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Biomedical subjects

Charalambos Menenakos

Publications and source records attributed to Charalambos Menenakos.

11 recordsLinked to original sources

Influence of intraperitoneal application of taurolidine/heparin on expression of adhesion molecules and colon cancer in rats undergoing laparoscopy.

BACKGROUND: Recent experimental studies have shown that intraperitoneal administration of taurolidine/heparin causes a reduction of local tumor growth after laparoscopy in rat models. It might be that the anti-adherent activities of these agents are responsible for this effect. In this study we investigated the adhesion molecules E-cadherin, beta1-integrin, and CD44. MATERIALS AND METHODS: Following a 10,000 colon adenocarcinoma cells' (DHD/K12/TRb) intraperitoneal application a cecum resection and a partial parietal peritoneum resection (1 x 1 cm) were performed using a three trocar technique in 30 BD IX rats. After randomization in two groups, the cecum suture line and the parietal peritoneal defect were either lavaged with 1 mL of 0.5% taurolidine/10 IU heparin or with equal amounts of 0.9% normal saline solution. Rats were sacrificed four weeks after operation and total tumor growth was determined. E-cadherin, beta1-integrin, and CD44 were assessed immunohistochemically on the tumor tissue. RESULTS: The expression of E-cadherin was significantly reduced to 46.7% (complete loss of staining) in the taurolidine/heparin group. Although no significant difference was detected concerning the beta1-integrin and CD44 expression, a slightly reduced expression level with 26.7% of negative staining in metastases of the taurolidine/heparin group was observed. The total tumor weight (171.1 +/- 181.2 mg) as well as the total number of tumor lesions was also reduced by the substances compared to the control group (283.2 +/- 91.4 mg). CONCLUSIONS: Taurolidine/heparin led to a significant reduction of local tumor growth. Additionally a reduction of the expression of E-cadherin was observed. However, the biological behavior of this molecule is multivariant, controversial and still unclear. Further studies should elucidate its role in the epithelial tumor genesis.

Adenocarcinoma↗

Prevention of disease progression in a patient with a gastric cancer-re-recurrence. Outcome after intravenous treatment with the novel antineoplastic agent taurolidine. Report of a case.

BACKGROUND: Taurolidine (TRD) is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. CASE PRESENTATION: A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2), N0, V0). 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. CONCLUSION: The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

Journal Article↗

Submandibular ectopic thyroid gland.

Ectopic thyroid glands are generally a rare entity appearing mostly in the cervical midline (90% of the cases) and even more rarely in other anatomical sites (10%). We present the case of an ectopic submandibular thyroid gland. An 81-year-old woman was referred to our department with a history of right-sided submandibular swelling. Preoperative FNA revealed benign ectopic thyroid tissue. The patient was submitted to resection of the mass. Histological examination of the specimen confirmed the diagnosis. A substitution treatment with thyroxin was initiated postoperatively, as this was the only functional thyroid tissue. Review of the literature revealed 18 similar cases. Physicians should be aware of the possibility that a submandibular swelling could be an ectopic thyroid gland. This entity poses specific diagnostic and therapeutic difficulties. Thorough preoperative diagnostics and resection of the ectopic tissue guarantee a good outcome.

Aged, 80 and over↗

Computer-assisted laparoscopic colon resection with the Da Vinci system: our first experiences.

PURPOSE: Telerobotic surgery is a developing and promising modality that highly improves the laparoscopic dexterity. We have performed more than 100 laparoscopic and thoracoscopic procedures since December 2002 with the aid of the Da Vinci robotic system. This study was designed to assess the value of robots in colonic laparoscopic surgery. We present our first cases of robotic-assisted colectomies. METHODS: Two patients underwent a telerobotic-assisted sigmoidectomy for sigmadiverticulitis. One of these cases was complicated with a sigmoid-bladder fistula. Three other patients were submitted to a colon resection for cancer: sigmoidectomy (n = 2), and right colectomy (n = 1). A four-trocar technique was used for all operations. Tissue dissection of colonic adhesions, mobilization of the colon, management of the fistula, mesenteric dissection and division, and bowel resection were fully performed with the telerobotic system. RESULTS: Three operations were completed using the Da Vinci system without any problems in acceptable times. In two patients, the operation had to be converted to laparotomy because of severe adhesions and locally extended tumor growth. Postoperative courses of all patients were uneventful. Patients were discharged between postoperative Days 9 and 20, and were well six months later. CONCLUSIONS: Colonic telerobotic surgery can be performed safely. Benefits were seen during dissection of the rectum in the small pelvis. A major limitation is a lack of a large operation field especially if there is the need to dissect a colonic flexure in the upper abdomen. The enormous costs and the lack of appropriate instruments can be a major problem in the further expansion of the telerobotic surgery.

Aged↗

Effects of increasing doses of a bolus injection and an intravenous long-term therapy of taurolidine on subcutaneous (metastatic) tumor growth in rats.

BACKGROUND: Experimental studies have shown that taurolidine suppresses intraperitoneal tumor growth following local application in rats. In opposite, a single intravenous therapy affected neither intraperitoneal nor subcutaneous growth of malignancies. Thus, an intravenous long-term therapy with taurolidine was investigated in rats after administration of a subcutaneous tumor load. VEGF and TNFalpha production and their effects on tumor growth have not been elucidated so far. METHODS: VEGF and TNFalpha levels of rat colon adenocarcinoma cells (DHD/K12/TRb) were analyzed in the supernatant undergoing treatment of increasing taurolidine doses in vitro. Besides the cell experiments rats were treated intravenously. At the beginning of the operation, 10 000 colon adenocarcinoma cells were applied subcutaneously at the back of the rats. Then the animals (n = 80, BD IX rats) were randomized into eight groups and underwent a standardized midline laparotomy for 30 min. At the end of the operation the animals were given either a bolus (1 ml Ringer's solution) or a long-term intravenous therapy (7 days, eight-hourly 1 ml 1%, 2%, or 3% taurolidine) were performed. For long-term therapy, a jugularis vein port catheter system was placed and left for 1 week. The influence on subcutaneous tumor growth, animal growth, general side effects and leukocyte/granulocyte levels were analyzed. Total tumor weights were determined 4 weeks after cell application. RESULTS: The VEGF and TNFalpha levels decreased rapidly after taurolidine therapy with low doses in vitro. The subcutaneous tumor growth showed a downtrend of tumor weight (P = 0.075) with a statistical significance in solid tumor counts (P = 0.04) at the back of the animals. A slight and temporary depression in animal growth was observed only in long-term therapy groups. Independent of the therapeutic agents and the application forms, the operation itself caused a slight leukopenia shortly after the operation compensated by a moderate leukocytosis in the following course. Fast injections of taurolidine led to a reduction of breathing rate. CONCLUSIONS: Only the intravenous long-term therapy of 3% taurolidine led to a slight downregulation in subcutaneous tumor growth. The changes of leukocyte counts were not affected by taurolidine. Fast injections have to be avoided. The findings prompted us to start new experiments to determine the influence of increasing doses of taurolidine on progressive tumor growth in rats.

Adenocarcinoma↗

High doses of taurolidine inhibit advanced intraperitoneal tumor growth in rats.

BACKGROUND: The antitumor agent taurolidine (TRD) affects tumor growth in animals. Thus far, no animal studies have been published concerning the systemic or local toxicity and the effectiveness of long-term intraperitoneal (i.p.) and intravenous (i.v.) administration on advanced tumor growths. MATERIALS AND METHODS: In a first experiment (A) the systemic toxicity of the liver and kidneys was examined only after i.v. treatment in 40 rats (BD IX). For local toxicity the superior vena cava (SVC) was histologically analyzed. In a second study (B) 20,000 colon adenocarcinoma cells (DHD/K12/TRb) were initially applied i.p. after laparotomy in 80 rats (BD IX). After 28 days a port catheter system was placed in the SVC and left for 1 week. The animals were randomized into eight groups (n = 10) and received a 7-day treatment (eight hourly, 1 ml): 1, 2, 3% TRD or Ringer's solution (control group) either i.p. or i.v. Total i.p. tumor weight was measured 4 weeks after the end of the therapy. Side effects on differential blood counts and animal weight changes were examined. RESULTS: No organ lesions were detected in liver, kidneys, and SVC in experiment A. The i.v. administration of 2% TRD (P = 0.034) and 3% TRD (P = 0.05) as well the i.p. application of 2% TRD (P = 0.05) decreased the development of advanced i.p. tumor lesions. No changes of differential blood count nor relevant animal weight changes resulted. Three port catheter-related infections were examined. CONCLUSIONS: TRD does not impair the liver tissue, kidneys, SVC, and leucopoiesis. The intravenous therapy of 2% TRD is safe and anti-tumorigenic in advanced local tumor growth in rats.

Adenocarcinoma↗

Taurolidine--a new drug with anti-tumor and anti-angiogenic effects.

Taurolidine [bis(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)-methane (TRD)], a product derived from the aminosulfoacid taurin, was first described as an anti-bacterial substance. It was mainly used in the treatment of patients with peritonis as well as antiendoxic agent in patients with systematic inflammatory response syndrome. Meanwhile, quite interesting new experimental findings elucidated several new mechanisms concerning not only antibiotic but also anti-tumor effects. TRD significantly reduces the pathogenicity of prokaryotes, leading to a degeneration of the bacterial wall, and binds free lipoplysaccharides (LPSs) and exotoxins. Furthermore syntheses of tumor necrosis factor-a and interleukin-1b are reduced in LPS-stimulated human macrophages in a dose dependent manner. Tumor angiogenesis is promoted by enhanced expression of all these endogenous angiogenic factors, indicating an anti-angiogenetic effect of TRD. Tumor angiogenesis has a key role in tumor growth. TRD additionally inhibits tumor cell growth by a mitochondrial cytochrome c-dependent apoptotic mechanism, has a direct and elective effect on glial and neuronal brain tumor cells via Fas-ligand-mediated cell death, and inhibits protein synthesis at an early phase of translation, which might explain its various apoptotic effects. Subsequent to these experimental observations, TRD has shown encouraging clinical results after intravenous administration in patients with gastrointestinal malignancies and tumors of the central nerve system. A remarkable experimental observation that comes to complete the above-mentioned findings is the low toxicity on leukopoiesis and erythropoiesis as well as on kidney and liver function in animal models. Several other data confirm low toxicity of the agent after its clinical administration in humans. Prospective clinical studies are currently investigating the efficacy of TRD on local and metastatic tumor growth in different malignancies.

Angiogenesis Inhibitors↗

Computer-assisted laparoscopic repair of "upside-down" stomach with the Da Vinci system.

Recently introduced telerobotic surgical systems attempt to elude the inherent limitations of traditional laparoscopic surgery. Four patients (3 male, 1 female) with mixed hiatal and paraesophageal hernias with fixed intrathoracic partial or complete displacement of the stomach were operatively treated using the Da Vinci robotic system. Tissue dissection, hiatoplasty, and anterior hemifundoplication (Dor) were performed with the telerobotic system. There were no surgical complications. The system broke down in the fourth patient due to a software defect. Advantages were seen in terms of the intrathoracic dissection of displaced stomach through a narrow hiatus, intracorporeal suturing due to 6 degrees of freedom plus grasping. At the moment, lack of the appropriate robotic instruments for abdominal surgery as well as the enormous functional cost of the robotic system are considered to be the most significant current impediment to the adoption of robotic abdominal surgery. The continuous evolution and upgrade of the system is quite promising so far. Telerobotic-assisted hiatal hernia operation is feasible with many advantages compared with the traditional laparoscopic approach, especially during the dissection in the mediastinum in patients with intrathoracic stomach. A prospective, randomized trial will be performed later to evaluate the advantages and limitations of robotic compared with traditional laparoscopy. Technological evolution will perhaps diminish the current problems and the cost associated with robotic surgery.

Aged↗

Sexual function before and after mesh repair of inguinal hernia.

AIM: Several factors having an influence on the quality of life after an inguinal hernia repair have been studied, yet little has been reported on sexual function before and after this operation. METHODS: In a prospective follow-up study from January 1999 to July 2002, 210 men and 14 women were asked to answer an anonymous questionnaire of 40 questions before elective inguinal hernia repair to assess pre- and postoperative sexual function (preoperatively, 3 months postoperatively and every 6 months afterwards). Inguinal hernia repair was performed using a standardized Plug and Patch mesh technique. RESULTS: Fifty-two (23.2%) patients mentioned preoperative sexual dysfunction related to the groin hernia. Postoperatively, the surgical repair had a positive influence on the sexual function in these patients. Thirty-six (16%) patients complained of postoperative sexual dysfunctions, which improved or disappeared over the next few months. All patients suffered surgical complications, which were surgically treated in six cases. Symptoms specifically associated with inguinal hernias can cause certain limitations in the sexual life. CONCLUSIONS: In most cases, and in the absence of postoperative complications, the operative repair can lead to a recovery of the sexual life in patients with preoperative sexual dysfunction, while, in most cases, it does not affect patients with a preoperative normal sexual life.

Female↗

Prevention of catheter disconnection after laparoscopic adjustable gastric banding.

In a consecutive series of 138 laparoscopic adjustable gastric bandings (LAGB) we observed disconnection of the gastric band catheter at the site of the port connector in 17 patients. During operative revision we established a new port position with a minimal distance of 10 cm between the connector and the entrance of the catheter to the abdominal cavity. Using this technique no complications and no catheter disruptions occurred during a median followup period of 25 months.

Adult↗