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Biomedical subjects

V Herlea

Publications and source records attributed to V Herlea.

At least 19 recordsLinked to original sources

Recurrent atrial myxoma.

We have chosen this case of sporadic atrial myxoma for our presentation because it had a particular evolution, with recurrence at 8 years after surgical excision (echocardiography was performed every year) and a particular diagnostic means - at echocardiographic follow-up, the patient being asymptomatic. This presentation, together with a review of literature included in the article, emphasizes the importance of a careful postoperative follow-up of the patients and the existence of some particular aspects of the evolution and symptomatology of recurrent atrial myxoma.

Echocardiography↗

Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype.

BACKGROUND: Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). METHODS: We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFbeta1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. RESULTS: BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGFbeta1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. CONCLUSIONS: BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors.

Adenosine Triphosphatases↗

Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes.

Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs) of 6 genes: TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR, and BLM. The following frequencies of mutations were detected: TGFbetaRII (70%), BAX (54%), hMSH3 (36.5%), IGFIIR (22%), hMSH6 (17.5%), and BLM (16%). The overall picture revealed combinations of mutations suggestive of a progressive order of accumulation, with mutations of TGFbetaRII and BAX first, followed by frameshifts in hMSH3, hMSH6, IGFIIR, and BLM. Correlations with 12 clinico-pathological parameters revealed that tumors with frameshifts in 1 or 2 CDRs were significantly better differentiated than tumors with frameshifts in more than 2 CDRs. We also found that mutations in the hMSH3 gene were significantly associated with decreased wall invasiveness and aneuploidy, and frameshifts in the BLM gene were significantly associated with the mucinous histotype. A trend toward an association between hMSH3 and IGFIIR with the medullary and conventional adenocarcinoma histotypes, respectively, was seen. Our results strengthen the concept that mutations in target genes have a role in the tumorigenic process of MSI-H tumors, and indicate that frameshifts in microsatellites located in CDRs occur in a limited number of combinations that could determine distinct clinico-pathological traits.

Adenosine Triphosphatases↗

Use of a repetitive mouse B2 element to identify transplanted mouse cells in mouse-chick chimeras.

Monitoring the migrations of cells during embryonic development requires a system in which cells can be identified in situ during locomotion. One promising system involves the generation of chimeras by transplanting mouse cells into chick embryos in ovo to exploit the wealth of mouse genetic variants. The success of this technique relies on the ability to detect individual mouse cells in a chick environment with high specificity. The murine B2 family of short interspersed elements is present in the mouse genome at copy numbers in excess of 10(5), whereas this sequence is absent in the chick genome based on hybridization techniques. This differential of five orders of magnitude produces signals in mouse cells that are easily identified, even in an environment that is predominantly chick. Thus, the B2 repeat probe is highly effective for the purpose of identifying mouse cells in mouse-chick chimeras.

Animals↗

The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors.

Microsatellite instability (MSI) characterizes the hereditary nonpolyposis colorectal cancer syndrome but is also found in sporadic tumors. Frameshifts in microsatellites found in the coding regions (CDRs) of the TGFbeta1-RII, IGFIIR, hMSH3, hMSH6, and BAX genes indicate that MSI is involved in tumorigenesis by targeting genes that are directly implicated in the tumorigenic process. To identify additional genes targeted for MSI, we performed an analysis of the GenBank database that revealed 21 microsatellite repeats located in the CDR of 18 genes (12% of the analyzed sequences) whose function could be potentially associated with the tumorigenic process. Mutational studies of 57 sporadic gastrointestinal tumor DNAs revealed the presence of length variations in three of them: (a) BLM; (b) CBL; and (c) HOXA1. In the BLM gene, we found a frameshift mutation in a polyadenine repeat, whereas in the CBL proto-oncogene, an expansion of a trinucleotide repeat was detected with no translation shift. These alterations were present in 18 and 9%, respectively, of the genetically unstable sporadic gastrointestinal tumors analyzed, but in none of the cancers without the mutator phenotype. These changes were present in the DNA from the tumor but not in that from normal cells of the same patient. The HOXA1 retraction of a trinucleotide repeat was as frequent in both types of cancers and was also found in some normal paired tissues, therefore behaving as a neutral polymorphism. Our data extend the spectrum of unstable microsatellites located in gene CDRs and suggest that BLM and possibly CBL are involved in gastrointestinal tumorigenesis. Based on its proposed function, the BLM gene could represent a link between MSI and chromosomal instability pathways, because MSI targeting of the BLM gene could generate hypermutability and/or chromosomal instability.

Adenosine Triphosphatases↗

Endotoxin translocation in two models of experimental acute pancreatitis.

To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the distal bilio-pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut-derived endotoxin to the mesenteric lymph nodes, liver and lung.

Animals↗

[Liver transplantation--considerations over 8 cases operated in the year 2000].

In the year 2000, at the Department for General Surgery and Liver Transplantation from The Fundeni Clinical Institute Bucharest, seven OLTs and one living-related transplantation were performed in 6 adults and 2 children. Postoperative complications were: bile leakage, hemoperitoneum, lower gastrointestinal hemorrhage, parietoabdominal hematoma. There was only one postoperative death due to septic complications in the 18th p.o.d. and one late death due to pneumonia of unknown origin. After the results in the year 2000 there was an increased number of donors and referrals. We consider that now in Romania this is an established program that will continue depending on the number of donors and financing.

Adult↗

[Periampullary carcinoma or tumor of the ampulla of Vater?].

The term periampullary carcinoma is widespread in the medical literature. This is a consequence of the difficulty to establish the histogenesis of the tumor. The question is open if the tissular origin of the mass can be established after an accurate pathological examination and if the effort to distinguish between the so called "periampullary tumors" originating in the pancreatic tissue and those of a biliary, ampullary, duodenal or papillary origin can be useful; if there are significant differences among clinical signs, surgical approach and prognosis of these two sub-classes of "periampullary carcinomas". Between 1990 and 1998 54 patients were operated with the operative diagnosis of periampullary carcinoma in our department. In 35 cases a resection was performed. This 35 operative specimens were retrospectively analysed (operative protocols, macroscopical description of the resected specimens, reevaluation of the slides and new sections from the parafin blocks). Same macroscopic pathological features of the tumors were taken into consideration as suggestive for the pancreatic origin as the concentric development. On the contrary, the infiltrative and exofitic aspects were considered signs for a biliary respectively duodenal origin. The microscopic examination showed 32 adenocarcinoma and 3 undifferentiated carcinomas. In 9 cases a squamous metaplasia, in 22 cases the microscopic invasion of the duodenal wall and in 8 the invasion of the pancreas tissue were present. In 6 cases we found lymph nodes metastasis. The ductal pattern and the squamous metaplasia are suggestive for a pancreatic histogenesis. The papillary proliferation is more characteristic for a biliary or a duodenal origin. After this retrospective analysis we were able to establish the histologic origin of the tumor as follows: 11 with biliary origin, 10 with pancreatic origin and in 14 cases the diagnosis remains "periampullary carcinoma". The term periampullary carcinoma is not a well defined pathological entity. It seems to be an expression of the impossibility to define more accurate the origin of these tumors. Until now, the term remains still useful. However it is reasonable and useful to make the effort to limit such an imprecise diagnosis and to specify the pancreatic, biliary or duodenal histogenesis of the tumor. According to our data as well as to other authors, this accuracy is beneficial for the therapeutic strategy.

Adenocarcinoma↗

[Central hepatectomy].

Central hepatectomy (CH) is a major liver resection that removes Couinaud's segments IV, V and VIII, indicated for centrally located lesions and designed to preserve functional parenchyma and prevent liver failure. During an 8-year period between January 1995-November 2002, 507 liver resections were performed in Fundeni Center of General Surgery and Liver Transplantation (Bucharest). There were three CH performed for colorectal metastases (1 case) and inflammatory pseudotumor (2 cases). The mean duration of the procedure and the mean blood loss were, respectively, 231 minutes and 915 ml. The patients had a good post-operative course, with only minor complications.

Adolescent↗

An unusual metastasis of a papillary thyroidian carcinoma with follicular pattern.

The case of a 67-year-old man is presented. He was admitted for the presence of a left parietal tumour with progressive growing, without any other objective or subjective symptomatology. CT-scan detects a left parietal osteolytic area. The histopathological aspect suggested an adenocarcinomatous metastasis with papillary pattern, moderately differentiated. With the purpose of diagnosing the original tumour, immunnohistochemical techniques were performed, which led to a diagnosis of a thyroidian carcinoma. At the histological examination of the surgical extirpated thyroid, it was proved to be a papillary carcinoma (Chan, 1990, Hay, 1990), the follicular pattern.

Adenocarcinoma, Follicular↗

[Upper digestive haemorrhage of a rare cause: benign duodenal schwannoma].

The upper gastrointestinal bleeding is a common cause of admission to hospital. Neurogenic tumors of the duodenum are extremely rare and represent an unusual cause of gastrointestinal hemorrhage. The treatment is endoscopic or surgical total excision. In case of ulcerated large tumors situated periampullary pancreaticoduodenectomy (Whipple's or Traverso-Longmire's) represents an efficient solution. In addition, their high index of malignancy justifies this trend. We present a case of schwannoma of the second portion of the duodenum with several episodes of upper GI bleeding treated by Trasverso-Longmire pancreaticoduodenectomy.

Duodenal Neoplasms↗

[Orthotopic liver transplantation in adult patients with cadaveric grafts. Experience of the Fundeni Center of General Surgery and Liver Transplantation].

We analyze the experience of the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest, Romania) regarding orthotopic liver transplantation (OLT) in adult recipients, with whole liver grafts from cadaveric donors, between April 2000 (when the first successful LT was performed in Romania) and December 2004. This series includes 37 OLTs in adult recipients (16 women and 21 men, aged between 29-57 years--average 46 years). Other two LT with whole liver cadaveric grafts and two reduced-size LT were performed in children; also, in the same period, due to the acute organ shortage, other methods of LT were performed in 28 patients (21 living donor LT, 6 split LT and one "do mino" LT), that were not included in the present series. The indications for OLT were HBV cirrhosis--10, HBV+HDV cirrhosis--4, HCV cirrhosis--11, HBV+HCV cirrhosis--2, biliary cirrhosis--5, Wilson disease--2, alcoholic cirrhosis--1, non-alcoholic liver disease--1, autoimmune cirrhosis--1. With three exceptions, in which the classical transplantation technique was used, the liver was grafted following the technique described by Belghiti. Local postoperative complications occurred in 15 patients (41%) and general complications in 17 (46%); late complications were registered in 18 patients (49%) and recurrence of the initial disease in 6 patients (16%). Intrao- and postoperative mortality was 8% (3/37). There were two patients (5%) who died because of immunosuppressive drug neurotoxicity at more than 30 days following LT. Four patients (11%) died lately because of PTLD, liver venoocclusive disease, recurrent autoimmune hepatitis and liver venoocclusive disease, myocardial infarction, respectively. Thirty-four patients survived the postoperative period (92%); according to Kaplan-Meier analysis, actuarial patient-survival rate at month 31 was 75%.

Adult↗

A rare indication for liver resection.

We present the rare case of a young female with a right upper abdomen tumoral mass and suffering abdominal discomfort. A combination of ultrasonography, computed tomography, magnetic resonance imaging and laparotomy was utilized to conclude a diagnosis of Riedel's lobe. Laparotomy and a resection of Riedel's lobe were selected as the correct therapeutic solutions.

Adolescent↗

[Pancreatic carcinoma with osteoclast-like giant cell tumor and portal vein fistula].

Osteoclast-like giant cell tumor of the pancreas (OGTP) is a rare neoplasm. We report a case of OGTP involving the head of the pancreas in a 64 year old woman with an uncommon complication--portal vein fistula. We present the diagnostic strategy and therapy. Postoperative outcome after Whipple's pancreatoduodenectomy was uneventful. The patient is still alive at 16 month after operation, without disease recurrence.

Female↗

[Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period].

We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.

Actuarial Analysis↗

[Double localization of pancreatic insulinoma. Diagnostic and therapeutic difficulties].

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Because most of insulinomas are less than 2 cm in size and rarely they not may be visible by CT scan or transabdominal ultrasonography. Intraoperative ultrasonography may be a solution. Although as surgical method is preferred enucleation because operative time is shorter and easier and the low frequency postoperative complications, pancreaticoduodenectomy Whipple is indicated in selected cases. We report a case of double insulinoma located in the head of the pancreas in which the diagnosis and surgical treatment presented difficulties which determined a particular clinical evolution.

Female↗

[D2 lymph node dissection in gastric cancer surgery: long term results--analysis of an experience with 227 patients].

AIM: The main objective of the study was to evaluate the postoperative mortality and 5 year survival in gastric cancer patients undergoing a minimum of D2 lymphadenectomy. MATERIALS AND METHODS: A retrospective study was conducted on 1170 patients operated for gastric adenocarcinoma in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute, between 1997 and April 2005. Only 443 patients underwent a curative resection, from which 216 patients had D1 resection and in 227 cases a D2 or D3/D4 lymphadenectomy was performed. Information about survival was available for 189 patients of those who had a D1 resection and for 210 of those who underwent a D2 or D3/D4 lymphadenectomy. RESULTS: Postoperative mortality was 6.5% in the group of curative resection, with 9.2% for D1 and 3.9% for D2/D3 D4. Five year survival according to Kaplan Meier curves was 32 % in the D1 group vs. 51,8% in D2/D3-D4 (p <0.0001). Significant differences were noted in the median survival-- D2/D3-D4 group 63 months vs. 28 months in D1 group. CONCLUSIONS: Our data support the gastric resection with a minimum of D2 lymphadenectomy in the radical surgery of gastric cancer. However, an accurate interpretation of the statistical interpretation between the different groups of patients is difficult, mainly because of the retrospective character of the study.

Adenocarcinoma↗