Masashi Noda

The timing of surgery after preoperative short-course S-1 chemoradiotherapy with delayed surgery for T3 lower rectal cancer.

PurposeThe purpose of this study was to analyze the influence of variations in clinical practice regarding the timing of surgery with short-course chemoradiotherapy with delayed surgery (SCRT-delay) for lower rectal cancer.MethodsA total of 171 patients with T3 N0-2 lower rectal cancer treated with SCRT-delay (25xa0Gy/10 fractions/5xa0days (S-1); days 1–10) were retrospectively evaluated. The median waiting period of 30xa0days was used as a discriminator (group A: waiting period, ≤30xa0days; group B: waiting period, ≥31xa0days). Preoperative treatment responses and oncological outcomes were analyzed.ResultsThe mean waiting periods for groups A and B were 24.4u2009±u20095.3 and 41.4u2009±u200912.3xa0days, respectively. There were no statistically significant differences between the two groups in any of the clinical variables. The clinicopathological outcomes were as follows: T downstaging (43.5 vs 37.2xa0%; pu2009=u20090.400), negative yp N (67.1 vs 75.6xa0%; pu2009=u20090.218), pCR (7.1 vs 1.2xa0%; pu2009=u20090.119). The 5-year local recurrence-free survival (89.3 vs 87.6xa0%; pu2009=u20090.956), the recurrence-free survival (82.2 vs 78.8xa0%; pu2009=u20090.662), and the overall survival (88.5 vs 84.4xa0%; pu2009=u20090.741), all of which were similar between the two groups.ConclusionsThe longer waiting period did not increase the tumor downstaging and not improve the oncological outcomes for T3 lower rectal cancer treated with SCRT-delay. In addition, considering that the impaired leukocyte response occurred during the sub-acute period, any time after the sub-acute period (day 12) up to 30xa0days after radiotherapy would be a suitable waiting period.

Short-course radiotherapy with delayed surgery versus conventional chemoradiotherapy: A comparison of the short- and long-term outcomes in patients with T3 rectal cancer.

INTRODUCTIONnThe aim of this study was to compare the short- and long-term outcomes between short-course radiotherapy with delayed surgery (SRT-delay) and a standard conventional chemoradiotherapy (CRT) regimen.nnnMETHODSnTwo collaborating institutions adopted different regimens; the SRT-delay regimen was selected by Meiwa Hospital and the CRT regimen was selected by Hyogo College of Medicine. The inclusion criteria were T3 middle and low rectal cancer patients treated with radical surgery after preoperative therapy. The median follow-up period was 44 months (range, 12-85).nnnRESULTSnFrom 2007 to 2013, 104 patients were treated using the SRT-delay regimen and 61 patients were treated using the CRT regimen. The pretreatment characteristics of the 2 groups were not significantly different. The sphincter-preserving rate (93.3%, 85.2%), T downstaging (37.5%, 37.7%), ypN(-) (74.0%, 67.2%), postoperative complications and the bowel, and urinary and sexual functioning of the SRT-delay regimen were noninferior to those of the CRT regimen. The 3-year local recurrence-free survival, recurrence-free survival, and overall survival in the SRT-delay and CRT groups were 90.6% and 90.6% (P = .764), 83.8% and 78.3% (P = .687) and 96.0% and 92.8% (P = .833), respectively.nnnCONCLUSIONnThe SRT-delay regimen was noninferior in terms of the downstaging effect, and oncologic and functional outcomes compared with the CRT regimen for T3 middle and low rectal cancer.

Pathologic evaluation of the response of mesorectal positive nodes to preoperative chemoradiotherapy in patients with rectal cancer

BACKGROUNDnThe response of positive mesorectal lymph nodes to chemoradiotherapy remains largely unstudied in patients with rectal cancer. The aim of this study was to investigate the requirements of the total regression of positive nodes treated with chemoradiotherapy.nnnMETHODSnThe response of the primary tumor was evaluated according to the tumor regression grade (TRG 0-4) in resected specimens, and positive lymph nodes were assessed according to the lymph node regression grade (LRG 1-3), with TRG 4 and LRG 3 indicating total regression. We investigated the relationships among TRG, LRG, and the sizes of positive lymph nodes.nnnRESULTSnAmong 178 patients, 68 (38.2%) had 200 positive lymph nodes. We first investigated the relationship of positive nodes to TRG and LRG and found that the response of the primary tumor to chemoradiotherapy correlated with the response of positive nodes. Next, we investigated the correlation between LRG and the size of positive nodes. At TRG 1 and 2, LRG score was not correlated with the positive node size. In contrast, at TRG 3, LRG score was correlated with the size of positive nodes. Next, our assessment of the relationship between the sizes of positive nodes and complete degeneration to LRG 3 showed that the most accurate cut-off score on receiver-operator-characteristics curve analysis was 6 mm in maximum diameter for TRG 3.nnnCONCLUSIONnThe requirements of the total regression of positive nodes are 1) degeneration of the primary tumor to TRG 3 and 2) a positive node diameter of <6 mm.

Laparoscopic intersphincteric resection and J-pouch reconstruction without laparotomy

In some cases, a J-pouch is not created after laparoscopic intersphincteric resection (Lap-ISR), because this procedure usually does not involve laparotomy. This study aimed to develop a new technique for Lap-ISR and J-pouch reconstruction without laparotomy and to assess the short- and long-term outcomes of this technique. After a rectal specimen is excised using the transanal approach, the reconstructed intestine is reinserted into the intra-abdominal space. To create the J-shape, the reconstructed intestine is looped back using Allis forceps, and the septum of the J-shape is divided using a surgical stapler. We performed 20 surgeries using the new technique. Although three patients developed pelvic infections, no J-pouch-related complications were noted. Intestinal continuity could be maintained in all patients who received a diverting stoma.

Comparison of the pathological response of the mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery and long-course chemoradiotherapy in patients with rectal cancer

BackgroundThe aim of this study was to compare the pathological response of mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery (SCRT-delay) and long-course chemoradiotherapy (LC-CRT) in patients with rectal cancer.MethodThe resected primary tumor specimens following the two different approaches were assessed utilizing the tumor regression grade (TRG 0–4), and each positive lymph node was assessed according to the lymph node regression grade (LRG 1–3), with TRG 4 and LRG 3 indicating total regression. The lymph node sizes were measured to elucidate any correlation with LRG scores.ResultsSeventy-four patients with ypN-positive rectal cancer had 220 positive lymph nodes following the SCRT-delay, and 48 patients had 141 positive lymph nodes following the LC-CRT. The distribution of LRG 1/2/3 in the two groups was 123/72/25 and 60/31/50 (pu2009<u20090.001), respectively, and the distribution of TRG 0/1/2/3/4 in the two groups was 36/19/19/0 and 12/15/20/1 (pu2009=u20090.005), respectively. The requirements of total regression of positive lymph nodes were a primary tumor degenerated to TRG 3 with a size less than 6xa0mm in SCRT-delay (sensitivity, 60.9xa0%) or a primary tumor degenerated to TRG 2–4 with a size less than 5xa0mm at TRG 2 (sensitivity, 57.6xa0%) or 6xa0mm at TRG 3 and 4 (sensitivity, 84.2xa0%) in LC-CRT as indicated by the receiver operating characteristic curve analysis.ConclusionThe tumor regression effect of LC-CRT on the primary tumor and positive nodes was more favorable than SCRT-delay, and LC-CRT is able to predict the LRG 3 response with a high sensitivity.

c-myc Amplification and Enhancement of Sensitivity to Cytosine Arabinoside: An In Vitro and In Vivo Study on Four Sublines Established from a Pulmonary Adenocarcinoma

Abstract.Abstract.Purpose: Meticulous treatment strategies taking tumor heterogeneity into account are considered essential to achieve breakthroughs in current cancer therapy. We analyzed tumor heterogeneity in the primary tumor of a patient with pulmonary adenocarcinoma characterized by a poor prognosis.Methods: Four sublines with different growth characteristics in vitro were established from the tumor using a method for short-term selective cultivation. We examined the differences in morphological, biochemical, and genetic findings of these sublines.Results: Differences in the histological features of the transplanted tumors were seen in the four sublines. The 88-2T and 88-2 tumors revealed a well-differentiated adenocarcinoma; the 88-2F tumor revealed a large cell-like carcinoma resembling the metastatic tumor in the lymph nodes; and the 88-2FA tumor was composed of signet-ring cells. There were differences in oncogenes, with the 88-2F line alone exhibiting 12-fold amplification of c-myc. Sensitivity to cytosine arabinoside (Ara C) was specifically increased in the 88-2F cell line, alone.Conclusions: These sublines demonstrate that human pulmonary adenocarcinoma has various types of heterogeneity within the primary tumor. Furthermore, c-myc amplification may play an important role in altering phenotype and growth characteristics in vitro and in vivo, and for increasing sensitivity to Ara C and the potential of cancer cells to metastasize to lymph nodes.

A‘high tie’confers an increased risk of anastomotic leakage for lower rectal cancer surgery in patients treated with preoperative radiotherapy

PurposeThis study aimed at analyzing retrospectively the risk factors for anastomotic leakage for lower rectal cancer treated with preoperative radiotherapy.MethodsThe subjects were 108 patients with T3 lower rectal cancer, who underwent curative resection following preoperative radiotherapy. All patients had a diverting stoma made. Univariate and multivariate analyses were conducted for the independent clinical variables.ResultsAnastomotic leakage developed in 19 (17.6xa0%) patients. Univariate analysis of the risk factors for anastomotic leakage revealed that arterial ligation with a high tie (pxa0=xa00.001), undifferentiated tumor type (pxa0=xa00.002), a shorter distance from the anal verge (pxa0=xa00.086), and a longer hospital stay (pxa0=xa00.0002) were significant predictors of leakage. Multivariate analysis revealed that a high tie [hazard ratio 12.22 (95xa0% confidence interval 2.83–87.94); pxa0=xa00.0003], undifferentiated tumor type [91.15 (5.98–3128.03); pxa0=xa00.0008], and a long hospital stay [13.03 (2.86–104.93); pxa0=xa00.0004] were independently associated with anastomotic leakage.ConclusionOur data suggest that preoperative radiotherapy and a high tie for lower rectal cancer are independent risk factors for anastomotic leakage.