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We developed a procedure that identifies "novel" biologically active compounds that are expected to be distinct from known active compounds with respect to specificity and other such characteristics. The procedure involves mapping a set of known active compounds (training set) onto all possible hydrogen bonding and lipophilic interaction sites of an enzyme active site and flagging those interactions that are utilized by the training set. These flagged sites are removed (except for those that are deemed critical binding sites), leaving only potential interaction sites not utilized by the active compounds. Once unflagged sites were enumerated, pharmacophore models were then generated, scored, and prioritized where the top pharmacophore model was used to search 3D databases for identifying new leads. This procedure was applied to HIV-1 protease inhibitors. Several compounds retrieved by the top pharmacophore model were identified as moderately active (in muMolar range).

Purpose: Totally implantable venous access devices (TIVADs) currently have an important place in medical oncology practice; however, their long-term availability deserves further investigation, since they are usually required by patients for prolonged periods. This study aimed to evaluate long-term availability of TIVADs in adult cancer patients, in conjunction with complication/removal rates over time and associated risk factors during 7-year follow-up., Methods: A total of 204 adult cancer patients who underwent TIVAD placement via subclavian vein using the Seldinger technique were included in this study. Medical data and catheter follow-up records were investigated retrospectively. Complications and port removals due to complications were evaluated over time., Results: During median 21.9 (range, 0.7-82.9) months of follow-up, great majority of the patients did not require catheter removal due to complications (91.7%). During a total follow-up of 183,328 catheter days, 20 (9.8%) patients had complications with an incidence of 0.109 cases per 1000 catheter days and 18 (8.8%) of them required TIVAD removal (0.098 cases per 1000 catheter days). Most device removals due to complications (15/18, 83.3%) occurred within the first 24 months. Multivariate analysis identified left-sided device location as the only significant independent predictor of short device availability (OR, 3.5 [95% CI, 1.1-11.1], p = 0.036)., Conclusion: TIVADs in cancer patients appear to be safe and their availability appears to be high in the long term. A decision for early removal might be revisited. Opting for the accustomed side (right side in the present study) for implantations seems to be associated with better outcomes.

Background: In rectal cancer, extramural vascular invasion (EMVI) is the presence of tumour cells in blood vessels outside the muscular layer, which is associated with poor prognosis. Regression of EMVI on MRI following neoadjuvant chemoradiotherapy or its persistence may have prognostic implications., Methods: This retrospective study included 52 patients with rectal cancer who underwent total mesorectal excision following long-course neoadjuvant chemoradiotherapy (CRT). EMVI assessments were done on previous pelvic MRIs obtained before neoadjuvant CRT and eight weeks after the completion of neoadjuvant chemoradiotherapy in initially EMVI positive cases., Results: Persistently EMVI positive patients had worse overall survival and disease-free survival compared to initially EMVI negative patients and patients who returned to negative (p < 0.001 for both). Multivariate analysis identified persistent EMVI positivity after neoadjuvant treatment (HR, 102.9; p = 0.003) as significant independent predictor of worse overall survival; and persistent EMVI positivity (HR, 17.0; p = 0.002), mesorectal fascia involvement after neoadjuvant treatment (HR, 8.0; p = 0.017), and poor differentiation (HR, 10.3, p = 0.012) as significant independent predictors of worse disease-free survival., Conclusion: Persistent EMVI positivity after neoadjuvant therapy appears to be an independent factor for poor overall survival; and persistent EMVI positivity as well as mesorectal fascia involvement on post neoadjuvant therapy MRI and poor differentiation appears to be important predictors of poor disease-free survival in rectal cancer patients., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest. All authors also declare that they have received no financial support., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Background: This study aimed to compare the standard one-stage coloanal anastomosis (CAA) technique plus diverting ileostomy and the Turnbull-Cutait (T-C) technique with delayed CAA in terms of early post-operative morbidity in patients with low rectal cancer., Methods: A total of 33 patients with non-metastatic distal rectal cancer who were operated with one of the two different reconstruction methods (one-stage CAA plus diverting ileostomy or two-stage T-C technique with delayed CAA) after total mesorectal excision were included in this retrospective study. The two groups were compared for early post-operative morbidity within 30 post-operative days using complication frequency, Clavien-Dindo classification and Comprehensive Complication Index scores., Results: The two groups did not differ in terms of morbidity parameters, including frequency of any morbidity, presence of grade 3b morbidity requiring management under general anaesthesia, as well as Comprehensive Complication Index score (P > 0.05 for all)., Conclusion: Our findings suggest that the two techniques did not differ in terms of early post-operative morbidity. Owing to its comparable morbidity and safety to CAA plus concomitant ileostomy performed at the same session, the T-C technique may be considered in distal rectal cancer patients refusing to have a temporary stoma and in patients in whom CAA poses technical difficulties during the initial operation., (© 2020 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Purpose: To evaluate utility and prognostic value of serum CA 19-9 levels in relation to serum CEA levels in the longterm follow up of patients with colorectal cancer (CRC) METHODS: A total of 315 patients with CRC who were treated over a 13-year period were included in this retrospective study. Data on tumor characteristics, CEA and CA 19-9 levels were recorded. Survival analysis was performed with respect to marker status, while receiver operating characteristics (ROC) curve was plotted to determine the performance of CEA in predicting survival during follow up with calculation of area under curve (AUC) and cut-off value via ROC analysis., Results: Advanced T stage (T3-4, p<0.001), presence of intramural invasion (p=0.019), lymphatic invasion (p=0.003) and larger tumor volume (p=0.02) were associated only with high CEA levels on admission, while poor histological differentiation (p=0.036) was only associated with high CA 19-9 levels on admission. Presence of normal CEA and CA 19-9 levels was associated with the longest survival time (131.6 and 46.8 months, respectively, p<0.001 for each) and 5-year OS rate of 90.5%, while ROC analysis revealed CEA levels >11 (AUC (95% CI): 0.636 (0.580-0.690), p<0.001) to be a potential marker of poor survival with a sensitivity of 75.0% and specificity of 45.9%., Conclusion: In conclusion, our findings seem to indicate a weaker poor prognostic value of high CA 19-9 levels when used alone and strongly suggest combined use of CEA and CA 19-9 markers in prognostic assessment and risk-adapted follow-up surveillance in CRC patients., Key Words: CEA, CA 19-9, Colorectal cancer, Prognosis, Survival.

Background: This study aimed to evaluate clinicopathological characteristics and long-term oncological outcome with respect to mucinous histology of tumor in colorectal cancer (CRC) patients., Methods: A total of 372 patients who underwent resection surgery due to CRC between March 2006 and March 2019 were included in this retrospective study. Patients were divided into two groups according to degree of mucinous component including mucinous carcinoma group (n=48, ≥50% mucinous component) and non-mucinous carcinoma (n=324, <50% mucinous component) group. Data on patient demographics, tumor characteristics, treatment characteristics, metastasis and recurrence rates, disease free survival (DFS), and overall survival (OS) times were recorded., Results: Mucinous vs. non-mucinous carcinoma was associated with higher rate of T4 stage (p=0.036) and high grade tumors (p=0.001) with extranodal invasion (p=0.019) Both the OS time (75.9±13.1 vs. 110.8±5.6 months, p=0.019) and DFS time (98.5±15.6 vs. 140.5±5.1 months, p=0.003) were significantly shorter in colon cancer patients with vs. without mucinous carcinoma despite their higher likelihood of receiving chemotherapy (89.6 vs. 71.9%, p=0.009). Multivariate analysis revealed presence of perineural invasion (HR 1.865, p=0.002), extranodal invasion (HR 1.869, p=0.009), T4 stage (HR 1.617, p=0.019), and M1 stage tumors (HR 3.643, p<0.001) but not mucinous carcinoma to significantly predict poor survival in CRC patients., Conclusion: In conclusion, our findings indicate colorectal tumors with mucinous carcinoma histology to have a more aggressive tumor characteristics and advanced disease stage on admission in CRC patients as well as shorter OS time and DFS time specifically in colon cancer patients despite receiving chemotherapy., Key Words: Chemotherapy, Colorectal cancer, Long-term follow up, Mucinous histology, Survival.

Background: Despite technical developments in transplantation surgery, complete portal vein thrombosis still remains a challenge for restoration of adequate portal vein inflow. Renoportal or varicoportal anastomosis provides an effective alternative solution for patients with complete portal vein thrombosis. This study describes our experience with renoportal and varicoportal anastomosis during liver transplantation., Patients and Methods: Between January 2014 and May 2016, 5 patients with complete portal vein thrombosis underwent extra-anatomic portal anastomosis. In 3 cases, varicoportal anastomosis was performed and for the others, end-to-end renoportal anastomosis. We used iliac cryopreserved vein grafts to restore portal anastomosis in 3 cases. Epidemiology, risk factors, surgical techniques, complications, and outcomes of these procedures were evaluated over short- and long-term follow-ups., Results: The follow-up time is 3 years for our first renoportal case, which was performed in a cadaveric liver transplantation; it was also first nationwide case. The other renoportal anastomosis was practiced in a living donor liver transplantation and the follow-up time is 8 months. The patient and graft survival rates were 100% at the last follow-up. The follow-up times are 10.9 and 4 months for the patients with varicoportal anastomosis. One of these patients died due to recurrence of hepatocellular carcinoma. The other two patients are alive with good graft functions., Conclusion: Our experience suggests that reno-varicoportal anastomosis is a useful technique for patients with complete portal vein thrombosis and cryopreserved grafts may be safely used., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Accidental ingestion of foreign bodies is common in clinical practice. While perforation of the ileum and jejunum due to the ingested foreign body is common, duodenal perforation is rare. In this report, our experience with this rare entity is shared., Case Report: Here we present a 31-year-old patient with gastrointestinal tract perforation at the second part of the duodenum due to an ingested fishbone. The patient was admitted to the emergency room with abdominal pain. Right upper quadrant tenderness was detected at physical examination, and leukocytosis on the laboratory test results. Ultra-sonography was not diagnostic, however, computerized tomo-graphy showed an ingested foreign body in the second part of the duodenum. A fishbone perforating the duodenum was retrieved by endoscopy. The patient was managed non-operatively, and discharged without any problems on the third day after endoscopy., Conclusion: Endoscopic removal and non-operative management may be feasible in carefully selected patients with duodenal perforated fishbone ingestion., (Celsius.)

Background: The deregulation and localization of the Annexins is consistently reported to have close relation to tumor cell malignancy, invasion, and metastasis as well as clinical progression of tumors. This study aimed to evaluate serum Annexin A2 (Anx A2) levels in patients with colon cancer in comparison to healthy controls and in relation to demographics and tumor pathology., Material and Methods: A total of 100 patients (mean (SD) age: 58 (5.8) years, 55.0% females) with colon cancer and 70 controls (mean (SD) age: 59 (5.4) years, 50.0% females) were included. Serum levels for Anx A2 were evaluated in relation to study group, demographics, and tumor pathology., Results: Serum levels for Anx A2 were significantly lower in patients with colon cancer than in controls (13.1 (4.5) vs. 22.8 (2.1) ng/mL, p<0.001) and significantly decreased with increase in tumor size (p=0.003), and at higher stages of TNM (p=0.004), tumor invasion (p=0.005), lymph node metastasis (p=0.003), and distant metastasis (p=0.005)., Conclusions: Our findings indicate a significant decrease in Anx A2 expression in colon cancer patients compared to healthy controls and in parallel with tumor progression.

Objective: The aim of this study was to evaluate preoperative serum oncostatin M (OSM) concentration as a diagnostic marker in colon cancer patients and its association with clinicopathologic variables., Patients and Methods: Preoperative serum OSM concentrations were measured in 100 colon cancer patients and 70 healthy volunteers by enzyme-linked immunosorbent assay (ELISA)., Results: Serum OSM concentrations were significantly higher in colon cancer patients than in controls (p < 0.001). Serum OSM concentrations increased significantly with higher T stage (p < 0.001) and were significantly higher in patients with increased tumor burden, lymphovascular involvement, and lymph node and distant metastasis (p < 0.001 for each)., Conclusions: To our knowledge, this is the first report showing that elevated OSM concentration was associated with colon cancer and its clinicopathologic variables, including invasion and metastasis. These findings indicate that serum OSM may serve as a novel biomarker in the diagnosis of colon cancer.

Objectives: To determine and correlate preoperative serum levels of CEA and Dickkopf-related protein 1 (DKK-1) in stage II and III colon cancer and so identify the patients at high risk for early relapse., Patients and Methods: A total of 100 patients with stage II (n = 50; median age: 53 years, 31 males) and III (n = 50; median age: 57 years, 32 males) colon cancer and 50 controls (median age: 53.9 years, 25 males) were included. Serum levels for CEA and DKK-1 were recorded in each subject., Results: Mean (SD) levels for serum CEA and DKK-1 were significantly higher in stage III patients than in stage II patients and controls (p < 0.001 for each). There was a significant correlation between serum levels of CEA and DKK-1 in stage II (r = 0.71, p < 0.001) stage III (r = 0.62, p < 0.001) patients., Conclusions: Preoperative serum levels for DKK-1 seem to be a potential marker in prediction of tumor invasion and relapse in stage II-III colon cancer.