Marital status after colorectal surgery in familial adenomatous polyposis: a nationwide multicenter study in Japan.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) experience psychological and social challenges concerning future events such as marriage and childbirth alongside the medical risks of colorectal cancer (CRC) and FAP-related disease. We retrospectively investigated the rate of marriage and childbirth postoperatively in Japanese patients with FAP. METHODS: We included 161 patients who had colorectal surgery and reported marital status from a national survey of 35 Japanese institutions. Participants were classified according to marital status: married before colectomy (80 patients), married after colectomy (13 patients), and unmarried (68 patients). RESULTS: The marriage rate for all 161 patients (57.8%, standardized ratio 0.95, 95% confidence interval [CI] 0.76-1.14) was comparable to that in the general Japanese population (57.1%). The marriage rate among the 81 patients who were unmarried before colectomy was low (16.0%); however, the standardized marital ratio (0.75, 95% CI 0.34-1.15) was not significantly lower than that of the general population. In multivariable logistic regression, younger age (born after 1980, odds ratio [OR] 0.12, p < 0.001) and genetic testing (OR 4.06, p = 0.001) were associated with postoperative marriage. Seventy-one percent of patients with FAP who married after colectomy became pregnant and achieved delivery. CONCLUSIONS: The marriage rate of patients with FAP was comparable to that of the general population whereas the rate after colectomy was low among patients with FAP. However, in patients with FAP, colorectal surgery itself may not lead to negative consequences in terms of fecundity.

Nutritional status indicators predict tolerability to adjuvant chemotherapy in patients with stage II/III rectal cancer undergoing neoadjuvant chemoradiotherapy.

INTRODUCTION: Adjuvant chemotherapy (AC) after radical surgery following preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is now the standard of care. The identification of risk factors for the discontinuation of AC is important for further improvements in survival. We herein examined the prognostic impact of chemotherapy compliance and its relationship with the prognostic nutritional index (PNI) before surgery. MATERIALS AND METHODS: A total of 335 Stage II-III LARC patients who underwent preoperative CRT between 2003 and 2022 at the University of Tokyo Hospital were retrospectively reviewed. We excluded patients with recurrence during AC and those who had not received AC. The relationship between AC and long-term outcomes and that between PNI values and the duration of AC were examined. RESULTS: Thirty-one patients discontinued AC and 62 continued AC. Recurrence-free survival (RFS) was significantly shorter in patients who discontinued AC (p = 0.0056). The discontinuation of AC was identified as an independent risk factor for RFS (HR 2.24, p = 0.0233). Twenty-one patients were classified as having low PNI (less than 40), which correlated with an older age, low BMI, and incomplete AC. Low PNI was an independent risk factor for a shorter duration of AC (HR 2.53, p = 0.0123). CONCLUSION: The discontinuation of AC was related to poor RFS in patients with LARC undergoing preoperative CRT. Furthermore, a low PNI value was identified as a risk factor for a shorter duration of AC.

Evaluation of anorectal function using real-time tissue elastography before and after preoperative chemoradiotherapy.

PURPOSE: This study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy. METHODS: This is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019-2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as "elasticity" (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures. RESULTS: A decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure. CONCLUSION: Internal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction.

Minimally invasive versus open multivisceral resection for rectal cancer clinically invading adjacent organs: a propensity score-matched analysis.

BACKGROUND: Minimally invasive surgery (MIS), such as laparoscopic and robotic surgery for rectal cancer, is performed worldwide. However, limited information is available on the advantages of MIS over open surgery for multivisceral resection for cases clinically invading adjacent organs. PATIENTS AND METHODS: This was a retrospective propensity score-matching study of consecutive clinical T4b rectal cancer patients who underwent curative intent surgery between 2006 and 2021 at the University of Tokyo Hospital. RESULTS: Sixty-nine patients who underwent multivisceral resection were analyzed. Thirty-three patients underwent MIS (the MIS group), while 36 underwent open surgery (the open group). Twenty-three patients were matched to each group. Conversion was required in 2 patients who underwent MIS (8.7%). R0 resection was achieved in 87.0% and 91.3% of patients in the MIS and open groups, respectively. The MIS group had significantly less blood loss (170 vs. 1130 mL; p < 0.0001), fewer Clavien-Dindo grade ≥ 2 postoperative complications (30.4% vs. 65.2%; p = 0.0170), and a shorter postoperative hospital stay (20 vs. 26 days; p = 0.0269) than the open group. The 3-year cancer-specific survival rate, relapse-free survival rate, and cumulative incidence of local recurrence were 75.7, 35.9, and 13.9%, respectively, in the MIS group and 84.5, 45.4, and 27.1%, respectively, in the open group, which were not significantly different (p = 0.8462, 0.4344, and 0.2976, respectively). CONCLUSION: MIS had several short-term advantages over open surgery, such as lower complication rates, faster recovery, and a shorter hospital stay, in rectal cancer patients who underwent multivisceral resection.

Differences in the Difficulty of Accessing Various 3-Dimensional Locations Under Mirror-Image Conditions During Laparoscopic Surgery.

BACKGROUND: Laparoscopic colon surgery frequently requires performing maneuvers under mirror-images conditions; the complexity differs depending on the surgical site location in the abdominal cavity. However, no previous reports have examined this. METHODS: Eleven surgeons participated in this study. Operations were performed on 25 points placed at the bottom and sides of a laparoscopic training box under mirror-image conditions. The mean time-point required to operate at each point and variation between surgeons were evaluated. RESULTS: When the right hand was used, time-points to touch the right side-superficial ends were 0.50 to 0.58 and 0.27 to 0.45 for the other sites. With the left hand, time-points to touch the left side-superficial ends were 0.58 to 0.63 and 0.28 to 0.51 for the other sites, indicating that the most difficult manipulation was at the proximal site of the surgical port. The variation in the difficulty according to the spots increased with a decrease in the surgeon's experience (right hand, r =-0.248; left hand, r =-0.491). CONCLUSIONS: In performing laparoscopic surgery under mirror-image conditions, the technical difficulty varies by location, and operating in locations close to the forceps port is the most difficult.

Risk of metachronous colorectal cancer after surgical resection of index rectal cancer in Lynch syndrome: a multicenter retrospective study in Japan.

PURPOSE: This study evaluated the risk of metachronous colorectal cancer (CRC) after resection of index (first) rectal cancer in patients with Lynch syndrome (LS). METHODS: Clinicopathological data of patients with genetically proven LS were retrospectively analyzed in this multicenter Japanese study. The cumulative incidence of metachronous CRC and the overall survival were compared between patients with index rectal cancer (rectal group) and those with index colon cancer (colon group). RESULTS: The median age at index CRC surgery was lower in the rectal group than in the colon group (37 vs. 46 years old, P = 0.01). The cumulative 5-, 10-, and 20-year incidences of metachronous CRC were 3.5%, 13.9%, and 21.1%, respectively, in the rectal cancer group and 14.9%, 22.0%, and 57.9%, respectively, in the colon cancer group (P = 0.02). The overall survival curves were not significantly different between two groups (P = 0.23). CONCLUSION: This is the first report from an East Asian country to report the risk of metachronous CRC after resection of index rectal cancer in patients with LS. Despite this study having several limitations, we cannot recommend extended resection, such as total proctocolectomy, for index rectal cancer as a standard surgical treatment in patients with LS.

Local excision versus radical surgery for anal squamous cell carcinoma: a multicenter study in Japan.

BACKGROUND: The standard treatment for anal squamous cell carcinoma is chemoradiation therapy (CRT), but there is a possibility of over-treatment for early-stage disease. cTisN0 and cT1N0 disease is currently indicated for local excision, but it is unclear whether the indication of local excision can be expanded to cT2N0 disease. METHODS: 126 patients with cTis-T2N0 anal cancer treated at 47 centers in Japan between 1991 and 2015 were included. Patients were first classified into the CRT group and surgical therapy group according to the initial therapy, and the latter was further divided into local excision (LE) and radical surgery (RS) groups. We compared prognoses among the groups, and analyzed risk factors for recurrence after local excision. RESULTS: The CRT group (n = 87) and surgical therapy group (n = 39) showed no difference in relapse-free survival (p = 0.29) and overall survival (p = 0.94). Relapse-free survival curves in the LE (n = 23) and RS groups (n = 16) overlapped for the initial 3 years, but the curve for the LE group went lower beyond (p = 0.33). By contrast, there was no difference in overall survival between the two groups (p = 0.98). In the LE group, the majority of recurrences distributed in locoregional areas, which could be managed by salvage treatments. Muscular invasion was associated with recurrence after local excision (hazard ratio: 22.91, p = 0.011). CONCLUSION: LE may be applied to selected patients with anal cancer of cTis-T2N0 stage. Given the high risk of recurrence in cases with muscular invasion, it may be important to consider close surveillance and additional treatment in such patients.

Risk of gastric adenoma and adenocarcinoma in patients with familial adenomatous polyposis in Japan: a nationwide multicenter study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) have an increased risk of developing gastric neoplasms. However, the clinical course of FAP with these gastric lesions has not yet been fully clarified. The present study aimed to clarify the changes in the incidence risk of developing gastric adenoma or gastric cancer during the lifespan of patients with FAP. METHODS: Four hundred forty-three patients with data regarding gastric adenoma and gastric cancer retrospectively registered in a nationwide Japanese multicenter study were enrolled. The cumulative incidences and hazard rates (HRs) of gastric neoplasms were evaluated. RESULTS: The cumulative incidence rates in 50-year-old patients with FAP were 22.8% for gastric adenoma and 7.6% for gastric cancer, respectively. No significant association was found between gastric neoplasms and the colonic phenotype. The peak age for the HR of gastric adenoma was 65 years, with the highest HR (0.043). Regarding the incidence of gastric cancer, the HR increased moderately up to the age of 40 years, but the increase accelerated from the age of 50 years (HR = 0.0067). CONCLUSION: Careful surveillance of the upper gastrointestinal tract in elderly patients with FAP, such as shortening the interval of follow-up according to age, may be helpful for early diagnosis of gastric cancer.

Preoperative stoma site marking reduces postoperative stoma-related complications in emergency surgery: A single center retrospective cohort study.

BACKGROUND AND OBJECTIVE: Stoma site marking is an important factor in reducing stoma-related complications, thereby influencing the long-term quality of life in the elective setting. The impact of preoperative stoma site marking in emergency stoma creation is largely unknown. We aimed to determine whether preoperative stoma site marking in emergency stoma creation reduces stoma-related complications. METHODS: Patients who underwent emergency stoma creation at our hospital between 2009 and 2022 were examined by reviewing our prospective database and retrospective chart review. Subjects were classified into the "marking (+)" or "marking (-)" group according to stoma site marking (194 and 151 patients, respectively). The changes in the frequency of stoma marking over time and the effects of stoma marking on stoma-related complications were analyzed. RESULTS: The overall frequency of grade 2 or higher stoma-related complications was lower in the marking (+) group than in the marking (-) group (24% versus 36%, p = 0.010). Stoma site marking was associated with fewer soma site bleeding (2% versus 10%, p < 0.001), and the frequency of peristomal dermatitis was also lower (10%) in the marking (+) group (versus 18%, p = 0.042). Moreover, the lack of stoma site marking was an independent risk factor for overall stoma-related complications (adjusted odds ratio: 1.69, p = 0.034). CONCLUSIONS: Preoperative stoma site marking was associated with stoma-related complications in emergency surgery. The clinical significance of our attempt is worth validating with prospective studies.

Poor prognosis of young male patients with stage III colorectal cancer: A multicenter retrospective study.

BACKGROUND AND OBJECTIVES: The number of young patients with colorectal cancer (CRC) is increasing. However, sex-dependent differences in the prognosis of young CRC remain unknown. METHODS: We investigated patients aged <70 years with stage III CRC treated between January 2000 and December 2010 in 24 Japanese referral hospitals. Patients were divided into subgroups by age of 50 years (early-onset and late-onset groups) and sex, and clinical characteristics and survival outcomes were compared. Risk factors associated with poor survival outcomes were also analyzed. RESULTS: Among 4758 consecutive patients, 771 (16%) were <50 years. Regardless of sex, there were more patients with rectal cancer and treated with adjuvant chemotherapy in the early-onset group. Among males, tumors in the early-onset group were poorly differentiated (p < 0.001), and patients were diagnosed at an advanced N stage (p = 0.010). Among females, there were more patients with left-sided cancer in the early-onset group (p < 0.001). Relapse-free survival (RFS) and overall survival (OS) were worse in the early-onset group than in the late-onset group (5-year RFS rates: 58% and 63%, p = 0.024; 5-year OS rates: 76% and 81%, p = 0.041, respectively), while there were no age-dependent differences in the survival outcomes of female CRC patients. A multivariate analysis identified age <50 years as one of the independent risk factors associated with poor RFS in male stage III CRC patients (p = 0.032) CONCLUSIONS: Young male patients with stage III CRC showed poorer survival outcomes than their older counterparts. Therefore, age- and sex-related differences in the incidence of CRC recurrence need to be considered.

Clinical features and distribution of the APC variant in duodenal and ampullary polyps in patients with familial adenomatous polyposis: a multicenter retrospective cohort study in Japan.

BACKGROUND: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients. METHODS: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps. RESULTS: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants. CONCLUSIONS: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps.

Essential anatomy for lateral lymph node dissection.

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential.

Unexplained increases in serum carcinoembryonic antigen levels in colorectal cancer patients during the postoperative follow-up period: an analysis of its incidence and longitudinal pattern.

BACKGROUND: Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. MATERIALS AND METHODS: We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. RESULTS: CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. CONCLUSIONS: Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.

Limited information is currently available on the frequency of and changes in falsely elevated carcinoembryonic antigen (CEA) levels after surgery for colorectal cancer. Unexplained postoperative CEA elevations were detected in 20% of colorectal cancer patients. The patterns of these elevations were classified into transient, repeated, and persistent.

Adjuvant chemotherapy for elderly patients with colorectal cancer: a single-centre observational study in Japan.

Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. The aim of the present study is to review appropriate chemotherapeutic regimens for elderly patients. We examined 1138 Japanese patients who were operated for high-risk stage II or stage III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70 years. The efficacy of adjuvant therapy was analyzed in association with age and adjuvant chemotherapeutic regimens. A total of 507 patients (45%) were ≥70 years old. They were less likely to receive adjuvant chemotherapy (p < 0.001) or palliative chemotherapy after recurrence (p < 0.001) than patients aged <70 years. Cancer-specific survival (CSS) in stage III CRC patients was longer in the <70 years group than in the ≥70 years group (p = 0.006); however, CSS by regimens did not significantly differ between these groups. Adjuvant chemotherapy was associated with the longer relapse-free survival of stage III CRC patients in the <70 years group (p = 0.005). Although adjuvant chemotherapy was associated with a favourable CSS regardless of age, the implementation rate of adjuvant chemotherapy for elderly CRC patients was low, which may explain shorter CSS in stage III CRC patients the ≥70 years group than in the <70 years group.

Does statin suppress oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer? A single-center observational study.

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting toxicity that markedly limits the use of oxaliplatin and affects quality of life. Statins have been shown to exert neuroprotective effects in preclinical settings. The aim of the present study was to clarify whether statins prevented OIPN in patients with colorectal cancer (CRC) receiving adjuvant CAPOX therapy. METHODS: We examined 224 patients who received adjuvant CAPOX therapy for CRC between July 2010 and December 2021 at our hospital. Patients were divided into "Statin" and "Non-statin" groups based on statin use. Details on and the adverse events of adjuvant CAPOX therapy were examined in association with statin use. RESULTS: Thirty-one patients (14%) were treated with statins. There were no intergroup differences in the relative dose intensity or number of CAPOX cycles between the Statin and Non-statin groups. In total, 94% of patients in the Statin group and 95% of those in the Non-statin group developed OIPN (p=0.67). The severity of OIPN was similar between the two groups (p=0.89). The frequency of treatment delays in CAPOX did not significantly differ between the Statin and Non-statin groups (16% vs. 11%, p=0.45). CONCLUSIONS: The efficacy of statins to attenuate OIPN during adjuvant CAPOX therapy was not apparent in the current study. Further studies are needed to confirm the present results.

Usefulness of genotyping APC gene for individualizing management of patients with familial adenomatous polyposis.

BACKGROUND: Colorectal polyp burden is crucial for the management of patients with familial adenomatous polyposis (FAP). However, accurate evaluation of polyp burden is difficult to standardize. This study aimed to examine the possible utility of genotype-oriented management of colorectal neoplasms in patients with FAP. METHODS: Clinicopathological data from genetically proven patients with FAP was analyzed using the database of a nationwide retrospective Japanese multicenter study. The cumulative incidence of CRC was evaluated between different genotype groups. Genotype-1 were defined as germline variants on attenuated FAP-associated regions (codons 1-177, alternative splice site of exon 10 (codon 312), 1581-2843) and Genotype-2 as the other variants. Weibull and Joinpoint analyses were performed to determine the annual percentage changes in CRC risk. RESULTS: Overall, 69 men and 102 women were included. Forty-eight patients underwent colorectal resection for the first CRC, and five patients underwent resection for first cancer in the remnant anorectal segment after prophylactic surgery. The 70-year cumulative incidence of CRC in all patients was 59.3%. Patients with Genotype-1 (n = 23) demonstrated a lower risk of CRC stages II-IV than those with Genotype-2 (n = 148, P = 0.04). The risk of stage II-IV CRC was estimated to increase markedly at the age of 49 years in the Genotype-1 patients and 34 years in the Genotype-2 patients, respectively. CONCLUSIONS: Different interventional strategies based on genotypes may be proposed for the clinical management of patients with FAP. This policy needs to be validated in further prospective studies focusing on long-term endoscopic intervention and optimal age at prophylactic (procto)colectomy.

Risk of metachronous colorectal cancer after colectomy for first colon cancer in Lynch syndrome: multicenter retrospective study in Japan.

BACKGROUND: We evaluated the risk of metachronous colorectal cancer (mCRC) and explored the optimal extent of colectomy in patients with Lynch syndrome (LS) and first colon cancer (fCC) in Japan, where the extent of colectomy for colon cancer (CC) is shorter than that in Western countries. METHODS: The clinicopathologic and survival data of patients with LS who developed CC were collected from a nationwide database and analyzed retrospectively. The cumulative incidence of mCRC after actual segmental colectomy was compared with that of mCRC when more extensive colectomy was assumed. RESULTS: There were 142 eligible patients (65 female). The median age at fCC surgery was 46.5 (range: 14-80) years. The cumulative incidence of 5-, 10-, and 20-year mCRC rate was 13.4%, 20.8%, and 53.6%, respectively. The incidence was higher in the left-sided group (splenic flexure to rectosigmoid colon, n = 54) than in the right-sided group (cecum to transvers colon, n = 88) (66.3% vs. 45.3% in 20 years, P < 0.01). Assuming that all patients would have undergone hemicolectomy or total colectomy, the estimated mCRC risk was 41.5% and 9.4% (P < 0.01, vs. actual procedures), respectively. The 20-year overall survival rate of all the patients was 83.3% without difference by fCC sidedness (P = 0.38). CONCLUSIONS: To reduce the incidence of mCRC, patients with genetically diagnosed LS and fCC, preferentially located in the left-sided colon, may need to undergo more extended colectomy than that usually performed in Japan. However, such extended colectomy should be counterbalanced with favorable overall survival and actual risk of mCRC development.

Apoptosis-related Prognostic Factors in Advanced Colorectal Cancer Determined Using Tissue Microarrays.

BACKGROUND/AIM: Cancer cells evade apoptosis in colorectal cancer (CRC); however, overlap between apoptosis and poor prognosis marker proteins in the invasive front of tumors has not been reported. Here, we aimed to clarify the relationship between apoptosis, apoptosis-related protein expression, and prognosis in the central and invasive front regions of CRC using tissue microarrays. PATIENTS AND METHODS: Data of 207 patients with pathological stage 3 CRC, who underwent radical surgery between October 2010 and November 2014, were retrospectively reviewed. We assessed apoptosis using M30 CytoDEATH, CD163, and p53 immunostaining in tumor sections in the center and invasive front using tissue microarrays and correlated the results with the survival outcomes. RESULTS: M30 CytoDEATH staining was negative; 134 cases (64.7%) were apoptosis-negative in the center and 103 (49.8%) were apoptosis-negative at the invasive front. CD163 positivity was observed in 16 cases (7.8%) in the center and in 36 cases (17.6%) at the invasive front; p53 positivity was observed in 33 (15.9%) and 64 (30.9%) cases in the center and invasive front, respectively. CD163 and p53 expression was not associated with survival outcomes; however, the apoptosis-negative group at the invasive front had significantly poorer survival outcomes (overall survival: p=0.044, relapse-free survival: p=0.001). We identified cases with a poor prognosis by combining apoptosis and CD163 expression. CONCLUSION: A lower apoptosis percentage at the invasive front is associated with a poorer prognosis. CRC cases with a poor prognosis can be identified by evaluating apoptosis and CD163 expression in the invasive front.

Prognosis of Inferior Mesenteric and Para-aortic Lymph Node Metastases in Rectal Cancer: A Multicenter Study.

BACKGROUND/AIM: In colorectal cancer cases, treatment strategies differ between those with regional and extra-regional lymph node metastases. The inferior mesenteric lymph nodes are categorized as regional lymph nodes, while the para-aortic lymph nodes are classified as extra-regional lymph nodes. Although inferior mesenteric and para-aortic lymph node metastases are both associated with a dismal prognosis, few prognostic comparisons have been conducted. The present study aimed to clarify the prognosis of inferior mesenteric and para-aortic lymph node metastases in rectal cancer. PATIENTS AND METHODS: We retrospectively evaluated 71 patients with pathologically diagnosed rectosigmoid or rectal cancer with inferior mesenteric lymph node metastasis and 27 with pathologically diagnosed rectosigmoid or rectal cancer with para-aortic lymph node metastasis who underwent curative surgery. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. Overall survival, recurrence-free survival, and recurrence patterns were compared between the two groups. RESULTS: The five-year recurrence-free survival rates of patients with inferior mesenteric and para-aortic lymph node metastases were 31.2 and 28.1%, respectively (p=0.37), and the five-year overall survival rates were 43.1 and 39.6%, respectively (p=0.60). Furthermore, the survival curves of the two groups almost overlapped for both recurrence-free survival and overall survival rates. Recurrence patterns did not significantly differ between the two groups. CONCLUSION: In rectal cancer, the prognosis of inferior mesenteric lymph node metastasis is similar to that of para-aortic lymph node metastasis. Inferior mesenteric lymph node metastasis has a poor prognostic impact on rectal cancer.

Prognostic Significance of Enlarged Lymph Nodes in Stage II Colorectal Cancer.

BACKGROUND: Many studies have reported a correlation between lymph node metastasis and prognosis in patients with colorectal cancer. However, the clinical significance of enlarged lymph nodes for prognosis has scarcely been explored. OBJECTIVE: This study aimed to assess the clinical significance of enlarged lymph nodes in stage II colorectal cancer. DESIGN: This is a multicenter retrospective observational study with a median follow-up period of 66.8 months. SETTINGS: Patients' medical records were retrospectively collected from the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer database. PATIENTS: This study included 2212 patients with stage II colorectal cancer who underwent surgical resection between January 2009 and December 2012. Patients were classified into the enlarged lymph node and nonenlarged lymph node groups and their data were compared. MAIN OUTCOME MEASURES: Clinicopathological characteristics and prognoses of the 2 groups were compared. The main outcomes measured were recurrence-free survival and overall survival. RESULTS: The enlarged lymph node group showed significantly better overall survival and recurrence-free survival in pT4b cases but not in pT3 or pT4a cases. In pT4b cases, an enlarged lymph node (HR, 0.53; 95% CI, 0.29-0.98) was an independent prognostic factor for longer recurrence-free survival, whereas a rectal lesion (HR, 3.46; 95% CI, 1.90-6.29) was an independent prognostic factor for shorter recurrence-free survival. An enlarged lymph node was associated with a lower distant recurrence rate (HR, 0.49; 95% CI, 0.26-0.92) and a tendency to correlate with better overall survival (HR, 0.50; 95% CI, 0.22-1.14). LIMITATIONS: The retrospective design may have increased the risk of selection bias. Inadequate information regarding enlarged lymph nodes is another study limitation. CONCLUSIONS: This study showed that enlarged lymph nodes are associated with a favorable prognosis in patients with pT4b stage II colorectal cancer. See Video Abstract at http://links.lww.com/DCR/C246 . IMPORTANCIA PRONSTICA DE LOS GANGLIOS LINFTICOS AGRANDADOS EN EL CNCER COLORRECTAL EN ESTADIO II: ANTECEDENTES:Muchos estudios han informado una correlación entre la metástasis en los ganglios linfáticos y el pronóstico en pacientes con cáncer colorrectal. Sin embargo, apenas se ha explorado la importancia clínica de los ganglios linfáticos agrandados para el pronóstico.OBJETIVO:El objetivo fue evaluar la importancia clínica de los ganglios linfáticos agrandados en el cáncer colorrectal en estadio II.DISEÑO:Este es un estudio observacional retrospectivo multicéntrico con una mediana de seguimiento de 66,8 meses.CONFIGURACIÓN:Los registros médicos de los pacientes se recopilaron retrospectivamente de la base de datos del Grupo de estudio japonés para el seguimiento posoperatorio del cáncer colorrectal.PACIENTES:Incluimos 2212 pacientes con cáncer colorrectal en estadio II que se sometieron a resección quirúrgica entre enero de 2009 y diciembre de 2012. Los pacientes se clasificaron en grupos de ganglios linfáticos agrandados y no agrandados y se compararon sus datos.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las características clinicopatológicas y los pronósticos de los dos grupos. Los principales resultados medidos fueron la supervivencia sin recurrencia y la supervivencia general.RESULTADOS:El grupo de ganglios linfáticos agrandados mostró una supervivencia general significativamente mejor y una supervivencia libre de recurrencia en los casos pT4b, pero no en los casos pT3 ni pT4a. En los casos de pT4b, el agrandamiento de los ganglios linfáticos (CRI, 0,53; IC 95 %, 0,29-0,98) fue un factor pronóstico independiente para una supervivencia sin recidiva más prolongada, mientras que la lesión rectal (CRI, 3,46; IC 95%, 1,90-6,29) fue un factor pronóstico independiente para RFS más cortos. Los ganglios linfáticos agrandados se relacionaron con una tasa más baja de recurrencia a distancia (CRI, 0,49; IC 95%, 0,26-0,92) y una tendencia a correlacionarse con una mejor supervivencia general (CRI, 0,50; IC 95%, 0,22-1,14).LIMITACIONES:El diseño retrospectivo puede haber aumentado el riesgo de sesgo de selección. La información inadecuada sobre el agrandamiento de los ganglios linfáticos es otra limitación del estudio.CONCLUSIONES:Este estudio mostró que los ganglios linfáticos agrandados están asociados con un pronóstico favorable en pacientes con cáncer colorrectal pT4b en estadio II. Consulte Video Resumen en http://links.lww.com/DCR/C246 . ( Traducción - Dr. Mauricio Santamaria ).