Ilias P. Gomatos

Fifteen-year, single-center experience with the surgical management of intrahepatic cholangiocarcinoma: Operative results and long-term outcome

BACKGROUND Limited data exist regarding the role of extended liver resection for the management of intrahepatic cholangiocarcinoma (ICC), most of which derive from small single-center or larger multicenter series. In the current report, we present our experience with the surgical management of ICC, analyze operative results, and investigate prognostic factors in resected patients. METHODS A total of 72 patients underwent operative exploration for ICC between 1991 and 2005; 54 patients were resected, and 18 patients were deemed unresectable based on intraoperative findings. Demographics, pathology, anatomic characteristics, operative results, and survival were analyzed. RESULTS The resectability rate was 71%, with negative margins achieved in 78% of the resected patients. Extended liver resections were performed in 24 (44%) of the 72 patients. Perioperative mortality after resection was 7%, with 11% morbidity. The 1-, 3- and 5-year survival rates after resection were 80%, 49% and 25%, respectively, and were significantly greater than for patients with unresectable disease (P < .001). R1 liver resections conferred increased 5-year survival compared with patients deemed unresectable (P = .03). None of the factors evaluated proved to be independent prognostic factors on multivariate analysis. CONCLUSIONS R0 resection of ICC provides the best chance for prolonged survival, whereas R1 resection appears to be superior to nonoperative treatment. Declining operative mortality as a result of improved intraoperative and perioperative care justifies the performance of extended liver resections in these patients, although benefit has to be evaluated with respect to nodal involvement.

Aggressive surgical resection for hilar cholangiocarcinoma: is it justified? Audit of a single center's experience

BACKGROUND The current study presents our experience with resectional surgery for patients with hilar cholangiocarcinoma (HC). METHODS Medical records of 73 HC patients who were referred to our department between 1988 and 2006 were reviewed. Resectability rate, surgical mortality, and factors contributing to survival were investigated. RESULTS Resectional surgery was performed in 59 patients (80.8%), 51 of whom (86.4%) underwent major hepatic resection. Negative margins were obtained in 35 of 51 patients (68.6%) and were associated with right-sided hepatectomy (80% vs 20%, P = .049). In-hospital mortality and morbidity were 6.8% and 25.4%, respectively. One-, 3- and 5-year survival rates after liver resection were 86%, 48.9%, and 34.9%, respectively. Histologic differentiation, left-sided hepatectomy, and inferior vena cava resection independently predicted survival. Patients undergoing R1 hepatectomy had significantly improved 5-year survival rates compared with patients who were unresectable (P <.01). CONCLUSIONS Major hepatic resections with concomitant vascular resection and reconstruction, when needed, are justified for patients with Bismuth type III and IV hilar cholangiocarcinoma with negative nodes. Reluctance to incorporate segments V and/or VIII into a left lobectomy often results in tumor-positive margins and unfavorable prognosis. Resections for hilar lesions less than stage IVB, even when resulting in microscopically positive margins, confer prolonged survival compared with untreated patients. The results are further improved for patients with well-differentiated HC.

Complete Endoscopic Axillary Lymph Node Dissection Without Liposuction for Breast Cancer: Initial Experience and Mid-term Outcome

Aim To present our initial experience with complete endoscopic axillary lymph node dissection (EALND) in 4 breast cancer patients with respect to feasibility, safety, and clinical outcome. Patients and Methods Between January 2003 and March 2004, 4 women consented to be treated with lumpectomy followed by complete (level I, II, and III) EALND without liposuction, at the Laparoendoscopic Unit of Athens Medical School. All 4 patients presented with a solitary breast cancer lesion smaller than 2 cm in diameter and a negative clinical and sonographic lymph node status (<1 cm). Results All the operations were completed endoscopically in less than 70 minutes (44 to 69 min). The axillary lymph node harvest ranged between 12 and 21 nodes. No lymphedema, motor nerve damage, seroma formation, or wound complications were observed. Prolonged hospitalization, owing to persistent lymphorrhoea was required for 1 patient. During a mean follow-up of 21.3 months, 2 patients reported mild hypoesthesia-paresthesia along the upper medial part of the respective arm, whereas no tumor recurrences were documented. Conclusions Although partial EALND has not been established as the treatment of choice for axillary management, complete EALND seems to be a feasible and effective minimally invasive treatment modality, which could be safely applied in patients with positive sentinel node biopsy, treated in specialized centers.

Protein Expression of bax, bcl-2, and p53 in Patients with Non-Hodgkin's Gastric Lymphoma: Prognostic Significance

Abstract. The biologic significance of bcl-2, bax, and p53 gene expression in patients with non-Hodgkins gastric lymphoma is unknown. We examined the prognostic value of these genes in 36 patients with gastric lymphoma treated in our clinic between 1990 and 1995. Paraffin-embedded specimens from 36 patients who underwent primary resection of the stomach for gastric lymphoma were analyzed immunohistochemically for p53, bax, and bcl-2 gene expression. Expression of bax was seen in 24 of 36 patients (66.7%), p53 expression was found in 8 of 36 tumors (22.2%), and bcl-2 cytoplasmic staining was detected in 6 of 36 patients (16.7%). We performed a univariate analysis to examine the possible correlation between the expression of these genes and the survival of our patients. Expression of bax protein proved to be a statistically significant prognostic factor (p= 0.049). Protein expression of p53 and bcl-2 did not statistically correlate with survival. In the bcl-2-negative (−) patient group (30 patients), those who were bax-positive had a statistically significant better survival than those who were bax-negative (63.3% vs. 36.7%, p= 0.03). There was also a statistically significant correlation between p53 expression and the grade of the tumor (p= 0.0014). P53 protein expression increased along with the grade. Expression of bax is a significant prognostic factor in patients with gastric lymphoma. Its prognostic value increases significantly when studied in bcl-2-negative patients; but expression of bax failed to be an independent prognostic factor. Expression of bcl-2 and p53 has no prognostic significance. Expression of p53 seems to represent a marker for loss of differentiation.

Review of the molecular profile and modern prognostic markers for gastric lymphoma: How do they affect clinical practice?

Primary gastric lymphoma is a rare cancer of the stomach with an indeterminate prognosis. Recently, a series of molecular prognostic markers has been introduced to better describe this clinical entity. This review describes the clinical importance of several oncogenes, apoptotic genes and chromosomal mutations in the initiation and progress of primary non-Hodgkin gastric lymphoma and their effect on patient survival. We also outline the prognostic clinical importance of certain cellular adhesion molecules, such as ICAM and PECAM-1, in patients with gastric lymphoma, and we analyze the correlation of these molecules with apoptosis, angiogenesis, tumour growth and metastatic potential. We also focus on the host-immune response and the impact of Helicobacter pylori infection on gastric lymphoma development and progression. Finally, we explore the therapeutic methods currently available for gastric lymphoma, comparing the traditional invasive approach with more recent conservative options, and we stress the importance of the application of novel molecular markers in clinical practice.

BCL-2, p53 and HLA-DR antigen expression in surgically treated parotid cancer patients

Our objective was to investigate the prognostic significance of bcl-2 protein, p53 protein and HLA-DR antigen expression in a group of surgically treated parotid cancer patients. We studied bcl-2, p53 and HLA-DR immunohistochemical expression in paraffin-embedded surgically removed tissue specimens derived from 26 patients with parotid cancer and 9 patients with Warthin parotid tumors operated between 2000 and 2006 at the Hippokration Hospital of Athens. The staining results were correlated with the patients’ clinicopathological characteristics and clinical outcome. Bcl-2 expression was associated with a significantly decreased survival in patients with advanced tumor stage (P = 0.04), high grade lesions (P = 0.02), or cervical node involvement (P = 0.03). Radiotherapy was associated with a significantly improved recurrence-free survival among patients with negative tumor staining for either bcl-2, or both HLA-DR and bcl-2 [HLA-DR(−)/Bcl-2(−)] (P = 0.04 for both comparisons). Classical clinicopathologic factors failed to show prognostic value both in the univariate and the multivariate analyses performed. Our results suggest that bcl-2 can be used to identify locally advanced or histologically aggressive tumors with a lower survival probability following the application of standard treatment modalities. Furthermore, bcl-2(+) patients should be considered for more aggressive adjuvant treatment protocols, since conventional radiotherapy often fails to decrease relapse rates in this setting of patients.

Prospective appraisal of a 2-day training course on laparoscopic sleeve gastrectomy: the ELTC experience

BackgroundThe increasing role of laparoscopic sleeve gastrectomy (LSG) in the treatment of morbid obesity dictates the need for greater acquaintance with this type of surgery. This study was designed to evaluate the impact of a 2-day LSG course and a 4-day laparoscopic bariatric mini-training program on the knowledge and training gained by participating surgeons.MethodsA total of 73 trainees (31 residents and 42 surgeons) completed a question survey immediately after completion of the respective courses. Questions probed demographic data, training experience before and after course completion, evaluation of course content, and operative experience.ResultsAll residents and four of the general surgeons found the laparoscopic bariatric mini-training program to be of value with respect to future professional orientations. Seven surgeons started performing LSGs, while another five surgeons decided to occupy themselves with various types of laparoscopic bariatric procedures. The most useful parts of the course included the identification and treatment of complications, the use of new instrumentation, and surgical demonstrations (video or live), as decided by more than 80% of the participants. On a 1–5 scale, the presentation of novel knowledge was evaluated to be ≥3 by all participants.ConclusionThe 2-day LSG course offered participants high-quality novel knowledge and excellent training quality, and exerted impact on their personal career.

Co-culture of primary human tumor hepatocytes from patients with hepatocellular carcinoma with autologous peripheral blood mononuclear cells: study of their in vitro immunological interactions

BackgroundMany studies have suggested that the immune response may play a crucial role in the progression of hepatocellular carcinoma (HCC). Therefore, our aim was to establish a (i) functional culture of primary human tumor hepatocytes and non-tumor from patients with hepatocellular carcinoma (HCC) and (ii) a co-culture system of HCC and non-HCC hepatocytes with autologous peripheral blood mononuclear cells (PBMCs) in order to study in vitro cell-to-cell interactions.MethodsTumor (HCC) and non-tumor (non-HCC) hepatocytes were isolated from the liver resection specimens of 11 patients operated for HCC, while PBMCs were retrieved immediately prior to surgery. Four biopsies were obtained from patients with no liver disease who had surgery for non malignant tumor (normal hepatocytes). Hepatocytes were either cultured alone (monoculture) or co-cultured with PBMCs. Flow cytometry measurements for MHC class II expression, apoptosis, necrosis and viability (7AAD) were performed 24 h, 48 h and 72 h in co-culture and monocultures.ResultsHCC and non-HCC hepatocytes exhibited increased MHC-II expression at 48h and 72h in co-culture with PBMCs as compared to monoculture, with MHC II-expressing HCC hepatocytes showing increased viability at 72 h. PBMCs showed increased MHC-II expression (activation) in co-culture with HCC as compared to non-HCC hepatocytes at all time points. Moreover, CD8+ T cells had significantly increased apoptosis and necrosis at 48h in co-culture with HCC hepatocytes as compared to monocultures. Interestingly, MHC-II expression on both HCC and non-HCC hepatocytes in co-culture was positively correlated with the respective activated CD8+ T cells.ConclusionsWe have established an in vitro co-culture model to study interactions between autologous PBMCs and primary HCC and non-HCC hepatocytes. This direct interaction leads to increased antigen presenting ability of HCC hepatocytes, activation of PBMCs with a concomitant apoptosis of activated CD8+ T cells. Although, a partially effective immune response against HCC exists, still tumor hepatocytes manage to escape.

Metzenbaum-assisted liver resection: a safe and effective liver resection technique.

Aim: We hereby present and evaluate a technique for hepatic parenchymal transection based on the application of Metzenbaum scissors and clips during liver ischemia. Methods: Our technique was retrospectively evaluated in 32 noncirrhotic, noncholestatic patients with intrahepatic cholangiocarcinoma and 32 patients with hepatocellular carcinoma (23 of whom cirrhotic, 71.9%). Patient data were retrieved from our Hepatobiliary Surgery Database. Type and duration of vascular clamping, blood transfusion requirements, marginal status and immediate postoperative complications were analyzed. Results: Twenty-seven extended (>4 liver segments; 42.2%) and 37 nonextended (≤4 liver segments; 57.8%) liver resections were analyzed. Warm liver ischemia duration was 14 (interquartile range: 11-17.8) min. Thirty-three patients (51.6%) were transfused with a median of 2 (1.5-3) units of packed red blood cells. Tumor-free margins were achieved in 90.6% of cases (n = 58). The overall morbidity rate was 18.8% with a 4.7% mortality rate. Our technique allowed for excellent identification and safe dissection and preservation, or ligation of major liver vessels. Conclusions: The proposed technique is simple, fast, safe and with low cost. It is associated with limited postoperative complications while from an oncologic standpoint it enables the surgeon to achieve a high percentage of tumor-free margins while protecting major vascular structures. i 2014 S. Karger AG, Basel