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Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers.Immune cell PD-L1-positivity, tumor size 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1

Right-sided colonic diverticulitis (RCD) and left-sided colonic diverticulitis (LCD) are considered distinct diseases. However, separate guidelines for RCD do not exist. Since the establishment of RCD management would first require evaluation of disease characteristics and recurrence patterns, this study has aimed to investigate the differences in the clinical characteristics between RCD and LCD and the recurrence patterns of RCD.Patients admitted for colonic diverticulitis between January 2012 and August 2020 were retrospectively reviewed. Clinical characteristics and recurrence rates in RCD and LCD patients, and predictors for recurrence and the recurrence patterns of RCD were analyzed.In total, 446 colonic diverticulitis patients (343 RCD, 103 LCD) were included in this study. RCD patients were more likely to be male, younger, taller, heavier, smoke, drink alcohol, have better physical performance scores, lower modified Hinchey stages and better initial laboratory findings. LCD patients were more likely to receive invasive treatments, have longer fasting and hospital days, higher mortality and cumulative recurrence rates (20.5% vs. 30.4%, P = 0.007). Recurrences in most RCD patients were of similar disease severity and received the same treatments for initial attacks, with rates of recurrence increasing after each recurrence. Predictors of the recurrence of RCD were complicated diverticulitis (hazard ratio[HR] 2.512, 95% confidence interval[CI] 0.127-5.599, p = 0.024) and percutaneous drainage (HR 6.549, 95% CI 1.535-27.930, p = 0.011).RCD is less severe and has a lower recurrence rate than LCD, suggesting that RCD should be treated conservatively. Patients with complicated diseases and those requiring percutaneous drainage are more likely to experience a disease recurrence, suggesting nonsurgical management may be insufficient.

Introduction As total neoadjuvant therapy for locally advanced rectal cancer (LARC) emerged, the possibility of skipping radiotherapy for poorly responsive patients arose. Machine-learning algorithms have focused on the radiopathologic features of tumor segmentation in order to predict responsiveness to radiotherapy. However, in addition to the tumor itself, there are several factors related to responsiveness, such as vasculature affecting hypoxia or MRI-detected extramural vascular invasion status. We aimed to predict poor responders using pretreatment rectal MRI images without segmentation and to identify which factors mainly contribute to the prediction algorithm. Methods Between Jan 1, 2000, and Dec 30, 2020, 689 consecutive patients were retrospectively included in two hospitals. Poor responders were defined by tumor regression grades (TRG) 2 and 3 that were determined through surgical resection. The ResNet-50 model was trained to predict poor responders from pretreatment rectal MRIs (T2-weighted axial, sagittal, and coronal images). We adopted a tenfold cross-validation for training and testing the model and used Gradient-weighted Class Activation Mapping (Grad-CAM) to highlight the important regions in the MRI scans that help predict poor responders. Results The number in each group of TRG was 108 (15.7%), 250 (36.3%), 265 (38.5%), and 66 (9.6%) for TRG0, TRG1, TRG2, and TRG3, respectively. There were 618 patients in the training cohort and 71 patients in the validation cohort. In the training and validation cohort, the accuracy for the prediction of poor responders was 85.6% (area under the curve (AUC) 0.856 [95% CI 0.761-0.950]) and 70.2% (AUC 0.703 [0.682-0.724]), although without segmentation. Our prediction model achieved a sensitivity of 0.724 (95% CI 0.700-0.748), a specificity of 0.684 (0.658-0.710), a positive predictive value of 0.697 (0.656-0.737), and a negative predictive value of 0.708 (0.666-0.751) in the validation cohort. Grad-CAM showed that the most important part of the accurately predicted images to contribute to the prediction was not the tumor (7/355, 1.9%) but the pelvic vasculature (353/355, 99.4%), including iliac vessels, femoral vessels, and presacral plexus, and followed by the mesorectum (38/355, 10.7%). Conclusion The pelvic vasculature contributes more to predicting poor responders to radiotherapy than the tumor itself. Therefore, when creating a prediction model for responsiveness to radiotherapy in LARC, this should be considered. Citation Format: Rumi Shin, Byunho Jo, Inyeop Jang, Cheong-Il Shin, Jin Sun Choi, Seung-Yong Jeong, Seung Chul Heo, Ji Won Park, Min Jung Kim, Tae Hyun Hwang. Why only focus on the tumor?: The crucial role of the extra-tumor environment to predict poor responders for locally advanced rectal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5374.

Purpose: This study aimed to evaluate real-world clinical outcomes from surgically treated patients for sigmoid volvulus.Methods: Five tertiary centers participated in this retrospective study with data collected from October 2003 through September 2018, including demographic information, preoperative clinical data, and information on laparoscopic/open and elective/emergency procedures. Outcome measurements included operation time, postoperative hospitalization, and postoperative morbidity.Results: Among 74 patients, sigmoidectomy was the most common procedure (n = 46), followed by Hartmann’s procedure (n = 23), and subtotal colectomy (n = 5). Emergency surgery was performed in 35 cases (47.3%). Of the 35 emergency patients, 34 cases (97.1%) underwent open surgery, and a stoma was established for 26 patients (74.3%). Elective surgery was performed in 39 cases (52.7%), including 21 open procedures (53.8%), and 18 laparoscopic surgeries (46.2%). Median laparoscopic operation time was 180 minutes, while median open surgery time was 130 minutes (P < 0.001). Median postoperative hospitalization was 11 days for laparoscopy and 12 days for open surgery. There were 20 postoperative complications (27.0%), and all were resolved with conservative management. Emergency surgery cases had a higher complication rate than elective surgery cases (40.0% vs. 15.4%, P = 0.034).Conclusion: Relative to elective surgery, emergency surgery had a higher rate of postoperative complications, open surgery, and stoma formation. As such, elective laparoscopic surgery after successful sigmoidoscopic decompression may be the optimal clinical option.

Background The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. “Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs),” and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of “tumoral PD-L1/immune cell PD-L1/CD8+ TILs” may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.

Cancer cachexia is a metabolic disease affecting multiple organs and characterized by loss of adipose and muscle tissues. Metabolic dysregulated of adipose tissue has a crucial role in cancer cachexia. β-Carotene (BC) is stored in adipose tissues and increases muscle mass and differentiation. However, its regulatory effects on adipose tissues in cancer cachexia have not been investigated yet. In this study, we found that BC supplementations could inhibit several cancer cachexia-related changes, including decreased carcass-tumor (carcass weight after tumor removal), adipose weights, and muscle weights in CT26-induced cancer cachexia mice. Moreover, BC supplementations suppressed cancer cachexia-induced lipolysis, fat browning, hepatic gluconeogenesis, and systemic inflammation. Altered diversity and composition of gut microbiota in cancer cachexia were restored by the BC supplementations. BC treatments could reverse the down-regulated adipogenesis and dysregulated mitochondrial respiration and glycolysis in adipocytes and colon cancer organoid co-culture systems. Taken together, these results suggest that BC can be a potential therapeutic strategy for cancer cachexia.

Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness.CD133BC inhibited self-renewal capacity and CSC markers, includingThese results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

Background Upregulation of SLC2A genes that encode glucose transporter (GLUT) protein is associated with poor prognosis in many cancers. In colorectal cancer, studies reporting the association between overexpression of GLUT and poor clinical outcomes were flawed by small sample sizes or subjective interpretation of immunohistochemical staining. Here, we analyzed mRNA expressions in all 14 SLC2A genes and evaluated the association with prognosis in colorectal cancer using data from the Cancer Genome Atlas (TCGA) database. Methods In the present study, we analyzed the expression of SLC2A genes in colorectal cancer and their association with prognosis using data obtained from the TCGA for the discovery sample, and a dataset from the Gene Expression Omnibus for the validation sample. Results SLC2A3 was significantly associated with overall survival (OS) and disease-free survival (DFS) in both the discovery sample (345 patients) and validation sample (501 patients). High SLC2A3 expression resulted in shorter OS and DFS. In multivariate analyses, high SLC2A3 levels predicted unfavorable OS (adjusted HR 1.95, 95% CI 1.22–3.11; P = 0.005) and were associated with poor DFS (adjusted HR 1.85, 95% CI 1.10–3.12; P = 0.02). Similar results were found in the discovery set. Conclusion Upregulation of the SLC2A3 genes is associated with decreased OS and DFS in colorectal cancer patients. Therefore, assessment of SLC2A3 gene expression may useful for predicting prognosis in these patients. Electronic supplementary material The online version of this article (10.1186/s12885-019-5475-x) contains supplementary material, which is available to authorized users.

Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Cytokine concentrations of peritoneal fluid from CRC patients were measured. Patients were grouped according to peritoneal cancer burden (PCB): no tumor cells (≤ pT3), microscopic tumor cells (pT4), or gross tumors (M1c). Cytokine concentrations were compared among the three groups and the associations of those in pT4 patients with and without postoperative PR were assessed. Of the ten cytokines assayed, IL6, IL10, and TGFB1 increased with progression of PCB. Among these, IL10 was a marker of PR in pT4 (N = 61) patients based on ROC curve (p = 0.004). The IL10 cut-off value (14 pg/mL) divided patients into groups with a low (7%, 2 of 29 patients) or high (45%, 16 of 32 patients) 5-year PR (p

Aims To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. Methods This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4–8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. Results Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17–359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004–125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826–37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). Conclusions DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. Trial registration: ClinicalTrials.gov (NCT03062072).

Summary: Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval [CI], −1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (−8•0 points; 95% CI, -14•1 to −1•8, p = 0•0108), male sexual problems (−19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (−5•4 points on a 35-point scale; 95% CI, −8•0 to −2•7, p

Introduction Although recent studies have demonstrated the safety of laparoscopic surgery in T4 colon cancer, some patients could have poor prognosis. In this study, we aimed to analyse the risk factors affecting oncologic outcome of laparoscopic surgery. Materials and methods Among the 1033 T4 colon cancer patients collected from a multicentre database (2004–2017), 584 patients (458 T4a and 126 T4b) underwent laparoscopic approach for radical surgery. Risk factors associated with 3-year disease-free survival (DFS) and overall survival (OS) were evaluated through multivariate analysis. In addition, subgroups were classified using a combination of risk factors, and the survival rate was evaluated. Results During this period, 188 (32.2%) had recurrence, and 151 (25.9%) died. In the multivariate analysis for oncologic outcome, elevated carcinoembryonic antigen level (hazard ratio [HR] 1.37) and absence of adjuvant chemotherapy (HR 1.60) were associated with poor DFS. T4b (HR 1.56, 1.46), right-sided location (HR 1.52, 1.42), and open conversion (HR 2.70, 2.12) were independently associated with both poor DFS and OS. When four subgroups were analysed through the combination of tumour location and T stage, the DFS and OS rates were significantly lower in patients with right-sided T4b cancer than in other groups (log-rank p Conclusion Right-sided T4b colon cancer for laparoscopic surgery may lead to poor oncologic outcome. This approach could be a caution in suspected cases preoperatively.

Self-expanding metallic stents (SEMSs) are used as a bridge to surgery in patients with obstructive colorectal cancer. However, the role of laparoscopic resection after successful stent deployment is not well established. We aimed to compare the oncologic outcomes of laparoscopic vs open surgery after successful colonic stent deployment in patients with obstructive left-sided colorectal cancer. In this multicenter study, 179 (97 laparoscopy, 82 open surgery) patients with obstructive left-sided colorectal cancer who underwent radical resection with curative intent after successful stent deployment were retrospectively reviewed. To minimize bias, we used inverse probability treatment-weighted propensity score analysis. The short- and long-term outcomes between the groups were compared. Both groups had similar demographic and tumor characteristics. The operation time was longer, but the degree of blood loss was lower in the laparoscopy than in the open surgery group. There were nine (9.3%) open conversions. After adjustment, the groups showed similar patient and tumor characteristics. The 5-year disease-free survival (DFS) (laparoscopic vs open: 68.7% vs 48.5%, p = 0.230) and overall survival (OS) (laparoscopic vs open: 79.1% vs 69.0%, p = 0.200) estimates did not differ significantly across a median follow-up duration of 50.5 months. Advanced stage disease (DFS: hazard ratio [HR] 1.825, 95% confidence interval [CI]: 1.072–3.107; OS: HR 2.441, 95% CI 1.216–4.903) and post-operative chemotherapy omission (DFS: HR 2.529, 95% CI 1.481–4.319; OS: HR 2.666, 95% CI 1.370–5.191) were associated with relatively worse long-term outcomes. Stent insertion followed by laparoscopy with curative intent is safe and feasible; the addition of post-operative chemotherapy should be considered after successful treatment.

Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to compare the quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer. Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were EORTC QLQ-C30 and CR38 quality-of-life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78·4%) underwent sphincter preservation surgery and 74 (21·6%) underwent abdominoperineal resection. After 3 years, abdominoperineal resection was associated with a worse body image (adjusted mean difference, 9·8 points on a 100-point scale; 95% CI, 2·9 to 16·6, p=0·0052), micturition symptoms (-8·0 points; 95% CI, -14·1 to -1·8, p=0·0108), male sexual problems (-19·9 points; 95% CI, -33·1 to -6·7, p=0·0032), less confidence in getting and maintaining an erection in males (0·5 points on a 5-point scale; 95% CI, 0·1 to 0·8, p=0·0155), and worse urinary symptoms (-5·4 points on a 35-point scale; 95% CI, -8·0 to -2·7, p

The relationship between duration of in-hospital waiting time and outcomes from appendectomy in patients with suspected appendicitis remains equivocal. The aim of this study was to investigate the influence of in-hospital waiting time on perforation rates and clinical outcomes in patients with suspected appendicitis who underwent appendectomy.A retrospective review of 5956 patients who underwent appendectomy at a single institution from January 2008 to December 2016 was performed. Patients were separated into two groups based on the duration from hospital arrival to surgery: patients with an in-hospital waiting time ≤ 12 h (no-delay group; n = 5287) and those with an in-hospital waiting time 12 h (delayed group; n = 669). One-to-one propensity score matching (n = 421 per group) was performed to compare perforation rates and postoperative outcomes between the groups.After propensity score matching, an in-hospital waiting time 12 h was not associated with increased rates of perforation and significant complications, such as wound infection and abscess. However, in the matched cohorts and in the patients whose initial CT scans suggested perforated appendicitis, the delayed group had a higher risk of developing postoperative ileus (OR 9.18, 95% CI 1.16-72.74, p = 0.021; OR 2.17, 95% CI 1.03-4.59, p = 0.048, respectively) and longer postoperative length of hospital stay (87.38 vs. 79.07 h, p = 0.008; 161.61 vs. 130.87 h, p 0.001, respectively) than the no-delay group.Our results indicate that a 12-h in-hospital waiting time to surgery for appendicitis presents very little risk to the patient. However, the surgeon needs to carefully weigh the "safety" of a delay to surgery for appendicitis in patients whose initial CT scans suggested perforated appendicitis.

Background Colonic self-expanding metallic stenting (SEMS) is widely used for the treatment of malignant colonic obstruction as a bridge to elective surgery. However, the effects of colonic stenting on long-term oncologic outcomes are debatable. This study aimed to compare the long-term oncologic outcomes of preoperative SEMS insertion with those of immediate surgery in patients with obstructing left-sided colorectal cancer. Methods A cohort of consecutive patients who underwent radical surgery for obstructing left-sided colorectal cancer between 2004 and 2011 in five tertiary referral hospitals were analyzed. Long-term survivals were analyzed and adjusted using the inverse probability of treatment weighting method, based on propensity scores, to reduce selection bias. Results One hundred and nine patients underwent immediate surgery, and 226 underwent stent insertion before surgery. Disease-free survival did not differ significantly in both the unadjusted population (hazard ratio [HR] 1.063, 95% confidence interval [CI] 0.730–1.548; Log-rank, p = 0.746) and the adjusted population (HR 0.122, 95% CI 0.920–1.987; Log-rank, p = 0.122). Overall survival also did not differ significantly in both the unadjusted population (HR 0.871, 95% CI 0.568–1.334; Log-rank, p = 0.526) and the adjusted population (HR 1.023, 95% CI 0.665–1.572; Log-rank, p = 0.916). Defunctioning stoma formation was less in the SEMS insertion group than immediate surgery group (adjusted, 14.6% vs. 41.3%, p Conclusion The ‘bridge to surgery’ strategy using metallic stents was oncologically comparable to immediate surgery in patients with malignant left-sided colorectal obstruction.

PURPOSE The preoperative diagnosis of acute appendicitis is often challenging. Sometimes, pathologic results of the appendix embarrass or confuse surgeons. Therefore, more and more imaging studies are being performed to increase the accuracy of appendicitis diagnoses preoperatively. However, data on the effect of this increase in preoperative imaging studies on diagnostic accuracy are limited. We performed this study to explore unexpected appendiceal pathologies and to delineate the role of preoperative imaging studies in the diagnosis of acute appendicitis. METHODS The medical records of 4,673 patients who underwent an appendectomy for assumed appendicitis between 1997 and 2012 were reviewed retrospectively. Pathological results and preoperative imaging studies were surveyed, and the frequencies of pathological results and preoperative imaging studies were investigated. RESULTS The overall rate of pathology compatible with acute appendicitis was 84.4%. Unexpected pathological findings, such as normal histology, specific inflammations other than acute appendicitis, neoplastic lesions, and other pathologies, comprised 9.6%, 3.3%, 1.2%, and 1.5%, respectively. The rate of unexpected pathological results was significantly reduced because of the increase in preoperative imaging studies. The decrease in normal appendices contributed the most to the reduction while other unexpected pathologies did not change significantly despite the increased use of imaging studies. This decrease in normal appendices was significant in both male and female patients under the age of 60 years, but the differences in females were more prominent. CONCLUSION Unexpected appendiceal pathologies comprised 15.6% of the cases. Preoperative imaging studies reduced them by decreasing the negative appendectomy rate of patients with normal appendices.

We report our experience in the use of transanal minimally invasive surgery (TAMIS) and the feasibility and safety of this surgical technique in operating for various rectal diseases that require a transanal approach.Between 2013 and 2019, 30 patients underwent TAMIS for a rectal lesion at Seoul National University Boramae Medical Center. The clinical data including age, gender, body mass index, tumour size, distance from the anal verge, diagnosis, operation time, postoperative complications, duration of hospital stay, and post-operative margin status were obtained retrospectively from the electronic medical records.The mean operation time was 52.1±33.5 and the mean duration of hospital stay after surgery was 4.3±4.2 days. Most of the patients had undergone TAMIS for neuroendocrine tumor (NET) (60%) followed by an adenoma (16.7%) and rectal cancer (13.3%). 4 patients (13.3%) had minor complications after TAMIS. 2 patients (50%) had complained of diarrhea, 1 patient (25%) complained of fecal incontinence and 1 patient (25%) been diagnosed fluid in the operation bed.TAMIS is a useful method for local excision of rectal lesion located in mid to upper rectum as well as other rectal pathologies that require a transanal approach.

Hypoxia-related gene (HRG) expression is associated with survival outcomes of colorectal cancer (CRC). Our aim was developing a nomogram predicting CRC overall survival (OS) with HRGs and clinicopathological factors. The Cancer Genome Atlas (TCGA) database was used as discovery cohort and two Gene Expression Omnibus databases (GSE39582 and GSE41258) served as validation cohorts. A genetic risk score model prognosticating OS was developed using mRNA expression level of HRGs. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables. The genetic risk score model included four HRGs (HSPA1L, PUM1, UBE2D2, and HSP27) and successfully prognosticated OS of discovery and two validation cohorts (p p p = 0.042 for the GSE41258 datasets). Nomogram included genetic risk score, age, and TNM stage. Harrell’s concordance indexes of the nomogram were higher than those of TNM stage alone in the discovery set (0.77 vs. 0.69, p p p

Background: We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (BRAFV600E, henceforth BRAF) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE39582) datasets. Materials and Methods: The effects of BRAF and KRAS mutations on overall survival (OS) and disease-free survival (DFS) of CRC were evaluated. Results: The mutational status of BRAF and KRAS genes was not associated with overall survival (OS) or DFS of the CRC patients drawn from the TCGA database. The 3-year OS and DFS rates of the BRAF mutation (+) vs. mutation (−) groups were 92.6% vs. 90.4% and 79.7% vs. 68.4%, respectively. The 3-year OS and DFS rates of the KRAS mutation (+) vs. mutation (−) groups were 90.4% vs. 90.5% and 65.3% vs. 73.5%, respectively. In stage II patients, however, the 3-year OS rate was lower in the BRAF mutation (+) group than in the mutation (−) group (85.5% vs. 97.7%, p < 0.001). The mutational status of BRAF genes of 497 CRC patients drawn from the GSE39582 database was not associated with OS or DFS. The 3-year OS and DFS rates of BRAF mutation (+) vs. mutation (−) groups were 75.7% vs. 78.9% and 73.6% vs. 71.1%, respectively. However, KRAS mutational status had an effect on 3-year OS rate (71.9% mutation (+) vs. 83% mutation (−), p = 0.05) and DFS rate (66.3% mutation (+) vs. 74.6% mutation (−), p = 0.013). Conclusions: We found no consistent association between the mutational status of BRAF nor KRAS and the OS and DFS of CRC patients from the TCGA and GSE39582 databases. Studies with longer-term records and larger patient numbers may be necessary to expound the influence of BRAF and KRAS mutations on the outcomes of CRC.

Background There has been no comparative study of the long-term oncological outcomes of appendiceal cancer and colon cancer. We hypothesized that the oncological outcome is worse in appendiceal cancer because perforation is more frequent than in colon cancer. Methods Patients with stage I–III were selected from 5046 patients with appendiceal or colon cancer, between September 2001 and June 2010. The 5-year disease-free survival (DFS) was the primary endpoint. Multivariate analyses with Cox proportional hazards model for DFS and logistic regression model for perforation were conducted. A matching model was used to compensate for the heterogeneity between groups. Results The perforation rate was 44.7% in appendiceal cancer (n = 47), but 1.1% in colon cancer (n = 2828) ( p = 0.001). The 5-year DFS rate was lower in appendiceal cancer than in colon cancer (57.9% vs . 85.2%, p = 0.001; matching model, 54.2% vs . 78.4%, p = 0.038), with a higher rate of peritoneal seeding (25.5% vs . 2.5%, p = 0.001; matching model, 24.0% vs . 4.0%, p = 0.007). Multivariate Cox regression showed that appendiceal cancer was an independent prognostic factor for poor DFS (hazard ratio = 2.602, 95% confidence interval = 1.26–5.35, p = 0.009), and logistic regression confirmed that appendiceal cancer was the risk factor associated with perforation (odds ratio = 66.265, 95% confidence interval = 28.21–155.61, p = 0.001). Conclusions This study suggested that the long-term oncological outcomes are worse for appendiceal cancer than for colon cancer, attributed to higher perforation rate in appendiceal cancer.

PURPOSE Stage-IIIC colon cancer is an advanced disease; however, its oncologic outcomes and prognostic factors remain unclear. In this study, we aimed to determine the predictors of disease-free survival (DFS) in patients with stage-IIIC colon cancer. METHODS From a multicenter database, we retrospectively enrolled 611 patients (355 men and 256 women) who had undergone a potentially curative resection for a stage-IIIC colon adenocarcinoma between 2003 and 2011. The primary end-point was the 5-year DFS. RESULTS The median age was 62 years; 213 and 398 patients had right-sided colon cancer (RCC) and left-sided colon cancer (LCC), respectively. The 5-year DFS in all patients was 52.0%; median follow-up time was 35 months (range, 1-134 months). A multivariate Cox regression revealed that female sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.19-1.90; P < 0.01), right-sided tumor location (HR, 1.65; 95% CI, 1.29-2.11; P < 0.01), lymphatic invasion (HR, 1.52; 95% CI, 1.08-2.15; P < 0.01) and a high (≥0.4) metastatic lymph node ratio (HR, 3.72; 95% CI, 2.63-5.24; P < 0.01) were independent predictors of worse 5-year DFS. Female patients with RCC were 1.79 fold more likely to experience recurrence than male patients with LCC. CONCLUSION Female sex and right-sided tumor location are associated with higher tumor recurrence rates in patients with stage-IIIC colon cancers. Aggressive treatment and close surveillance should be planned for patients in these groups.

A laparoscopic approach can be attempted for pathologic T4 (pT4) colon cancer. Our aim was to evaluate the clinico-oncologic outcomes following laparoscopic versus open surgery for right and left-sided pT4 colon cancer. From a multicentric collaborative database, we enrolled 245 patients with right-sided colon cancer (RCC, 128 laparoscopy and 117 open) and 338 with left-sided colon cancer (LCC, 176 laparoscopy and 162 open). All patients underwent intended curative surgery for histologically proven T4 adenocarcinoma, between 2004 and 2013. The primary end-point of our analysis was the oncologic outcome, including the 5-year disease-free survival (5 year-DFS) and the 5-year overall survival (5 year-OS). The secondary end-points included the R0 resection rate and postoperative complications. Our study group included 224 T4N0 and 359 T4N+ tumors. The median follow-up was 53 months. For patients with RCC, the rate of postoperative morbidities was lower for the laparoscopy than that for the open surgery group (12.5 vs. 22.2%, p = 0.044). There was no difference in the R0 resection rate (94.5 vs. 96.6%, p = 0.425) between the groups. The 5 year-DFS and 5 year-OS rates were lower for the laparoscopy than that in the open group (48.9% vs. 59.2%, p = 0.093; 60.0% vs. 70.0%, p = 0.284, respectively), but this difference was not statistically significant. Among patients with LCC, there were no differences in the rate of postoperative complication and R0 resection (15.3 vs. 21.0%, p = 0.307; 96.0 vs. 95.7%, p = 0.875, respectively). Both groups had comparable 5 year-DFS and 5 year-OS rates (62.7% vs. 61.1%, p = 0.552; 72.0% vs. 71.8%, p = 0.611, respectively). Laparoscopic surgery appears to be a safe procedure for patients with pT4 LCC, but requires careful consideration for patients with pT4 RCC.

Purpose: This study was conducted to evaluate the initial experience of 24 cases of laparoscopic liver resection by a single surgeon to determine its feasibility and report perioperative complications associated with this technique. Methods: A retrospective analysis of data from 24 patients who received attempted laparoscopic liver resections for primary liver tumors from November 2008 to April 2012 was conducted. Sixteen benign and eight primary malignant lesions were included. The patient’s electronic medical records including age, gender, underlying disease, past medical history, type of operations, operative time, complications, conversion rates, and length of hospital stay were reviewed. Results: The mean age of the patients was 52.6 years and the mean operation time was 263.7 minutes. The overall morbidity was 12.5% and the mortality was zero. One case was converted to open surgery (4.2%), while intraoperative transfusion was conducted in four cases. The types of operations included left hepatectomy (n=12, 50%; 3 with CBD exploration), left lateral sectionecectomy (n=4, 16.7%; 1 with cholecystectomy), partial hepatectomy for benign tumor (n=3, 12.5%: 1 with cholecystectomy), right hepatectomy (n=1, 4.1%), S6 segmentectomy (n=1, 4.1%), and tumorectomy (n=3, 12.5%). The mean estimated blood loss during operation was 375.3 cc and the postoperative hospital stay was 7.7 days. Additionally, one intraoperative complication and two postoperative complications occurred (12.5%). There was no postoperative mortality. Conclusion: The results of this study indicate that laparoscopic surgery with HBP training is suitable for laparoscopic liver resection. However, to ensure safety of the liver resection and the advantages of laparoscopic surgery, a thorough understanding of hepatic anatomy and elaborate surgical planning is essential.

More than half of all rectal cancers are T3 lesions, but they are classified as a single-stage category.The aim of this study was to validate prognostic significance of mesorectal extension depth in T3 rectal cancer.This study is a retrospective analysis of oncologic outcomes of patients with T3 rectal cancer grouped by mesorectal extension depth (T3a,1 mm; T3b, 1-5 mm; T3c, 5-15 mm; T3d,15 mm).This study was conducted at a tertiary referral cancer hospital.From 2003 to 2009, 291 patients who underwent a curative surgery were included.Oncologic outcomes in terms of disease-free survival were analyzed.The 5-year disease-free survival rate according to T3 subclassification was 86.5% for T3a, 74.2% for T3b, 58.3% for T3c, and 29.0% for T3d. It was significantly higher in T3a,b tumors than that in T3c,d tumors (77.6% vs 55.2%, p0.001). On univariate and multivariate analysis, prognostic factors affecting recurrence were preoperative CEA level ≥ 5 ng/mL (HR 2.617, 95% CI 1.620-4.226), lymph node metastasis (HR 3.347, 95% CI 1.834-6.566), and mesorectal extension depth5 mm (HR 1.661, 95% CI 1.013-2.725). In subgroup analysis, independent prognostic factors were preoperative CEA level and mesorectal extension depth5 mm for 200 patients with ypT3 rectal cancer and preoperative CEA level and lymph node metastasis for 91 patients with pT3 rectal cancer.This study lacks quality of surgery plane evaluation because of its retrospective nature. Moreover, pathologic examination was not done with a whole-mount section.Depth of mesorectal extension5 mm is a significant prognostic factor in patients with T3 rectal cancer. Depth of mesorectal extension especially may be more important than the nodal status in predicting the oncologic outcome for patients who had received preoperative chemoradiotherapy.

Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133(+)CD44(+) cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133(+)CD44(+) HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the beta-catenin/p-GSK3 beta signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.

Although laparoscopic surgery may permit earlier recovery compared with open surgery, no published randomized controlled trial has investigated the benefit of a multimodal rehabilitation program after laparoscopic colonic resection. This study aimed to evaluate the efficacy of a rehabilitation program after laparoscopic colon surgery in the context of a randomized controlled trial.Between September 2007 and October 2009, 100 patients who had received laparoscopic colon surgery were selected for the study and randomly assigned on a 1:1 basis to a rehabilitation program group with early mobilization and diet (n = 46) or conventional care group (n = 54). The rehabilitation program group received early oral feeding, early ambulation, and regular laxative. The primary outcome was recovery time, measured with criteria of tolerable diet for 24 hours, safe ambulation, analgesic-free, and afebrile status without major complications. Secondary outcomes were postoperative hospital stay, complications, quality of life by Short Form 36, pain by visual analog scale, and readmission. This study was registered (ID number NCT00606944, http://register.clinicaltrials.gov).Recovery time was shorter in the rehabilitation program group than in the conventional care group (median (interquartile range), 4 (3-5) d vs 6 (5-7) d, respectively; P.0001). There was no difference in postoperative hospital stay between the 2 groups (rehabilitation program group, 7 (6-8) d vs conventional care group, 8 (7-9) d; P = .065). There was no difference in complication rates between the rehabilitation program group and conventional care group (10.9% vs 20.4%, respectively; P = .136). Quality of life and pain were similar in both groups. There were no readmissions or mortality.A rehabilitation program with early mobilization and diet after laparoscopic colon surgery results in reduced recovery time without increased complications. These results suggest that a multimodal rehabilitation program may increase the short-term benefits after laparoscopic colon surgery.

97 Background: Immunoediting other than PD-1 works in colorectal cancer (CRC), except for some MSI high tumors. Study of immune response to cancers in the primary CRC is difficult due to interference by the colonic microorganisms. If a clinical model reflecting tumor progression, free from microbial antigens and characterizing the microenvironment is developed it will help us understand the immunoediting of CRC. We studied immunologic changes, according to the peritoneal tumor progression, in ascites and peritoneal immune cells of CRC patients. These results will provide clues to the immunoediting of CRC and to immunotherapy of peritoneal carcinomatosis. Methods: Ascites and peritoneal cells were collected from CRCs during surgery or malignant ascites drainage. Forty-two immune molecules and ratios of immune cells were assayed. Patients with intestinal perforation or leukocytosis were excluded to remove interference by the foreign antigens. Patients were grouped according to the peritoneal tumor progression (PC stages) as follows; SE-: without peritoneal exposure of cancer cells (T3 or lower T stage, no tumor cells in peritoneal cavity); SE+: with peritoneal exposure without peritoneal seeding (T4, microscopic tumor cells in peritoneal cavity); l-PC: localized peritoneal seeding; g-PC: generalized peritoneal seeding. Molecular and cellular changes were evaluated according to PC stages. Results: Of the 42, five (IL-10, IL-6, VEGF, CCL20 and TGF-b) increased with the PC stage progression, meanwhile IL-18 decreased. CXCL8 was elevated in only g-PC. However, 14 molecules could not be assayed due to lower level than the references and other 3 could be assayed in only some g-PCs. The other 18 were not different among PC stages. Especially, IL-10 is a prognostic factor of peritoneal recurrence in SE+. IL-10 and IL-6 are highly correlated. The ratio of CD56+ cells, but not the others, increased according to PC stages. Conclusions: Intraperitoneal CRC growth accompanied IL-10, IL-6, VEGF, CCL20, TGF-b and NK cell increase, meanwhile IL-18 decrease. IL-10 is a prognostic factor of peritoneal recurrence. Identification of secreting and targeting cells of each molecules as well as immune network will provide the clues to immunoediting of CRC.

Purpose Although lymph node (LN) metastasis is an important prognostic marker of colorectal cancer (CRC), the effect of LN metastasis on the survival of stage IV CRC is debated yet. Methods LN status and survivals as well as clinicopathological features of synchronous stage IV CRC patients, operated for 8 years, were analyzed. Patients with hematogenous metastases were included only but those with peritoneal seeding or preoperative adjuvant therapy were not included. Results Total 850 patients were enrolled and 77 (9.1%) were without LN metastases (N0M1). N0M1 patients were older and have favorable pathological features including lower CEA than patients with LN metastasis (N + M1). The pathologically poor features accumulated with N stage progression within N + M1. N0M1 had better 5-year overall survival (OS) and disease free survival than N + M1. And 5-year OS's within N + M1 group were stratified and different according to N stage progression, although the effect of N stage progression is different according to curative resection or not. When compared with stage III, 5-year OS of N0M1 with curative resection was comparable to that of anyTN2aM0 and was better than anyTN2bM1. Conclusion LN metastasis is a significant prognostic factor in stage IV by hematogenous metastasis, too. N stage progression accumulates pathologically poor prognostic factors. However, the effect on survival of each N stage progression differs depending on curative resection or not of the hematogenous metastases.

Presentamos un caso de pseudoaneurisma de la vena cefalica diagnosticado en un nino de 13 anos de edad que se presento con una masa superficial en el brazo derecho. El paciente carecia de antecedentes de traumatismo, puncion venosa o drogodependencia por via intravenosa. El examen ecografico revelo una dilatacion al nivel de la pared anterior de la vena cefalica con trombosis mural. La masa se separo facilmente y se reseco por completo tras la ligadura de la vena cefalica aferente y eferente. El examen patologico revelo que era un pseudoaneurisma de esta vena. Entre la literatura anglosajona, este paciente podria representar el primer caso publicado de pseudoaneurisma venoso espontaneo. Tambien se describen las caracteristicas clinicas, incluida la etiologia, diagnostico, tratamiento y complicaciones de esta lesion sumamente infrecuente.

Activated beta-catenin is suggested to inhibit NF-kappaB activation, and we previ- ously demonstrated that NF-kappaB nuclear positivity was more frequent in Epstein- Barr virus (EBV)-infected gastric carcinomas. It is controversial that beta-catenin and E-cadherin are prognostic markers in gastric carcinomas. To define a relation- ship between beta-catenin and EBV, and the prognostic value of beta-catenin and E-cadherin, we analyzed in situ hybridization for EBV-encoded small RNAs, beta- catenin, and E-cadherin immunohistochemistry, and clinicophatological features in 111 gastric carcinomas. EBV infection was detected in seven carcinomas (6.3%); none of seven showed beta-catenin nuclear accumulation, and five out of seven revealed beta-catenin membranous loss or cytoplamic expression. Eighty cases (72.1%) showed beta-catenin alteration; i.e., loss of membrane staining in 65 (58.6 %), cytoplasmic expression in 35 (31.5%), and nuclear accumulation in 15 (13.5%). E-cadherin alteration was observed in 34 cases (30.6%) and correlated with beta- catenin alteration. On multivariate analysis, the combined immunoexpression group of beta-catenin nuclear accumulation/ E-cadherin alteration and the advanced TNM cancer stage group showed poor patient's survival ( p

To elucidate possible associations between dietary factors and colorectal cancer in the context of the Korean diet, a case-control study was conducted in Seoul, Korea. Cases (n = 136) were patients either newly diagnosed with colorectal cancer or with large bowl adenomatous polyps. Control patients (n = 134) included those with no history of cancer and conditions potentially unrelated to nutritional status and digestive tract diseases from the same hospitals. Intakes of nutrients and food groups were assessed by a semiquantitative food frequency questionnaire and analyzed by the logistic regression model adjusted for possible confounding variables. Significant trends of decreasing risk of colorectal cancer emerged with more frequent intakes of vitamin A (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.15-0.65 for the highest tertile), β-carotene (OR = 0.25, 95% CI = 0.12-0.52), and vitamin C (OR = 0.29, 95% CI = 0.14-0.61). The protective associations were also observed for calcium (OR = 0.43, 95% CI = 0.21-0.86) and fiber (OR = 0.51, 95% CI = 0.25-1.05). Energy consumption was associated with an increased risk in the highest tertile of consumption (OR = 2.04, 95% CI = 1.01-4.12). The highest tertiles of rice, cake, and fish intakes were related to higher colorectal cancer risk (OR = 3.12, 95% CI = 1.41-6.91; OR = 2.39, 95% CI = 1.13-5.03; OR = 2.52, 95% CI = 1.21-5.26, respectively). Inverse associations of risk were found for milk (OR = 0.29, 95% CI = 0.15-0.58), kimchi (OR = 0.41, 95% CI = 0.20-0.84), vegetable (OR = 0.34, 95% CI = 0.16-0.71), and fruit (OR = 0.49, 95% CI = 0.24-1.02) intakes. This study further supports the protective effects of antioxidant vitamins and calcium associated with vegetable and milk consumptions and confirms a relevant role of dietary intake against colorectal cancer risk for Koreans.

Purpose: The aim of this study was to evaluate the clinical value of whole body F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the patient with a recurrence of a previously treated colorectal malignancy. Materials and Methods: Fifty-eight cases were scanned using PET at the PET Center of Seoul National University Hospital between May 1995 and Aug 2002. All the patients had had a previous operation for a colorectal malignancy. The PET scans were performed for the following reasons: - investigation of a recurrence (n=12), investigation of the operability (n=38) and clinical follow up (n=8). In these 58 cases, 47 of the CT scans and 55 of the CEA (Carcinoembryonic antigen) were checked prior to the FDG- PET. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PET scans were calculated, and compared with those of conventional CT scan and CEA, which were also compared with the previous reported data. Eight cases, whose managements were influenced by the PET findings, were analyzed. Results: Recurrences, or metastases, of colorectal cancer developed in 51 cases, with 49 of these being detected by the PET. The accuracy, sensitivity and specificity of the PET were 96.6 (56/58), 96.1 (49/51) and 100% (7/7), respectively. The PPV and NPV of the PET were 100 (49/49) and 77.8% (7/9), respectively. The accuracy and sensitivity of the PET were higher than those of the CT (85.1 and 88.1%), with the differences being statistically significant (p-value 0.001 and 0.003, respectively). Conclusion: It is concluded that a FDG-PET scan is a more accurate and sensitive diagnostic tool than a CT scan for the detection of a recurrence or metastasis in a colorectal malignancy. In addition, a FDG-PET may alter the management of patients with recurrent colorectal cancer. Therefore, it is recommended that a PET should be considered when a tumor recurrence is suspected during conventional follow up.

Purpose Recently, transoral endoscopic thyroidectomy (TOET) is receiving attention because it is regarded as a true minimally invasive surgery in that it does not leave scars on any part of the body and the area of flap dissection is similar to that of open surgery. In this study, we present the surgical procedures and initial outcomes of TOET in the treatment of papillary thyroid microcarcinoma (PTMC) patients. Methods The medical records of patients who underwent TOET for PTMC between July 2016 and February 2017 were retrospectively reviewed. Indication of TOET was PTMC without capsular invasion or lymph node metastasis on preoperative imaging studies. Results Ten female patients were enrolled. Seven patients underwent thyroid lobectomy and three patients underwent isthmusectomy. The mean age and tumor size was 43.3 ± 11.5 years and 0.6 ± 0.2 cm, respectively. Operation time for lobectomy and isthmusectomy was 121.1 ± 30.7 (range, 65-148) and 90.0 ± 9.2 minutes (range, 82-100 minutes), respectively. The mean number of retrieved lymph nodes was 2.7 ± 1.7. Two patients had transient vocal cord palsy, which recovered in three months. There was no case with subcutaneous emphysema, surgical site infection, postoperative bleeding, or mental nerve injury. Conclusion TOET was feasible and could be performed safely for PTMC. TOET might become a new treatment option for the patients who do not want to leave visible scars on the body.

See Article on Page 294-298 Condyloma acuminata arising from human papillomavirus (HPV) infection may cause anal squamous cell cancer and can have a recurrence rate of up to 50% of patients after surgical treatment because surgery cannot control latent HPV infection in surrounding tissue [1]. Therefore, trials using interferon, imiquimod, 5-fluorouracil, vaccine and natural products have been performed to reduce the recurrence rate. That the immune function of the host is important to the recurrence of condyloma is supported by the higher recurrences in patients with immune-suppressants and with human immunodeficiency virus (HIV) infection and by condyloma acuminate being a viral infection [2]. The incidence of HPV infection is more than twice in homosexual man than in others, and anal condyloma increases the incidence of anal cancer; hence, anal cancers are increasing in men who have sex with men [3]. With the increases in homosexuality and homosexual marriage, anal condyloma has become a disease deserving attention. Anal condylomas have more dysplasia in homosexual man and a more frequent neoplastic process in HIV-positive patients [4, 5]. Moreover, frequent multiple infections of oncogenic HPV strains such as HPV-type 16 or 18 are seen in HIV-positive patients [6]. Highly active antiretroviral therapy is thought by some researchers to contribute to reduce morbidity and mortality due to HIV infection, resulting in a decreased incidence of HPV infection and anal cancer while other researchers suggest that prolonged survival of HIV-positive patients may increase the prevalence of anal cancers [7]. Few data exist on the incidence of anal condyloma and associated anal squamous cell cancer in Korea. However, the increases in the number of HIV-positive patients and in their survival [8] will eventually make condyloma acuminata and associated anal cancer an important issue. As uterine cervical cancer, a typical cancer caused by HPV infection, diminishes in incidence and mortality because of publicity and education, the time to start surveillance and to increase education to prevent and to reduce the incidence of anal cancer due to HPV infection has arrived.

Background: Tumors grow in accordance with immunoediting. If we can see the changes of immune characteristics in the microenvironment during tumor growth, we can have much information of the mechanism of immunoediting. Peritoneal tumor cells from colorectal cancers are mostly derived from the shedding of tumor cells exposed on the visceral peritoneum. After the surgical removal of the primary tumors of which cells are exposed on the visceral peritoneum (T4 stage) but without macroscopic tumor seedings in the peritoneal cavity, some patients experience peritoneal recurrence but others do not. This implies that in the patients with future peritoneal recurrences the microscopic tumor cells in the peritoneal cavity have already been immunoedited. In addition, ascites and peritoneal immune cells are components of tumor microenvironment during peritoneal tumor growth if the peritoneal cavity is not contaminated by microorganisms by bowel perforation. And ascites and peritoneal cells are appropriate materials for immediate analysis after collection. Therefore, if we establish peritoneal immune characteristics of each T4 patient and compare those between the recurred and non-recurred patients in the peritoneal cavity afterwards, we can hold the clues of immunoediting during the peritoneal tumor growth. In this study we tested this autologous human growing tumor model for the relevance of research subject for cancer-associated immune response, as a pilot study. Method: Ascites and peritoneal cells were collected during the operation of colon cancer patients. If blood were mixed during the collection, the ascites and cells were discarded. The patients, whose ascites and peritoneal cells had been harvested, were classified into four groups (PC stages) according to the progression of peritoneal tumor growth on the basis of pathological report. SE-(serosa exposure negative; no tumor cells in peritoneal cavity) is a group of patients without exposure of cancer cells to peritoneal cavity (T3 or lower T stage). SE+(serosa exposure positive; microscopic tumor cells in peritoneal cavity) is a group of patients of T4 lesion without peritoneal seedings. l-PC represents localized peritoneal seedings which could be removed entirely during surgery. g-PC is a group of generalized peritoneal seeding. We performed ELISA and flow cytometry analysis as well as immune cell activation. Result: Of the 10 cytokines assayed in ascites, IL10, IL6 and TGF-beta increased according to the tumor progression in the peritoneal cavity, while the other cytokines (IL2, IL4, IL5, IL12, IL17, TNF and IFN-gamma) did not show any changes. Of the 42 SE+ patients, eleven experienced peritoneal recurrences. Mean IL10 (42 vs 24 pg/mL) and IL6 (2,092 vs 4472 pg/mL) levels of patients with peritoneal recurrence were higher than those without recurrence although we could not have significance (P = 0.113 and 0.180 each, Mann-Whitney U test). Activation of peritoneal cells by LPS increased IL6 as well as IL10 while activation by antiCD3 and antiCD28 did not. Intracellular IL10 was stained in T cells while IL6 in CD14 cells after LPS stimulation. Moreover, although ascitic IL6 increased up to tens of thousands pg/mL in g-PC patients, the blood level stayed at tens pg/mL. This means the ascites and peritoneal immune cells belong to a microenvironment which is seldom reflected in peripheral blood. Conclusion: This model showed the possibility of relevance to explore cancer-associated immune response in the tumor microenvironment during tumor growth in colorectal cancer. It is expected that further studies will provide much information of the mechanism of suppression of anti-tumor immune response. And the results derived from this model can help to extend understandings of immunoediting in primary tumors, metastatic tumors and, further, in other cancers. Citation Format: Seung Chul Heo, Sang Mok Lee, Beonghoon Sohn, Ji-Eun Kim, Rumi Shin. Autologous human growing tumor model and its immunological relevance for cancer immunology research [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B140.

Purpose An intestinal perforation is a rare condition, but has a high mortality rate, even after immediate surgical intervention. The clinical predictors of postoperative morbidity and mortality are still not well established, so this study attempted to identify risk factors for postoperative morbidity and mortality after surgery for an intestinal perforation. Methods We retrospectively analyzed the cases of 117 patients who underwent surgery for an intestinal perforation at a single institution in Korea from November 2008 to June 2014. Factors related with postoperative mortality at 1 month and other postoperative complications were investigated. Results The mean age of enrolled patients was 66.0 ± 15.8 years and 66% of the patients were male. Fifteen patients (13%) died within 1 month after surgical treatment. Univariate analysis indicated that patient-related factors associated with mortality were low systolic and diastolic blood pressure, low serum albumin, low serum protein, low total cholesterol, and high blood urea nitrogen; the surgery-related factor associated with mortality was feculent ascites. Multivariate analysis using a logistic regression indicated that low systolic blood pressure and feculent ascites independently increased the risk for mortality; postoperative complications were more likely in both females and those with low estimated glomerular filtration rates and elevated serum C-reactive protein levels. Conclusion Various factors were associated with postoperative clinical outcomes of patients with an intestinal perforation. Morbidity and mortality following an intestinal perforation were greater in patients with unstable initial vital signs, poor nutritional status, and feculent ascites.