Risk Factor Analysis of Lymph Node Metastasis for Rectal Neuroendocrine Tumors: Who Needs a Radical Resection in Rectal Neuroendocrine Tumors Sized 1-2 cm?

BACKGROUND: Rectal neuroendocrine tumors (NETs) have malignant potential, and lymph node (LN) or distant metastases can occur; however, treatment of NETs 1-2 cm in size is controversial. OBJECTIVE: This study aimed to identify predictive factors for LN metastasis and prognostic factors for recurrence of rectal NETs, especially tumors 1‒2 cm in size. METHODS: Between October 2004 and November 2020, 453 patients underwent endoscopic or surgical treatment for rectal NETs in Seoul National University Hospital. The data on these patients were prospectively collected in our database and reviewed retrospectively. In cases of local excision, we evaluated LN metastasis with radiologic imaging, including computed tomography or magnetic resonance imaging before treatment and during the follow-up periods. RESULTS: LN metastasis was observed in 40 patients (8.8%). A higher rate of LN metastasis was observed in larger-sized tumors, advanced T stage, lymphovascular invasion (LVI), perineural invasion (PNI), and high tumor grade. In multivariable analysis, the significant risk factors for LN metastasis were tumor size (1 ≤ size < 2 cm: hazard ratio [HR] 64.07; size ≥2 cm: HR 102.37, p < 0.001) and tumor grade (G2: HR 3.63, p = 0.034; G3: HR 5.09, p = 0.044). In multivariable analysis for tumors 1-2 cm in size, the risk factor for LN metastasis was tumor grade (G2: HR 6.34, p = 0.013). CONCLUSIONS: Tumor grade and size are important predictive factors for LN metastasis. In NETs 2 cm in size, tumor grade is also important for LN metastasis, and radical resection should be considered.

Prognostic roles of leptin-signaling proteins, PD-L1, and tumor-infiltrating lymphocytes in surgically-resected biliary tract cancers.

BACKGROUND: Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8+ and forkhead box P3 (FOXP3)+ lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers. METHODS: Immunohistochemistry 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. RESULTS: 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-L1(-) and leptin(-) subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1+ and leptin+ subgroups. CONCLUSIONS: The 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(-) or tumor leptin(-) subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1+ or leptin+ subgroups.

Safety of early surgery after self-expandable metallic stenting for obstructive left-sided colorectal cancer.

BACKGROUND: Self-expanding metallic stenting (SEMS) is usual for the temporary resolution of obstructive left-sided colorectal cancer (CRC) as a bridge to elective surgery. However, there is no consensus regarding adequate time intervals from stenting to radical surgery. The aim of this study was to identify the optimal time interval that results in favorable short- and long-term outcomes. METHODS: Data on patients with obstructive left-sided CRC who underwent elective radical surgery after clinically successful SEMS deployment in five tertiary referral hospitals from 2004 to 2016 were analyzed, retrospectively. An inverse probability treatment-weighted propensity score analysis was used to minimize bias. Postoperative short- and long-term outcomes were compared between two groups: an early surgery (within 8 days) group and delayed surgery (after 8 days) group. RESULTS: Of 311 patients, 148 (47.6%) underwent early and 163 (52.4%) underwent delayed surgery. The median surgery interval was 9.0 days. After adjustment, the groups had similar patient and tumor characteristics. In terms of short-term outcomes, there was no difference in hospitalization length or postoperative complications. No deaths were observed. With a median follow-up of 71.0 months, no significant difference was observed between the groups in 5-year overall survival (early vs. delayed surgery: 79.6% vs. 71.3%, P = 0.370) and 5-year disease-free survival (early vs. delayed surgery: 59.1% vs. 60.4%, P = 0.970). CONCLUSIONS: In obstructive left-sided CRC, the time interval between SEMS and radical surgery did not significantly influence short- and long-term outcomes. Therefore, early surgery after SEMS could be suggested if there is no reason to postpone surgery for preoperative medical optimization.

Oncologic safety of laparoscopic surgery after metallic stent insertion for obstructive left-sided colorectal cancer: a multicenter comparative study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Stent insertion followed by laparoscopy with curative intent is safe and feasible; the addition of post-operative chemotherapy should be considered after successful treatment.

Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data.

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.

Laparoscopic approach for left-sided T4 colon cancer is a safe and feasible procedure, compared to open surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Laparoscopic surgery appears to be a safe procedure for patients with pT4 LCC, but requires careful consideration for patients with pT4 RCC.

Survival paradox between stage IIB/C (T4N0) and stage IIIA (T1-2N1) colon cancer.

BACKGROUND: The survival paradox between stage IIB/C (T4N0) and stage IIIA (T1-2N1) colon cancer remains in the 7th edition of the American Joint Committee on Cancer staging system. This multicenter study aimed to compare the oncologic outcomes of T4N0 and T1-2N1 colon cancers and to investigate the presumptive prognostic factors that might influence the survival paradox. METHODS: Patients who underwent curative surgery for pT4N0 (n = 224) and pT1-2N1 (n = 135) primary colon cancer between January 1999 and December 2010 at five tertiary referral cancer centers were included for analysis. The clinicopathologic, treatment-related factors, and oncologic outcomes in terms of the 5-year overall survival (5-OS) and 5-year disease-free survival (5-DFS) were compared. RESULTS: The T4N0 group had significantly worse 5-OS and 5-DFS rates than the T1-2N1 group (5-OS: 84.0 vs. 92.3 %, p = 0.012; 5-DFS: 73.6 vs. 88.0 %, p = 0.001). T4N0 cancers more frequently showed elevated preoperative carcinoembryonic antigen, lower grade of differentiation, larger tumor size, and higher proportions of perineural invasion, microsatellite instability, obstruction, and perforation than T1-2N1 cancers. Peritoneal seeding and liver metastasis were the predominant recurrence pattern in the T4N0 and T1-2N1 groups, respectively (p = 0.042). The T4N0 group showed inferior survival to the T1-2N1 group in postoperative adjuvant chemotherapy (5-OS: 87.1 vs. 93.2 %, p = 0.045; 5-DFS: 76.1 vs. 89.0 %, p = 0.001). CONCLUSIONS: T4N0 colon cancer had significantly worse oncologic outcomes than T1-2N1 cancer regardless of adjuvant chemotherapy. The survival paradox may result from the biologic aggressiveness of T4N0 colon carcinomas.

Early postoperative small bowel obstruction is an independent risk factor for subsequent adhesive small bowel obstruction in patients undergoing open colectomy.

BACKGROUND: This prospective study was performed to investigate whether postoperative ileus (POI) or early postoperative small bowel obstruction (EPSBO) affects the development of adhesive small bowel obstruction (SBO) in patients undergoing colectomy. METHODS: We prospectively enrolled 1,002 patients who underwent open colectomy by a single surgeon. POI was defined as the absence of bowel function for more than 5 days or as a delay in oral intake beyond 7 days postoperatively. EPSBO was defined as the clinical and radiologic identification of SBO after resuming oral intake between postoperative days 7 and 30. Adhesive SBO was defined as SBO developing after 30 days because of intraperitoneal adhesion. The associations between POI, EPSBO, patient- and surgery-related variables, and the development of adhesive SBO were analyzed. RESULTS: A total of 85 (8.5 %) patients developed POI, and 42 patients (4.2 %) developed EPSBO, with seven patients experiencing both POI and EPSBO. During the follow-up period (median 51 months), 70 patients (7.0 %) developed adhesive SBO, six (8.6 %) of whom needed laparotomy. The occurrence of adhesive SBO was significantly higher in patients with EPSBO than in those without EPSBO (26.5 vs. 7.5 % at 5 years, P < 0.001), but not in patients with POI (13.4 vs. 7.8 % at 5 years, P = 0.158). Multivariable analysis showed colostomy (hazard ratio [HR] 2.530, P = 0.006) and EPSBO (HR 4.063, P < 0.001) as independent risk factors for adhesive SBO. CONCLUSIONS: The development of adhesive SBO after colectomy is more frequent in patients with EPSBO and colostomy; however, POI does not increase the risk of adhesive SBO.

Combination of oxaliplatin and ß-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro.

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. ß-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G2/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

ß-Carotene suppresses cancer cachexia by regulating the adipose tissue metabolism and gut microbiota dysregulation.

Cancer cachexia is a metabolic disease affecting multiple organs and characterized by loss adipose and muscle tissues. Metabolic dysregulated of adipose tissue has a crucial role in cancer cachexia. ß-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.

Depth of mesorectal extension has prognostic significance in patients with T3 rectal cancer.

BACKGROUND: More than half of all rectal cancers are T3 lesions, but they are classified as a single-stage category. OBJECTIVE: The aim of this study was to validate prognostic significance of mesorectal extension depth in T3 rectal cancer. DESIGN: 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). SETTINGS: This study was conducted at a tertiary referral cancer hospital. PATIENTS: From 2003 to 2009, 291 patients who underwent a curative surgery were included. MAIN OUTCOME MEASURES: Oncologic outcomes in terms of disease-free survival were analyzed. RESULTS: 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%, p < 0.001). 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 depth >5 mm (HR 1.661, 95% CI 1.013-2.725). In subgroup analysis, independent prognostic factors were preoperative CEA level and mesorectal extension depth >5 mm for 200 patients with ypT3 rectal cancer and preoperative CEA level and lymph node metastasis for 91 patients with pT3 rectal cancer. LIMITATIONS: This study lacks quality of surgery plane evaluation because of its retrospective nature. Moreover, pathologic examination was not done with a whole-mount section. CONCLUSIONS: Depth of mesorectal extension >5 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.

Apical-node metastasis in sigmoid colon or rectal cancer: is it a factor that indicates a poor prognosis after high ligation?

PURPOSE: The prognostic significance of apical-node metastasis around the inferior mesenteric artery (IMA) remains unclear. We investigated the oncological relevance of apical-node metastasis detected after high ligation of the IMA in stage III sigmoid colon or rectal cancer. METHODS: Between May 2003 and December 2007, 229 consecutive patients with stage III sigmoid colon or rectal cancer, who had undergone curative resection with high ligation, were analyzed. Cox proportional regression model was used to identify the prognostic factors for disease-free survival. RESULTS: Thirty-one patients (13.5%) had apical-node metastases: 0% with T0-1, 3.8% with T2, 11.5% with T3, and 29.3% with T4 disease (p = 0.017). Additionally, the factors related to apical-node metastasis were tumor size, number of metastatic lymph nodes, lymph-node ratio, and N-stage. Multivariate analysis showed that the lymph-node ratio (odds ratio (OR) = 40.53, 95% confidence interval (CI) = 8.41-195.22, p < 0.001) was an independent prognostic factor for disease-free survival but that apical-node metastasis was not a factor that predicted a poor outcome (OR = 1.53, 95% CI = 0.81-2.91, p = 0.192). Apical-node metastasis was not a prognostic factor for disease-free survival on multivariate analysis of the subgroups based on tumor location (sigmoid colon cancer: OR = 1.42, 95% CI = 0.42-1.82, p = 0.577; rectal cancer: OR = 1.82, 95% CI = 0.82-4.06, p = 0.141). CONCLUSIONS: This study suggests that apical-node metastasis is not a poor prognostic factor for stage III sigmoid colon or rectal cancer after high ligation.

ß-carotene regulates cancer stemness in colon cancer in vivo and in vitro.

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). ß-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133+CD44+ HCT116 and CD133+CD44+ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/ß-catenin signaling were examined. In addition, CD133+CD44+ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and ß-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133+CD44+ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/ß-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

Investigation of the clinical features and recurrence patterns of acute right-sided colonic diverticulitis: A retrospective cohort study.

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

Comparison of early mobilization and diet rehabilitation program with conventional care after laparoscopic colon surgery: a prospective randomized controlled trial.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Risk factors for persistent anal incontinence after restorative proctectomy in rectal cancer patients with anal incontinence: prospective cohort study.

BACKGROUND: This study evaluated the notion that preoperative anal incontinence might be a potent predictive factor for anal incontinence (AI) after restorative proctectomy in rectal cancer patients. The principal objective of this study was to determine the risk factors for persistent anal incontinence following restorative proctectomy. METHODS: This study was designed as a single-center, prospective cohort study of a single group of 93 patients who had AI before restorative proctectomy for rectal cancer. The study group was re-evaluated for the presence of AI 12 months after restorative proctectomy or ileostomy takedown. Incontinence severity was determined using the Fecal Incontinence Severity Index (FISI). Logistic regression analysis was performed to identify the clinicopathologic factors associated with persistent AI. RESULTS: Fifteen patients were excluded from analysis due to death within the 12 months after surgery (n = 7), no ileostomy repair (n = 5), loss to follow-up (n = 2), or previous treatment for anal incontinence (n = 1). At 12 months, 53 of 78 patients (67.9%) had persistent AI and 25 patients (32.1 %) had recovered. Multivariate analysis demonstrated that preoperative FISI scores higher than 30 (OR = 11.61, 95% CI 1.43-94.01, p = 0.022) and lower tumor location 5 cm or less from the anal verge (OR = 84.46, 95% CI 3.91-1822.85, p = 0.005) were independent factors for persistent AI. CONCLUSIONS: Anal incontinence may persist after restorative proctectomy in rectal cancer patients with high preoperative incontinence scores and lower tumor location. Therefore, this information should be provided when restorative proctectomy is offered for rectal cancer patients.

Interleukin 10 level in the peritoneal cavity is a prognostic marker for peritoneal recurrence of T4 colorectal cancer.

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 < 0.001). Multivariable analysis identified high IL10 levels as the independent risk factor for PR. Separation of patients into training and test sets to evaluate the performance of IL10 cut-off model validated this cytokine as a risk factor for PR. Peritoneal IL10 is a prognostic marker of PR in pT4 CRC. Further research is necessary to identify immune response of intraperitoneal CRC growth.

Laparoscopic approach for T4 colon cancer can be associated with poor prognosis in right-sided T4b tumours.

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 < 0.001). 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.

Incidence and disease course of new-onset diabetes mellitus in breast and colorectal cancer patients undergoing chemotherapy: A prospective multicenter cohort study.

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).

Quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer (ASPIRE): A long-term prospective, multicentre, cohort study.

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 < 0•0001). The 5-year overall survival was worse with abdominoperineal resection in unadjusted (92•2% vs 80•9%; difference 11•3%, hazard ratio 2•38; 95% CI, 1•27 to 4•46, p = 0•0052), but did not differ after adjustment. INTERPRETATION: In this long-term prospective study, abdominoperineal resection failed to meet the superiority to sphincter preservation surgery in terms of quality of life. Although the global quality of life scores did not differ between groups, this study suggests that sphincter preservation surgery can be an acceptable alternative to abdominoperineal resection for low rectal cancer, offering a better quality of life and sexual-urinary functions, with no increased oncological risk even after 3 years. FUNDING: Seoul National University Bundang Hospital, Korea.