Long-term Outcome After Surgical Resection of Paraaortic Lymph Node Metastasis of Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: The significance of resection of paraaortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after paraaortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. PATIENTS: Patients with resected and pathologically proven paraaortic lymph node metastasis of CRC between 2010 and 2015. DATA SOURCES: Database and medical records at each institution. MAIN OUTCOME MEASURES: Overall survival after paraaortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of paraaortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% confidence interval [CI]) was 41.0% (32.0, 49.8), and the median survival (95% CI) was 4.1 (3.4, 4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs. pT1- 3, adjusted hazard ratio [aHR]: 1.91, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.98, p = 0.005), time to metastases (synchronous vs. metachronous, aHR: 2.02, p = 0.02), and number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5, 29.7), with a median (95% CI) of 1.2 (0.9, 1.4) years. The primary tumor location (left- vs. right-sided colon, aHR: 4.77, p = 0.01; rectum vs. right-sided colon, aHR: 5.27, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.90, p = 0.03), number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.20, p = 0.001), and hospital volume (<10 vs. ≥10, aHR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Paraaortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than three paraaortic lymph node metastasis was a favorable prognostic factor for both overall survival and recurrence-free survival. However, paraaortic lymph node metastases were considered to be a systemic disease and the significance of resection was limited. See Video Abstract.

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study).

BACKGROUND AND AIMS: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. METHODS: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. RESULTS: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.05, p = 0.0002), combined resection of adjacent organs [+/-] (OR 7.92, 95% CI 3.14-19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [-/+] (OR 4.46, 95% CI 2.01-9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99-1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54-8.04, p = 0.0028), combined resection of adjacent organs [+/-] (OR 5.96, 95% CI 2.15-16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [-/+] (OR 6.26, 95% CI 3.01-13.05, p < 0.0001). CONCLUSIONS: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Proportions and characteristics of interval cancer in annual fecal immunochemical test screening and postcolonoscopy colorectal cancer: Results from a Japanese multicenter prospective study using questionnaires, the C-DETECT study.

OBJECTIVES: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics. METHODS: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed. RESULTS: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%). CONCLUSIONS: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs.

Acute Infectious Purpura Fulminans Complicated by Bacterial Translocation after Rectal Cancer Surgery: A Case Report.

The patient was a man in his 80s who had undergone laparoscopic anterior resection for rectal cancer. Bowel obstruction occurred on the third postoperative day but improved with a decompression tube by the fifth postoperative day. A high fever (in the 38 °C range) was also observed. Blood culture tests detected two sets of the gram-negative bacilli Klebsiella aerogenes within 24 h of collection. On the seventh postoperative day, the patient subsequently went into septic shock with disseminated intravascular coagulation (DIC). On the eighth postoperative day, the fingertips and toes became black, and the palms and dorsal surfaces of both feet were dark purple due to peripheral circulatory failure. This suggested acute infectious purpura associated with sepsis (acute infectious purpura fulminans (AIPF)). Intensive care was provided; however, the necrosis of both middle fingers worsened, both middle fingers were gangrenous, and the patient died on the thirtieth postoperative day. AIPF is rarely reported, especially in early-onset cases after elective surgery. We encountered a rare complication of bacterial translocation from postoperative bowel obstruction, leading to AIPF.

Enhanced Clinical Utility of Molecular Budding Signature as a Recurrence Risk Determinant in Stage II and III Colon Cancer Patients.

BACKGROUND: A molecular budding signature (MBS), which consists of seven tumor budding-related genes, was recently presented as a prominent prognostic indicator in colon cancer (CC) using microarray data acquired from frozen specimens. This study aimed to confirm the predictive power of MBS for recurrence risk based on formalin-fixed, paraffin-embedded (FFPE) materials. METHODS: This research utilized the same microarray data from a prior multicenter study using FFPE whole tissue sections, which retrospectively reviewed 232 stage II CC patients without adjuvant chemotherapy and 302 stage III CC patients with adjuvant chemotherapy. All patients underwent upfront curative surgery without neoadjuvant therapy between 2009 and 2012. An MBS score was calculated using the mean of log2 [each signal] of seven genes (MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, and FOXC1) as described before. RESULTS: The MBS-low group exhibited a better relapse-free survival (RFS) than the MBS-high group in stage II (P = 0.0077) and in stage III CC patients (P = 0.0003). Multivariate analyses revealed that the MBS score was an independent prognostic factor in both stage II (P = 0.0257) and stage III patients (P = 0.0022). Especially among T4, N2, or both (high-risk) stage III patients, the MBS-low group demonstrated markedly better RFS compared with the MBS-high group (P = 0.0013). CONCLUSIONS: This study confirmed the predictive power of the MBS for recurrence risk by employing FFPE materials in stage II/III CC patients.

Mid-term outcomes of intracorporeal versus extracorporeal anastomosis after laparoscopic colectomy: a propensity score-matched cohort study from a single institution.

PURPOSE: There is still insufficient discussion of the mid- to long-term safety of the intracorporeal anastomosis (IA) method of reconstruction after laparoscopic colectomy (LAC) for colon cancer. The present study clarified the postoperative mid-term results of IA based on recurrence and the incidence of incision hernia. METHODS: This single-institution observational retrospective study included 268 patients with colon cancer who underwent IA or extracorporeal anastomosis (EA) after LAC at our institution between 2018 and 2021. The mid-term results of the IA group were compared with those of the EA group using a propensity score matching method. RESULTS: The median follow-up periods were 36 and 25 months in the EA and IA groups, respectively (p < 0.0001). In this matched cohort study, the recurrence-free survival (RFS) rates were comparable between the IA and EA groups (each group, n = 72; 3-year RFS: IA, 92.1%; EA, 88.2%; hazard ratio, 0.78; 95% confidence interval, 0.25-2.40; p = 0.66). The cumulative incisional hernia rates were 9.8% and 9.9% (p = 0.99) for the IA and EA groups, respectively. CONCLUSION: The safety of IA after LAC was demonstrated in this study, as IA after LAC showed good mid-term results, including with regard to the rates of recurrence and incisional hernia.

Management of inguinal lymph node metastases from rectal and anal canal adenocarcinoma.

AIM: The surgical treatment of inguinal lymph node (ILN) metastases secondary to anorectal adenocarcinoma remains controversial. This study aimed to clarify the surgical treatment and management of ILN metastasis according to its classification. METHODS: This retrospective, multi-centre, observational study included patients with synchronous or metachronous ILN metastases who were diagnosed with rectal or anal canal adenocarcinoma between January 1997 and December 2011. Treatment outcomes were analysed according to recurrence and prognosis. RESULTS: Among 1181 consecutively enrolled patients who received treatment for rectal or anal canal adenocarcinoma at 20 referral hospitals, 76 (6.4%) and 65 (5.5%) had synchronous and metachronous ILN metastases, respectively. Among 141 patients with ILN metastasis, differentiated carcinoma, solitary ILN metastasis and ILN dissection were identified as independent predictive factors associated with a favourable prognosis. No significant difference was found in the frequency of recurrence after ILN dissection between patients with synchronous (80.6%) or metachronous (81.0%) ILN metastases. Patients who underwent R0 resection of the primary tumour and ILN dissection had a 5-year survival rate of 41.3% after ILN dissection (34.1% and 53.1% for patients with synchronous and metachronous ILN metastases, respectively, P = 0.55). CONCLUSION: The ILN can be appropriately classified as a regional lymph node in rectal and anal canal adenocarcinoma. Moreover, aggressive ILN dissection might be effective in improving the prognosis of low rectal and anal canal adenocarcinoma with ILN metastases; thus, prophylactic ILN dissection is unnecessary.

Usefulness of Carcinoembryonic Antigen Doubling Time in Prognosis Prediction after Curative Resection of Locally Recurrent Rectal Cancer: A Retrospective Study.

INTRODUCTION: Given that doubling time is an indicator of tumor growth, we assessed the usefulness of carcinoembryonic antigen doubling time (CEA-DT) in prognosis prediction after curative resection for locally recurrent rectal cancer. METHODS: During January 1986-December 2016, 33 patients with locally recurrent rectal cancer who underwent curative resection at our hospital were retrospectively reviewed. The primary endpoint was the 3-year recurrence-free survival (RFS) rate. The Kaplan-Meier method was used to compare RFS rates and evaluate univariate and multivariate analyses for factors associated with oncologic outcomes, including CEA-DT. CEA-DT was classified into 2 groups: the short and long CEA-DT groups. RESULTS: The 3-year overall survival and RFS rates were 62.6% and 42.4%, respectively. In multivariate analyses, CEA-DT was an independent risk factor for poor RFS. The 3-year RFS rate was significantly better in the long CEA-DT group than in the short CEA-DT group (58.8% vs. 25.0%, p = 0.0063). CONCLUSION: CEA-DT is a useful prognostic factor that can be assessed before surgery for locally recurrent rectal cancer. Long CEA-DT may indicate a favorable prognosis. Contrarily, short CEA-DT is associated with poor prognosis; therefore, further treatment intervention is necessary for patients with short CEA-DT.

Short-term outcomes of intracorporeal versus extracorporeal anastomosis after laparoscopic colectomy: a propensity score-matched cohort study from a single institution.

PURPOSE: To compare the postoperative short-term results of intracorporeal anastomosis (IA) using overlap anastomosis (OLA), with those of extracorporeal anastomosis (EA) using functional end-to-end anastomosis (FEEA) or hand-sewn anastomosis (HSA), after laparoscopic colectomy (LAC). METHODS: The subjects of this retrospective study were 208 patients with colon cancer who underwent OLA, FEEA, or HSA after LAC at our institution, between 2018 and 2021. The short-term results of the OLA group were compared with those of the FEEA and HSA groups, respectively, using a propensity score-matching method. RESULTS: The mean operative time for anastomosis was longer in the OLA group than in the FEEA and HSA groups (p < 0.0001). The mean blood loss volume was less in the OLA group than in the FEEA and HSA groups (p = 0.0344 and p = 0.0002, respectively). The mean skin incision size was smaller in the OLA group than in the FEEA and HSA groups (p < 0.0001 and p = 0.0031, respectively). None of the patients in the OLA group had surgical site infections. Three to five patients were required for the surgeon to plateau on the learning curve. CONCLUSION: Although IA required more time than EA, the skills appeared to improve with experience and the short-term results were superior to those of EA.

[Retrospective Analysis of Adjuvant Chemotherapy for Elderly Patients with Stage â ¢ Colorectal Cancer].

OBJECTIVE: To investigate the efficacy and toxicity of adjuvant chemotherapy(AC)in elderly patients with Stage Ⅲ colorectal cancer(CRC). METHODS: We performed a single-institutional retrospective analysis of 84 patients aged≥75 years with Stage Ⅲ CRC who underwent curative resection from August 2009 to February 2018. RESULTS: Thirty-seven(44.0%) patients received AC. Eleven(29.7%)patients required dose reduction at the start of AC. Twenty-three(62.2%)patients accomplished AC, and 13(35.1%)needed dose reduction during AC. Although toxicities of Grade 3 or higher occurred in 56.8% of patients, they were controllable. The 3-year recurrence-free survival rate was significantly better in the AC group than in the non-AC group(70.3% versus 50.5%, respectively; p=0.011). The prognosis tended to be worse in the group that started AC with dose reduction than in the group with the normal dose. CONCLUSION: AC is effective and well tolerated in elderly patients with Stage Ⅲ CRC. When reducing the initial dose, the need for dose reduction should be carefully considered.

[Usefulness of Nutritional Evaluation in Adjuvant Chemotherapy for Colorectal Cancer in Older Patients].

OBJECTIVE: To clarify the usefulness of Onodera's prognostic nutritional index(OPNI)in adjuvant chemotherapy(AC)for older patients with colorectal cancer. MATERIALS AND METHODS: This study included 39 patients aged over 70 years who underwent AC for colorectal cancer from August 2009 to February 2018. We evaluated the association of OPNI with AC toxicities and prognosis. RESULTS: OPNI was an independent predictor of toxicities of Grade 3 or higher(OR: 0.18, 95%CI: 0.043-0.75, p=0.019). The 3-year recurrence-free survival rate was significantly better in the higher OPNI group than in the lower OPNI group(89.9% and 66.7%, respectively; HR: 0.19, 95%CI: 0.04-0.92, p=0.038). There was a positive correlation with Spearman's rank correlation coefficient of 0.66 in OPNI before and after AC(p<0.001). CONCLUSION: OPNI could be one of the valuable predictors of AC toxicities and the prognosis. There was a high correlation between OPNI before and after AC. These findings suggest the importance of early nutritional support for patients with lower OPNI.

Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients.

BACKGROUND: Adjuvant chemotherapy reduces the risk of recurrence of stage III colon cancer (CC). However, more effective prognostic and predictive biomarkers are needed for better treatment stratification of affected patients. Here, we constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC. METHODS: We retrospectively identified patients aged 20-79 years, with stage III CC, who received adjuvant chemotherapy with or without oxaliplatin, between the years 2009 and 2012. RESULTS: Among 938 eligible patients, 203 and 201 patients who received adjuvant chemotherapy with and without oxaliplatin, respectively, were selected by propensity score matching. Of these, 95 patients from each group were analyzed, and their 5-year relapse-free survival (RFS) rates with and without oxaliplatin were 73.7 and 77.1%, respectively. The hazard ratios for 5-year RFS following adjuvant chemotherapy (fluoropyrimidine), with and without oxaliplatin, were 1.241 (95% CI, 0.465-3.308; P = 0.67) and 0.791 (95% CI, 0.329-1.901; P = 0.60), respectively. Stratification using the 55GC revealed that 52 (27.3%), 78 (41.1%), and 60 (31.6%) patients had microsatellite instability (MSI)-like, chromosomal instability (CIN)-like, and stromal subtypes, respectively. The 5-year RFS rates were 84.3 and 72.0% in patients treated with and without oxaliplatin, respectively, for the MSI-like subtype (HR, 0.495; 95% CI, 0.145-1.692; P = 0.25). No differences in RFS rates were noted in the CIN-like or stromal subtypes. Stratification by cancer sidedness for each subtype showed improved RFS only in patients with left-sided primary cancer treated with oxaliplatin for the MSI-like subtype (P = 0.007). The 5-year RFS rates of the MSI-like subtype in left-sided cancer patients were 100 and 53.9% with and without oxaliplatin, respectively. CONCLUSIONS: Subclassification using 55GC and tumor sidedness revealed increased RFS in patients within the MSI-like subtype with stage III left-sided CC treated with fluoropyrimidine and oxaliplatin compared to those treated without oxaliplatin. However, the predictive power of 55GC subtyping alone did not reach statistical significance in this cohort, warranting larger prospective studies. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID: 000023879 ).

Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study.

BACKGROUND: For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. METHODS: We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin-eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. RESULTS: Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). CONCLUSIONS: This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

Clinical impact of non-predominant histopathological subtypes on the long-term prognosis of colorectal cancer patients in Japan.

PURPOSE: We performed a retrospective study to clarify the long-term prognosis of patients with histopathological high-grade colorectal cancer (CRC). METHODS: We reviewed data from 24 institutions for 18,360 patients with pStage I to III CRC who had undergone curative surgery between 2004 and 2012. The patients were classified into seven groups according to the proportion of the histopathological component: classical adenocarcinoma (CAC) group, M-l and M-h groups (< 50% and ≥ 50% mucinous adenocarcinoma, respectively), P-l and P-h groups (< 50% and ≥ 50% poorly differentiated adenocarcinoma, respectively), and S-l and S-h groups (< 50% and ≥ 50% signet-ring cell carcinoma (SRCC), respectively). RESULTS: The 5-year recurrence-free survival (RFS) rates of the M-l, P-l, and S-l groups were 75.5%, 68.4%, and 52.4%, respectively, and were significantly lower than those of the CAC group (83.5%, hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01-1.48, p = 0.0365; HR 1.60, 95% CI 1.32-1.91, p < 0.0001; HR 2.61, 95% CI 1.30-4.57, p = 0.0090, respectively). The 5-year RFS of the P-l and S-l groups was as poor as that of the P-h and S-h groups, respectively (HR 0.87, 95% CI 0.68-1.10, p = 0.25; HR 0.90, 95% CI 0.37-2.13, p = 0.81, respectively). The histopathological component of the S-l group was an independent factor affecting overall survival in multivariate analysis. CONCLUSION: The long-term prognoses of the non-predominant poorly differentiated adenocarcinoma (PAC) groups were as poor as those of the predominant group. In particular, the histopathological component of the P-l and S-l groups could be classified into predominant PAC and SRCC subtypes for appropriate prognostic predictions.

Verifying the M1c category of CRC: analysis of the data from a Japanese multi-institutional database.

BACKGROUND/AIMS: In the TNM classification 8th edition, colorectal cancer (CRC) with peritoneal metastasis, one of the most poor prognostic factors, is classified as M1c (stage IVC), regardless of the presence/absence of other distant metastasis. Several cases with peritoneal metastasis have been successfully managed by surgical treatment; therefore, there is need to give more consideration for uniform differentiation of peritoneal metastasis. This study was aimed at verifying the classification of M1c in CRC. MATERIALS AND METHODS: Data from a multi-institutional retrospective cohort of 2929 CRC patients who were diagnosed as having stage IV CRC from 1997 to 2007 were analyzed. Peritoneal metastasis alone was defined as M1c1 and peritoneal metastasis with other organ metastasis was defined as M1c2. RESULTS: The 3-year OS of patients with M1c1 was significantly higher than that of patients with M1b (25.6% vs. 18.1%; HR 0.77; 95% confidence interval (CI) 0.65-0.92; p = 0.005); in particular, the prognosis of patients with M1c1 with localized peritoneal metastasis and R0 resection was equivalent to that of patients with M1a (3-year OS 40.5% vs. 39.2%, p = 0.41). On the other hand, among the stage IV cases, patients with M1c2 had a low R0 resection rate (5.9%) and the worst prognosis (3-year OS, 9.1%). CONCLUSIONS: The prognosis of M1c1 with localized peritoneal metastasis is relatively good, and can be further improved by surgical intervention. Combined evaluation of the M1c1/2 classification with the peritoneal metastasis grade may help in establishing more individualized treatment strategies.

Prognostic impact of the number of lateral pelvic lymph node metastases on rectal cancer.

BACKGROUND: This study aimed to clarify the number of lateral pelvic lymph node metastases of colorectal cancer for which prognosis could be improved by dissection. METHODS: We analysed the data of 30 patients with lateral pelvic lymph node metastases of rectal cancer that underwent a total mesorectal excision with lateral pelvic lymph node dissection at our institute from 1986 to 2016. We performed survival analysis on the number of lateral pelvic lymph node metastases in each of these patients and identified an optimal cut-off point of the number of lateral pelvic lymph node metastases that would predict recurrence-free survival using the receiver operating characteristic curves and an Akaike information criterion value. RESULTS: The 5-year recurrence-free survival and overall survival of patients with one or two lateral pelvic lymph node metastases were significantly better than that of those with three or more (5-year recurrence-free survival, 63.3 vs. 0.0%, respectively; hazard ratio, 0.23; 95% CI, 0.07-0.72; P = 0.0124) (5-year overall survival, 68.2 vs. 15.6%, respectively; hazard ratio, 0.29; 95% CI, 0.09-0.92; P = 0.0300). All of the metastatic lateral pelvic lymph nodes in the group with one or two lateral pelvic lymph node metastases were restricted to the internal iliac artery or obturator nerve regions. CONCLUSIONS: The cut-off number of lateral pelvic lymph node metastases in the internal iliac artery or obturator nerve regions of colorectal cancer cases in whom prognosis was improved by lateral pelvic lymph node dissection was 2; patients who had <3 lateral pelvic lymph node metastases had better prognoses than those with ≥3 lateral pelvic lymph node metastases.

Factors affecting R0 resection of colorectal cancer with synchronous peritoneal metastases: a multicenter prospective observational study by the Japanese Society for Cancer of the Colon and Rectum.

BACKGROUND: In Japan, R0 resection has been recommended for colorectal cancer patients with peritoneal metastases confined to the adjacent peritoneum and those with a few metastases to the distant peritoneum. R0 resection for M1c disease has drawn attention in Western countries and is currently considered an acceptable therapeutic option in the US National Comprehensive Cancer Network guidelines. However, clinical factors that affect the choice of R0 resection are unknown. METHODS: This multicenter, prospective, observational study was conducted by the Japanese Society for Cancer of the Colon and Rectum. Colorectal cancer patients with synchronous peritoneal metastases were enrolled at 28 institutions in Japan from October 2012 to December 2016. To determine factors affecting R0 resection and R1 resection with intended R0 resection, stepwise logistic regression analyses were performed on clinical factors including age, sex, performance status (PS), body mass index, peritoneal cancer index (PCI) score, presence of ascites, presence of distant metastases, and primary tumor site. RESULTS: R0/R1 resection was performed in 36 (31/5; 25%) of 146 patients. No distant metastases [odds ratio (OR) 52.9; 95% confidence interval (CI) 13.3-210.1; p < 0.0001], low PCI score (1-6) (OR 20.0; 95% CI 4.8-83.4; p < 0.0001), and high PS (0) (OR 2.40; 95% CI 0.66-8.68; p = 0.18) were independent factors affecting R0/R1 resection. PCI score and PS were also independent factors affecting R0/R1 resection in M1c patients without non-peritoneal distant metastases (n = 59). CONCLUSION: Distant metastases, PCI score, and PS are three factors which affect R0 resection for M1c disease.

Preoperative chemoradiotherapy versus surgery alone for advanced low rectal cancer: a large multicenter cohort study in Japan.

PURPOSE: To clarify the usefulness of chemoradiotherapy (CRT) for low rectal cancer, we investigated the current status of CRT in Japan and its short- and long-term outcomes versus surgery alone for low rectal cancer in a large multicenter cohort study. METHODS: Between January 2010 and December 2011, data from 1608 patients with clinical Stage II-III rectal adenocarcinoma were collected from 69 specialized centers. Of these 1608 patients, 923 were diagnosed with clinical stage III low rectal cancer, 838 were enrolled in this study, divided into the surgery-alone group (n = 649) and preoperative CRT group (n = 189), and analyzed. RESULTS: The following parameters were significantly lower in the CRT versus surgery-alone group: blood loss (210 vs. 431.5 mL), postoperative complications (27.5% vs 39.0%), and the incidence of anastomotic leakage (3.7% vs. 8.8%). The 3-year overall survival, relapse-free and local recurrence-free survival rates did not between the two groups to a statistically significant extent (91.2% vs. 87.4%, 68.8% vs. 66.4%, and 88.2% vs. 88.4%, respectively). CONCLUSIONS: The present study revealed the current status of CRT for low rectal cancer in Japan. The results showed that CRT could be safely performed for advanced low rectal cancer in comparison to surgery alone.

Changes in the rate of and trends in colectomy for ulcerative colitis during the era of biologics and calcineurin inhibitors based on a Japanese nationwide cohort study.

PURPOSE: We evaluated the recent incidence of surgery and the changing surgery trends for ulcerative colitis (UC) in Japan due to the increasing use of anti-tumor necrosis factor (TNF) agents. METHODS: A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017. RESULTS: A total of 3801 surgical cases were reported over 11 years. The prevalence of UC surgery decreased over the period studied. The rate of prednisolone (PSL) use did not change. The prevalence of both calcineurin inhibitors (CNIs) and anti-TNF agents increased during the period studied (p < 0.01). The prevalence of urgent/emergent surgery did not change. The most distinctive change in surgical indications was the increase in cancer/dysplasia (CAC), the prevalence of which increased from 20.2% in 2007 to 34.8%. CONCLUSION: The prevalence of UC surgery seems to be decreasing according to the increasing rate of anti-TNF agent and CNI administration. However, the indication of CAC significantly increased. Further research should evaluate whether or not long-term remission maintained with several agents can lead to increasing CAC.