Gabriel Karatzas

Circulating VEGF levels in the serum of gastric cancer patients: Correlation with pathological variables, patient survival, and tumor surgery

ObjectiveTo evaluate the clinical usefulness of serum vascular endothelial growth factor (VEGF) levels in gastric cancer patients. Summary Background DataVascular endothelial growth factor plays an important role in the formation of new blood vessels involved in the growth and metastatic spread of solid tumors, but there is limited information regarding the clinical significance of serum VEGF levels in cancer patients. MethodsSerum VEGF concentrations were measured by an enzyme linked immunosorbent assay in 61 healthy controls and in 58 gastric cancer patients before surgery, and then again at 7 and 30 days after surgery. The association between preoperative serum VEGF levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. ResultsSerum VEGF levels in gastric cancer patients were significantly higher than those in controls. There was a significant association between serum VEGF levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases. Serum VEGF levels decreased significantly after radical resection of the primary tumor and increased in patients with unresectable tumors. Multivariate regression analysis showed that serum VEGF level is an independent prognostic factor for survival. ConclusionsSerum VEGF levels in gastric patients are significantly higher compared with normal controls and correlate with local tumor extent, disease stage, and the presence of distant metastases. Preoperative serum VEGF concentration decreases significantly after radical resection of the primary tumor and is an independent prognostic factor for patient survival suggesting that determination of serum VEGF levels may be clinically useful.

Central Venous and Mixed Venous Oxygen Saturation in Critically Ill Patients

Background: Although mixed venous O₂ saturation (SvO₂) accurately indicates the balance of O₂ supply/demand and provides an index of tissue oxygenation, the use of a pulmonary artery (PA) catheter is associated with significant costs, risks and complications. Central venous O₂ saturation (ScvO₂), obtained in a less risky and costly manner, can be an attractive alternative to SvO₂. Objectives: To investigate whether the values of ScvO₂ and SvO₂ are well correlated and interchangeable in the evaluation of critically ill ICU patients and to create an equation that could estimate SvO₂ from ScvO₂. Methods: Sixty-one mechanically ventilated patients were catheterized upon admission and ScvO₂ and SvO₂ values were simultaneously measured in the lower part of the superior vena cava and PA respectively. Results: SvO₂ was 68.6 ± 1.2% (mean ± SEM) and ScvO₂ was 69.4 ± 1.1%. The difference is statistically significant (p < 0.03). The correlation coefficient r is 0.945 for the total population, 0.937 and 0.950 in surgical and medical patients, respectively. In 90.2% of patients the difference was <5%. When regression analysis was performed, among 11 models tested, power model [SvO₂ = b0(ScvO₂)^b1] best described the relationship between the two parameters (R² = 0.917). Conclusions: ScvO₂ and SvO₂ are closely related and are interchangeable for the initial evaluation of critically ill patients even if cardiac indices are different. SvO₂ can be estimated with great accuracy by ScvO₂ in 92% of the patients using a power model.

A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer.

Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m2 IV or IP plus CTX 600 mg/m2 IV (in both groups) every 3–4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter ≤2 or >2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5–84.0) of the IV group and in 33/44 = 75% (95/CI 59.7–86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8–62+) for the IV group and 18 (6–72+) for the IP group. Median survivals were: 25 months (6–80+) and 26 months (6–72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0.01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950–1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.

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

Background and Objectives: Decreased expression of the E‐cadherin/α‐catenin cell–cell adhesion complex is considered to elicit detachment of tumor cells from primary lesions and development of metastases. The immunohistochemical profile of α‐catenin in colorectal cancer, as well as its correlation with differentiation, lymph node/liver metastasis and patient survival is presented in this study.

Protective effect of remote ischemic preconditioning in renal ischemia/reperfusion injury, in a model of thoracoabdominal aorta approach.

BACKGROUND Thoracoabdominal aortic aneurysm open surgery is accompanied by a significant incidence of renal failure due to renal ischemia. The effect of remote ischemic preconditioning (RIPC) in renal ischemia/reperfusion (IR) injury during a thoracoabdominal aortic aneurysm open repair approach was examined on an animal model. MATERIALS AND METHODS Three groups of rats underwent the following operations respectively: (a) Sham operation in control group; (b) Renal IR injury produced by subphrenic aortic cross-clamping (45/45 min IR), in IR group; (c) The same renal IR injury following RIPC produced by a brief occlusion of the infrarenal aorta (15/15 min IR) in RIPC group. Levels of lactate, base excess, and malondialdehyde (MDA) were measured in selective blood samples from the left renal vein, while levels of MDA were measured in samples of kidney tissues. RESULTS Renal blood base excess was significantly reduced in IR and RIPC groups as compared to sham group, but it was significantly higher in RIPC compared to the IR group (-7.69 +/- 0.62 versus -15.15 +/- 0.86, P < 0.001). Renal blood lactate was significantly increased in both IR and RIPC groups as compared to the sham group, but it was significantly lower in RIPC group compared to IR group (6.76 +/- 0.19 versus 11.99 +/- 0.33, P < 0.001). Renal blood MDA was increased in both IR and RIPC groups compared to the sham group, but it was significantly less compared in the RIPC group compared to IR group (1.55 +/- 0.38 versus 2.94 +/- 0.16, P = 0.002). Finally, kidney tissue MDA was increased in both IR and RIPC groups versus sham group, but it was significantly lower in RIPC group compared to the IR group (5.92 +/- 0.82 versus 13.98 +/- 2.41, P = 0.005). CONCLUSIONS RIPC induced by a temporary infrarenal aortic occlusion decreased the IR renal injury caused by subphrenic aortic cross-clamping.

Primary tuberculosis of the pancreas mimicking a pancreatic tumor

SummaryBackground. 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°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.

Expression of PDGF-A, tgfb and VCAM-1 during the developmental stages of experimental atherosclerosis

Purpose: A considerable number of growth factors, cytokines, and adhesion molecules are implicated in the development of atherosclerotic lesions. These molecules interact in a complex network influencing the evolution of several processes, such as lipid metabolism, cellular proliferation and tissue repair. The aim of this study was to evaluate the expression of the growth factors PDGF-A, and TGFb, and the adhesion molecule VCAM-1 in the sequential steps of experimental atherogenesis. Methods: Forty-two New Zealand white male rabbits were divided into 4 groups. The group A rabbits (n = 8) received normal diet and served as control animals. The remaining groups were fed with a diet enriched with 1% cholesterol and 6% corn oil. The rabbits of group B (n = 9) were sacrificed 1 month after the beginning of the study, of group C (n = 15) after 2 months and of group D (n = 10) after 3 months. In tissue sections of the aortic arch the antibodies of the prementioned factors were detected immunohistochemically. Results: In group A only TGFb and PDGF-A were detectable. In lesions of the first month PDGF-A expression was high but declined towards the third month. VCAM-1 expression was getting more intense up to the second month and subsided thereafter. TGFb expression intensified towards the third month. Changes in the expression of these factors were statistically significant. Conclusion: PDGF-A, responsible for the uncontrollable growth of smooth muscle cells, and VCAM-1, regulating monocyte recruitment in the intima, acts mainly during the early stages of atherogenesis. TGFb, one of the main factors controlling the formation of connective tissue matrix, has a gradually increasing expression towards the third month contributing probably to the fibrous plaque formation.

Anal lesion resulting from implantation of viable tumour cells in a pre-existing anal fistula. A case report.

Abstract Colorectal cancer exfoliates cancer cells into the lumen of the bowel, and possibly, raw bowel mucosa should provide a good medium for the exfoliated cancer cells. We report an extremely rare case of a sigmoid carcinoma metas-tasizing to a low fistula in ano. The patient was operated on for a fistula in ano. Biopsy demonstrated a moderate differentiated adenocarcinoma. Thereafter, sigmoidoscopy revealed an intraluminal mass at the sigmoid colon. The patient subsequently underwent abdominoperineal resection of the sigmoid colon and rectum. In conclusion, surgeons should be aware of the possibility of cancer spread incidence, distally beyond the initial site by exfoliated cancer cells into the lumen of the bowel.

Prognostic Significance and Correlation with Survival of bcl-2 and TGF-β RII in Colon Cancer

Bcl-2 and TGF-β receptors type II (RII) in colon carcinomas were studied in a series of 113 patients, to determine their prognostic significance and to correlate their expression with other prognostic indicators. Bcl-2 expression in the tumor cells showed a reverse relation with tumor size (P=0.018), histological grade (P=0.04), and stage (P=0.013). Univariate survival analysis using the log rank test showed that the survival of patients with bcl-2-positive tumors was significantly better than the survival of patients with bcl-2-negative tumors (P=0.02). However, when entered into a multivariate analysis model, it was not found to be of independent prognostic significance. TGF-β RII expression was correlated with stage (P=0.03), while no statistically significant correlation was found between TGF-β RII expression and histological grade or survival. In conclusion, these results provide additional evidence for the role of bcl-2 and TGF-β RII in carcinogenesis of the colon, while they do not support the use of these factors as prognostic markers in patients with colon cancer.

Total thyroidectomy for the treatment of thyroid diseases in an endemic area.

Introduction: Thyroidectomy is a common operation with very low mortality and an acceptable morbidity rate. Total thyroidectomy has become the predominant type of surgery used today for the treatment of thyroid diseases. In this retrospective study, we analyzed the complications of thyroid surgery according to the operative technique used in our department. Material and Methods: A retrospective analysis was performed for all patients who underwent thyroid surgery during the previous 11 years. The period under study was divided into two sections: phase A (1995–1999) and phase B (2000–2005). Patient characteristics, type of operation, histologic diagnoses and postoperative complications were compared in the two study periods according to the type of surgery. Results: A total of 264 patients between the ages of 18 and 89 underwent thyroid surgery during the study period (133 in phase A and 131 in phase B). Overall histopathological diagnoses were nodular goiter (54.9%), hyperplastic nodules (14.7%), adenoma (8.3%), thyroid cancer (18.2%), and Hashimoto thyroiditis (3.8%). Total thyroidectomy was performed in 91 patients in phase A versus 115 patients in phase B (P < 0.001), whereas the use of subtotal thyroidectomy and lobectomy decreased over time. A trend toward increased morbidity was noted in phase B. Seven patients had hypocalcemia in phase A, whereas 11 patients had hypocalcemia in phase B. Similarly, 5 patients had some degree of vocal cord paralysis in phase A, compared with 7 in phase B (P > 0.05). Morbidity was significantly increased in the case of cancer or reoperation. Conclusion: Despite the slightly higher risk of complication associated with total thyroidectomy, this has gradually replaced more conservative approaches for the treatment of both benign and malignant thyroid diseases. Reoperations and surgery for thyroid cancer carried a higher risk of complications.