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Large‐scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted‐capture sequencing of 171 potentially colorectal cancer‐associated genes was performed, and somatic single‐nucleotide variants and insertion–deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra‐mutated tumors with POLE mutations. Genes with alterations associated with relapse‐free survival were analyzed using multivariable Cox regression models. In all patients (184 right‐sided, 350 left‐sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty‐one tumors were hypermutated (5.8%; 14.1% right‐sided, 1.4% left‐sided). Modest associations were observed: poorer relapse‐free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse‐free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse‐free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse‐free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer. We demonstrated that the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort (534 patients) was largely similar to that in Western populations, but the frequencies of mutation for TP53 (75.3%), SOX9 (11.8%), and FBXW7 (18.5%) were higher, and the proportion of hypermutated tumors (5.8%) was lower. We also revealed that poorer relapse‐free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055) as well as hypermutated tumors (0.53; p = 0.229), whereas better relapse‐free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093), suggesting that tumor genomic profiling has the potential to support precision medicine for patients with colorectal cancer.

Aim The purpose was to clarify the oncological outcomes of rectal cancer (RC) with lateral lymph node metastasis (LLNM) on high‐resolution MRI (HRMRI), considering preoperative treatments. Methods Two hundred and twelve patients, from 13 hospitals, diagnosed with RC with lateral lymph node dissection (LLND), between 2017 and 2019, were prospectively registered. LLNM was defined as a short‐axis size ≥5 mm. Ultimately, this study included 102 patients. Upfront surgery (Upfront), chemoradiotherapy (CRT), and neoadjuvant chemotherapy (NAC) were performed at each institution's discretion. Results Sixty‐six (64.7%) had mesorectal fascia (MRF) involvement, 35 (34.3%) had extramural venous invasion, and 33 (32.4%) had bilateral LLNMs. A positive radial margin (RM1) was observed in nine patients (8.8%), and 35 (34.3%) had pathological LLNM (pLLNM). Overall, 3‐year relapse‐free survival (3yRFS) and local recurrence‐free survival (3yLRFS) were 69.6% and 92.9%. Upfront 3yRFS (N = 54), CRT (N = 23) and NAC (N = 25) constituted 62.9%, 82.6%, and 72.0%; 3yLRFS was 92.4%, 100%, and 88.0%. RM1 and pLLNM were significantly associated with LRFS (RM0 vs. RM1, 3yLRFS 96.7% vs. 50.0%; pLLNM negative vs. positive, 97.0% vs. 84.7%). 3yRFS Upfront non‐MRF (N = 21), post CRT non‐MRF (N = 15), and post NAC non‐MRF (N = 14) were 61.9%, 86.7%, and 100%; 3yLRFS was 90.2%, 100%, and 100%. Conclusions Good local control of Upfront LLND for RC with LLNM was shown, but multidisciplinary treatments were required. CRT followed by surgery was preferable for RC with LLNM, but a radiation‐sparing strategy is promising for post NAC non‐MRF. Kaplan–Meier analyses of RFS (A) and LRFS (B) in non‐MRF groups. RFS, relapse‐free survival; LRFS, local recurrence‐free survival; MRF, mesorectal fascia; Upfront, upfront surgery; CRT, chemoradiotherapy; NAC, neoadjuvant chemotherapy.

Despite the development of new therapies, including anti-TNF alpha antibodies and immunosuppressants, a substantial proportion of patients with ulcerative colitis (UC) still require surgery. Restorative proctocolectomy with ileal-pouch anal anastomosis is the standard surgical treatment of choice for UC. With the advent of laparoscopic techniques for colorectal surgery, ileal-pouch anal anastomosis has also been performed laparoscopically. This paper reviews the history and current trends in laparoscopic surgery for UC. The accumulation of experience and improvement of laparoscopic devices have shifted the paradigm of UC surgery towards laparoscopic surgery over the past decade. Although laparoscopic surgery requires a longer operation, it provides significantly better short and long-term outcomes. The short-term benefits of laparoscopic surgery over open surgery include shorter hospital stays and fasting times, as well as better cosmesis. The long-term benefits of laparoscopy include better fecundity in young females. Some surgeons favor laparoscopic surgery even for severe acute colitis. More efforts are being made to develop newer laparoscopic methods, such as reduced port surgery, including single incision laparoscopic surgery and robotic surgery.

Aim To clarify the usefulness of intraoperative lavage cytology in patients undergoing curative resection for pStage II‐III colorectal cancer in a prospective multicenter study. Methods Patients preoperatively diagnosed with stage II‐III colorectal cancer between 2013 and 2017 from 20 hospitals were enrolled. Lavage cytology was performed twice during the surgery. The primary endpoint was the effect of lavage cytology on the 5‐year relapse‐free survival (RFS) in patients with pStage II‐III colorectal cancer. The secondary endpoint was the effect of lavage cytology on the 5‐year overall survival (OS) and peritoneal recurrence. Results A total of 1378 patients were eligible for analysis. The number of patients with pStage II‐III colorectal cancer was 670 and 708, respectively. Fifty‐four patients (3.9%) had positive cytological results. In pStage II patients, the 5‐year RFS rates with positive and negative cytology were 61.1% and 81.6%, respectively (p = 0.023). The 5‐year OS rates were 67.1% and 91.7%, respectively (p = 0.0083). However, there was no difference in RFS or OS between pStage III patients with positive and negative cytology results. The peritoneal recurrence rates were 11.8% and 1.5% in pStage II patients with positive and negative cytology results, respectively (p = 0.032). These rates were 10.5% and 2.5% in patients with stage III disease, respectively (p = 0.022). Conclusion Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II‐III colorectal cancer. Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II‐III colorectal cancer.

PurposeThe significance of peritoneal lavage cytology as a prognostic marker has been examined in various types of cancer. However, the meaning of positive peritoneal lavage cytology in colorectal cancer is still controversial. The aim of this review is to evaluate the prognostic significance of positive peritoneal lavage cytology in colorectal cancer.MethodsAn English literature search was performed on all studies published between 1998 and 2014 that compared the detection of peritoneal free cancer cells with survival or recurrence.ResultsEighteen articles met the inclusion criteria. All studies employed one (or more) of the three techniques used to detect free cancer cells in the peritoneal cavity: (1) conventional cytology, (2) immunocytochemistry or (3) polymerase chain reaction. The incidence of positive peritoneal lavage cytology ranged from 2.2 to 47.2 % across the studies. The factors correlated with positive peritoneal lavage cytology were tumor penetration and metastases (lymph node, liver and peritoneum). In nine studies, positive lavage findings were associated with a worse survival, and it was associated with increased recurrence in 13 studies.ConclusionPositive peritoneal lavage cytology seems to be an indicator of a poor prognosis in colorectal cancer patients. Further studies are needed to clarify the prognostic impact of peritoneal lavage cytology, by comparing the different methods used for the collection of the peritoneal lavage.

Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li–Fraumeni syndrome.

PurposeThe clinical implications of mucinous components in rectal tumors, especially with regard to the efficacy of neoadjuvant chemoradiotherapy, remain unclear.MethodsOne hundred and thirty rectal cancer patients who received curative resection after neoadjuvant chemoradiotherapy were retrospectively reviewed. Patients were classified into 3 groups according to the proportion of extracellular mucin: low (<5 %), moderate (5–25 %), and high (>25 %).ResultsThere were 82 (63.1 %), 26 (20.0 %), and 22 (16.9 %) patients in the low, moderate, and high mucin groups, respectively. Patients with a high mucinous tumor component were significantly more likely to have an advanced tumor stage (p = 0.010) and a shorter disease-free (p = 0.002) and distant recurrence-free survivals (p < 0.001), whereas the mucinous tumor component showed no correlation with local recurrence (p = 0.101). A high mucinous component was also an independent predictive factor for a shorter disease-free survival (p = 0.041, hazard ratio = 2.56) and distant recurrence-free survival (p = 0.001, hazard ratio = 5.74) according to a multivariate analysis.ConclusionsBecause the mucinous components showed little correlation with local recurrence, mucinous cancer should not be a determining factor for chemoradiotherapy. However, the frequent occurrence of metachronous distant metastasis among patients with a high mucin component makes this a possible indicator for more robust postoperative adjuvant treatment and close surveillance of recurrence.

Background Paraganglioma of the urinary bladder (Pub) is rare and presents with clinical symptoms caused by catecholamine production and release. The typical symptoms of Pub are hypertension, macroscopic hematuria, and a hypertensive crisis during micturition. The average size of detected Pubs is approximately 3 cm. Herein, we report a case of a large Pub in which the symptoms were masked by oral medication, precise preoperative diagnosis was difficult, and intraoperative confirmation of tumoral adhesion to the rectum resulted in hypertensive attacks during surgery. Case presentation A 64-year-old Japanese male with a history of hypertension and arrhythmia controlled with oral medication presented with a large tumor in the pelvic region, detected on examination for weight loss, with no clinical symptoms. Computed tomography and magnetic resonance imaging revealed a tumor measuring 77 mm in diameter in the posterior wall of the urinary bladder. The border with the rectum was unclear, and the tumor showed heterogeneous enhancement in the solid part with an enhancing hypodense lesion. Cystoscopy revealed compression of the bladder trigone by external masses; however, no tumor was visible in the lumen. Endoscopic ultrasonography-guided fine-needle aspiration revealed CD34-positive spindle-shaped cells in the fibrous tissue, suggestive of a mesenchymal neoplasm. The tumor was suspected to be a gastrointestinal stromal tumor, and surgery was performed. After laparotomy, we suspected that the tumor had invaded the rectum, and total cystectomy and anterior resection of the rectum were performed. Histologically, the tumor cells had granular or clear amphophilic cytoplasm with an oval nucleus and nests of cells delimited by connective tissue and vascular septations. Immunohistochemically, the tumor was positive for chromogranin A, CD56, and synaptophysin, and a diagnosis of paraganglioma of the urinary bladder was confirmed. There was no tumor recurrence at the 7-month follow-up. Conclusion This case highlights the importance of careful examination of pelvic tumors, including endocrine testing, for detecting paraganglioma of the urinary bladder in patients with a history of hypertension or arrhythmia.

Cluster of differentiation 133 (CD133) and leu cine-rich orphan G-protein-coupled receptor 5 (LGR5) are the most putative stem cell markers for colorectal cancer (CRC), and are associated with poor prognosis of patients with CRC. However, the role of CD133 and LGR5 in the inflammation-dysplasia-carcinoma sequence has not been fully elucidated. We examined the expression of CD133 and LGR5 in ulcerative colitis-associated CRC (UC-CRC; n=20) and UC-associated colorectal dysplasia (n=16) by immunohistochemistry. The rate of CD133-positive cases in UC-CRC was significantly higher than that in dysplasia (p=0.026), but that of LGR5 expression was not. Moreover, LGR5 expression was significantly positively associated with p53 expression (p=0.03), whereas CD133 expression positively correlated with p53 expression, but not significantly (p=0.10). CD133 may play an important role in tumor development in the context of the inflammation-dysplasia-carcinoma sequence. LGR5-positive cancer stem cells may play a critical role in the development of UC-CRC, particularly upon loss of p53 function.

Appendiceal cancer is rare and associated with a poor prognosis because it is usually found at an advanced stage. We report a case of appendiceal adenocarcinoma manifesting as a colonic obstruction with a lower abdominal mass. Laparotomy revealed bilateral ovarian tumors and a small appendiceal tumor with peritoneal metastases. We performed ileocecal resection, colectomy, and oophorectomy, following which a histological diagnosis of signet ring cell carcinoma was made. Immunohistochemical analysis revealed positive expression of cytokeratin 7 and 20, and mucin core protein 2 (MUC2), compatible with appendiceal cancer and Kruckenberg metastases. When a patient is found to have disseminated pelvic signet ring cell carcinoma of unknown origin, the appendix should be considered as a possible primary site.