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Fluoropyrimidine chemotherapy is a primary component of many solid tumor treatment regimens, particularly those for gastrointestinal malignancies. Approximately one-third of patients receiving fluoropyrimidine-based chemotherapies experience serious adverse effects. This risk is substantially higher in patients carrying DPYD genetic variants, which cause reduced fluoropyrimidine metabolism and inactivation (ie, dihydropyridine dehydrogenase [DPD] deficiency). Despite the known relationship between DPD deficiency and severe toxicity risk, including drug-related fatalities, pretreatment DPYD testing is not standard of care in the United States. We developed an in-house DPYD genotyping test that detects 5 clinically actionable variants associated with DPD deficiency, and genotyped 827 patients receiving fluoropyrimidines, of which 49 (6%) were identified as heterozygous carriers. We highlight 3 unique cases: (1) a patient with a false-negative result from a commercial laboratory that only tested for the c.1905 + 1G>A (*2A) variant, (2) a White patient in whom the c.557A>G variant (typically observed in people of African ancestry) was detected, and (3) a patient with the rare c.1679T>G (*13) variant. Lastly, we evaluated which DPYD variants are detected by commercial laboratories offering DPYD genotyping in the United States and found 6 of 13 (46%) did not test for all 5 variants included on our panel. We estimated that 20.4% to 81.6% of DPYD heterozygous carriers identified on our panel would have had a false-negative result if tested by 1 of these 6 laboratories. The sensitivity and negative predictive value of the diagnostic tests from these laboratories ranged from 18.4% to 79.6% and 95.1% to 98.7%, respectively. These cases underscore the importance of comprehensive DPYD genotyping to accurately identify patients with DPD deficiency who may require lower fluoropyrimidine doses to mitigate severe toxicities and hospitalizations. Clinicians should be aware of test limitations and variability in variant detection by commercial laboratories, and seek assistance by pharmacogenetic experts or available resources for test selection and result interpretation.

Background: The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration., Methods: The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study., Results: There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC ( P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival ( P = .20), R0 resection ( P = .090), or 30-day readmission rates ( P = .30) in the NAC cohort compared to the non-NAC cohort., Conclusions: Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A 51-year-old woman presented to our hospital complaining of a lower abdominal mass and dysuria. She was diagnosed with advanced sigmoid colon cancer. The tumor was large, involving the bladder, and occupying the pelvic cavity. She received neoadjuvant chemotherapy with 4 courses of mFOLFOX6, in addition to panitumumab. The treatment resulted in a marked reduction of the tumor. A laparoscopic sigmoid colon resection, total cystectomy, neobladder reconstruction, complete uterine and bilateral adnexa resection and partial ileal resection were performed. The histopathological diagnosis was ypT4b(bladder), ypN0, ypStage Ⅱc, all with negative surgical margins. Adjuvant chemotherapy was not administered owing to the patient's refusal. She remained recurrence-free for 3 years of postoperative follow up.

A male patient in his 80s underwent colonic stenting for obstructive sigmoid colon cancer with multiple liver metastases. With systemic chemotherapy for approximately 1 year, the liver metastasis disappeared, so laparoscopic sigmoid colectomy was performed for the primary lesion. No recurrence was observed for a while, although CT revealed liver metastasis in the liver S4, and radiofrequency ablation was performed. Radiation therapy was performed for the liver metastasis of liver S2 that subsequently appeared. After a recurrence-free period of approximately 2 years, a rapid regrowth of liver metastasis in liver S2 was observed. Thus, 4 years and 3 months after the initial diagnosis, lateral segmentectomy of the liver was performed. Five years have passed since the first visit, and he is alive without recurrence. The patient had obstructive colorectal cancer with unresectable liver metastasis, and as the obstruction was released by a colonic stent, systemic chemotherapy was prioritized. Hence, liver metastasis was controlled, and the primary lesion was resected. Furthermore, for the liver metastasis that appeared later, various loco-regional cancer therapies were provided to achieve a cancer-free state.

The patient underwent sigmoidectomy with D3 lymph node dissection and partial bladder resection for sigmoid colon cancer(cT4bN1M0, cStage Ⅲa), after preoperative chemotherapy with mFOLFOX plus panitumumab, and FOLFOXIRI plus bevacizumab. Postoperative adjuvant chemotherapy was performed by 8 courses of CAPOX. He relapsed hilar lymph nodes and peritoneal dissemination after 13 months after surgery, he underwent resection of the recurrent lesions. Four months after, he developed recurrence in liver and peritoneum. Although he was treated with FOLFIRI plus ramucirumab or aflibercept, resulted in progression of disease, then he received trifluridine tipiracil hydrochloride plus bevacizumab. At this point, the Japanese health insulance had started to cover pembrolizumab, this therapy was started as the fourth chemotherapy after the diagnosis of high frequency microsatellite instability(MSI), and then tumor markers rapidly declined. He underwent 38 courses of pembrolizumab, the recurrent lesions both liver and peritoneum disappeared. He had stoma closure, peritoneal dissemination disappeared not only intraoperatively but also in histologically from the peritoneal scar. He has received pembrolizumab for 4 years without another recurrence. Here, we report a case of MSI-high sigmoid colon cancer in which long-term survival was achieved by pembrolizumab for recurrent lesions resistant to conventional chemotherapy.

A 50-year-old man presented with fecaluria and was diagnosed with sigmoid colon cancer with a colovesical fistula. Total bladder resection was determined to be necessary for curative resection at the time of diagnosis. In anticipation of bladder preservation, 6 courses of mFOLFOX6 plus panitumumab were administered after transverse colostomy, resulting in marked tumor regression and a decision to proceed with surgery. The patient underwent robotic-assisted low anterior resection of the rectum and partial cystectomy, which yielded pathological radical treatment. We report a case of sigmoid colon cancer with a colovesical fistula complicated by bladder invasion, in which preoperative chemotherapy was effective and total cystectomy was avoided, allowing bladder preservation.

The case is a woman in her 60s. Sigmoid colon cancer surgery, liver metastasis surgery, and adjuvant chemotherapy were performed at another hospital 2 years ago. Later, she developed a metastasis in her liver and was recommended surgery, but she refused treatment and was transferred. Her liver metastasis had invaded the stomach and formed a giant gastric ulcer. This time she had an adhesive ileus and underwent laparoscopic surgery at our hospital. At that time, we observed the state of liver metastasis and gastric infiltration by laparoscopy, so we thought that palliative surgery was possible and recommended it. Although she initially refused treatment, the relative ease with which her ileus surgery was performed encouraged her to undergo palliative surgery. Laparoscopic-assisted gastrectomy and partial hepatectomy were performed, and she was discharged on hospital day 13 after surgery. She subsequently developed liver metastases and died 8 months after palliative surgery, although she was able to eat and maintain her ADL until the end of life. By staying close to the patient, we were able to lead the patient from refusal of surgery to palliative surgery, and we felt that we were able to make the patient reach a favorable end.

A 64-year-old man was diagnosed with KRAS-mutant type sigmoid colon cancer with metastasis in the lung, liver, left adrenal gland, and para-aortic lymph node(T3N1M1b, Stage ⅣB[Union for International Cancer Control 8th edition]). Laparoscopic transverse colostomy was performed to treat colonic obstruction. Subsequently, a combination regimen of capecitabine plus oxaliplatin plus bevacizumab was administered. After 5 courses of chemotherapy, the S8 liver tumor disappeared completely. Sigmoidectomy, para-aortic lymph node dissection, and left adrenal gland resection were performed. After 3 months, right S3 segmental pneumonectomy and right S8 and S10 partial pneumonectomy were performed. R0 resection for the primary lesion and metastatic lesions of the chest and abdomen was achieved. Following the conversion surgery, he was administered the adjuvant chemotherapy regimen of uracil-tegafur plus Leucovorin. After 2 courses of chemotherapy, he presented to our hospital complaining of vomiting and dizziness. Contrast-enhanced magnetic resonance imaging revealed multiple brain metastases. Thus, we should be mindful of the possibility of brain metastasis in cases of unresectable colon cancer showing satisfactory response to chemotherapy with an indication of conversion surgery.

We report a case of a patient with sigmoid colon cancer and multiple liver metastases who underwent hepatectomy after chemotherapy and pathological results showed complete remission. However, after chemotherapy was discontinued, the patient developed a local recurrence of the liver metastasis and underwent rehepatectomy. The patient came to our hospital with lower abdominal pain. Colonoscopy revealed a circumferential type Ⅱ, well-differentiated adenocarcinoma. Laparoscopic sigmoidectomy with lymph node dissection was performed. Postoperative CT scan showed multiple liver metastases at S5, S7, and S8. 11 cycles of bevacizumab plus modified FOLFOX(mFOLFOX)were subsequently performed. The liver metastases shrank at all sites, and the patient underwent right hepatectomy. The resected specimen was considered to be in complete remission, with no evidence of viable malignant cells. Postoperatively, bevacizumab plus mFOLFOX was resumed for 6 cycles and the patient remained in remission. However, 3 months after stopping chemotherapy and 1 year and 6 months after hepatectomy, a follow-up CT scan showed local recurrence of the liver edge, and a diagnosis of local recurrence of liver metastasis was made, and a partial hepatectomy was performed. The patient is recurrence-free and resuming modified FOLFOX 9 months after surgery.

The patient underwent partial sigmoid colon resection for sigmoid colon cancer with hyper CEA blood(1,110.6 ng/mL) and concurrent liver metastases mostly in the right lobe of the liver, followed by systemic chemotherapy(SOX plus BEV). Seven courses of chemotherapy resulted in PR on imaging, and CEA was reduced to 5.0 ng/mL, which was within reference values. As he continued chemotherapy, frequent hematologic toxicities and adverse events forced frequent dose reductions and changes in the chemotherapy schedule. About 2 years after surgery(19 courses of SOX plus BEV), the liver metastases became slightly enlarged on imaging, and the CEA was also increasing. The patient did not wish to undergo systemic chemotherapy and requested hepatic arterial infusion chemotherapy(HAIC), which has relatively few side effects and adverse events. HAIC with pyrimidine fluoride alone is ongoing for 22 courses, and tumor markers have decreased again with PR on imaging. Performance status has been good without hematologic toxicity or adverse events for approximately 1 year during the course of HAIC. HAIC is a weakly recommended therapy in the colorectal cancer treatment guidelines, but it is considered one of the most effective therapies with relatively few side effects.

A 78-year-old man had undergone a laparoscopic sigmoid colon resection; left ureteral resection; and a ureteral reconstruction for sigmoid colon cancer with left ureteral invasion. The patient did not wish to undergo postoperative adjuvant chemotherapy, and he was followed up at fixed intervals. Six months after surgery, CT revealed peritoneal metastasis and liver metastasis(S6). Considering his advanced age and adverse events, the patient was started on capecitabine plus bevacizumab therapy. The patient was able to continue the treatment, even though he had to suspend and reduce the dose due to adverse events of hand-foot syndrome, and achieved CR by CT after 21 courses of treatment. Chemotherapy was discontinued after 24 courses, CR was maintained for 5 years, and the patient is still alive with no evidence of recurrence.

A 71-year-old woman was hospitalized with loose stools and lightheadedness. She was subsequently diagnosed with sigmoid colon cancer for which we performed a laparoscopic sigmoid colectomy, small intestine partial resection, partial bladder resection, and open conversion. The intraoperative findings and histopathological analysis showed secondary lymph node metastasis in the mesentery of the ileum, and the surgery resulted in R2 resection. Chemotherapy(CAPOX plus Bev) was initiated thereafter, and the L-OHP and Bev were discontinued over time. A complete response was achieved at 1 year postoperative. Capecitabine alone was continued, and no signs of recurrence were noted at 2 years postoperative.

A 73-year-old man underwent distal pancreatectomy for invasive pancreatic ductal carcinoma in 2018. He showed stenosis of sigmoid colon due to recurrence of pancreatic cancer and received transverse colostomy in 2020. One year after initiation of gemcitabine monotherapy, he complained of abdominal pain. CT images and colonoscopy revealed accumulation of mucus in sigmoid colon due to stenotic lesions. Because conservative treatment using antibiotics was not effective, we performed sigmoidectomy. Histological examination revealed that tubular adenocarcinoma located mainly in the muscularis propria invaded into the colonic mucosa. Immunohistochemical analysis showed positive staining for CK7, and negative for CK20. We diagnosed sigmoid colon metastases of pancreatic cancer.

The patient is a 52-year-old woman who visited the general practitioner because of positive fecal occult blood test by medical examination. The patient underwent colonoscopy at the hospital, which revealed sigmoid colon cancer. Therefore, the patient was referred to our hospital for surgery. Preoperative CT scan revealed a well-defined and lobulated 54 mm tumor on the caudal side of the duodenal third portion. On MRI, the tumor showed low T1-weighted image signal and high T2-weighted and diffusion-weighted images signal, with low ADC. For preoperative diagnosis, we diagnosed sigmoid colon cancer and transverse colon mesenteric and performed laparoscopic sigmoid colon and transverse colon mesenteric tumor resections. The histopathological tumor diagnoses were sigmoid colon cancer(S, type 2, 30×30 mm, 1/2 circumference, moderately differentiated adenocarcinoma, pT3[SS], INF b, Ly1a, V1a, pN1b[#252: 2/4], sM0, fStage Ⅲb)and transverse colon mesentery primary solitary fibrous tumor. The patient was treated with XELOX as the adjuvant chemotherapy and survived without recurrence until present.

A 35-year-old women with sigmoid cancer(pT4aN1aM0, pStage Ⅲb)underwent laparoscopic sigmoidectomy. She had 8 courses of CapeOX for adjuvant chemotherapy, but follow up CT scan 1 year after the operation detected intraabdominal nodules in anastomotic site and in left lower quadrant of abdomen. After 10 courses of IRIS plus bevacizumab, the both intraabdominal nodules decreased in size. Robot assisted laparoscopic lower anterior resection and laparoscopic disseminated nodule resection were performed. The patient had no postoperative complications and the postoperative course was good. She remains alive without recurrence at 6 months after the second operation.

We report 2: Cases of advanced colorectal cancer that developed nephrotic syndrome after ramucirumab(RAM)administration. Case 1: A 54-year-old woman with rectal cancer, liver and lung metastases, and peritoneal dissemination underwent sigmoid colon double-barrel colostomy for perforation management. The patient received 15 postoperative CAPOX plus bevacizumab(Bev)courses. FOLFIRI plus RAM was introduced as the second-line treatment. After 2 courses, the patient showed marked proteinuria and hypoalbuminemia and was diagnosed with nephrotic syndrome. The patient's condition improved promptly with administrating diuretics and antihypertensive drugs. Case 2: A 72-year-old man underwent sigmoid colon cancer resection with duodenal infiltration. Despite the treatment, a tumor was identified at the radial margin(RM1), with a positive cytological test(CY1)result. Therefore, postoperative mFOLFOX6 plus Bev was administered for 17 courses. FOLFIRI plus RAM was introduced as the second-line treatment due to residual tumor growth. After 2 courses, the patient showed accentuated proteinuria and was diagnosed with nephrotic syndrome and heart failure. The patient's condition improved after administrating diuretics, antihypertensive drugs, and V2-receptor antagonists. In both cases, marked proteinuria was observed after shifting to second-line treatment with two RAM administrations. Therefore, monitoring nephrotic syndrome development during the early RAM introduction stage is essential.

The patient was male, 50s. He visited his local doctor with complaints of hematochezia and hematuria. He underwent colonoscopy, which revealed a circumferential lesion in the sigmoid colon, and he was referred to our department for further examination and treatment. A urinalysis at the time of admission revealed leukocytes(3+)and bacteria(2+), suggesting that the sigmoid colon cancer was invading the bladder. The urologist performed cystoscopy, which showed internal invasion of the bladder, and at this point, including the CT findings, it was needed that a combined bladder resection was necessary. We decided to undergo neoadjuvant chemotherapy(NAC)with the possibility of bladder preservation. FOLFOXIRI plus bevacizumab was selected as the regimen, and a total of 6 courses were performed. After NAC, the effect was judged PR. The patient underwent laparoscopy-assisted resection of the sigmoid colon and partial resection of the bladder wall. The pathological diagnosis was ypStage Ⅱc. Postoperatively, the patient received 6 courses of FOLFOX as adjuvant chemotherapy. Currently, about 8 months after surgery, no recurrence has been observed.

We report a case of laparoscopic sigmoidectomy for sigmoid colon cancer where a laparotomy transition prevented peritoneal metastasis from being missed. Case: A 64-year-old woman was diagnosed with sigmoid colon cancer. Computed tomography revealed a large bowel obstruction and a 12 mm wide basal bulge in the gallbladder. A laparoscopic sigmoidectomy( D3 dissection)was first performed, and intra-abdominal observation revealed no disseminated nodules. A laparoscopic cholecystectomy was performed continuously but, due to strong adhesions, a laparotomy was administered. Three disseminated nodules were observed in the omentum during the laparotomy and a postoperative pathological examination revealed pT4aN1b(2/23)M1c1(P2), pStage Ⅳc. Adjuvant chemotherapy of 8 courses of CAPOX was performed and there has been no recurrence 20 months after surgery.

Sigmoid colon cancer often has an unsatisfactory prognosis. This study explored the effect of tumor deposits (TDs) on survival, and whether their presence/absence influence individualized treatment. Data of postoperative patients with sigmoid colon cancer were extracted from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) was calculated using the Kaplan-Meier method and prognostic factors were identified using Cox regression analysis and random forest (RF). The nomogram's discrimination performance was evaluated using a concordance index (C-index), integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis. The N1c group showed a worse prognosis than the N0 group. For N1c patients, a combination of surgery and chemotherapy prolonged survival, compared to surgery alone; however, the chemotherapy-surgery combination did not affect the OS of patients younger than 70 years, in stage T1-2, and/or of black race. Multivariable analysis and RF presented Age, T stage, and N stage were the most important predictors for OS. The novel nomogram had superiority to the TNM staging system with improved C-index and IDI, as well as good consistency and higher clinical benefit. TDs are associated with poor survival from sigmoid colon cancer, and considering TDs can inform the formulation of individual treatment regimens. The nomogram shows satisfactory prediction ability for OS., (© 2022. The Author(s).)

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.

Oral uracil and tegafur plus Leucovorin(UFT/LV)therapy is one of the standard adjuvant chemotherapies for colorectal cancer, and is widely used without any serious adverse events. Herein, we describe a case of UFT/LV-induced acute liver failure in a 75-year-old woman who underwent laparoscopic sigmoidectomy for sigmoid colon cancer. She was diagnosed with advanced colon cancer and lymph node metastasis by postoperative histopathological analysis, and adjuvant chemotherapy was initiated. After 30 days of commencing the therapy, the patient visited our hospital with complaints of severe diarrhea and difficulty in food intake. The apparent cause of these symptoms was unclear on computed tomography(CT), and mild liver damage was revealed in blood test results. The hepatic disorder gradually progressed after the hospitalization, and the condition was diagnosed as acute hepatic insufficiency. Additionally, obvious atrophy of the liver parenchyma and significant ascites were confirmed on CT. Two months later, the platelet count decreased markedly, but fortunately, no bleeding occurred. There has been no recurrence since 2 years after the surgery without any additional adjuvant therapy.

The patient was a woman in her 70 s. Computed tomography(CT)showed a sigmoid colon tumor invading the uterus and ovaries, and a fistula to the bladder. The patient was scheduled to receive neoadjuvant chemotherapy(NAC), but while waiting for treatment, generalized peritonitis due to perforation of the tumor was observed, and a laparoscopic transverse colostomy was performed. After NAC with CAPOX and FOLFIRI plus panitumumab, the tumor was found to have shrunk, and a laparoscopic posterior pelvic exenteration was performed. The bladder including the fistula was partially resected, and the tumor, uterus, and right ovary were resected in combination as R0, besides the ureter and remaining bladder could be preserved. The postoperative course was uneventful, and the patient is alive without recurrence to date. In this article, we report a case of a patient with sigmoid colon cancer with a bladder fistula who underwent laparoscopic surgery after NAC, and bladder function could be preserved, with some discussion of the literature.

Neoadjuvant systemic therapy is a preferred treatment approach for a number of tumor types due to many potential advantages over upfront surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. For colon cancer, current standard of care is upfront surgery followed by adjuvant systemic therapy in high-risk patients. Concerns about inaccurate radiological staging and tumor progression during preoperative treatment, as well the lack of randomized data demonstrating benefit, are among the reasons for the limited use of neoadjuvant therapy in this disease. Locally advanced colon cancer, defined as primary colon cancer with direct invasion into the adjacent structures or extensive regional lymph node involvement, is not always amenable to pathological complete resection, and when attempted it comes with high incidence of postoperative morbidity and mortality because of the required multivisceral resection. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been promising with downstaging of disease and higher rates of R0 resection. Here, we report a case of a patient with locally advanced, unresectable, mismatch repair deficient sigmoid colon cancer who was treated with neoadjuvant chemoimmunotherapy followed by surgical resection leading to a complete pathologic response after preoperative systemic chemoimmunotherapy.

A 60-year-old man was referred to our hospital for the evaluation and treatment of general malaise. Contrast-enhanced computed tomography detected sigmoid colon cancer that had invaded the bladder, multiple liver metastases, and a small intestinal tumor. Hartmann's procedure was performed, with partial bladder and small bowel resection. A pathological examination revealed that the patient had sigmoid colon cancer and a gastrointestinal stromal tumor. The biopsy findings of a tumor in segment 8 of the liver indicated the presence of adenocarcinoma, thereby indicating the origin of multiple liver metastases from sigmoid colon cancer. On chemotherapy, the tumors in liver segments 2/3 and 8 shrank. However, the tumor in segment 6 enlarged. Since radical resection of all metastatic liver tumors was possible, hepatectomy was performed 10 months after the initial surgery. A pathological examination revealed that the tumors in segments 2/3, 4, and 8 were adenocarcinomas and the tumors in segments 4, 6, and 7 had originated from the gastrointestinal stromal tumor. This suggested the coexistence of liver metastases from sigmoid colon cancer and the gastrointestinal stromal tumor. In cases involving multiple primary tumors, it is necessary to consider the possible coexistence of multiple metastases from different primary tumors., (© 2021. Japanese Society of Gastroenterology.)

Case: A woman in her 50s underwent sigmoid colectomy and D3 lymph node dissection for sigmoid cancer(pT3, N0, M0, Stage Ⅱ: Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma 9th). She received adjuvant chemotherapy with capecitabine. Seven months after surgery, contrast-enhanced computed tomography( CECT) scan revealed a small mass in the segment 2 (S2) of the liver with dilation of peripheral intrahepatic bile duct, and the size of this mass and the bile duct dilatation were gradually increased. FDG positron emission tomography(FDG-PET)/CT showed abnormal FDG uptakes in the lesion of S2, and EOB-MRI detected other small lesions in the S6 and S7. Considering the results of image examinations, multiple lesions intrahepatic cholangiocarcinoma was firstly assumed. However, immunohistochemistry of the tumor obtained by endoscopic retrograde cholangiopancreatography (ERCP) showed cytokeratin 7-negative. Based on preoperative diagnosis of liver metastasis from colon cancer rather than intrahepatic cholangiocarcinoma, we performed left lobectomy, partial hepatectomy of S6 and S7 and cholecystectomy. In the resected specimen, the tumor was macroscopically located in the intrahepatic bile ducts. Microscopically, there existed atypical epithelial cells with glandular duct-like structure, and the lesions was histopathologically diagnosed as metastasis from colon cancer. She was discharged on the 10th postoperative day, and she is alive without recurrence one year after surgery.

We report 2 cases of locally advanced colorectal cancer in which complete response(CR)was achieved after chemotherapy. Case 1 involved a 71-year-old male diagnosed with rectal cancer invading the bladder. Chemotherapy with SOX plus bevacizumab and IRIS plus bevacizumab was administered for rectal cancer. Post-chemotherapy, the disease showed clinical CR(cCR)according to the Response Evaluation Criteria in Solid Tumors(RECIST). A laparoscopic abdominoperineal resection was then performed, with pathological findings showing no viable cancer cells. Eleven months postoperatively, the patient remains alive without disease recurrence. Case 2 involved a 54-year-old female diagnosed with a peritoneal abscess resulting from perforated sigmoid colon cancer. She received chemotherapy with SOX plus bevacizumab. Post-chemotherapy, the disease showed cCR according to the RECIST. A sigmoidectomy was performed, with pathological findings showing no viable cancer cells. Ten months postoperatively, the patient remains alive without disease recurrence. We believe that neoadjuvant chemotherapy is a feasible treatment option for locally advanced colorectal cancer.

Immediate decompression and induction of chemotherapy are exceedingly critical for obstructive colorectal cancer patients with unresectable liver metastasis. Systematic chemotherapy was administered after self-expandable metallic stent(SEMS) placement in 2 patients with obstructive sigmoid cancer with unresectable liver metastasis. Chemotherapy-induced tumor shrinkage led to SEMS migration, enabling the use of an anti-VEGF drug. Eventually, both patients underwent successful management without restenosis.

A 56-year-old man was referred to our hospital for multidisciplinary treatment of advanced sigmoid colon carcinoma with a suspected bladder invasion. The patient received 8 courses of modified Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6)plus panitumumab as neoadjuvant chemotherapy for reliable and safe radical resection after ileostomy construction. There was a significant reduction in the tumor size following chemotherapy; hence, low anterior resection was performed. In addition, since preoperative and intraoperative findings suggested bladder invasion, a total cystectomy with ileal conduit urinary diversion was performed. The pathological diagnosis was ypT4b, N0, M0, and ypStage Ⅱc, with all surgical margins being negative. Subsequently, the patient received adjuvant chemotherapy with 4 courses of mFOLFOX6, and his condition improved with no incidence of cancer recurrence following 8 months after the operation. Neoadjuvant chemotherapy for locally advanced colon cancer is one of the effective treatments for reliable and safe radical resection.

Mucinous adenocarcinoma of the colon occasionally develops from the submucosa, depending on the pattern of onset; therefore, in many cases, it is already advanced at the time of diagnosis. This type of cancer is known to have a poor prognosis. We report the case of a 59-year-old woman who presented with abdominal pain on defecation for 1 month. A mass was palpable in the lower part of her abdomen. On computed tomography(CT), an extrinsic mass was seen in the sigmoid colon, and lower gastrointestinal endoscopy findings suggested an invasive tumor originating from another organ outside the intestinal wall. A high level of the tumor marker CEA(40.8 ng/mL)was observed. No findings suggestive of malignancy were present on biopsy examination, Colorectal cancer was suspected, for which a sigmoidectomy was performed. On histopathological examination, though there was little to indicate a primary colon tumor on HE staining, due to strong CDX2 positivity it was suspected to be an intestinal-type adenocarcinoma. The final clinical diagnosis was unclassifiable, poorly differentiated, mucinous adenocarcinoma of the colon. Multiple liver metastases appeared 4 months postoperatively, which were treated with XELOX plus BV and FOLFIRI plus BV. CT evaluation 24 months postoperatively showed a complete response radiographically. This case of mucinous adenocarcinoma of the colon, in which chemotherapy was successful and long-term survival of 5 years and 2 months was achieved postoperatively, is reported together with a discussion of the literature.

A 78-year-old man was diagnosed with sigmoid colon cancer, and laparoscopic sigmoidectomy was performed. On pathological examination, he was diagnosed with RAS-wild type sigmoid colon cancer with regional lymph node metastasis (T3, N1, M0, Stage ⅢB[Union for International Cancer Control 8th edition]). Computed tomography revealed S8 and S7 liver metastasis, 3 months after the initial surgery. The location of the S8 tumor was close to the inferior vena cava(IVC), right hepatic vein(RHV)and segment Ⅷ hepatic vein(V8). He was administered cetuximab plus modified FOLFOX6. After 6 courses of chemotherapy, the S8 and S7 liver tumor shrank. S8 plus 4 plus 1 and S7 partial hepatectomy was performed and R0 resection was achieved. The RHV and V8 were resected, while right superficial and middle hepatic veins were preserved. An IVC invasion was not observed. He was administered 12 courses of adjuvant modified FOLFOX6. After the partial hepatectomy, he has been followed up for 1.5 years with no recurrence.

Introduction: We report a case of submucosal(SM)adenocarcinoma of the sigmoid colon which developed distant metastasis 3 months after endoscopic mucosal resection(EMR)., Case: 54-year-old, male. Colonoscopy, which was performed due to positive fecal occult blood test, revealed 18 mm Isp sigmoid polyp. EMR was performed with en bloc resection. Pathological examination revealed adenocarcinoma(tub>por>sig), pT1b, Ly1c, V1a, pHM0, and pVM1. Therefore, laparoscopic sigmoidectomy(D2 dissection)was performed. Postoperative pathological examination revealed pT1b, pN2b(10/11), PN1b, pPM0, pDM0, pStage Ⅲb. Distant nodal involvement were found on computed tomography 3 months after EMR, although systemic chemotherapy(mFOLFOX6 plus panitumumab 18 courses and FOLFIRI plus bevacizumab 4 courses)was performed, the patient died of liver failure caused by liver metastasis 21 months after EMR., Conclusion: We present a case of T1 sigmoid adenocarcinoma which developed distant metastasis 3 months after EMR with literature review.

Background: Anastomosis-related complications are common after the radical resection of colon cancer. Among such complications, severe stenosis or completely occluded anastomosis (COA) are uncommon in clinical practice, and the separation of the anastomosis is even rarer. For such difficult problems as COA or anastomotic separation, clinicians tend to adopt surgical interventions, and few clinicians try to solve them through endoscopic operations., Case Presentation: In this article, we present a case of endoscopic treatment of anastomotic closure and separation after radical resection for sigmoid carcinoma. After imaging examination and endoscopic evaluation, we found that the patient had a COA accompanied by a 3-4 cm anastomotic separation. With the aid of fluoroscopy, we attempted to use the titanium clip marker as a guide to perform an endoscopic incision and successfully achieved recanalization. We used a self-expanding covered metal stent to bridge the intestinal canal to resolve the anastomotic separation. Finally, the patient underwent ileostomy takedown, and the postoperative recovery was smooth. The follow-up evaluation results showed that the anastomotic stoma was unobstructed., Conclusions: We reported the successful application of endoscopic technique in a rare case of COA and separation after colon cancer surgery, which is worth exploring and verifying through more clinical studies in the future.

The case is a 59‒year‒old woman. A detailed examination of fecal occult blood revealed a diagnosis of cStage Ⅳ sigmoid colon cancer cT3N1M1b(liver H2, hilar liver and celiac artery lymph nodes). After excision of the primary lesion, decided to give chemotherapy. The gene test was RAS gene mutation negative and EGFR positive, and mFOLFOX6 plus panitumumab (pani)was started as the first‒line treatment. Imaging tests at the end of 13 courses showed that the maximum diameter of liver metastases was reduced from 54 mm to 16 mm, and CEA was normalized from 93.9 ng/mL. However, metastasis was found in the hilar lymph nodes, it was judged that hepatectomy is not indicated, radiofrequency ablation therapy was performed. But FOLFIRI plus pani was restarted because metastatic liver tumor relapsed on CT 5 months later. After 6 courses, she felt tired, so I consulted her and changed to TAS‒102 plus bevacizumab. Sudden headache and vomiting appear during 3 courses, head CT revealed subarachnoid hemorrhage. No brain metastases or organic lesions such as cerebral aneurysms and stenotic lesions, the relationship with bevacizumab was strongly suspected.

A 60-year-old man with sigmoid colon cancer invading the urinary bladder underwent sigmoid colectomy and partial cystectomy. He developed headache and vomiting 12 weeks after surgery, and urgently hospitalized. Contrast MRI of head and whole spinal cord inspected no abnormality. CSF examination showed elevated CA19-9 20,551 U/mL, and the cytology revealed atypical cells similar to the sigmoid colon cancer cells. He was diagnosed as meningeal carcinomatosis, and received 1 course of CAPOX plus bevacizumab chemotherapy. He died 18 weeks after the surgery.

The efficacy of pembrolizumab has been demonstrated for all solid tumors showing high frequency microsatellite instability- high(MSI-High). It is a possible treatment option even in cases which do not respond to other forms of chemotherapy. We report a case of a 69-year-old man with MSI-High recurrent colorectal cancer with complete response(CR)after pembrolizumab therapy. Sigmoidectomy, extensive lymph node dissection, and partial bladder resection were performed for sigmoid colon cancer at another hospital. Histopathological examination revealed a T4a, N0, M0, Stage Ⅱb tumor. Six months after the operation, Hartmann's operation and partial resection of the small intestine were performed for local recurrence. However, the tumor invading the retroperitoneum was unresectable. Postoperative SOX therapy was performed, but it was discontinued due to Grade 3 diarrhea during the first course. The laboratory test showed MSI-High during the first course. Pembrolizumab chemotherapy was introduced as second-line therapy. Computed tomography examination after 2 courses (6 weeks)revealed reduction in the major axis of the tumor by 30% or more. After 4 courses(12 weeks), the tumor was further reduced, and a partial response(PR)was diagnosed. The tumor completely disappeared after 6 courses, and a complete response was achieved after 8 courses. The CR has been maintained for about 7 months.

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.

A 50's man was referred to our hospital because of sigmoid colon cancer with multiple liver metastases and para-aortic lymph node metastases. Although blood test showed elevated D-dimer(50 μg/mL), there was no significant thrombus in contrast-enhanced CT scan. Since cancer pain and symptoms of bowel obstruction had continued after endoscopic stent placement, we resected primary lesion. Despite anemia and elevated D-dimer level had persisted after the operation, there were no obvious bleeding source nor thrombus. Continuous intravenous heparin infusion was started for hypercoagulability. Then, D-dimer and CRP levels were promptly decreased. Since schizocyte and giant platelets were observed in peripheral blood smear, he was eventually diagnosed with thrombotic microangiopathy as a paraneoplastic syndrome. However D- dimer and CRP levels were re-elevated, and it seemed to be necessary to control cancer progression. Thus, cetuximab monotherapy was started considering his performance status. After starting cetuximab, fever and CRP level were immediately improved. Cetuximab appeared to be very effective, but he died of acute subdural hematoma. Continuous intravenous heparin infusion was supposed to be effective in the treatment of thrombotic microangiopathy along with the management of cancer.

A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.

Neoadjuvant chemoradiotherapy is a standard mode of therapy for rectal cancer but not colon cancer. A 74-year-old man undergoing treatment for prostate cancer was found to have a tumor in both the sigmoid colon and liver. Colonoscopy showed a type 2 tumor of the sigmoid colon, with a biopsy confirming a diagnosis of well differentiated tubular adenocarcinoma. Computed tomography demonstrated a tumor of the sigmoid colon with metastasis to the liver. As there was a high suspicion of invasion of the left ureter, we decided to administer mFOLFOX6 as neoadjuvant chemotherapy prior to tumor resection. After 8 courses of mFOLFOX6, both the primary lesion and liver metastasis significantly decreased in size. Subsequently, the patient underwent a sigmoidectomy and partial hepatectomy. Histopathological examination revealed pathological complete response(Grade 3). It is important to reveal effective cases of neoadjuvant chemotherapy, the appropriate treatment regime and timing of surgical intervention so as to advance therapeutic strategies for the treatment of colon cancer.

We report a case of a male in his sixties with appendiceal cancer who underwent radical resection following CAPOX plus bevacizumab neoadjuvant chemotherapy. The patient presented to our hospital with a chief complaint of chronic low abdominal pain. Contrast-enhanced CT before neoadjuvant chemotherapy revealed an inhomogeneous tumor in the ileocecal region. Invasion to the bladder and the sigmoid colon was also observed. A colonoscopy showed an elevated lesion, which was caused by extramural invasion to the sigmoid colon. Pathological examination of the sigmoid colon tumor revealed well differentiated tubular adenocarcinoma and KRAS codon13 G13D. Hence, we diagnosed the patient with locally advanced appendiceal cancer with invasion to the bladder and sigmoid colon. We administered CAPOX plus bevacizumab as neoadjuvant chemotherapy. Contrast-enhanced abdominal CT after neoadjuvant chemotherapy revealed shrinkage of the primary tumor and reduction in the invasion to the bladder and sigmoid colon. We performed ileocecal resection(+D3), a partial sigmoidectomy, and partial bladder resection on the 135th day from the diagnosis. The resected specimen showed an appendiceal tumor with invasion to the bladder and sigmoid colon. The pathological diagnosis was Ⅴ, yType 5, tub2>tub1, ypT4b, ypN0, ycH0, ycM0, ycPUL0, Ly1b, V1b(VB), Pn01b, pStage Ⅱa, and the histological treatment effect of preoperative therapy was Grade 1b. Our experience indicates that in patients with locally advanced appendiceal cancer, multimodal treatment with neoadjuvant chemotherapy is an effective option.

A 30's extremely obese patient(body mass index: BMI 45 kg/m2)was referred to our hospital with a chief complaint of bloody urine and stool. Colonoscopy revealed a sigmoid colon tumor. Barium enema examination revealed stenosis of the sigmoid colon. CT scan showed a tumor in the sigmoid colon, with bladder invasion. The para-aortic lymph node was partially swollen. We considered surgery to be high risk because of the patient's severe obesity. Therefore, we decided to examine the possibility of radical surgery followed by chemotherapy(mFOLFOX6/cetuximab)with weight reduction. Following this, the tumor had shrunk remarkably, and the patient's BMI decreased from 45 kg/m2 to 39 kg/m2. The visceral fat area was reduced from 298 cm2 to 199 cm2 at the umbilical level. We then performed a sigmoid colectomy with partial resection of the bladder. Thus, chemotherapy combined with weight loss enabled us to perform radical surgery safely for a locally advanced sigmoid colon cancer in a patient with severe obesity.

An 83-year-old man visited our hospital with liver tumors detected by abdominal ultrasonography. On investigation, he was diagnosed with sigmoid colon cancer with metastasis in the supraclavicular lymph node, liver, and para-aortic lymph node(T3N1M1b, Stage ⅣB[Union for International Cancer Control 8th edition]). He was administered combination therapy with capecitabine and bevacizumab owing to the increased age and Eastern Cooperative Oncology Group performance status score of 1. After 8 courses of chemotherapy, the primary tumor and liver metastases shrank. As he developed Grade 2 hand-foot syndrome, the dose of capecitabine was decreased to 75%(1,500 mg/m2)from the 11th course and to 50% (1,000 mg/m2)from the 31st course. Until 2 years after initiation of the chemotherapy, the patient showed progression-free survival. Heparinoid-containing moisturizer and steroid ointment were administered for treatment of hand-foot syndrome. This report suggests that capecitabine plus bevacizumab therapy can maintain the quality of life and is safe with dose reduction and treatment of adverse reactions for elderly patients with colon cancer.

A 77-year-old man was diagnosed with obstructive sigmoid colon cancer invading the psoas major and iliac muscles. To avoid the postoperative paralysis of the lower limb, a self-expandable metallic stent(SEMS)was placed, and systemic chemotherapy was administered subsequently. After 4 courses of SOX, Hartmann's procedure was performed. The patient did not develop lower limb paralysis and is alive without recurrence 2 years and 3 months postoperatively. This case suggests that preoperative metallic SEMS placement and neoadjuvant chemotherapy could be an effective treatment for locally advanced colon cancer with obstruction and invasion of the adjacent tissues.

Background/aim: Right ventricular cardiac metastasis from colorectal cancer (CRC) is rare and clinically silent. There is no standardised treatment. To date, only twelve cases have been reported in the literature. This is a case report and literature review of right ventricular cardiac metastasis from CRC., Case Report: A 75-year-old woman with a history of CRC treated with sigmoidectomy followed by liver and lung metastasectomy presented with a right ventricle tumour. Biopsy showed metastatic adenocarcinoma not suitable for resection because multiple lung metastases coexisted. The metastases were controlled for a prolonged duration by chemotherapy with capecitabine plus bevacizumab. According to the review of 13 cases, the median age of metastatic CRC that involves the right ventricle is 71 years and the primary site is half the colon and rectum. Half of cases have non-cardiac metastases at cardiac metastasis diagnosis. Chemotherapy is more suitable than resection in cases with metastases other than heart because resection of the right ventricle has a high risk., Conclusion: Cardiac right ventricular metastasis from CRC can be controlled by capecitabine plus bevacizumab., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rationale: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention., Patient Concerns: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made., Diagnoses: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke., Interventions: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7., Outcomes: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent., Lessons: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.

A 63-year-old man was diagnosed with advanced sigmoid cancer of pT3, pN0, sM1c, sP3, fStage Ⅳ post-operation. After CAPOX plus Bmab as the first-line chemotherapy, he underwent IRIS plus Bmab as the second-line chemotherapy. After 1 course of IRIS plus Bmab, he was admitted to the hospital for fever, dyspnea, and general fatigue. The white blood cell count was 6.2×10 3/mL, and the C-reactive protein was elevated to 12.9 mg/dL. The PaO2 of the artery blood gas analysis in room air was 46.3 mmHg, suggesting respiratory failure. He was diagnosed with PCP based on the bilateral diffused ground-glass opacities on chest CT along with an elevated serum b-D-glucan. The treatment of trimethoprim-sulfamethoxazole and steroid was then initiated. After the patient's clinical condition improved, he was discharged on day 27 post-admission.

Diffuse cavernous haemangioma is a rare disease of the rectum. It usually presents with a history of rectal bleeding in children and young adults. When conservative methods fail to control bleeding, traditionally resection is recommended. A 50-year-old man presented with per rectal bleeding and was diagnosed with diffuse cavernous haemangioma of the sigmoid and rectum extending up to 40 cm in the left colon through endoscopy, magnetic resonance imaging and computed tomography. The diagnosis was confirmed by biopsy. This patient was successful managed conservatively with tranexamic acid as needed, avoiding the need for resection.

A92 -year-old woman underwent laparoscopic sigmoid colectomy with D3 lymphadenectomy. Histological examination confirmed a pT3(SS), pN0, pM0, pStageⅡ tumor. Abdominal CT 6 months after surgery revealed liver metastasis close to the right branch of the portal vein in the S6 region of the liver. There were no indications for transcatheter arterial embolization, radiofrequency ablation, or hepatectomy. Although she had Grade 3 neutropenia, the patient received 15 courses of oral UFT/LV. Three courses of UFT/LV plus bevacizumab were also administered. She was judged to have achieved stable disease (SD); however, Grade 4 proteinuria was observed. After she was administered 2 courses of TAS-102, we shifted to best supportive care. She died of a sigmoid cancer 32 months after UFT/LV initiation. Careful adaptation of chemotherapy can be used to control a patient's condition during certain periods, even in patients with super-advanced age.