Purpose: Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy ([C]RT) have improved local control of rectal cancer; however, we have been unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs. Patients and Methods: Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features. Results: On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042). Conclusion: LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.

Local recurrence rates in rectal cancer have reduced dramatically since the introduction of the total mesorectal excision (TME) technique.¹ These rates have been lowered further with the use of neoadjuvant chemoradiotherapy or radiotherapy ([C]RT) regimens in appropriate cases, decreasing overall rates of 5-year local recurrence to 5% to 10%.^2-4 Western surgeons have always relied on (C)RT to sterilize the lateral compartment, containing internal iliac and obturator lymph nodes, and to alleviate fears of operative morbidity and nerve function disorders associated with a lateral lymph node dissection (LLND), which is mainly performed in the East.⁵ Furthermore, most Western clinicians consider lateral nodal disease to represent metastatic disease not amendable to cure.^5,6

Background: The association of sarcopenia and visceral obesity to treatment outcome is not clear for locally advanced rectal cancer. This study evaluates the influence of skeletal muscle and visceral fat on short‐term and long‐term outcomes in locally advanced rectal cancer patients treated with neoadjuvant chemoradiation therapy followed by curative resection.Methods: A total of 188 patients with locally advanced cancer were included between January 2009 and December 2013. Neoadjuvant chemoradiotherapy was followed by curative resection. Sarcopenia and visceral obesity were identified in initial staging CT by measuring the muscle and visceral fat area at the third lumbar vertebra level.Results: Among the 188 included patients, 74 (39.4%) patients were sarcopenic and 97 (51.6%) patients were viscerally obese. Sarcopenia and high levels of preoperative carcinoembryonic antigen were significant prognostic factors for overall survival (P = 0.013, 0.014, respectively) in the Cox regression multivariate analysis. Visceral obesity was not associated with overall survival; however, it did tend to shorten disease‐free survival (P = 0.079).Conclusions: Sarcopenia is negatively associated with overall survival in locally advanced rectal cancer patients who underwent neoadjuvant chemoradiation therapy and curative resection. Visceral obesity tended to shorten disease‐free survival. Future studies should be directed to optimize patient conditions according to body composition status.

Background: The need for an initial learning experience in laparoscopic colorectal cancer surgery has been well established. However, the inherent differences in the complexity and results of laparoscopic rectal cancer surgery, as compared to colon surgery, warrant a study to analyze the learning curve exclusively for rectal cancer resections. Materials and Methods: four hundred thirty-one patients operated on between April 1994 and March 2006 were analyzed retrospectively for changes in surgical outcomes according to case sequence. A multidimensional analysis was done, based on the following parameters: conversion to laparotomy, intraoperative complications, postoperative complications, reoperations, operative time, and transfusion volumes. Multiple statistical methods were used for evaluation of the learning curve, which included the cumulative sum (CUSUM) method, risk-adjusted CUSUM, moving average method, and analysis of variance (ANOVA). Results: The risk factors for conversion were prior abdominal surgery (hazard ratio, 2.52; 95% CI, 1.04–6.10; P = 0.04) and tumor size ≥3.5 cm (hazard ratio, 5.05; 95% CI, 1.95–13.08; P = 0.001). Risk-adjusted CUSUM analysis showed that case 61 was the peak change point for conversion. Postoperative complications occurred in 56 patients (13.0%), and the rate was associated significantly with case sequence (P < 0.001). The turning point in the CUSUM model occurred at case 79, and the complication rates decreased thereafter. Operative time and intraoperative transfusion volumes stabilized over cases 61–75 and declined thereafter. Conclusions: Multidimensional analysis considering various surgical outcomes is necessary to evaluate the learning curve for laparoscopic rectal cancer surgery. The effective surgical learning curve was approximately 60–80 procedures in this series.

Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor and acts as a coregulator of various nuclear receptors. Herein, we examined a novel cross talk between SHP and a forkhead transcription factor HNF3 (hepatocyte nuclear factor 3/Foxa. Transient transfection assay demonstrated that SHP inhibited the transcriptional activity of all three isoforms of HNF3, HNF3alpha, beta, and gamma. In vivo and in vitro protein interaction studies showed that SHP physically interacted with HNF3. Adenovirus-mediated overexpression of SHP significantly decreased the mRNA levels of glucose-6-phosphase (G6Pase), cholesterol 7-alpha-hydroxylase (CYP7A1), and phosphoenolpyruvate carboxykinase (PEPCK) in HepG2 cells and rat primary hepatocytes. Moreover, the mRNA level of G6Pase was notably increased by down-regulation of SHP with small interfering RNA. Interestingly, HNF3 transactivity was still repressed by SHPDelta128-139 that fails to repress nuclear receptors. Mapping of interaction domain revealed that SHP interacted with forkhead DNA binding domain of HNF3alpha. Gel mobility shift and chromatin immunoprecipitation assays demonstrated that SHP inhibits DNA binding of HNF3. These results suggest that SHP is involved in the regulation of G6Pase, CYP7A1, and PEPCK gene expression via novel mechanism of inhibition of HNF3 activity and expand the role of SHP as a coregulator of other family of transcription factors in addition to nuclear receptors.