Phenotypic spectrum and hormonal profile in hypogonadotropic hypogonadism.

BACKGROUND: Hypogonadotropic hypogonadism (HH) is characterized by inappropriately low serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulated hormone) in the setting of hypogonadism. A number of pathologic processes cause Hypogonadotropic hypogonadism but it can also occur as a part of various congenital syndromes. Objectives. To characterize the morphotypes and the hormonal profile of the HH patients enrolled in the COST Action BM1105 within "C.I. Parhon" National Institute of Endocrinology from May 2012 onward. Methods. The eligible patients were selected by using a general protocol that included: a detailed familial and personal history; a clinical evaluation focusing on genital development; a hormonal evaluation that aimed to exclude the acquired causes of HH and to characterize the basal/stimulated (triptoreline) profile of gonadotropins; a DNA extraction for genetic studies. RESULTS: We examinated the medical records of patients admitted in our institute with the diagnosis of hypogonadotropic hypogonadism from May 2012 onward. There were 19 patients: 12 males and 7 females, age at diagnosis 28.03 ± 11.45 years (13.4-56 years). The phenotypic expressions were variable and the hormonal evaluation showed low values of basal and stimulated gonadotropins. CONCLUSIONS: Although hypogonadotropic hypogonadism is a rare disease, the monospeciality profile of National Institute of Endocrinology enable the enrolment of a high number of patients in order to create clinical guidelines for evaluation/diagnosis and for treating GnRH deficient patients.

Prognostic significance of KRAS gene mutations in colorectal cancer--preliminary study.

OBJECTIVE: The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Retrospective study involving 58 patients diagnosed with CRC and treated between 2003 and 2010 in the General and Esophageal Surgery Clinic of "Sf. Maria" Hospital, Bucharest. The macroscopic and microscopic examination of the resected specimens was also processed for genetic analysis in NIRDPBS, where KRAS status was determined by using two methods: PCR-RFLP and pyrosequencing. RESULTS: The clinical and biological parameters of the patients were assessed for 72 months in average. A relapse in 21 patients and a 5-year survival rate of 79.3% was discovered. The genetic analyses of KRAS gene found mutations in 22 cases (45.3%): 17 cases had mutations in codon 12, 5 cases in codon 13. The survival rate analyses of patients with wild KRAS gene compared with the patients carrying the mutation on codon 12 /13 revealed a superposition of the survival curve. The statistical analysis based on the TNM stage revealed different survival curves in stage I and II, shorter survival period in patients with KRAS mutation on codon 13 than in those with wild type gene (stage I--p_value=0.015; stage II--p_value=0.000). CONCLUSIONS: It was not found that KRAS gene status had any prognostic significance. Nevertheless, for stage I and II patients, the mutation found on codon 13 determined a statistic significant shorter survival rate than for those with wild type. The results obtained by using the pyrosequencing method for the determination of KRAS gene status proved that it represented a reliable and reproducible method.

Therapeutic strategies in colonic cancer.

Colonic cancer is the most common malignancy of the digestive tract, representing 13% of all malignancies. The aim of the study is to evaluate the current therapeutic strategy in patients with CC. Mortality from the disease is declining in many Western countries; this may be the result of screening for CC, resection of adenomas, early detection of tumoral lesions and the use of individualized therapeutic strategies. The multimodal treatment of the disease includes different sequences such as: surgery, chemotherapy, radiotherapy,immunotherapy. Current advances in the research of mechanisms of carcinogenesis in CC make it possible to use genetic information in order to establish the prognostic and predictive factors for selecting the patients for individualized therapy. The current methods of CC evaluation allow the planning of individualized therapeutic strategies, which would lead to optimal results.

Solitary ganglioneuromatosis of the descending colon, presenting as giant retroperitoneal tumour.

Ganglioneuroma (GN) is a benign neoplasia of the autonomous nervous system, colonic GN is uncommon in adults. There are three subgroups: polypoid GN, ganglioneuromatous polyposis and diffuse ganglioneuromatosis. Ganglioneuromatosis is highly-associated to neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2b (MEN2B). A 68-year-old female, with a discrete retarded emission of stools, was admitted for a large tumor in the left flank; CT scan, urography and barium enema demonstrated a large retroperitoneal mass, presumed as sarcoma. Open surgery discovered a 16 10 11 cm solid and encapsulated tumor, attached to the retroperitoneal descending colon, with no macroscopic mucosal involvement; the pathologic diagnosis of the resected specimen (en-bloc tumorectomy with limited colectomy) was intramural colonic ganglio-neuromatosis. Anamnesis, physical examination and complete endoscopic explorations showed no evidence of personal bearing or familial aggregation of genetic syndromes. In adults, association of transmural ganglioneuromatosis to NF1 or MEN2B is not mandatory; presentation often mimics obstructive carcinoma and positive diagnosis is provided by pathological examination of the resected specimen. In this peculiar case, the loose tissue of the retroperitoneal space favoured a slow development of intramural ganglioneuromatosis, presenting as a gigantic retroperitoneal mass with no radiological evidence of its colonic origin.

Association of common genetic variants with colorectal cancer risk in a Romanian sample.

Recently, several genome-wide association studies identified and validated loci at which common genetic variants influence the risk of colorectal cancer. We aimed to test the association between eight SNPs and colorectal cancer in a Romanian case-control sample. We genotyped rs10795668, rs16892766, rs3802842, rs4444235, rs4779584, rs4939827, rs6983267, and rs9929218 and we statistically tested the association with the disease. Five SNPs (rs6983267, rs4939827, rs3802842, rs4444235, rs10795668) showed an association with colon and rectal cancer. Three of them proved to be statistically significant: rs6983267 and rs4939827 risk alleles were significantly associated with rectal cancers (p = 0.031 and p = 0.004 for homozygous, p = 0.002 and p = 0.005 for heterozygous). For rs3802842 we found a greater risk for colon than rectal cancer with an OR of 2.26 (CI = 1.04-5.88, p = 0.040) for the dominant model. The rs4444235 confirmed the risk for both homozygous and heterozygous carriers, with the greatest ORs of 1.49 (CI = 0.61-3.61) for heterozygote. For rs10795668 we found an increased risk for rectum cancer vs. controls with an OR of 1.46 (CI = 0.66-3.21), and for rectum cancer vs. colon cancer (OR = 2.19; CI = 0.87-5.55). This is the first Romanian study that confirms previously-identified associations with colorectal cancer risk for five out of eight SNPs investigated and underlines the necessity of extensive replication using larger samples.

[Roux-en-Y gastrojejunostomy: indications, technique, results]. / Rezectia gastrica cu gastrojejunostomie à la Roux-indicatii, tehnica, rezultate.

61 gastrojejunostomies were constructed between 1981-1999 in 58 cases (43 cases were operated between 1991-1999). 30 cases have previously suffered various gastric operations; in 28 cases the Roux-en-Y was the first gastric operation (27 operated on between 1991-1999). Radiologic and endobioptic studies were routine for diagnostic and follow-up evaluation, but various scintigraphic studies were performed in selected cases. The surgical technique was tailored for each case, according to the preoperative strategy. The indications for surgery were the following: 19-reflux disease; 14-severe peptic disease (9-reccurence, 3-postbulbar lesion, 2-juxtacardial ulcer); 8-peptic disease associated to reflux disease; 8-gastric cancer; 8-various early or late complications after gastrectomy; 1-lymphocytic gastritis. There were 4 early reoperations and 3 deceased. In 3 cases late reintervention was mandatory (for Zollinger-Ellison syndrome, peptic ulcer secondary to gastrectomy for cancer, Roux-stasis syndrome) and the Roux pattern was preserved; in 2 cases the antireflux effect of the operation was lost after the reoperation.

[Long-term evolution of a T-tube in the common bile duct]. / Evolutia pe termen lung a tubului Kehr în calea biliara principala.

We present the case of an elderly and frail woman, admitted for obstructive jaundice 9 years after cholecystectomy, lithotomy and T-tube drainage. The presence of a T-tube remnant in the common bile duct was suggested by imaging techniques, along with a megacholedocus. Because of the risks associated with advanced biliary cirrhosis, the endoscopic retrieval and lithotripsy was the first therapeutical attempt but failed. Lithotomy and cholangio-jejunostomy by open surgery were followed by a surprising favourable course.

[Total duodenal diversion in hiatal hernia with pathological duodenoesophageal reflux (preliminary results)]. / Diversie duodenala totala în hernia hiatala cu reflux duodenoesofagian patologic (rezultate preliminare).

For some patients, reflux disease means also duodenogastric, as well as gastroesophageal reflux; they may suffer because of duodenoesophageal reflux. For these patients, a simple surgical restoration of the cardial competence may prove to be insufficient; on the contrary, an indirect approach, using vagotomy and duodenal diversion may be a good therapeutical option in selected cases. In our hands, total duodenal diversion has already proven to be a good technical solution for the surgical treatment of the postoperative reflux disease, so we decided to expand its first choice indications to hiatal hernia cases, in the presence of duodenoesophageal reflux. Therefore, our study presents the results of the first 7 cases, operated on since 1995. No case had been gastric operated before, but 4/7 had already suffered a cholecystectomy. Duodenoesophageal reflux is discussed: etiopathogenesis related to surgical approach, using standard antireflux surgery (failures of the hiatal techniques and their causes) or total duodenal diversion (technical aspects, antireflux efficiency, secondary functional effects, pros and cons, therapeutical indications).

[Clinical and therapeutic considerations in pseudomyxoma peritonei]. / Consideratii clinice si terapeutice despre pseudomixomul peritoneal.

Pseudomyxoma peritonei (PMP) is an uncommon clinical entity, lacking a precisely defined etiopathogenesis. Its clinical features are not specific and diagnosis is difficult. We analysed 10 patients, all of them women, whom we had treated surgically in combination with intraperitoneal chemotherapy. Postoperative complications had been minimal and no death had occurred. 5 patients were followed up in time, 4 of them presenting a favourable evolution (2 required reintervention), and 1 patient decreased. We analysed up-to-date therapeutic approaches and the benefit of their combinations in order to identify the optimal therapeutic strategy. We consider that the combinations surgery + intraperitoneal chemotherapy or surgery + intracavitary radiotherapy are the most effective up to date.

[Motility deficits in Roux-loop gastrojejunal reconstruction after the surgical treatment of reflux diseases (the Roux stasis syndrome)]. / Deficite ale motricitatii montajului gastrojejunal pe ansa Roux dupa tratamentul chirurgical al bolii de reflux (sindromul de staza Roux).

Motor disorders due to Roux-en-Y gastrojejunostomy are not uncommon, although not yet fully explained. Facing Roux stasis syndrome in patients who underwent Roux-en-Y diversion for secondary reflux pathology, we decided to study the motoric outcome of all 28 cases operated on for benign conditions in 1981-1996. We were interested only in motility disturbance related to our surgical act, so other therapeutic results were neglected. Since we could not perform manometric research and scintigraphic clearance was performed only in selected cases, our study was mainly clinical and based on radiology. There was no late stasis symptomatology in 19 patients operated for non-reflux pathology, but one third of refluxers developed Roux stasis syndrome, occasionally revisional surgery was performed.

[Functional recovery in strabismus]. / Recuperarea functionala în strabism.

The paper enumerates the objectives of functional recovery in strabismus and the approaches to the achievement of these objectives. The goal in the treatment of the strabismus is obtaining a binocular sight with the remake of the divergence-convergence synergism. A three stage scheme for the treatment is made: 1st stage--the treatment of the amblyopia; 2nd stage--the correction of the strabismus deviation; 3rd stage--the recovery of the binocular sight. The conclusion is that the healing of the strabismus with "restitutio ad integrum" is a distant desire.