Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy

Local tumor immune response and host immunity have been suggested as important prognosticators respectively in colorectal cancer. However, the utility of combination of these parameters remains inconclusive. The aim of this study was to investigate the combinational impact of local and host tumor immune response, as determined by tumor-infiltrating lymphocytes (TILs) and neutrophil-to-lymphocyte ratio (NLR), in patients with stage III colon cancer. Patients with stage III colon cancer homogeneously treated with surgery followed by FOLFOX chemotherapy between Jan 2007 and Aug 2013 were included retrospectively. Hematoxylin and eosin (H&E) stained tumor sections of local inflammatory infiltrate (TILs) were classified as 0-3 by the Klintrup-Mäkinen grading method. NLR was measured within 1 month of surgery. The association of NLR and TILs with survival, alone or combined, were measured using multivariate Cox proportional hazard regression analysis. Among 137 patients, 75 (54.7%) were identified as the high TIL group (TILs 2 and 3) and 97 (70.8%) as the low NLR group (NLR < 3). Of the patients with high TILs, 51 (68%) had a low NLR. In univariate analysis, operation time, complications, lymph node ratio (LNR), stage, TILs, and high TILs with low NLR were significantly associated with overall survival(OS). Multivariate Cox regression identified operation time, stage, and TILs as independent risk factors for OS. When high TILs with low NLR vs. others was entered into multivariate analysis, this also proved to be a significant predictor of OS (HR 4.1, 95% CI 1.1-14.2, P = 0.025), with an increased C-index and lower AIC value compared to TILs. Measuring TILs using H&E stained sections could stratify the prognosis of stage III colon cancer. Considering host immunity, using the combination of TILs and NLR, allowed the prognosis to be stratified in more detail.ope

Robotic Surgery for Rectal Cancer and Cost-Effectiveness

Robotic surgery is considered as one of the advanced treatment modality of minimally invasive surgery for rectal cancer. Robotic rectal surgery has been performed for three decades and its application is gradually expanding along with technology development. It has several technical advantages which include magnified three-dimensional vision, better ergonomics, multiple articulated robotic instruments, and the opportunity to perform remote surgery. The technical benefits of robotic system can help to manipulate more meticulously during technical challenging procedures including total mesorectal excision in narrow pelvis, lateral pelvic node dissection, and intersphincteric resection. It is also reported that robotic rectal surgery have been shown more favorable postoperative functional outcomes. Despite its technical benefits, a majority of studies have been reported that there is rarely clinical or oncologic superiority of robotic surgery for rectal cancer compared to conventional laparoscopic surgery. In addition, robotic rectal surgery showed significantly higher costs than the standard method. Hence, the cost-effectiveness of robotic rectal surgery is still questionable. In order for robotic rectal surgery to further develop in the field of minimally invasive surgery, there should be an obvious cost-effective advantages over laparoscopic surgery, and it is crucial that large-scale prospective randomized trials are required. Positive competition of industries in correlation with technological development may gradually reduce the price of the robotic system, and it will be helpful to increase the cost-effectiveness of robotic rectal surgery.ope

Changes in Body Composition During Adjuvant FOLFOX Chemotherapy and Overall Survival in Non-Metastatic Colon Cancer

The impact of longitudinal anthropometric changes during adjuvant chemotherapy on long-term survival in non-metastatic colon cancer is unclear. Herein, we analyzed the prognostic significance of computed tomography (CT)-measured body composition changes in colon cancer patients who underwent surgery followed by adjuvant FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) chemotherapy. Data of 167 patients with stage III or high-risk stage II colon cancer were analyzed. Skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral fat index (VFI), subcutaneous fat index (SFI), and total fat index (TFI) changes during chemotherapy were calculated using preoperative and postchemotherapy CT image data. The Cox proportional hazard model was used to determine the correlation between changes in anthropometric values and overall survival (OS). The median changes (%) in SMI, SMR, VFI, SFI, and TFI over 210 days during chemotherapy were 8.7% (p < 0.001), 3.4% (p = 0.001), -19% (p < 0.001), -3.4% (p = 0.936), and -11.9% (p < 0.001), respectively. Cut-off values of changes in SMI (skeletal muscle index change, SMIC) and SMR (skeletal muscle radiodensity change, SMRC) were defined at -2% and -2 Hounsfield units (HU) respectively, whereas those of changes in VFI (visceral fat index change, VFIC), SFI (subcutaneous fat index change, SFIC), and TFI (total fat index change, TFIC) were based on values that provided the largest χ2 on the Mantel-Cox test. Multivariable analysis revealed that low SMR measured on a postchemotherapy CT scan (hazard ratio, HR: 0.32, 95% confidence interval, CI: 0.15-0.70, p = 0.004) and visceral fat loss of at least 46.57% (HR: 0.31, 95% CI: 0.14-0.69, p = 0.004) were independent poor prognostic factors for OS. Severe visceral fat loss during FOLFOX chemotherapy and low skeletal muscle radiodensity measured on postchemotherapy CT scans are associated with poor OS in stage III and high-risk stage II colon cancer patients.ope

Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment

Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1-20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.ope

Clinical outcomes of complete cytoreduction with concurrent liver resection followed by hyperthermic intraperitoneal chemotherapy for synchronous peritoneal and liver metastatic colorectal cancer

BACKGROUND: This study aimed to evaluate the clinical outcomes of concurrent liver resection with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer patients with synchronous liver and peritoneal metastases. METHODS: Patients with colorectal liver and peritoneal metastasis who underwent complete cytoreduction and hyperthermic intraperitoneal chemotherapy with concurrent liver surgery between September 2014 and July 2018 were included. Perioperative outcomes, overall survival, and progression-free survival were analyzed retrospectively. RESULTS: In total, 22 patients were included. The median peritoneal cancer index was 13 (range, 0-26), and the median number of liver metastases was 3 (range, 1-13). The mean total operative time was 11.4 ± 2.6 h. Minor postoperative complications (Clavien-Dindo grade I-II) were reported in 10 patients (45.5%), and major postoperative complications (grade III-V) were reported in five patients (22.7%), including one mortality patient. The median overall survival since diagnosis with metastasis was 27.4 months. The median overall survival since surgical intervention and the progression-free survival were 16.7 months and 7.1 months, respectively. CONCLUSIONS: This short-term follow-up study showed that, in an experienced center, combined resection with hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases was feasible and safe with acceptable oncologic outcomes.ope

Robotic colorectal surgery

Robotic colorectal surgery has gradually been performed more with the help of the technological advantages of the da Vinci system. Advanced technological advantages of the da Vinci system compared with standard laparoscopic colorectal surgery have been reported. These are a stable camera platform, three-dimensional imaging, excellent ergonomics, tremor elimination, ambidextrous capability, motion scaling, and instruments with multiple degrees of freedom. However, despite these technological advantages, most studies did not report the clinical advantages of robotic colorectal surgery compared to standard laparoscopic colorectal surgery. Only one study recently implies the real benefits of robotic rectal cancer surgery. The purpose of this review article is to outline the early concerns of robotic colorectal surgery using the da Vinci system, to present early clinical outcomes from the most current series, and to discuss not only the safety and the feasibility but also the real benefits of robotic colorectal surgery. Moreover, this article will comment on the possible future clinical advantages and limitations of the da Vinci system in robotic colorectal surgery.ope

Is Low-Dose-Rate Endorectal Brachytherapy a New Treatment Method for Locally Advanced Distal Rectal Cancer?

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Korean Society of Coloproctology (KSCP) trial of cONsolidation Chemotherapy for Locally advanced mid or low rectal cancer after neoadjUvant concurrent chemoraDiothErapy: a multicenter, randomized controlled trial (KONCLUDE)

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) has been a standard treatment option for locally advanced rectal cancer with improved local control. However, systemic recurrence despite neoadjuvant CRT remained unchanged. The only significant prognostic factor proven to be important was pathologic complete response (pCR) after neoadjuvant CRT. Several efforts have been tried to improve survival of patients who treated with neoadjuvant CRT and to achieve more pCR including adding cytotoxic chemotherapeutic agents, chronologic modification of chemotherapy schedule or adding chemotherapy during the perioperative period. Consolidation chemotherapy is adding several cycles of chemotherapy between neoadjuvant CRT and TME. It could increase pCR rate, subsequently could show better oncologic outcomes. METHODS: Patients with advanced mid or low rectal cancer who received neoadjuvant CRT will be included after screening. They will be randomized and assigned to undergo TME followed by 8 cycles of adjuvant chemotherapy (control arm) or receive 3 cycles of consolidation chemotherapy before TME, and receive 5 cycles of adjuvant chemotherapy (experimental arm). The primary endpoints are pCR and 3-year disease-free survival (DFS), and the secondary endpoints are radiotherapy-related complications, R0 resection rate, tumor response rate, surgery-related morbidity, and peripheral neuropathy at 3 year after the surgery. The authors hypothesize that the experimental arm would show a 15% improvement in pCR (15 to 30%) and in 3-year DFS (65 to 80%), compared with the control arm. The accrual period is 2 years and the follow-up period is 3 years. Based on the superiority design, one-sided log-rank test with α-error of 0.025 and a power of 80% was conducted. Allowing for a drop-out rate of 10%, 358 patients (179 per arm) will need to be recruited. Patients will be followed up at every 3 months for 2 years and then every 6 months for 3 years after the last patient has been randomized. DISCUSSION: KONCLUDE trial aims to investigate whether consolidation chemotherapy shows better pCR and 3-year DFS than adjuvant chemotherapy alone for the patients who received neoadjuvant CRT for locally advanced rectal cancer. This trial is expected to provide evidence to support clear treatment guidelines for patients with locally advanced rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov NCT02843191 (First posted on July 25, 2016).ope

Development of a Rating System for Digestive System Impairments: Korean Academy of Medical Sciences Guideline

A systematic and effective welfare system for people with digestive system impairments is required. In Korea, an objective and scientific rating guideline does not exist to judge the digestive system impairments. Whether the impairments exist or not and the degree of it need to be examined. Thus, with these considerations we need a scientific rating guideline for digestive system impairments to fit our cultural and social background. In 2007, a research team, for the development of rating impairment guidelines, was organized under the supervision of Korean Academy of Medical Sciences. The rating guidelines for digestive system impairments was classified into upper and lower gastrointestinal tracts impairments and liver impairment. We developed objective rating guidelines for the upper gastrointestinal tract, the impairment generated after surgery for the stomach, duodenum, esophagus, and for the lower gastrointestinal tract, the impairment generated after construction and surgery for colon, rectum, anus, and intestinal stomas. We tried to make the rating impairment guidelines to include science, objectivity, convenience, rationality, and actuality. We especially emphasized objectivity as the most important value. We worked to make it easy and convenient to use for both the subjects who received the impairment ratings and the doctors who will give the ratings.ope

Characteristic Phenotypes in Korean Crohn’s Disease Patients Who Underwent Intestinal Surgery for the Treatment

There are no previous large scale studies which have evaluated the phenotypes and clinical characteristics of Korean Crohn's disease patients who underwent intestinal resection. The purpose of this multicenter retrospective cohort study was to evaluate the clinical characteristics of Korean Crohn's disease patients who underwent intestinal resection during the study period. A total of 686 patients were enrolled in this study. The study period was over a 20-yr period (1990-2009). The patients were divided into the first-10-yr group and the second-10-yr group. The phenotypes and clinical characteristics were compared between the groups. The most common site of the disease was the ileal area (37.8%) and stricturing behavior was observed in 38.3% patients. The most common type of surgery was segmental resection of the small bowel (30.6%). These phenotypes showed a similar pattern in both the first and second study period groups and did not show any significant differences between the groups. The number of registered patients increased continuously. The phenotypes of Korean Crohn's disease patients who underwent intestinal resection are different compared with previously reported clinical characteristics of general Crohn's disease patients.ope