Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Patients Using Harmonized Radiomics of Multcenter 18F-FDG-PET Image.

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.

Stimulatory Anticancer Effect of Resveratrol Mediated by G Protein-Coupled Estrogen Receptor in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

Fisetin induces the upregulation of AKAP12 mRNA and anti-angiogenesis in a patient-derived organoid xenograft model.

Colorectal cancer (CRC) is associated with high incidence and mortality rates. Targeted therapies for CRC cause various adverse effects, necessitating the development of novel approaches to control CRC progression. In this milieu, we investigated the anti-CRC effects of fisetin, a natural plant flavonoid. Cytotoxicity was performed in CRC patient-derived organoids (30 T and 33 T). Fisetin-induced tumor growth was evaluated in a CRC patient-derived organoid xenograft (PDOX) model. RNA sequencing, immunohistochemistry, and western blotting were performed subsequently. Fisetin significantly decreased organoid viability in a dose-dependent manner. In the PDOX model, fisetin significantly delayed tumor growth, showing a decrease in Ki-67 expression and the induction of apoptosis. In tumor tissues, four genes were identified as differentially expressed between the control and fisetin-treated groups. Among these, A-kinase anchoring protein 12 (AKAP12) level was significantly increased by fisetin treatment (fold change > 2, p < 0.05). Notably, fisetin significantly inhibited vascular endothelial growth factor (VEGF) and epithelial cell adhesion molecule (EpCAM) via upregulation of AKAP12. Our results demonstrate the upregulation of AKAP12 mRNA and inhibition of angiogenesis by fisetin as a therapeutic strategy against CRC.

Neuromedin U contributes to radiation resistance in colorectal cancer via YAP/TAZ signaling activation.

Resistance to radiation therapy remains a treatment obstacle for patients with high­risk colorectal cancer. Neuromedin U (NMU) has been identified as a potential predictor of the response to radiation therapy by RNA sequencing analysis of colorectal cancer tissues obtained from patients. However, the role of NMU in colorectal cancer remains unknown. In order to investigate role of NMU in colorectal cancer, NMU expression was regulated using small interfering RNA or an NMU­expression pCMV3 vector, and cell counting, wound­healing and clonogenic assays were subsequently performed. NMU knockdown decreased colorectal cancer cell proliferation and migration, and sensitized the cells to radiation. Conversely, NMU overexpression increased radiation resistance, proliferation and migration of colorectal cancer cells. Furthermore, by western blotting and nuclear fractionation experiments, NMU knockdown inhibited the nuclear translocation of yes­associated protein (YAP) and transcriptional co­activator with PDZ­binding motif (TAZ), resulting from the phosphorylation of these proteins. By contrast, the nuclear translocation of YAP and TAZ was increased following NMU overexpression in colorectal cancer cells. Recombinant NMU regulated YAP and TAZ activity, and the expression of the YAP and TAZ transcriptional target genes AXL, connective tissue growth factor and cysteine­rich angiogenic inducer 61 in an NMU receptor 1 activity­dependent manner. These results suggested that NMU may contribute to the acquisition of radioresistance in colorectal cancer by enhancing the Hippo signaling pathway via YAP and TAZ activation.

IGFL2-AS1, a Long Non-Coding RNA, Is Associated with Radioresistance in Colorectal Cancer.

Precise prediction of radioresistance is an important factor in the treatment of colorectal cancer (CRC). To discover genes that regulate the radioresistance of CRCs, we analyzed an RNA sequencing dataset of patient-originated samples. Among various candidates, IGFL2-AS1, a long non-coding RNA (lncRNA), exhibited an expression pattern that was well correlated with radioresistance. IGFL2-AS1 is known to be highly expressed in various cancers and functions as a competing endogenous RNA. To further investigate the role of IGFL2-AS1 in radioresistance, which has not yet been studied, we assessed the amount of IGFL2-AS1 transcripts in CRC cell lines with varying degrees of radioresistance. This analysis showed that the more radioresistant the cell line, the higher the level of IGFL2-AS1 transcripts-a similar trend was observed in CRC samples. To directly assess the relationship between IGFL2-AS1 and radioresistance, we generated a CRC cell line stably expressing a small hairpin RNA (shRNA) targeting IGFL2-AS1. shRNA-mediated knockdown of IGFL2-AS1 decreased radioresistance and cell migration in vitro, establishing a functional role for IGFL2-AS1 in radioresistance. We also showed that downstream effectors of the AKT pathway played crucial roles. These data suggest that IGFL2-AS1 contributes to the acquisition of radioresistance by regulating the AKT pathway.

Clinical outcomes of locking polymeric clip for laparoscopic appendectomy in patients with appendicitis: a retrospective comparison with loop ligature.

PURPOSE: This study aimed to compare the clinical outcomes of laparoscopic appendectomy (LA) according to the method of appendiceal stump closure. METHODS: Patients who underwent LA for appendicitis between 2010 and 2020 were retrospectively reviewed. Patients were classified into locking polymeric clip (LPC) and loop ligature (LL) groups. Clinical outcomes were compared between the groups. RESULTS: LPC and LL were used in 188 (56.6%) and 144 patients (43.4%), respectively for appendiceal stump closure. No significant differences were observed in sex, age, comorbidities, and the severity of appendicitis between the groups. The median operative time was shorter in the LPC group than in the LL group (64.5 minutes vs. 71.5 minutes, P=0.027). The median hospital stay was longer in the LL group than in the LPC group (4 days vs. 3 days, P=0.020). Postoperative incidences of intraabdominal abscess and ileus were higher in the LL group than in the LPC group (4.2% vs. 1.1%, P=0.082 and 2.8% vs. 0%, P=0.035; respectively). The readmission rate was higher in the LL group than that in the LPC group (6.3% vs. 1.1%, P=0.012). CONCLUSION: Using LPC for appendiceal stump closure during LA for appendicitis was associated with lower postoperative complication rate, shorter operative time, and shorter hospital stay compared to the use of LL. Operative time above 60 minutes and the use of LL were identified as independent risk factors for postoperative complications in LA. Therefore, LPC could be considered a more favorable closure method than LL during LA for appendicitis.

Advanced Xenograft Model with Cotransplantation of Patient-Derived Organoids and Endothelial Colony-Forming Cells for Precision Medicine.

Preclinical evaluation models have been developed for precision medicine, with patient-derived xenograft models (PDXs) and patient-derived organoids (PDOs) attracting increasing attention. However, each of these models has application limitations. In this study, an advanced xenograft model was established and used for drug screening. PDO and endothelial colony-forming cells (ECFCs) were cotransplanted in NRGA mice (PDOXwE) to prepare the model, which could also be subcultured in Balb/c nude mice. Our DNA sequencing analysis and immunohistochemistry results indicated that PDOXwE maintained patient genetic information and tumor heterogeneity. Moreover, the model enhanced tumor growth more than the PDO-bearing xenograft model (PDOX). The PDO, PDOXwE, and clinical data were also compared in the liver metastasis of a colorectal cancer patient, demonstrating that the chemosensitivity of PDO and PDOXwE coincided with the clinical data. These results suggest that PDOXwE is an improvement of PDOX and is suitable as an evaluation model for precision medicine.

A Patient-Derived Organoid-Based Radiosensitivity Model for the Prediction of Radiation Responses in Patients with Rectal Cancer.

Patient-derived tumor organoids closely resemble original patient tumors. We conducted this co-clinical trial with treatment-naive rectal cancer patients and matched patient-derived tumor organoids to determine whether a correlation exists between experimental results obtained after irradiation in patients and organoids. Between November 2017 and March 2020, we prospectively enrolled 33 patients who were diagnosed with mid-to-lower rectal adenocarcinoma based on endoscopic biopsy findings. We constructed a prediction model through a machine learning algorithm using clinical and experimental radioresponse data. Our data confirmed that patient-derived tumor organoids closely recapitulated original tumors, both pathophysiologically and genetically. Radiation responses in patients were positively correlated with those in patient-derived tumor organoids. Our machine learning-based prediction model showed excellent performance. In the prediction model for good responders trained using the random forest algorithm, the area under the curve, accuracy, and kappa value were 0.918, 81.5%, and 0.51, respectively. In the prediction model for poor responders, the area under the curve, accuracy, and kappa value were 0.971, 92.1%, and 0.75, respectively. Our patient-derived tumor organoid-based radiosensitivity model could lead to more advanced precision medicine for treating patients with rectal cancer.

Implication of FDG-PET/CT without synchronous colonic lesion in patients with stenotic left-sided colorectal cancer.

Although 18-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for detecting synchronous colorectal cancer (CRC) in stenotic CRC, long-term outcomes of patients without synchronous FDG-avid lesions are not well reported. We investigated postoperative colonoscopy results in patients with left-sided stenosing CRC without synchronous FDG-avid lesions. In this retrospective review, 754 patients with left-sided CRC without synchronous FDG-avid lesions on preoperative 18F-FDG PET/CT were divided into two groups based on the completeness of preoperative colonoscopy. Propensity score matching was performed to balance baseline characteristics. Results of postoperative colonoscopy were compared in both the unmatched and matched cohorts. At 1 and 5 years after surgery, the cumulative risk of advanced adenoma (AA) or carcinoma (CA) in all patients, risk of CA, and additional surgical risk were 1.8% and 10.1%, 0.1% and 0.4%, and 0% and 0.5%, respectively. In both cohorts, the AA risk was significantly higher in the incomplete colonoscopy group. However, the risk of CA showed no between-group difference in the matched cohort. Additional surgical risk did not differ between the two groups. Thus, the finding of negative FDG-avid lesions in the proximal colon in addition to the target CRC ensures the absence of additional lesions warranting surgical plan changes.

The Impact of Primary Tumor Resection on Survival in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases.

PURPOSE: This study was conducted to evaluate the effectiveness of primary tumor resection (PTR) in asymptomatic colorectal cancer (CRC) patients with unresectable metastases using the inverse probability of treatment weighting (IPTW) method to minimize selection bias. METHODS: We selected 146 patients diagnosed with stage IV CRC with unresectable metastasis between 2001 and 2018 from our institutional database. In a multivariate logistic regression model using the patients' baseline covariates associated with PTR, we applied the IPTW method based on a propensity score and performed a weighted Cox proportional regression analysis to estimate survival according to PTR. RESULTS: Upfront PTR was performed in 98 patients, and no significant differences in baseline factors were detected. The upweighted median survival of the PTR group was 18 months and that of the non-PTR group was 15 months (P = 0.15). After applying the IPTW, the PTR was still insignificant in the univariate Cox regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.5-1.21). However, in the multivariate weighted Cox regression with adjustment for other covariates, the PTR showed a significantly decreased risk of cancer-related death (HR, 0.61; 95% CI, 0.40-0.94). CONCLUSION: In this study, we showed that asymptomatic CRC patients with unresectable metastases could gain a survival benefit from upfront PTR by analysis with the IPTW method. However, randomized controlled trials are mandatory.

Valproic acid protects intestinal organoids against radiation via NOTCH signaling.

Radiotherapy is a leading treatment for various types of cancer. However, exposure to high-dose ionizing radiation causes acute gastrointestinal injury and gastrointestinal syndrome. This has significant implications for human health, and therefore, radioprotection is a major area of research. Radiation induces the loss of intestinal stem cells; hence, the protection of stem cells expressing LGR5 (a marker of intestinal epithelial stem cells) is a key strategy for the prevention of radiation-induced injury. In this study, we identified valproic acid (VPA) as a potent radioprotector using an intestinal organoid culture system. VPA treatment increased the number of LGR5+ stem cells and organoid regeneration after irradiation. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, an inhibitor of NOTCH signaling) blocked the radioprotective effects of VPA, indicating that NOTCH signaling is a likely mechanism underlying the observed effects of VPA. In addition, VPA acted as a radiosensitizer via the inhibition of histone deacetylase (HDAC) in a colorectal cancer organoid. These results demonstrate that VPA exerts strong protective effects on LGR5+ stem cells via NOTCH signaling and that the inhibition of NOTCH signaling reduces these protective effects, providing a basis for the improved management of radiation injury.

Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient­derived organoids.

Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that short­chain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allowing the administration of a lower and safer dose of radiation. To test this hypothesis, the responses of three­dimensional­cultured organoids, derived from CRC patients, to radiotherapy, as well as the effects of combined radiotherapy with the SCFAs butyrate, propionate and acetate as candidate radiosensitizers, were evaluated via reverse transcription­quantitative polymerase chain reaction, immunohistochemistry and organoid viability assay. Of the three SCFAs tested, only butyrate suppressed the proliferation of the organoids. Moreover, butyrate significantly enhanced radiation­induced cell death and enhanced treatment effects compared with administration of radiation alone. The radiation­butyrate combination reduced the proportion of Ki­67 (proliferation marker)­positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be non­responsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiation­induced cell death and improved regeneration capacity after irradiation in normal organoids. These results suggest that butyrate could enhance the efficacy of radiotherapy while protecting the normal mucosa, thus highlighting a potential strategy for minimizing the associated toxicity of radiotherapy.

5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy.

Colorectal cancer (CRC) is a major cause of mortality that can be treated effectively with chemotherapy and radiotherapy, although resistance to these therapeutic modalities often occurs. Tumor-treating fields (TTFields) can block tumor growth by selectively impairing tumor cell division. In this study, we investigated the mechanism by which 5-fluorouracil (5-FU) sensitizes tumor cells to TTFields. Human HCT116 and SW480 CRC cells were treated with 5-FU and/or TTFields, and characterized in vitro in terms of cell viability, apoptosis through reactive oxygen species production, autophagy, and metastatic potentials. The biological effects of 5-FU and/or TTFields were studied via positron emission tomography and computed tomography on xenograft tumor growth and were confirmed with organoid models of patients. Our results revealed that combination treatment with 5-FU and TTFields increased the efficiency of TTFields therapy in colon cancer cells by downregulating signaling pathways associated with cell proliferation, survival, cell invasion, and migration while upregulating pathways mediating apoptosis and autophagic cell death. The novel mechanistic insights gleaned in this study suggest that combination therapy with TTFields and 5-FU may be effective in treating CRC, although safety and efficacy testing in patients with CRC will need to be performed before this strategy can be implemented clinically for TTF-sensitization.

Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery.

PURPOSE: In this study, we investigated the role of neutrophil to lymphocyte ratio (NLR) as a predictor of tumor response and as a prognostic factor in patients with rectal cancer who had undergone curative surgery after neoadjuvant chemoradiation therapy (nCRT). METHODS: Between January 2009 and July 2016, we collected 140 consecutive patients who had undergone curative intent surgery after nCRT due to rectal adenocarcinoma. We obtained the pre- and post-nCRT NLR by dividing the neutrophil count by the lymphocyte count. The cutoff value was obtained using receiver operating characteristic analysis for tumor response and using maximally selected rank analysis for recurrence-free survival (RFS). The relationship among NLR, tumor response, and RFS was assessed by adjusting the possible clinico-pathological confounding factors. RESULTS: The possibility of pathologic complete response (pCR) was significantly decreased in high pre- (>2.77) and postnCRT NLR (>3.23) in univariate regression analysis. In multivariate analysis, high post-nCRT NLR was an independent negative predictive factor for pCR (adjusted odds ratio, 0.365; 95% confidence interval [CI], 0.145-0.918). The 5-year RFS of all patients was 74.6% during the median 37 months of follow-up. Patients with higher pre- (>2.66) and post-nCRT NLR (>5.21) showed lower 5-year RFS rates (53.1 vs. 83.3%, P = 0.006) (69.2 vs. 75.7%, P = 0.054). In multivariate Cox analysis, high pre-nCRT NLR was an independent poor prognostic factor for RFS (adjusted hazard ratio, 2.300; 95% CI, 1.061-4.985). CONCLUSION: Elevated NLR was a negative predictive marker for pCR and was independently associated with decreased RFS. For confirmation, a large-scale study with appropriate controls is needed.

Detection of Methylated SEPT9 in Korean Colorectal Cancer Patients: Comparison with Previous Studies.

BACKGROUND: This study aimed to investigate the detection of methylated Septin 9 (mSEPT9) in Korean patients with colorectal cancer (CRC) and compare the results with those of previous studies. METHODS: A total of 127 plasma samples (111 patients with untreated CRC, 5 patients with adenomas, and 11 CRC patients treated with concurrent chemoradiotherapy before surgery) were collected. mSEPT9 was measured qualitatively with the Abbott RealTime ms9 Colorectal Cancer Assay. RESULTS: mSEPT9 was detected in 44 of 111 (39.6%) cases of untreated CRC but was not detected in the adenoma cases. The difference in the sensitivity of mSEPT9 among patients with adenomas and those with each stage of untreated CRC was statistically significant (Dukes' staging, p = 0.002 and TNM staging, p = 0.008). The sensitivity of mSEPT9 for each of the stages (I - IV) of untreated CRC patients were 20.7%, 54.1%, 36.6%, and 75.0%, respectively. The positive mSEPT9 results in untreated CRC patients reverted to negative in 19 of 21 patients (90.5%) after treatment. CONCLUSIONS: Compared to previous studies, the overall sensitivity of mSEPT9 was lower, but similar patterns were found in the sensitivities for each stage. Additionally, mSEPT9 appeared to have potential as a monitoring tool for CRC.

Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells.

Protein arginine methyltransferase 5 (PRMT5) is a protein that catalyzes transfer of methyl groups to the arginine residues of proteins and is involved in diverse cellular and biological responses. While the participation of PRMT5 in cancer progression has been increasingly documented, its association with the invasive phenotype currently remains poorly understood. In the present study, we revealed that PRMT5 is overexpressed in human hepatocellular carcinoma (HCC) and in colon cancer and its depletion leads to the suppression of cell invasive activity via the reduction of the expression of MMP-2. Real-time quantitative RT-PCR analysis of 120 HCC patient tissues revealed the overexpression of PRMT5 in HCC and the association of PRMT5 with aggressive clinicopathological parameters, such as poorer differentiation (P=0.004), more frequent hepatic vein invasion (P=0.019), larger tumor size (P=0.011) and higher α-fetoprotein levels (P=0.020). Similarly to the data obtained with HCC, overexpression of PRMT5 was also displayed in colon cancer tissues, compared to matched non-tumor regions. Consistent with the significant association of the overexpression of PRMT5 with hepatic vein invasion in patient specimens, PRMT5 depletion via siRNA transfection led to a marked reduction in the invasion rate in both HCC and colon cancer cells. Reduced invasion associated with PRMT5 depletion was accompanied by a decrease in the expression of MMP-2. Collectively, our results indicated that PRMT5 overexpression in HCC and colon cancer cells contributed to their acquisition of aggressive characteristics, such as invasiveness, thus presenting a promising therapeutic target for the treatment of these diseases.

Oncological Outcomes After Robotic Proctectomy for Rectal Cancer: Analysis of a Prospective Database.

OBJECTIVE: The aim of this study is to evaluate the oncological outcomes of robotic total mesorectal excision (TME) at an NCI designated cancer center. SUMMARY BACKGROUND DATA: The effectiveness of laparoscopic TME could not be established, but the robotic-assisted approach may hold some promise, with improved visualization and ergonomics for pelvic dissection. Oncological outcome data is presently lacking. METHODS: Patients who underwent total mesorectal excision or tumor-specific mesorectal excision for rectal cancer between April 2009 and April 2016 via a robotic approach were identified from a prospective single-institution database. The circumferential resection margin (CRM), distal resection margin, and TME completeness rates were determined. Kaplan-Meier analysis of disease-free survival and overall survival was performed for all patients treated with curative intent. RESULTS: A total of 276 patients underwent robotic proctectomy during the study period. Robotic surgery was performed initially by 1 surgeon with 3 additional surgeons progressively transitioning from open to robotic during the study period with annual increase in the total number of cases performed robotically. Seven patients had involved circumferential resection margins (2.5%), and there were no positive distal or proximal resection margins. One hundred eighty-six patients had TME quality assessed, and only 1 patient (0.5%) had an incomplete TME. Eighty-three patients were followed up for a minimum of 3 years, with a local recurrence rate of 2.4%, and a distant recurrence rate of 16.9%. Five-year disease-free survival on Kaplan-Meier analysis was 82%, and 5-year overall survival was 87%. CONCLUSIONS: Robotic proctectomy for rectal cancer can be performed with good short and medium term oncological outcomes in selected patients.

Preoperative radiation dose escalation for rectal cancer using a concomitant boost strategy improves tumor downstaging without increasing toxicity: A matched-pair analysis.

PURPOSE: Pathologic complete response to neoadjuvant chemoradiation therapy (CRT) is associated with improved outcomes for patients with locally advanced rectal cancer (LARC). Increased response rates have been reported with higher radiation doses, but these studies often lack long-term outcome and/or toxicity data. We conducted a case-control analysis of patients with LARC who underwent definitive CRT to determine the efficacy and safety of intensified treatment with a concomitant boost (CB) approach. METHODS AND MATERIALS: From 1995 to 2003, a phase 2 protocol examined CRT with 5-fluorouracil and CB radiation therapy (52.5 Gy in 5 weeks) for patients with LARC. Seventy-six protocol patients were matched (case-control approach) for surgery type, tumor (T) stage, and clinical nodal (N) stage with patients who received standard dose (SD) CRT (5-fluorouracil, 45 Gy). A chart review was performed. McNemar's test and Kaplan-Meier analyses were used for statistical analysis. RESULTS: The SD and CB groups did not differ in tumor circumferential involvement and length, but the tumors of CB patients were closer to the anal verge (4.7 vs 5.7 cm; P = .02). Although tumor downstaging was higher in the CB cohort (76% vs 51%; P < .01), pathologic complete response rates did not differ (CB, 17.1% vs SD, 15.8%, P = 1.00). The incidence of grade ≥3 radiation-related toxicities was low and similar in both groups (CB, 10% vs SD, 3%, P = .22). Postoperative (anastomotic leak, wound complications/abscess, bleeding) and late (small bowel obstruction, stricture) complication rates did not differ between the groups (P > .05). The median follow-up was 11.9 years. The 5-year local control rates were higher for CB (100.0%) compared with SD (90.0%) patients (P = .01). CB patients had higher rates of 10-year progression-free survival (71.9% vs 57.6%, P < .01) and overall survival (71.6% vs 62.4%, P = .01) compared with SD patients. CONCLUSIONS: CRT dose escalation for patients with LARC is safe and effective. The improved T-downstaging and local control observed in CB patients should encourage further dose escalation studies.

Is the Location of the Tumor Another Prognostic Factor for Patients With Colon Cancer?

PURPOSE: In this study, we investigated both the characteristics of right colon cancer (RTCC) in comparison with those of left colon cancer (LTCC) and the impact of the location of the colon cancer on the prognosis. METHODS: We retrospectively analyzed the cases of 974 patients with nonmetastatic colon cancer who had undergone surgery with a curative intent from January 2001 to December 2011. RTCC was defined as a tumor located proximal to the splenic flexure. The characteristics of RTCC cancer were investigated by using descriptive analyses, and their impacts on the prognosis were assessed by using a Cox multivariate regression. RESULTS: Compared to LTCC, RTCC showed a female-dominant feature, and an undifferentiated pathology was more frequently observed. The number of lymph nodes retrieved from patients with RTCC was significantly higher than that retrieved from patients with LTCC. During 75 months of follow-up, peritoneal recurrence was more common in patients with RTCC than it was in patients with LTCC, and among the patients with stage III colon cancer, the disease-free and the overall survival rates were significantly worse in patients with RTCC. After adjustments with the other prognostic factors associated with colon cancer had been made, a tumor located at the right colon was found to be independently associated with poor prognosis. CONCLUSION: RTCC showed unique clinicopathologic features and was associated with a poorer prognosis.

Oncologic Outcomes of Extended Robotic Resection for Rectal Cancer.

BACKGROUND: Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane. METHODS: The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015. RESULTS: Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %. CONCLUSIONS: Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.