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

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

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

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

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

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

[A Case of 30s Female with Advanced Anal Canal Adenocarcinoma Managed with Adolescent-And-Young-Adult Team].

A 30s female complaining of anal pain and melena was referred to our hospital. The support by adolescent-and-young- adult(AYA)team was initiated after the first encounter. Colonoscopic examination revealed an ulcerated tumor on the anterior wall of anal canal with its anal margin on anal verge and the tumor was diagnosed as an adenocarcinoma. Contrast- enhanced CT and MRI revealed adjacency of tumor and vagina, enlarged lymph nodes and multiple pulmonary nodules. 18F-fluorodeoxyglucose(FDG)-positron emission tomography(PET)additionally revealed tracer accumulation in left sciatica, which led us to the diagnosis of advanced anal cancer. We planned and safely performed concomitant partial vaginal resection in robot-assisted laparoscopic abdominoperineal resection for the palliative purpose after discussion on physical and psychosocial issues including stoma and fertility with the patient, her family and AYA members. The pathological diagnosis was pT4b(vagina)N1aM1b, pStage ⅣB, and the local margin was pathologically negative. The postoperative course was smooth and she was discharged on postoperative day 16. Fifty one days after operation, she started systemic chemotherapy after decision on not to take ovarian samples and continues systemic chemotherapy as of writing. Support by AYA team was effective to facilitate the patient's decision-making and the communication between the patient and the medical team.

[Questionnaire Survey on Oral Care and Oral Troubles for Patients with Gastric Cancer Received Chemotherapy].

BACKGROUND: The actual situation of oral care and oral troubles for patients with gastric cancer received chemotherapy is not clear. METHODS: Questionnaire survey in the form of oral questions was performed for patients with gastric cancer who received chemotherapy from December 2021 to February 2022. The relevance between the survey results and background factors was examined using the χ2 test. RESULTS: We performed the questionnaire survey for 36 patients. Of the 36 patients, 29 patients received dental check-up before starting chemotherapy. Fourteen of the 29 patients(48%)continued the dental check-up. Of 14 patients who continued the dental check-up, 9 patients were 65 years or older, while 14 of 15 patients who discontinued the dental check-up were 65 years or older. Continuity of dental check-up was low among the elderly patients. The rate of dysgeusia were 78 vs 30% in the patients who adopted and who did not adopt oral care other than toothbrushing(p=0.01). The frequency of oral troubles was dysgeusia(47%), stomatitis(42%), and dry mouth(36%). The severity of the oral troubles was, in order, dysgeusia, dry mouth, and pain. The most common side effect due to chemotherapy causing decreased food intake was dysgeusia. CONCLUSIONS: Dysgeusia was the most frequent and severe oral trouble.

[Regimen Selection by Narrative Approach in Patients with Advanced Gastric Cancer-Paclitaxel or Nab-Paclitaxel?]

BACKGROUND: According to the sixth Gastric Cancer Treatment Guideline, the regimen included nab-paclitaxel(nab-PTX) is a conditional recommendation as second-line treatment for advanced gastric cancer. However, the selection criteria of nab-PTX is not clear. METHOD: Questionnaire survey as narrative approach on the problems of paclitaxel premedication, the symptoms due to paclitaxel containing alcohol, and infusion time was conducted for patients who had been treated with paclitaxel. RESULTS: Thirty-six patients answered the questionnaire. Nonelderly patients(<65 years)or patients without comorbid medications complained of dissatisfaction with the inconvenience due to premedication significantly more than elderly patients(≥65 years)or patients with comorbid medications. Females or nonelderly patients were significantly more troubled by sleepiness due to premedication than males or elderly patients. Eight out of 11 patients who had visited hospital by driving a car for first-line treatment were troubled by prohibition of driving on the day of treatment. Thirty out of 36 patients answered that they would feel benefits from 30-minutes shortening of infusion time. CONCLUSION: Questionnaire survey suggests that we may select the patients for nab-PTX properly by clarifying the inconvenience of daily life associated with premedication, the way of transportation for visiting hospital, and the benefits by shortening of infusion time.

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

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

The effect of specimen processing time on HER2 expression in gastric cancer and esophagogastric junction cancer: a single-center retrospective observational study.

BACKGROUND: Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation. METHODS: The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing. RESULTS: Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44-8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51-10.55, p = 0.005), and time to specimen processing of < 120 min (OR: 2.65, 95% CI: 1.01-6.98, p = 0.049) were independent factors that affected HER2-positivity. CONCLUSIONS: The outcomes of the present study indicated that intestinal type, pM, and time to specimen processing are important factors affecting HER2-positive rates in GC and EGJC. Therefore, the risk of false-negative HER2 results may be reduced by decreasing the time required to process the resected specimen. Additionally, accurate diagnosis of HER2 expression may increase the opportunity to administer molecular-targeted drugs that can expect therapeutic effects to patients appropriately. TRAIL REGISTRATION: Retrospectively registered.

Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

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

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

[A Case Report of the Ascending Colon Cancer with Bullous Pemphigoid].

The patient was a 70-year-old man. The patient had progressive anemia while taking 10 mg/day of prednisolone and 100 mg/day of mizoribine orally for bullous pemphigoid, a colonoscopy diagnosed ascending colon cancer. Adenocarcinoma, Group 5 was detected on biopsy. Abdominal computed tomography showed no metastases. The tumor was diagnosed as ascending colon cancer, cT4aN0M0, cStage Ⅱb. We performed laparoscopic right hemicolectomy and D3 dissection. Histopathological examination revealed pT3N0M0, pStage Ⅱa. In the present report, we describe a case of the ascending colon cancer with bullous pemphigoid, and discuss the case with a review of the literature.

[A Case Report of SOX Therapy for an Elderly Patient with Hemorrhagic Primary Duodenal Carcinoma].

BACKGROUND: Although pancreatoduodenectomy is recommended as a radical surgery for duodenal carcinoma, it has been reported that pancreatoduodenectomy in elderly patients has a high risk of surgical complications. CASE PRESENTATION: A man in his 80's was diagnosed with advanced duodenal carcinoma, presenting with anemia(Hb 5.4 g/dL). Computed tomography scanning showed wall thickening in the descending leg of the duodenum, pancreatic invasion was suspected, and clinical diagnosis was Stage ⅡB(cT4N0M0). Although radical surgery was possible, the patient refused surgery considering the risks of surgical complications. The gastroduodenal bypass surgery was performed to control bleeding, and the patient was treated with S-1 plus oxaliplatin(SOX; S-1 100 mg/body, days 1-14; oxaliplatin 100 mg/m2, day 1 q21 days). After 6 courses of the SOX regimen, the wall thickening of duodenum disappeared, and SOX was switched to S-1 monotherapy (S-1 100 mg/body, days 1-28, q42 days)according to Grade 2 thrombocytopenia and decreased performance status. After 11 courses of S-1, upper gastrointestinal endoscopy showed that the tumor had disappeared, the biopsy of duodenum showed no evidence of malignancy, and chemotherapy was terminated. The patient has been followed up for 7 months without recurrence. CONCLUSIONS: SOX for elderly patient showed efficacy against hemorrhagic duodenal carcinoma.

[Tolerability and Outcome of Neoadjuvant GS Therapy for Resectable Pancreatic Cancer].

INTRODUCTION: Neoadjuvant chemotherapy with gemcitabine plus S-1(NAC GS)has been reported to prolong the prognosis of resectable pancreatic cancer, and is now being used in daily practice. In this study, we investigated the tolerability and outcome of neoadjuvant GS therapy for resectable pancreatic cancer in our hospital. PATIENTS: Fifty-two patients who underwent NAC GS for resectable pancreatic cancer between November 2019 and March 2023 were included in this study. RESULTS: The mean age of all 52 patients was 75 years, 28 were male and 24 were female. Tumor site was pancreatic head cancer in 32 patients, pancreatic body cancer in 13 patients, and pancreatic tail cancer in 8 patients. Only 2 patients of the 52 patients completed 2 cycles of GS therapy with full dose, and dose reduction and treatment deferral were performed in remaining 50 patients. The dose intensity was 78.4% for gemcitabine and 66.7% for S-1. Grade 3 or higher adverse events included neutropenia in 21 patients(40.4%), biliary tract infection in 6 patients(11.5%), fatigue, anorexia, hepatic dysfunction, and constipation in 1 patient each(1.9%). 47 patients(90.4%)underwent R0 resection. 4 patients had pancreatic fistula, which was classified as Grade Ⅲ by Clavien-Dindo, and one of them died in the hospital due to bleeding from a pseudoaneurysm. CONCLUSION: NAC GS therapy for resectable pancreatic cancer was considered feasible with appropriate management of adverse events.

The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial.

OBJECTIVE: This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. BACKGROUND: No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. METHODS: This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3-4, N0-2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. RESULTS: Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%-81.0%] and 76.2% (95% CI 71.9%-80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800- 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. CONCLUSION: The present study failed to confirm the superiority of the no touch.

Impact of aspirin discontinuation on thrombotic complications in laparoscopic colorectal cancer surgery.

BACKGROUND: The number of patients taking antiplatelet therapy is increasing. However, there is no definitive guideline for the perioperative management of antiplatelet therapy. Conventionally, the discontinuation of antiplatelet drugs has been the basic treatment as perioperative management. Therefore, we investigated the risk of discontinuing aspirin concerning thrombotic complications in laparoscopic colorectal cancer surgery. METHODS: Between January 2015 and December 2019, a total of 729 patients underwent laparoscopic colorectal cancer surgery in Toyonaka Municipal Hospital. Sixty-four patients taking antithrombotic drugs aside from aspirin were excluded from this study; the remaining 665 patients were considered eligible and divided into three groups. The patients not taking aspirin were classified as the "Control group" (n = 588). Among the patients taking aspirin, those who continued preoperative aspirin were classified as the "Aspirin group" (n = 30), and those who discontinued preoperative aspirin were classified as the "No-aspirin group" (n = 47). The Aspirin, No-aspirin, and Control groups were compared retrospectively. RESULT: Among the 3 groups, there were no significant difference in operative time (p = 0.14), bleeding volume (p = 0.63), or postoperative hospital stay (p = 0.06). Assessing the postoperative complication, bleeding complications were significantly more frequent in the Aspirin group (p < 0.01), although those complications were all Clavien-Dindo grade II. In contrast, thrombotic complications were significantly more frequent in the No-aspirin group (p < 0.01). Note that those complications were all Clavien-Dindo Grade III/IV. This result suggested that discontinuing aspirin increased the risk of severe thrombotic complication. CONCLUSION: Discontinuation of aspirin as perioperative management in laparoscopic colorectal cancer surgery increased the risk of severe thrombotic complications.

Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study.

BACKGROUND: Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site. METHODS: Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC. RESULTS: Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14-2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer). CONCLUSIONS: Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.

[A Case of Peritoneal Recurrence from Ascending Colon Cancer Successfully Treated with Laparoscopic Concomitant Right Seminal Vesiculectomy in Low Anterior Resection].

A 60s male, who had laparoscopic ileocecal resection for ascending colon cancer 2 years ago, had enhanced computed tomography(CT)for follow-up and a 12-mm nodule in Douglas' pouch adjacent to right seminal vesicle and rectum was found. 18F-fluorodeoxyglucose(FDG)-positron emission tomography CT revealed abnormal accumulation of 18F-FDG only to the lesion(standardized uptake value max 2.60)and the diagnosis of peritoneal recurrence of ascending colon cancer was made. We planned and safely performed laparoscopic concomitant right seminal vesiculectomy in low anterior resection. The pathological diagnosis was peritoneal dissemination of colon cancer and the margin was pathologically negative. The postoperative course was smooth except for temporary dysuria and he was discharged on postoperative day 17. As of writing 1 year after surgery, the patient continues to do well with no sign of recurrence. Laparoscopic concomitant seminal vesiculectomy in low anterior resection can be a good option for the curative resection of peritoneal recurrence.

[A Case of Effective Plasma Exchange for Thrombotic Microangiopathy during Chemotherapy for Pancreatic Cancer].

The patient was a 78-year-old man. After 4 courses of GEM plus nab-PTX therapy for multiple recurrent liver metastases after pancreatic body cancer surgery, the patient was aware of general malaise and edema of the extremities. Blood tests showed pancytopenia, and he was admitted to the hospital with a diagnosis of chemotherapy-induced pancytopenia. On the second day, hemolytic anemia with crushed red blood cells was observed, suggesting thrombotic microangiopathy (TMA). Considering the possibility of thrombotic thrombocytopenic purpura(TTP), the patient was started on plasma exchange with steroids. After 7 days of plasma exchange, his thrombocytopenia, hemolytic anemia, and renal dysfunction improved, and he was discharged from the hospital on the 28th day. Although GEM-induced TMA is a life-threatening complication, there is no established treatment for it. We report a case of GEM-induced TMA that was successfully treated with plasma exchange.

Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial).

BACKGROUND: The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). METHODS: The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. RESULTS: The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell's C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. CONCLUSIONS: Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.

Application of targeted nanopore sequencing for the screening and determination of structural variants in patients with Lynch syndrome.

Lynch syndrome is a hereditary disease characterized by an increased risk of colorectal and other cancers. Germline variants in the mismatch repair (MMR) genes are responsible for this disease. Previously, we screened the MMR genes in colorectal cancer patients who fulfilled modified Amsterdam II criteria, and multiplex ligation-dependent probe amplification (MPLA) identified 11 structural variants (SVs) of MLH1 and MSH2 in 17 patients. In this study, we have tested the efficacy of long read-sequencing coupled with target enrichment for the determination of SVs and their breakpoints. DNA was captured by array probes designed to hybridize with target regions including four MMR genes and then sequenced using MinION, a nanopore sequencing platform. Approximately, 1000-fold coverage was obtained in the target regions compared with other regions. Application of this system to four test cases among the 17 patients correctly mapped the breakpoints. In addition, we newly found a deletion across an 84 kb region of MSH2 in a case without the pathogenic single nucleotide variants. These data suggest that long read-sequencing combined with hybridization-based enrichment is an efficient method to identify both SVs and their breakpoints. This strategy might replace MLPA for the screening of SVs in hereditary diseases.