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Biomedical subjects

G Kouraklis

Publications and source records attributed to G Kouraklis.

At least 37 records · Page 2Linked to original sources

An alternative approach for the surgical management of hydatid disease of the liver.

Hydatid disease of the liver still remains a serious medical problem. As a result of increased travelling and immigration, it has also appeared in previously unaffected countries and is now well manifested in countries where the medical personnel lack the experience to treat this problem. We report an alternative method for the surgical management of hydatid disease of the liver, especially that located over the right superior-posterior aspect of the liver. Through a lateral right thoracotomy, we have a better exposure of the cyst and by using the right hemidiaphragm we achieve the same beneficial effect as omentoplasty does.

Echinococcosis, Hepatic↗

Primary tuberculosis of the pancreas mimicking a pancreatic tumor.

BACKGROUND: Diagnosis of tuberculosis of the pancreas is often missed, and may present to the clinician as a difficult diagnostic problem. METHODS: We report an extremely rare case of a 35-year-old woman who admitted for acute pain in the right upper quadrant, jaundice, fever 38 degrees C and chills. During the last 8 mo, she developed increasing fatigue and a weight loss of approx 10 kg. RESULTS: Computed tomography (CT) of the abdomen showed a mass in the head of the pancreas, and upper gastrointestinal endoscopy revealed a stenosis of the second part of duodenum and a pancreatico-duodenum fistula. Frozen sections by direct trucut needle biopsy raised suspicions of a malignancy, and a Whipple procedure was performed as a radical procedure. The final histopathology revealed a chronic granulomatous lesion with caseating necrosis. Mycobacterium of tuberculosis was detected using the polymerase chain reaction-based assay. CONCLUSION: This unusual case emphasizes that in suspected cases of pancreatic carcinoma with an atypical presentation, an attempt should be made to confirm the diagnosis by CT-guided needle biopsy, or by ultrasound endoscopic fine-needle aspiration.

Adult↗

Glioma cells deficient in urokinase plaminogen activator receptor expression are susceptible to tumor necrosis factor-alpha-related apoptosis-inducing ligand-induced apoptosis.

PURPOSE: The urokinase plasminogen activation system comprises the ligand urokinase plasminogen activator and the receptor urokinase plasminogen activator receptor (uPAR), which play an important role in the activation of matrix-degrading enzymes that enhance the invasion of cancer cells. Earlier studies have indicated that SNB19 glioblastoma cells expressing antisense uPAR constructs lose their invasive properties when injected in vivo. Additional observations indicated that injected antisense uPAR:SNB19 cells were being lost through apoptotic elimination. EXPERIMENTAL DESIGN: SNB19, Vector, and SNB19:asuPAR were analyzed to determine cytotoxicity of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), receptor expression, and underlying signaling pathways using flow cytometry, immunohistochemistry, RNase protection assay, and c-Jun-NH(2)-terminal kinase activity. RESULTS: This study elucidated the susceptibility of antisense uPAR:SNB19 cells to TRAIL under certain experimental conditions in vitro. These uPAR-deficient transfected cells had higher levels of the TRAIL receptors DR4 and DR5 than did the control and vector population as detected by flow cytometry. An RNase protection assay confirmed the elevation of DR4 and DR5 mRNA in the antisense uPAR cells. CONCLUSIONS: These findings provide preliminary evidence of a link between TRAIL-induced apoptosis and cell cycle progression in antisense uPAR:SNB 19 cells.

Apoptosis↗

Gene therapy for cancer: from the laboratory to the patient.

Gene therapy is a new form of therapeutic intervention with applications in many areas of medical treatment. There are still many technical difficulties to be overcome, but recent advances in the molecular and cellular biology of gene transfer have made it likely that gene therapy will soon start to play an increasing role in clinical practice and particularly in the treatment of cancer. The first clinical gene transfer in an approved protocol took place exactly 10 years ago, and it was for the transfer of gene-marked immune cells into patients with advanced cancer. Now there are 218 active clinical protocols in the United States, and they have involved over 2000 patients worldwide. Among the conditions and diseases for which gene transfer is being tried as treatment, cancer comes first with 130 clinical trials. Fundamental research in the mechanisms of cancer and the development of molecular biology tools are crucial for the success of the treatments in the future. The identification of tumor rejection antigens from a variety of cancers and the immune response that is defective in cancer patients are important topics for future studies. The evaluation of gene therapy combinations involving use of tumor suppressor genes and constructs that inactivate oncogenes is also another important area for future research. The future improvement of present viruses as well as the use of new viral vectors will likely expand the applicability and efficacy of gene therapy. During the next decade technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful clinical practice of gene therapy.

Clinical Trials as Topic↗

Progress in cancer gene therapy.

Many technical difficulties have to be overcome before effective gene therapy can be achieved. Strategies for gene therapy include 'suicide' gene therapy, transfer of a tumor suppressor gene, inhibition of activated oncogenes by antisense mechanisms, and cytokine gene transfer and tumor cell vaccination. Gene therapy will have a major impact on the healthcare of our population only when vectors are developed that can safely and efficiently be injected directly into patients as drugs. One of the most promising areas of vector development is that of non-viral vectors, which consist of liposomes, molecular conjugates, and naked DNA delivered by mechanical methods. Future research should be focused on modifying viral vectors to reduce toxicity and immunogenicity, increasing the transduction efficiency of non-viral vectors, enhancing vector targeting and specificity, regulating gene expression, and identifying synergies between gene-based agents and other cancer therapeutics. The evaluation of gene therapy combinations is another important area for future research. The identification of tumor rejection antigens from a variety of cancers and the immune response that is defective in cancer patients are important topics for future studies. A universal gene delivery system has yet to be identified, but the further optimization of each of these vectors should result in each having a unique application. Gene therapy has still a long way to go and requires the efforts of investigators in the basic and clinical sciences. Despite substantial progress, a number of key technical issues need to be resolved before gene therapy can be effectively applied in the clinic.

Clinical Trials as Topic↗

Myc oncogene expression and nude mouse tumorigenicity and metastasis formation are higher in alveolar than embryonal rhabdomyosarcoma cell lines.

Accumulated clinical evidence suggests that alveolar rhabdomyosarcoma (ARMS) is more aggressive than embryonal rhabdomyosarcoma (ERMS). Here, we study six childhood rhabdomyosarcoma cell lines, three ERMS and three ARMS. We have assayed the ability of the tumor cells to grow in culture and in nude mice as well as their propensity for pulmonary metastasis formation by tail vein injection. We also compared levels of c- and N-myc oncogene expression and DNA copy number. We find no correlation of histologic tumor type (i.e. ERMS versus ARMS) with growth rate in culture, but we do find suggestive correlations of histologic type with tumorigenicity (mean tumor diameter in millimeters at 6 wk: ARMS 30, ERMS 10; p1 = 0.1) and metastasis formation (ARMS 12, ERMS 0; p1 = 0.1). These properties also correlate with uniform greater overexpression of c-myc in ARMS (mean 39.3-fold, range 16-83) compared with ERMS (mean 5.3, range 4-8) (p1 = 0.05, control fibroblasts = 1). Although c-myc was often amplified in vitro (four of six lines), there was no correlation with histologic type (2/3 ARMS, 2/3 ERMS). These data on rhabdomyosarcoma cell lines derived from verified ERMS and ARMS tumors support the impression from previous clinicopathologic observations that ARMS is a more malignant form of rhabdomyosarcoma than ERMS.

Animals↗

Changing patterns in advanced gastric carcinoma.

A retrospective study on patients with gastric cancer during the periods 1984-88 (n = 63 patients) and 1989-93 (n = 59 patients) was made. The aim of the study was to assess any changing patterns in tumour distribution, surgical management and survival during the two periods. When the diagnosis was made, the majority of tumours were advanced: 58 were stage IV and 21 were stage IIIB, with 43 tumours at earlier stages. The incidence of proximally located gastric adenocarcinomas increased from 15.9 to 27.1%, while the incidence of carcinomas located in the body decreased from 34.9 to 23.7%. The majority of patients underwent conservative gastrectomy. The proportion of proximal gastrectomies increased from 3.2 to 15.3 per cent (p = 0.02), whereas the proportion of combined resection of adjacent organs decreased from 38.1 to 22.0 per cent (p = 0.04). Perioperative mortality rate decreased from 17.5 to 1.7 per cent (p = 0.003). Prognosis remained unchanged in the two periods; overall 5-year survival is calculated as 12 per cent.

Adenocarcinoma↗

Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival.

BACKGROUND AND OBJECTIVES: Decreased expression of the E-cadherin/alpha-catenin cell-cell adhesion complex is considered to elicit detachment of tumor cells from primary lesions and development of metastases. The immunohistochemical profile of alpha-catenin in colorectal cancer, as well as its correlation with differentiation, lymph node/liver metastasis and patient survival is presented in this study. METHODS: Alpha-Catenin expression was investigated with immunohistochemistry technique, in 85 paraffin-embedded and 21 fresh frozen specimens, including 82 colon adenocarcinomas, 10 adenomas, 10 lymph nodes, and 3 liver metastases. Preserved alpha-catenin expression was considered for those tumors that demonstrated more than 90% alpha-catenin(+) cancer cells and reduced alpha-catenin expression for those tumors with less than 90% alpha-catenin(+) cancer cells. The chi2-test was used to calculate the statistical correlation of alpha-catenin expression with grade of differentiation and metastatic potential and the log-rank test for the correlation with survival rate. RESULTS: Normal mucosa, as well as 8/10 of the colon adenomas, showed strong membranous alpha-catenin expression. Reduced alpha-catenin expression was found in 32/82 (39%) colorectal cancers examined, which was associated with de-differentiation (P < 0.01), lymph node metastasis (P < 0.025), and poor clinical outcome (P < 0.012). Alpha-Catenin expression was preserved in 3 liver metastases and their corresponding primary tumors. By contrast, 6/10 of lymphogenous metastases showed decreased alpha-catenin expression. CONCLUSIONS: Our findings demonstrate a significant down-regulation of alpha-catenin expression in colorectal cancer which is associated with poor differentiation, higher metastatic potential and unfavorable prognosis. These preliminary results suggest that alpha-catenin may be a useful marker of invasiveness, metastatic potential, and survival in colorectal cancer patients.

Adenocarcinoma↗

Massive intraperitoneal hemorrhage caused by a giant exogastric leiomyoblastoma.

Leiomyoblastomas account for a small percentage of smooth muscle tumors of the stomach. Intraperitoneal bleeding is an unusual and unexpected presenting sign. We herein present a 43-year-old woman who was urgently operated on due to signs of collapse. A large hemorrhagic mass measuring 25 x 18 x 15 cm was found arising from the greater curvature of the stomach. A histologic examination demonstrated rounded and spindle cells, and rare mitoses were also seen. Although the number of mitoses was small, the lesion was nevertheless felt to be consistent with malignant leiomyoblastoma because of its large size. Three years later the patient is doing well with no evidence of tumor recurrence. We conclude that intraperitoneal bleeding due to leiomyoblastoma of the gastrointestinal tract is an extremely rare phenomenon and has been described only in a few reports, and only one other previous case presented with signs of collapse.

Adult↗

Surgical treatment of gastrointestinal B-cell mucosa-associated lymphoid tissue lymphomas.

We retrospectively evaluated clinicopathologic features of 35 patients treated for primary gastrointestinal lymphomas of MALT type (mucosa-associated lymphoid tissue) between 1970 and 1993. Fourteen patients (40%) were treated for acute abdominal conditions (bowel obstruction in 8, perforation in 2, and gastrointestinal bleeding in 4), and the rest had exploratory laparotomy. The tumor was located in the stomach in 23 patients (66%), in the jejunum and ileum in 10 (29%), and in the large intestine in 2 (6%). The type of operation was defined according to site and extent of disease. Most patients received chemotherapy postoperatively. Staging was done according to the Ann Arbor classification. Survival depended on stage and extension of the disease; 5-year survival was 45%. Surgical resection followed by adjuvant chemotherapy is warranted when the patient is considered to be a surgical candidate.

Adolescent↗

Management of foreign bodies of the rectum: report of 21 cases.

This is a report of 21 patients treated for non-therapeutic introduction of rectal foreign bodies in our institution. Nine out of 18 patients had manual transanal extractions performed under general anaesthesia while eight patients required insertion of retractors and gynaecological forceps. In three patients the vacuum from the hollow objects was abolished by passing a catheter through the anus to a point above the object. One of the patients required colotomy for retrieval of a wooden object. In three patients free perforations were obvious clinically with peritoneal signs and free air on plain abdominal radiographs. Treatment was end-sigmoid colostomy and mucous fistula, oversewing of the perforation and peritoneal irrigation. There were no deaths and only one complication occurred, a rectovaginal fistula.

Adult↗

Cystic dilatations of the common bile duct in adults.

Cystic dilatations of the common bile duct are believed to be of congenital etiology with most cases presenting in childhood. During the last 20 years, 10 patients with cystic dilatations of the bile duct were treated in our Department. There were 5 men and 5 women with an age range of 35-81 years. Clinical presentation consisted of right hypohondrial pain, nausea, vomiting and a history of obstructive jaundice. Diagnosis was established by ultrasound, cholangiography and ERCP in most cases. According to the Todani classification system, 5 patients had type I cysts, 4 had type II and one had type III. At the time of surgery, main associated diseases were choledocholithiasis in 3 cases and cholangitis in 2 cases. One patient (type III) underwent endoscopic sphincterotomy; 4 patients underwent internal drainage and 2 of them developed mild cholangitis postoperatively; 5 patients underwent excision of the cyst and a biliary-enteric bypass and developed no main complications. Patients remained in good health during long-term follow-up. We conclude that cyst excision is the treatment of choice for adults in order to reduce postoperative morbidity and the potential risk of malignancy.

Adult↗

Hamartoma of Brunner's glands causing massive haematemesis.

BACKGROUND: Brunner's gland hamartomas are very uncommon lesions and are usually asymptomatic. METHODS: A 77-year-old man was urgently operated on for massive upper gastrointestinal bleeding, associated with haematemesis. RESULTS: A 3.5 x 3 x 3 cm mass arising from the anterior aspect of the first part of the duodenum was found. Histologic examination showed groups of Brunner-type glands without atypia; these coexisted with heterotopic pancreatic acini and ducts. CONCLUSIONS: This is a very rare cause of massive upper gastrointestinal bleeding and may easily be confused with bleeding from a peptic ulcer.

Aged↗