Comparison Between Dunking (Invagination) Pancreaticojejunoanastomosis and Double Layer Duct to Mucosa Anastomosis After Cephalic Duodenopancreatectomy-Whipple Procedure for Pancreatic Cephalic Carcinoma.

INTRODUCTION: Pancreatic cancer is malignancy with poor prognosis for quality of life and overall survival. The incidence is variant, 7.7/100,000 in Europe, 7.6/100,000 in the USA, 2.2/100.000 in Africa. The only real benefit for cure is surgery, duodenopancreatectomy. The key points for this procedure are radicality, low morbidity and low mortality, the follow up and the expected overall survival. The benchmark of the procedure is the pancreaticojejunoanastomosis, with its main pitfall, postoperative pancreatic fistula B or C. Subsequently, the manner of creation of pancreaticojejunoanastomosis defines the safety, thus the postoperative morbidity and mortality. Finally, this issue remarkably depends on the surgeon and the surgical technique creating the anastomosis. We used 2 techniques with interrupted sutures, dunking anastomosis and duct-to-mucosa double layer technique. The objective of the study was to compare these 2 suturing techniques we applied, and the aim was to reveal the risk benefit rationale for dunking either duct to mucosa anastomosis. MATERIAL AND METHOD: In our last series of 25 patients suffering pancreatic head carcinoma we performed a standard dodenopancreatectomy. After the preoperative diagnosis and staging with US, CICT, tumor markers, they underwent surgery. Invagination-dunking anastomosis was performed in 15, whereas, duct-to-mucosa, double layer anastomosis was performed in 10. In the first group with dunking anastomosis, we had 6 patients with soft pancreas and 8 with narrow main pancreatic duct, less than 3 mm. In the duct-to-mucosa group there were 5 patients with soft pancreas and 4 with narrow main pancreatic duct. All other stages of surgery were unified, so the only difference in the procedure remained on the pancreatojejunoanastomosis. The onset of the postoperative pancreatic fistula was estimated with revelation of 3 fold serum level of alfa amylases from the third postoperative day in the drain liquid. RESULTS: In the duct to mucosa group there wasn't a clinically relevant postoperative pancreatic fistula, while in the dunking anastomosis group we had 4 postoperative pancreatic fistula B, 26 %. One of these 4 patients experienced intraabdominal collection - abscess, conservatively managed with lavation through the drain. Comparing the groups, there was no significant difference between the groups concerning the appearance of postoperative pancreatic fistula: p>0.05, p=0.125. From all 25 patients, in 21 patients biliary stent was installed preoperatively to resolve the preoperative jaundice. All 21 suffered preoperative and postoperative reflux cholangitis, extending the intra-hospital stay. CONCLUSION: So far, there have been many trials referring to opposite results while comparing these 2 techniques in creation of the pancreticojejunoanastomosis. In our study, the duct to mucosa anastomosis prevailed as a technique, proving its risk benefit rationale. However, further large randomized clinical studies have to be conducted to clarify which of these procedures would be the prime objective in the choice of the surgeon while creating pancreatojejunoanastomosis.

Tertiary Lymphoid Structures in Colorectal Cancers and Their Prognostic Value.

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in tumour stroma are considered to be involved in the elimination of malignant cells and prevention of metastasis formation. TIL consist of T lymphocytes including cytotoxic lymphocytes that are a constituent part of the effector mechanism of anti-tumour immunity and B lymphocytes that can form tertiary lymphoid structures (TLS). TLS has been described in several solid tumours and colorectal carcinoma (CRC), and the influence on the local and systemic anti-cancer response. AIM: This study aimed to quantify the presence of TLS in CRC patients and to determine their role in tumour progression. PATIENTS AND METHODS: The study included 103 patients with CRC who underwent surgery at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The density of TLS was determined and correlated with the neoplasm status of local growth (T), positive lymph nodes, lymphatic invasion, and stage of the disease and tumour grade. RESULTS: The density of TLS was significantly higher in patients with higher stage, lower T status, and negative lymph nodes, in patients with no lymphatic invasion and with better-differentiated tumours. CONCLUSION: The density of TLS plays an important role in controlling the tumour growth, and it can be a parameter for neoplasm progression in CRC patients. The density of TLS influences the control of tumour progression.

EBV Positive Gastric Carcinomas and Their Clinicopathological Characteristics.

BACKGROUND: The understanding of the etiopathogenesis of gastric carcinoma (GC) can be a base for development of new therapeutic methods to reduce mortality and to increase survival in patients with GC. The percentage of Epstein - Barr virus (EBV) positive gastric carcinomas is uncertain, and the etiologic importance of EBV in the pathogenesis of GC has still not been elucidated. AIM: This study aimed to determine the percentage of EBV associated GC as well as to determine their clinicopathological characteristics. MATERIAL AND METHODS: The study included 80 patients with GC who were analysed for ethnicity, local growth of a tumour (T status), the presence of nodal metastases (N), the presence of distant metastases (M), stage of the disease and degree of carcinoma differentiation. For detection of EBV, immunostainings were performed on tumour tissue and the peripheral non-tumour gastric mucosa. RESULTS: Positive immunostaining with an antibody against EBV was found in 19 (23.75%) of the 80 patients with gastric carcinomas. EBV immunostainings were significantly different in patients with or without metastasis and between patients of Macedonian and Albanian ethnicity (p < 0.0001, p < 0.009, respectively). EBV immunoexpression was significantly associated with the presence of distant metastases and with patients of Albanian ethnicity. CONCLUSION: Association of EBV immunostainings with distant metastasis in patients with GC suggests the influence of EBV infection on the progression of gastric carcinoma. Due to scarce and doubtful literature data on EBV associated GC, further studies are necessary to determine the role of EBV regarding aetiology, treatment and prognosis in patients with EBV associated gastric carcinoma.

HER2 Positive Gastric Carcinomas and Their Clinico-Pathological Characteristics.

BACKGROUND: HER2 protein expression in gastric carcinoma, in correlation with existing, acknowledged prognostic factors which include the parameters that determine the TNM stage of the disease, could become the basis for ongoing research in the field of molecular targeted and personalised therapy. AIM: To determine the expression of the HER2 protein in gastric carcinoma and to correlate the expression of a HER2 protein with clinicopathological characteristics of the disease. MATERIAL AND METHODS: The data of HER2 protein expression and the parameters of the TNM classification were obtained from the histopathological reports of the Institute of Pathology in Skopje, and for the clinical stage we used patient's files from the University Clinic for Abdominal Surgery in Skopje. RESULTS: The analysis of the correlation of HER2 protein expression and TNM classification parameters pointed out a significant correlation between HER2 protein expression and intragastric localisation of gastric carcinoma (P = 0.005), and the tumour grade of differentiation (P = 0.034). There was also a positive correlation between HER2 protein expression pattern and positive lymph nodes in patients with gastric carcinoma (P = 0.03). The expression pattern of HER2 +++ was significantly more common registered in patients with positive lymph nodes (P = 0.03). CONCLUSION: The expression of HER2 protein could represent a biological marker with prognostic and predictive value in patients with gastric carcinoma. Considering the high mortality rate in patients with gastric carcinoma and lack of international standardised therapeutic approach, research of the role and significance of HER2 overexpression and Trastuzumab therapy may prove useful in the development of new therapeutic strategies.

Tumour Lymphocytic Infiltration, Its Structure and Influence in Colorectal Cancer Progression.

BACKGROUND: The role of the immune system in the control of tumour progression has been stressed, recently. Many studies indicate the fact that the immune system can prevent tumour progression in several types of human malignant neoplasms including colorectal cancer. According to some authors, a higher density of "tumour-associated lymphocytes" (TAL), in malignant neoplasms, correlate with prolonged survival of patients. AIM: This study aims to determine the structure and the influence of the immune cells, TAL, in the progression of colorectal cancer (CRC). PATIENTS AND METHODS: The study included 103 patients with CRC operated at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The structure of tumor-associated cells and their density were determined and were correlated with neoplasm's grade, local growth (T), positive lymph nodes, lymphatic invasion and stage of the disease. RESULTS: CD4+, CD8+ and CD20+ lymphocytes (Ly) were found in TAL. The density of TAL was significantly different in neoplasms with different T status, lymphatic invasion, patients with and without nodal metastasis and patients with a different stage of the disease. The density of CD4+, CD8+, and CD20+ cells were significantly different in neoplasms with different T. The density of CD8+ and CD20+ lymphocytes was lower in patients with nodal metastasis and higher stage. CONCLUSION: The density of tumor-associated lymphocytes can anticipate the disease progression in patients with colorectal cancer, and the density of TAL influences the control of tumour progression.

New Surgical Technologies Could Facilitate Surgical Hemostasis in Hemophilic Patients.

BACKGROUND: It's assumed that surgery in haemophilia can be accomplished these days safely. AIM: The aim of this study was to investigate the influence of new surgical technologies in the perioperative management and outcome of surgical procedures in haemophiliacs. METHODS: Two patients with mild haemophilia A underwent surgery (laparoscopic appendectomy and inguinal hernia repair). In both patients, the replacement therapy, with factor VIII, started 30 min before surgery. We used the available surgical technologies and techniques with a proven value in the best clinical practice, to achieve proper and permanent hemostasis. Postoperatively, the replacement therapy and thromboembolic prophylaxis was continued according to the international guidelines for the management of haemophilia. RESULTS: The operative and post-operative periods were uneventful. No significant differences were found in the operation time in our hemophilic patients versus non-hemophilic patients. Significant differences related to the hospital stay duration were found in both patients compared with controls, due to the necessary replacement therapy. CONCLUSION: With new surgical technologies, proper and permanent hemostasis can be achieved, without prolonging the operation time.