DIFFERENCE IN PREDICTORS OF ANASTOMOTIC LEAKAGE DEPENDING ON THE LEVEL OF ANASTOMOSIS AFTER COLORECTAL CANCER SURGERY.

Anastomotic leak (AL) after colorectal cancer surgery is one of the most serious postoperative complications which has major impact on outcomes. The aim of this study was to investigate preoperative and intraoperative risk factors for AL, as well as to examine whether there are differences in risk factors for AL depending on the primary tumor location. We retrospectively reviewed records of patients having undergone colorectal surgical procedures for malignancies between January 2013 and December 2017 in a single institution. Only procedures with primary anastomosis were included. Of the 153 patients, AL occurred in 10.6% of patients with primary tumor in the sigmoid colon and rectum, and in 8.2% of patients with primary tumor in the proximal sections of the colon. On univariate analysis, delayed oral intake and more advanced histologic stages of the tumor were significantly correlated with AL in patients with tumors in the sigmoid colon and rectum, and multiorgan resection and distant metastases in patients with tumors in the proximal sections of the colon. In conclusion, risk factors for the occurrence of AL vary depending on the primary tumor location and further investigation is needed to provide better insight into these differences.

Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients.

Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.

Anastomotic leak after colorectal cancer surgery - risk factors in 21thcentury.

PURPOSE: The purpose of our study was to investigate preoperative and intraoperative risk factors for anastomotic leak (AL) after elective colorectal resections performed for malignancies. In addition, we studied some features of postoperative recovery and their influence on AL occurrence. METHODS: We retrospectively reviewed the records of patients that underwent colorectal surgical procedures for malignancies between January 2013 and December 20017 in a single institution. Only procedures with primary anastomosis were included. RESULTS: Of the 153 patients, 56.2% were male. The mean age was 67.5 years. AL occurred in 15 patients (9.8%). In univariate analysis, multiorgan resection, delayed postoperative bowel movement and delayed onset of per oral intake were significantly correlated with AL. Gender, preoperative albumin level, primary cancer site and surgery duration did not have significant correlation with AL. CONCLUSIONS: Risk factors described in the literature of the 20th century are no longer current. The main findings that feature postoperative recovery were associated with increased risk of AL and should be more carefully investigated in further studies which could lead towards the development of new specific post-operative protocols.

Clinical significance of neoangiogenesis and index of proliferation in the signet ring type of gastric adenocarcinoma.

PURPOSE: The purpose of this study was to examine whether microvascular density and the level of proliferation in gastric signet ring cell carcinoma (SRCC) are important factors in the locoregional control of the disease. METHODS: Over a period of eight years, gastric resection specimens from 37 patients were examined. The proliferative index (labelled by Ki67) and microvascular density (MVD) index (mvdIDX) (labelled by CD105) were determined for each case of SRCC. RESULTS: Gastric SRCC was diagnosed more often in female than in male patients (21 females, 16 males ; p≤0.05) . The average age of female patients was 63 years, while the male patients were 62 years old on average (p=0.702). Immunohistochemical analysis showed that the median numbers of Ki67 positive cells and CD105 positive blood vessels were higher in tumors compared to surrounding non-tumor tissue. Higher proliferative index and higher mvdIDX were also established relative to tumor stage. Correlation analysis showed a high positive correlation between proliferation index and microvascular density (MVD) index (mvdIDX) (correlation coefficient=0.784). Receiver operating characteristics (ROC) analysis showed progression of both indices examined. CONCLUSION: Our results showed that, although both proliferative and mvdIDXs are reliable, the former had better performance in identifying of disease progression (AUC=0.970).

Laparoscopic gastric wedge resection as the method of choice in the treatment of gastrointestinal stromal tumors--A case report.

INTRODUCTION: The gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the gastrointestinal tract. The surgery of resectable gastric GIST is the primary therapy for these tumors, but the decision regarding the surgical radicality of the procedures is still a point of discussion among surgeons and oncologists. CASE OUTLINE: A 74-year-old patient was admitted to hospital with signs of bleeding from the upper parts of the gastrointestinal tract. Urgent gastroscopy was performed and a subepithelial gastric lesion with bleeding ulceration was noted in the region of the fornix. A computed tomography scan of the abdomen showed a tumor in the fornix region with the dimensions of 48 x 32 mm, which was growing mostly intraluminally. After an adequate preoperative preparation the patient underwent a laparoscopic wedge resection of gastric fornix with intramural tumor lesion. The histopathological analysis of the specimen showed a well differentiated GIST (histological grade Gi), of the spindle cell type. Based on the immunohistochemical analysis of thespecimen it was concluded that the patient was in the IA stage of the disease with a low risk of malignant progression. In the population of patients with GIST, this is the most common group (43%), with low malignant potential, and relapses present in only 3.6% of cases.The patient started with oral food intake on the first postoperative day, the first bowel movement occurred 36 hours after surgery, and the patient was released from hospital on the fourth postoperative day. CONCLUSION: Based on the aforementioned, we consider that the laparoscopic gastric wedge resection is a safe and efficient surgical procedure. This is primary therapy for most common group of patients with resectable gastric GIST.

Resection or radiofrequency ablation of colorectal liver metastasis.

BACKGROUND/AIM: Liver resection is the treatment of choice for solitary colorectal liver metastases in suitable candidates. Recently, radiofrequency ablation (RFA) has become a very popular procedure in the treatment of liver metastases. The aim of this study was to compare outcomes in patients with solitary colorectal liver metastasis who had been subjected to resection or ablation. METHODS: In this retrospective study we analyzed and compared patients with solitary colorectal liver metastases treated by resection or ablation in the University Hospital Centre "Dr Dragisa Misovic" in Belgrade from January 2002 until December 2009. RESULTS: In this study 94 (67.1%) patients underwent resection whereas 46 (32.9%) patients underwent RFA. Most of the resected patients (59.6%) required major hepatectomy. The median follow-up time was 28.4 months. Tumor ablation was a significant predictor of the overall survival (p = 0.002; OR 3.75; 95% CI 1.696-8.284). Our study demonstrated longer disease free-survival in the group of resected patients compared to the RFA group (37.6 vs 22.3 months, p = 0.073). The median overall survival was 56.3 months for patients who underwent resection vs 25.1 months for those in the RFA group (p = 0.005). CONCLUSION: This study shows that the patients with solitary hepatic colorectal cancer metastases should be considered for hepatic resection whenever it is feasible, because this procedure provides superior long-term survival as compared to radiofrequency ablation.

[Carcinoid of pancreas--case report].

INTRODUCTION: Carcinoid tumors are very common tumors of gastro-intestinal tract even though they are very rare in pancreatic area. A large number of patients with pancreatic carcinoma have nonspecific symptoms of disease which is the main cause of late operative treatment of advanced tumors as well as for a low rate of 5-years surviving (28,9% +/- 16%). CASE REPORT: A 69-year-old female patient was operated for a 7 cm large carcinoid in pancreatic corpus. Prior to the operation the patient did not have any symptoms of disease. Serotonin and 5-HIAA level was normal before the operation as well as afterwards. In this case distal hemipancreatectomy was done along with celiac, hepatic and lienal lymphadenoctomy. Liver metastasis was not found. The diagnosis of carcinoid was verified by postoperative histopathologic and imunohistochemical analysis. DISCUSSION: According to the experience of other authors, the operative treatment of pancreatic carcinoid is very often undertaken when dimensions of tumor exceed 7 cm. In this stage of disease distant metastases are present in more than 60% of patients. Only 23% of examinated patients have had carcinoid syndrome symptoms. According to this conclusion, the main role of diagnostic procedures is attributed to the computer tomography of abdomen as well as ERCP. The radical resection of pancreas with lymphadenectomy is recommended in order to have a precise histological examination and detect occult lymph node metastases. With radical surgical procedures even at this stage of disease the operation may be curative. CONCLUSION: Any kind of radical surgical treatment (depending of localizations of tumor, proximal or distal) is the main therapeutic procedure in pancreatic carcinoid.

[Gastrointerstinal stromal tumors of the stomach--case reports].

INTRODUCTION: Gastrointestinal stromal tumors are the most common mesenchimal tumors of the gastrointestinal tract. Despite the enormous progress made in the field of diagnostics, most often diagnosis is made during the explorative laparotomy and postoperative immunohystochemical analysis of specimen. The surgical treatment is often indicated, although scarce preoperative diagnosis causes intraoperative dilemma concerning the level of radicality. MATERIAL AND METHODS: In this paper we have analyzed two patients with gastric GIST. The first patient was 59 years old male, with preoperatively diagnosed colonic cancer. Intraoperatively besides the transverse colon cancer, we found intramural gastric tumor. This patient underwent subtotal gastrectomy and subtotal colectomy. The immunohystochemical analysis of gastric tumor proves benign GIST. The second patient was 50 year old male presented with repeated upper GI bleeding. The endoscopic ultrasound showed intramural tumor of the anterior gastric wall, with a visible blood vessel bleeding during endoscopy. After the resuscitation, we performed subtotal gastrectomy. The immunohystochemical analysis proved malignant GIST. DISCUSSION: In the cases with inadequate preoperative diagnoses, the level of resection procedure is based on the size of tumor and the presence of necrosis and bleeding inside the tumor. Tumors larger than 5 cm in diameter with signs of necrosis and bleeding are parameters of malignant nature of GIST, therefore demanding a radical surgical treatment. CONCLUSION: The surgical resection is a treatment of choice for gastrointestinal stromal tumors. It has been shown that adequate surgical resection correlates with high 5-years survival rates for patients with gastric GIST.

[Tumor volume in advanced gastric cancer as a prognostic factor correlating with lymph node involvement].

INTRODUCTION: It has been established that measurement of tumor volume, rather than its diameter, is a better indicator of the depth of tumor invasion and lymph node involvement. The present study evaluates the significance of tumor volume as a prognostic factor in gastric cancer. MATERIAL AND METHODS: This prospective clinical trail included 87 patients with gastric cacncer admitted to Surgery Clinic "Dr. Dragisa Misovic" in Belgrade from 1998 to 2003. All patients were evaluated by standard diagnostic procedures, and after that underwent radical surgical treatment. Oncologic-surgical principles recommended by Japanese Research Society for Gastric Cancer were respected. Tumor volume was determined by measurement of specimens that had been obtained during surgery and by histopathological analysis. These criteria were analyzed and correlated with the lymph node status and clinicopathological factors. RESULTS: Single-factor analysis showed that lymph node metastases correlated with larger tumor diameter, larger tumor volume, depth of tumor invasion, diffuse and low-grade differentiation of the intestinal type of gastric carcinoma. Using a linear correlation coefficient, it was found that there was a highly significant correlation of tumor volume and number of metastatic nodes in groups between lymph nodes r = 0.567; p < 0.0001 in drainage group 1, r = 0.511; p < 0.0001 in drainage group II, r = 0.579; p < 0.0001 in drainage group III. Also, there was highly significant correlation with the total number of metastatic nodes (r = 0.577; p < 0.0001) and significant correlation with the depth of tumor invasion and tumor diameter (p < 0.05). With 97% sensitivity and 88% specificity, "cut off" point was established by determining the tumor volume above which there were metastases into lymph nodes. In this study that volume was 2750 cmm. CONCLUSION: Tumor volume can be used as a valuable prognostic factor for advanced gastric cancer, and hopefully it will be calculated preoperatively by 3D-EUS volumetric analysis.

[Effect of systematic lymphadenectomy on postoperative mortality and morbidity in patients with gastric cancer]. / Uticaj sistematske limfadenektomije na postoperantivni mortalitet i morbiditet pacijenata sa karcinom zeluca.

INTRODUCTION: Surgical techniques and postoperative care for gastric cancer have significantly improved in recent years. However, whether postoperative morbidity and mortality rates after gastrectomy for gastric cancer have been reduced or not in recent years is still unclear. In this study we would like to point out the role of systematic lymphadenectomy in postoperative mortality and morbidity. MATERIAL AND METHODS: In this investigation we analyzed two groups of patients. The first group of 126 patients with gastric carcinoma underwent peritumor lymphadenectomy DI. The second group of 114 patients with gastric carcinoma underwent more radical types of lymphadenectomy (D2, D2+, D3). In this study we analyzed differences between these two groups of patients in regard to. 1) early postoperative mortality, 2) early postoperative complications and 3) long-term postoperative complications. RESULTS: Early postoperative mortality rate was 4.76% in D1 group and 5.26% in group with systematic lymphadenectomy (SL). 14.3% of patients in D1 group and 15.7% of patients in SL group had postoperative complications. The most frequent complications in D1 group were non-surgical complications of the respiratory system. In SL group the most common postoperative complications were anastomotic leakage (5/18, 27.77%) and wound infection (6/18, 33.3%). The most common long-term complications in both groups were: ventral postoperative hernia, anemia, small bowel obstruction and gallbladder calculosis. DISCUSSION: Early postoperative death occurred in patients with stage IV gastric cancer. The rates of anastomotic leakage, as main cause of early postoperative mortality and morbitity in patients with systematic lymphadenectomy, were reduced in the last few years with stapling surgery. CONCLUSIONS: There were no significant differences in the postoperative mortality and morbidity rates between the two analyzed groups in our investigation.

[Multiorgan resection in patients with gastric cancer]. / Vrednost multiorganske resekcije kod bolesnika sa karcinomom zeluca.

INTRODUCTION: Multiorgan resection for a malignancy is a very complicated procedure, but there is always the question: does it work? In everyday clinical practice gastric cancer in phases III and IV is rather frequent. Unfortunately, our patients are under the age of 55 years. D2 lymphadenectomy is not as extensive as D2 +/ or D3, so one must ask himself if multiorgan resection is worth the risk MATERIAL AND METHODS: We evaluated two groups of patients: group I consisted of 34 patients who underwent total or subtotal gastrectomy, systematic lymphadenectomy and resection of one or more organs; group II (control) consisted of 167 patients who underwent total or subtotal gastrectomy and systematic lymphadenectomy. These two groups of patients were analzyed in regard to: Bormann's classification, histopathologic type, early mortality, early postoperative complications, lymph node dissection and long-term survival. RESULTS: According to Bormann's classification the most common type of carcinoma in both groups was ulcerovegetativ tumor (70.6% in I and 58% in II). In the first group of patients a great number of patients had poorly differentiated adenocarcinomas (47%), while in the second group the most common histologic type was well differentiated intestinal carcinoma (28%). Patients with multiorgan resections had higher rates of early postoperative mortality and morbiditiy (mortality--14.7% and complications--26.5%) than patients in control group (mortality--4.8% and complications--11.4%). The most frequent causes of postopertive mortality and morbidity were anastomotic leakage and wound infections in both groups. Metastatic lymph node invelvement was higher in the first group (41%), than in the second (28%). Long-term survival was best in the control group (38.5 months). Patients with multiorgan resection had better survival (25.4 months) than inoperable cases (only 5 months). DISCUSSION: Patients undergoing multiorgan resection usually have advanced gastric cancer with tumor infiltration in surrounding structures. Only these cases are absolute indications for this radical operation, because patients have better chances for survival. CONCLUSION: Multiorgan resections are extensive procedures with high rates of postoperative mortality and morbidity, but represent the only way for better survival of patients with advanced gastric cancer.

[Importance of extensive lymphadenectomy in relation to the extent of metastatic lymph node involvement in patients with gastric carcinoma surgery]. / Procena znacaja sistematske limfadenektomije data kroz prikaz obima metastatske zahvacenosti limfnih zlezda kod bolesnika operisanih zbog karcinoma zeluca.

INTRODUCTION: Formation of lymphatic metastasis is an important prognostic factor in treatment of gastric carcinoma. In this paper we would like to point to the importance of systematic lymphadenectomy in regard to extent of metastatic lymph node involvement in patients with gastric carcinoma. MATERIAL AND METHODS: This investigation included 114 patients with diagnosis of gastric carcinoma undergoing systematic lymphadenectomy. We analyzed metastatic lymph node involvement considering: 1. tumor localization; 2. histopathologic type; 3. depth of tumor invasion; 4. extent of lymph node resection; 5. stage of disease. RESULTS: In the course of this study, 2100 lymph nodes were extracted by systematic lymphadenectomy (18.42 lymph nodes per patient on average). Out of this number, about 27% of lymph nodes were involved with metastasis, and 60% of positive lymph nodes belonged to the first, 25.7% to the second, 10.2% to the third and 3.8% to the fourth drainaged group. The most frequent localization (over 56%) of tumors was the distal third region of stomach. Histopathologically, most common type of carcinoma was intestinal carcinoma, with metastasis in first and second drainage group. A great number of patients have tumors with infiltration of the serosa. Those patients had metastases in lymph nodes in over 42%. Most patients (58%) belonged to IV stage of disease and presented with highest number of involved metastatic lymph nodes in all drainage groups. DISCUSSION: In our patients high metastatic involvement of all four drainage groups of lymph nodes was established. Up to date standard lymphadenectomy (D1) which has been performed increased the length of survival of these patients. CONCLUSION: By systematic lymphadenectomy we removed a great number of metastatic lymph nodes with beneficial effect on survival of patients with gastric carcinoma.