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.

Abstract Objective The optimal perioperative chemotherapy for lower rectal cancer with lateral pelvic lymph node metastasis remains unclear. We evaluated the efficacy and safety of perioperative mFOLFOX6 in comparison with postoperative mFOLFOX6 for rectal cancer patients undergoing total mesorectal excision with lateral lymph node dissection. Methods We conducted an open label randomized phase II/III trial in 18 Japanese institutions. We enrolled patients with histologically proven lower rectal adenocarcinoma with clinical pelvic lateral lymph node metastasis who were randomly assigned (1:1) to receive postoperative mFOLFOX6 (12 courses of intravenous oxaliplatin [85 mg/m2] with L-leucovorin [200 mg/m2] followed by 5-fluorouracil [400 mg/m2, bolus and 2400 mg/m2, continuous infusion, repeated every 2 weeks]) or perioperative mFOLFOX6 (six courses each preoperatively and postoperatively). The primary endpoint was overall survival (OS). The trial is registered with Japan Registry of Clinical Trials, number jRCTs031180230. Results Between May 2015, and May 2019, 48 patients were randomized to the postoperative arm (n = 26) and the perioperative arm (n = 22). The trial was terminated prematurely due to poor accrual. The 3-year OS in the postoperative and perioperative groups were 66.1 and 84.4%, respectively (HR 0.58, 95% CI [0.14–2.45], one-sided P = 0.23). The pathological complete response rate in the perioperative group was 9.1%. Grade 3 postoperative surgical complications were more frequently observed in the perioperative arm (50.0 vs. 12.0%). One treatment-related death due to sepsis from pelvic infection occurred in the postoperative group. Conclusions Perioperative mFOLFOX6 may be an insufficient treatment to improve survival of lower rectal cancer with lateral pelvic lymph node metastasis.

Objective: This study aimed to validate surgical outcomes of robot-assisted rectal surgery for highly difficult cases. Methods: Highly difficult cases who underwent robot-assisted or laparoscopic rectal surgery between June 2019 and October 2020 were included in this retrospective study. Surgical outcomes including patient characteristics, perioperative outcomes and pathological findings were compared between the robotic and laparoscopic groups. The highly difficult cases were defined as all low rectal cancer or middle rectal cancer with any of the following characteristics: male gender, BMI ≥ 25 kg/m 2 and tumor size ≥ 5 cm. Results: A total of 50 patients were enrolled: 24 cases in the robotic group and 26 cases in the laparoscopic group. In the robotic group, blood loss was less (p = 0.007) and postoperative stay was shorter (p = 0.024). There were no statistically significant differences in operating time, conversion rate, postoperative complications or pathological findings between the two groups. Conclusion: These results suggest that robot-assisted rectal surgery for highly difficult cases has several benefits in terms of surgical outcomes.

81歳女性．食欲不振を主訴に近医を受診，直腸に60mm大の粘膜下腫瘍を認め当院に紹介された．直腸診で肛門縁より5cm，前壁に基部を有し内腔に突出する腫瘤を触知した．造影CT検査で直腸（Rb）に59×51mm大の造影効果が内部不均一な腫瘍を認め，周囲リンパ節に最大短径12mm以内のリンパ節腫大を認めた．MRI検査ではDWIで腫大したリンパ節に拡散能低下を認めた．下部内視鏡検査では弾性硬の粘膜下腫瘍を認め，生検で粘膜固有層に紡錘形細胞を認め，免疫染色では，S-100蛋白（+），c-kit（－），CD34（－），SMA（－），Desmin（－）であり，直腸神経鞘腫と診断した．画像上リンパ節腫大を認め，悪性症例の報告もあることからリンパ節郭清を伴う腹腔鏡下低位前方切除術を施行した．病理組織学的診断は神経鞘腫で，リンパ節転移（0/51）や悪性所見は認めなかった．リンパ節腫大を伴った直腸神経鞘腫の1例を経験したため若干の文献的考察を加えて報告する．

3607 Background: To date, large-scale genomic sequencings of colorectal cancers (CRC) have been reported mainly from Western countries. However, ethnic diversities, differences by stage, and the prognostic impact of the genomic landscape in CRC remain poorly identified. Methods: The subjects were 534 patients (pts) with stage III CRC from the JCOG0910 study—a randomized phase-III trial conducted in Japan on 1564 pts to assess the efficacy of S-1 versus capecitabine as adjuvant chemotherapy. Targeted-capture sequencing of 171 potentially CRC-associated genes was performed on both normal tissue and tumor samples, and somatic single-nucleotide variants and insertion/deletions were determined. Tumors with MSIsensor scores > 7 and ultra-mutated tumors with POLE mutations were grouped as hypermutated tumors. Genes whose alterations were associated with recurrence-free survival (RFS) were evaluated using multivariable Cox regression models. Results: Of the 534 pts (right-sided: 184, left-sided: 350), 109 pts had recurrences or died during the study. Mutation frequencies were as follows: 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%) (right: 14.1%, left: 1.4%). None of the 49 genes with mutation frequencies > 3% showed a significant association with RFS based on Bonferroni’s adjustment for multiple testing. The following modest associations were observed: mutant KRAS [HR, 1.66; p=0.011] and mutant RNF43 [HR, 2.17; p=0.055] had poorer RFS, whereas mutant COL6A3 [HR, 0.35; p=0.040] and mutant NOTCH3 [HR, 0.18; p=0.093] had better RFS. RFS tended to be better for hypermutated than for non-hypermutated tumors [HR, 0.53; p=0.229]. Conclusions: The overall mutation spectrum of our stage III CRC cohort was generally similar to that of the Cancer Genome Atlas (TCGA). However, the mutation frequencies of TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations seemed to impact RFS, indicating that tumor genomic profiling has a high potential to support precision medicine for pts with CRC.

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on F-18-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on 18F-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.

AbstractObjectiveTo determine risk factors for early postoperative complications after D3 dissection for stage II/III colon cancer.BackgroundIdentification of risk factors for postoperative complications is essential in patients surgically treated for colon cancer. The Japan Clinical Oncology Group (JCOG) conducted a randomized controlled trial, JCOG0404, to confirm the non‐inferiority of laparoscopic surgery (LAP) to open surgery (OP) with D3 dissection for stage II/III colon cancer. This supplementary analysis was made to assess risk factors for surgery requiring D3 dissection using data from JCOG0404.MethodsProportion of postoperative complications of any grade (CTCAE ver. 3.0) until first discharge and risk factors for the most frequent complications were analyzed by univariable and multivariable analysis.ResultsAmong 1057 randomized patients treated between October 2004 and March 2009, 520 patients with OP and 525 patients with LAP were analyzed. Overall postoperative complications of all grades occurred in 190 patients (18.2%). Multivariable analysis showed that the risk factors for overall early postoperative complications were OP itself (odds ratio [OR] 2.01, 95% confidence interval [CI]: 1.38‐2.91, P = 0.0003) and operation time of >240 minutes (OR 1.94, 95% CI: 1.24‐3.02, P = 0.0036). The most frequent adverse event was wound complication (50/1045, 4.8%). In the univariable analysis, reconstruction, greater blood loss, OP, and higher body mass index were significantly associated with wound complication.ConclusionOpen surgery and longer operation time of >240 minutes were significant risk factors for postoperative complications. LAP surgery and shorter operation time could contribute to fewer postoperative complications in patients undergoing colectomy with D3 dissection. (Japan Clinical Oncology Group study JCOG 0404: NCT00147134/UMIN‐CTR: C000000105.)

above the anal canal. Aspiration biopsy was positive for c-kit and CD34, and the tumor was diag-nosed as a gastrointestinal stromal tumor of the rectum. Computed tomography revealed a tumor measuring 10 cm in diameter between the vagina and the lower rectum. There was no evidence of either lymph node or distant metastasis. Although preoperative imatinib mesylate therapy was considered, surgical resection was selected, because immunohistochemical examination of a biopsy specimen revealed an Exon-9 KIT mutation. Therefore, abdominoperineal resection with resection of the posterior wall of the vagina was performed. The defect in the vaginal wall was reconstructed using a gluteal fold flap by plas-tic surgeons. The patient did not receive adjuvant therapy, but remains alive 18 months after the opera-tion with no evidence of recurrence.

症例は66歳の男性で，S状結腸癌腹壁浸潤の診断にて手術予定となったが，入院数日前より腹部膨満および左下腹部の発赤・緊満が出現し，入院時にはS状結腸腹壁浸潤部を中心に腹壁膿瘍を形成し，広範な皮下気腫を認め，さらに閉塞性イレウスを来していた．まず人工肛門造設術および切開排膿術を施行した．全身状態の改善を待って，初回手術から42日目に腹壁合併切除を伴うS状結腸切除を施行した．腹壁の欠損部は13×17 cmとなり，有茎大腿筋膜張筋皮弁を用いて腹壁を再建した．腹壁膿瘍を伴う大腸癌症例では，局所の浸潤傾向に比べて遠隔転移は比較的少ないという報告もあり，切除可能であれば必ずしも予後不良ではないと考えられる．広範な腹壁合併切除を要しても，筋皮弁による腹壁再建を行うことで切除可能となるならば，切除を行う意義は十分にあると考えられた．

Few cases of recurrent colorectal carcinomas were treated non-surgically and cured. Here, we report 3 such cases. Case No. 1 was of a 66-year-old woman, who underwent ISR for very low rectal cancer. Her disease Stage was tub2, T2N0M0. Two years and 6 months later, she developed intrapelvic recurrence involving sacral bones(S1-S3). Radiotherapy of 50 Gy followed by mFOLFOX6 with bevacizumab was administered for a year. She has been cancer-free for 6 years. Case No. 2 was of a 47-year-old man who underwent preoperative CRT of 40 Gy with 5-FU plus Leucovorin, and LAR was performed for very low rectal cancer. The disease Stage was tub2, T3N2M0. One year later, he was diagnosed with recurrent aortic lymph node metastasis. After 7 months of mFOLFOX6 with bevacizumab, he developed an anastomotic fistula. His chemotherapy was discontinued; he was cancer-free for 6 years. Case No. 3 was of a 56-year-old man who underwent TPE for low rectal cancer. The disease Stage was muc, T4b(urinary bladder)N0M1a(perianal skin). One year and 6 months later, he developed ileus and was diagnosed with intrapelvic recurrence. He underwent intestinal bypass operation, and CRT of 46 Gy with capecitabine was administered. He attained CR quickly, and was cancer-free for 5 years. Collecting similar cases to analyze the key to successful treatment is important.

症例は30歳，女性，Lynch症候群の未発症変異保有者であり，サーベイランスの下部内視鏡が施行された．盲腸に0-IIa病変を認め，後日ESDが予定されたが内視鏡挿入困難で外科切除の方針となった．注腸検査で上行結腸の固定不全，造影CTでSMV rotation sign，3D-CT angiographyでSMA右側に小腸枝を認め，腸回転異常症を伴う盲腸癌と診断した．手術は腹腔鏡下回盲部切除を施行した．盲腸・上行結腸の後腹膜との固定は認められず，Ladd靭帯を介して右腹壁と連続していた．小腸は右側腹部に偏在し，小腸間膜は後腹膜と軽度の癒着を認めるのみであった．通常通りの内側アプローチで手術を開始，回結腸静脈を腹側に展開した際にSMVも腹側に吊り上がるため，腹膜切開ラインの決定に注意を要した．術後経過良好で第9病日に退院，腸回転異常症を伴う症例に対しても腹腔鏡手術は安全に施行できると考えられた．

We experienced 3 impressive colorectal cancer patients who developed peritoneal recurrences and underwent surgery several times and survived for more than 5 years. Case No. 1 was of a 44-year-old woman who underwent right hemicolectomy for her stage II A ascending colon cancer. She developed left ovarian metastasis, which was resected 3 years later. Five years later, she developed a pelvic peritoneal recurrence, which was resected successfully. Thirteen years later, she is doing well. Case No. 2 was of a 61-year-old man who underwent transverse colectomy for his stage II B colon cancer. He developed ileus 2 years 9 months later due to peritoneal recurrence, which was removed successfully. He underwent another resection for peritoneal metastasis 2 years 6 months later. He was administered 15 courses of FOLFOX6. He has remained cancer-free since 2009. Case No. 3 was of a 62-year-old man who underwent sigmoidectomy for his stage II A colon cancer. One year 8 months later, he underwent resection for a painful abdominal wall metastasis. Eight months later, he developed another abdominal wall recurrence, which was resected successfully. He underwent thoracoscopic resection 4 times for lung metastases and was given 16 courses of FOLFOX6. In 2009, he developed pelvic peritoneal nodules, which were resected. He later needed lymphadenectomy twice. He has remained cancer-free for the last 5 years and 6 months. Curative resection must be performed for a patient with peritoneal recurrence of colorectal cancer when surgery is indicated.

大腸癌の腹膜播種再発症例は，一般的に切除が敬遠されることが多い．われわれは大腸癌は，再発例でも播種個数が少数であることが多いことを経験し，積極的切除を施行している．今回，その長期成績を検討した．【対象】2000年1月から2014年12月までの腹膜再発を切除してR0/R1にできた再発例80症例，101回手術を検討対象とした．同期間で腹膜再発切除R2となった45例を対照とした．【結果】R0/R1症例は平均61.6歳で男女比46：34，播種個数は1個から70個に及び，中央値で3個であった．術後5年生存率はR0/R1症例全体では26.5％で，そのうち腹膜播種単独群では34.2％であった．R2群では最長生存が34.0ヵ月でMSTは12ヵ月であった．【結論】大腸癌の腹膜播種は他臓器原発癌の腹膜播種とは違い，R0/R1切除が可能ならば，積極的切除の意義はあると思われた．

We analyzed whether TUR was feasible in 4 cases of urinary bladder recurrence of sigmoid colon cancer that invaded into the bladder. Case No. 1 involved a 66-year-old male who presented with sigmoid colon cancer that had invaded the urinary bladder; he underwent sigmoidectomy with partial bladder resection. Six months after the operation, a small, protruded lesion in his urinary bladder was detected and TUR was performed. He has been cancer free for 10 years. Case No. 2 involved a 53- year-old female who underwent sigmoidectomy and hepatectomy for her sigmoid colon cancer and liver metastasis. She developed bladder and liver metastases, which were resected. Four months later, she underwent TUR because she developed a small recurrent tumor in the bladder. Since then, she has had no intrapelvic recurrence for 6 years. Case No. 3 was a 44- year-old male who underwent bladder-preserving resection for a sigmoid colon cancer that had invaded his bladder. He developed a relatively large bladder tumor 1 year 6 months later. TUR was performed and he was administered CRT. He has had no recurrences for 2 years 5 months. Case No. 4 was a 68-year-old male who underwent bladder-preserving surgery for a sigmoid colon cancer that had invaded his bladder. Because he developed a recurrence in the bladder, he underwent TUR 3 months later. He developed a recurrence in the bladder again 1 year 7 months later, and he underwent TUR again. Multiple organ metastases became evident and was prescribed chemotherapy for 2 years. From these cases, we conclude that TUR may be a feasible option for small, protruded recurrences in the bladder, but we should not hesitate to perform total cystectomy if the first TUR is unsuccessful.

669 Background: S-1 has demonstrated antitumor effects in various cancers. Gastrointestinal (GI) toxicities associated with S-1 sometimes cause treatment interruption or termination, and previous reports suggested that low creatinine clearance (Ccr) was associated with the dose reduction and schedule modification during adjuvant S-1 therapy for gastric cancer. However, there are few reports evaluating these associations in colorectal cancer (CRC). Methods: We used the data of patients (pts) allocated to S-1 arm in JCOG0910 trial which evaluated the non-inferiority of S-1 to capecitabine as adjuvant therapy for stage III CRC. The association between pts’ background factors including age, gender, BSA, BMI, surgical procedures, Ccr, AST, ALT, and T-bil, versus treatment termination due to toxicity, and ≥ Grade 2 (G2) diarrhea, ≥ G2 anorexia, and ≥ G2 nausea were evaluated by using logistic regression. Results: Between Mar. 2010 and Aug. 2013, 1564 pts were enrolled, 782 pts were randomized to S-1 arm and 766 pts were analyzed. Pts’ background factors were as follows: ≥ 70 years, 34%; male, 49%; BSA higher, 28%; BMI ≥ 25 kg/m2, 17%; low anterior resection (LAR) or abdominoperineal resection (APR), 19%; Ccr < 50 ml/min, 7%; AST or ALT ≥ upper limit of normal, 16%; T-bil ≥ 1.0 mg/dL, 7%. Among them, 139 pts (18%) terminated treatment due to toxicity or death. The incidence of ≥ G2 diarrhea, anorexia, and nausea were observed in 18, 14 and 10%. The multivariate analysis revealed that some pts’ background factors were significantly associated with the incidence of treatment termination, or ≥ G2 GI toxicities (see table). Conclusions: Low Ccr, female, higher age or lower BMI might be risk factors of treatment termination due to toxicity or > G2 GI toxicities for pts treated with S-1. Clinical trial information: UMIN000003272. [Table: see text]

A 65-year-old man with bloody stools was diagnosed with sigmoid colon cancer on colonoscopy. A preoperative barium enema and a computed tomography colonography scan showed a medial displacement of his descending colon. The preoperative clinical diagnosis was stage cT1 colon cancer, N0, M0, cStage I . Laparoscopic sigmoidectomy was performed. We found adhesions between the descending colon mesentery and the pelvic wall, and noted that the descending colon was not fused with the retroperitoneum and was shifted to the midline. The patient was diagnosed with persistent descending mesocolon (PDM). PDM is a congenital anomaly of fixation resulting from the failure of the descending colon mesentery to fuse with the parietal peritoneum. Anatomical findings should have been noted during the operation, including the fact that the descending colon artery, sigmoid colon artery, and superior rectal artery often branch radially from the inferior mesenteric artery. It is important to understand the anatomical characteristics of PDM and to improve on existing surgical procedures to ensure safe laparoscopic surgery for these patients.

A 67-year-old man was operated for sigmoid colon cancer. Histopathological examination revealed pT3 (SS), N0, M0, Stage Ⅱ cancer. In March 2005, abdominal computed tomography (CT) showed recurrences in the abdominal wall and associated localized dissemination. The patient underwent chemotherapy using TS-1 and CPT-11; however, the disease progressed. Therefore, surgery was performed to resect the recurrences. A re-recurrence developed during the adjuvant chemotherapy. The patient was operated 9 times for recurrences, which were macroscopically resectable, in addition to chemotherapy and radiation. It has been 3 years and 7 months since the last operation, and he is alive with no recurrence. Metachronous peritoneal seeding and distant metastasis developed, but we have observed that surgical resection of each recurrence can prolong patient survival. We conclude that surgical resection can become a treatment of choice for resectable metachronous peritoneal seeding from colon cancer.