before because of the recurrent malignant PT. She presented to our hospital with massive upper gastrointestinal bleeding. Clinical evaluation revealed a huge mass originated from duodenum. Urgent laparotomy and pancreaticoduodenectomy were carried out in order to remove the bleeding duodenal mass. The pathologic examination of the resected specimen showed a malignant spindle cell tumor consistent with metastatic malignant PT. Our case of gastrointestinal bleeding due to an isolated duodenal metastasis as a result of hematogenous spread from malignant phyllode tumor of breast is unique in the English literature and pancreaticoduodenectomy is a curative treatment for patients with isolated duodenal involvement.

Does the early ligation of the splenic artery reduce hemorrhage during laparoscopic splenectomy?

The aim of this study was to investigate whether early ligation of the splenic artery before splenic lysis has an effect on the amount of intraoperative bleeding and conversion rate during laparoscopic splenectomy. Laparoscopic splenectomy was performed in 34 patients with hematological diseases or splenic cysts between January 1993 and January 2003. The splenic artery was ligated before manipulation of the spleen in 22 patients (group 1) and laparoscopic splenectomy was performed with no previous ligation of the splenic artery in 12 patients (group 2). Prospective data was collected and the groups compared regarding intraoperative blood loss, platelet count, operative time, hospital stay, and conversion rate. Laparoscopic splenectomy was successfully completed in 30 (88%) patients. One patient in group 1 (5%) and 3 patients in group 2 (25%) required conversion due to bleeding. Estimated average blood loss was 161 mL (range 70-450 mL) in group 1, and 292 mL (range 100-700 mL) in group 2 (P < 0.001). The average operative time was 140 minutes (range 80-240) in group 1, and 155 minutes (range 80-200) in group 2 (P > 0.05). There were no statistically significant differences between the two groups comparing splenic size, conversion rate, hospital length of stay and platelet count. Early ligation of the splenic artery is feasible, safe and effective and may provide easy dissection and manipulation of the spleen during laparoscopic splenectomy with decreased intraoperative blood loss and no extension of the operative time.

Does the complication rate increase in laparoscopic cholecystectomy for acute cholecystitis?

BACKGROUND: Laparoscopic cholecystectomy (LC) has replaced open cholecystectomy for the treatment of gallbladder disease. Despite the well-accepted success of LC in chronic cholecystitis, the efficacy of this technique has been subject to some debate in acute cholecystitis (AC). This study was designed to evaluate our institution's experience with LC for AC and chronic symptomatic calculous cholecystitis (CC), based on complication and conversion rates to open surgery. PATIENTS AND METHODS: The records of 1158 patients with LC from September 1991 to December 2001 were analyzed. The parameters of age, gender, early and late complication rates, and conversion rates from LC to open cholecystectomy were compared in patients with AC and CC. RESULTS: During the study period, LC was performed in 1158 patients. Of these, 162 patients had AC (group 1) and 996 patients had CC (group 2). The conversion rates were 4.3% (7/162) in group 1 and 2.4% (24/996) in group 2. The complication rates were not significantly different (5.6% in group 1, 5.1% in group 2, P > 0.05). Difficulty in dissection around Calot's triangle and obscure anatomy were the main reasons for conversion to conventional open surgery. The mortality rate was 1.2% in group 1 and 0.01% in group 2. CONCLUSION: LC appears to be a reliable, safe, and effective treatment modality for AC and CC. The surgical approach should be performed carefully because of the spectrum of potential hazards of the laparoscopic procedure. Conversion and complication rates are similar in both AC and CC groups, and improve as surgeons gain experience.