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.

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.

A Case of Gallbladder Metastasis of Malignant Melanoma.

In the clinical course of malignant melanoma, which can metastasize to multiple organs, gallbladder metastases are rarely detected. A 69-year-old man who underwent resection of a primary malignant melanoma was subsequently treated with nivolumab for lung metastases and achieved complete response. Seven years after surgery, multiple nodules were found in the gallbladder, and he underwent laparoscopic cholecystectomy. The postoperative diagnosis was metastases of malignant melanoma. He has been recurrence-free 8 months after surgery. If radical resection is possible, such surgery should be performed for gallbladder metastases found in patients with other controlled lesions of malignant melanoma.

Predictive modeling for the germline pathogenic variant of the APC gene in patients with adenomatous polyposis: proposing a new APC score.

BACKGROUND: The precise diagnosis and medical management of patients with suspected familial adenomatous polyposis should be based on genetic testing, which may not always be available. Therefore, establishing a new model for predicting the likelihood of a germline pathogenic variant (GPV) of APC based on its clinical manifestations could prove to be useful in clinical practice. METHODS: The presence of GPVs of APC gene was investigated in 162 patients with adenomatous polyposis (≥ 10 polyps) using a multigene panel or single-gene testing. To generate a predictive model for GPV of the APC gene, a logistic regression analysis was performed using the clinicopathological variables available at the time of the diagnosis of adenomatous polyposis. RESULTS: Ninety (55.6%) patients had GPV of the APC gene. According to a multivariate logistic regression analysis, age < 40 years, polyps ≥ 100, fundic gland polyposis, and a family history of colorectal polyposis were found to be independent predictors of the GPV of APC and were used to establish a formula for predicting the GPV of APC using the four predictors. The prediction model had an area under the curve of 0.91 (0.86-0.96) according to a receiver operating characteristic analysis. CONCLUSION: The model for predicting the GPV of APC will help patients with adenomatous polyposis and physicians make decisions about genetic testing.

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.

The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.

Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.Ser2616Phe) variant that was interpreted as a VUS. This variant recurs only in families from Japan and has not been reported in the global general population databases. A Japanese patient with Fanconi anemia with compound heterozygous variants c.7847C>T (p.Ser2616Phe) and c.475+1G>A in BRCA2 was reported. In silico predictions and quantitative cosegregation analysis suggest a high probability of pathogenicity. The clinical features of the variant carriers were not specific to, but were consistent with, those of patients with hereditary breast and ovarian cancer. A validated functional assay, called the mixed-all-nominated-in-one-BRCA (MANO-B) method and the accurate BRCA companion diagnostic (ABCD) test, demonstrated the deleterious effects of the variant. Altogether, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, this variant satisfied the "PS3," "PM2," "PM3," and "PP3" criteria. We thus conclude that the BRCA2 c.7847C>T (p.Ser2616Phe) variant is a "likely pathogenic" variant that is specifically observed in the Japanese population, leading to a breast and ovarian cancer predisposition.

Incidence of Metachronous Remnant Gastric Cancer after Proximal Gastrectomy with the Double-flap Technique (rD-FLAP-rGC Study): A Multicenter, Retrospective Study.

BACKGROUND: Although proximal gastrectomy (PG) with the double-flap technique (DFT) is a function-preserving surgery that prevents esophagogastric reflux, there is a risk of developing metachronous remnant gastric cancer (MRGC). Moreover, details of MRGC and appropriate postoperative follow-up after PG with DFT are unclear. METHODS: We reviewed the medical records of 471 patients who underwent PG with DFT for cancer in a preceding, multicenter, retrospective study (rD-FLAP Study). We investigated the incidence of MRGC, frequency of follow-up endoscopy, and eradication of Helicobacter pylori (H. pylori) infection. RESULTS: MRGC was diagnosed in 42 (8.9%) of the 471 patients, and 56 lesions of MRGC were observed. The cumulative 5- and 10-year incidence rates were 5.7 and 11.4%, respectively. There was no clinicopathological difference at the time of primary PG between patients with and without MRGC. Curative resection for MRGC was performed for 49 (88%) lesions. All patients with a 1-year, follow-up, endoscopy interval were diagnosed with early-stage MRGC, and none of them died due to MRGC. Overall and disease-specific survival rates did not significantly differ between patients with and without MRGC. The incidence rate of MRGC in the eradicated group after PG was 10.8% and that in the uneradicated group was 19.6%, which was significantly higher than that in patients without H. pylori infection at primary PG (7.6%) (p = 0.049). CONCLUSIONS: The incidence rate of MRGC after PG with DFT was 8.9%. Early detection of MRGC with annual endoscopy provides survival benefits. Eradicating H. pylori infection can reduce the incidence of MRGC.

Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study.

BACKGROUND: Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. METHOD: A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. RESULTS: 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %). CONCLUSION: IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed.

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

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

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

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

[Two Cases of Closed LECS for Early Gastric Cancer].

In recent years, laparoscopy and endoscopy cooperative surgery(LECS)is reported as the treatment of gastric cancer. We report closed LECS performed for an elderly patient with remnant gastric cancer and gastric cancer in a patient with lung cancer. Case 1 is an 85-year-old male. Early gastric cancer was pointed out in the remnant stomach after distal gastrectomy. ESD was not indicated because of the size of tumor. Because of his age and many comorbidities, closed LECS was performed. Postoperative pathological diagnosis was pT1a(M), pPM0, pDM0, Ly0, v0. Case 2 is a 56-year-old male. He was undergoing chemotherapy for lung cancer with pleural dissemination. Upper gastrointestinal endoscopy revealed early gastric cancer. ESD was not indicated for this lesion because of the depth of tumor. Pleural dissemination of lung cancer is his prognostic factor, and gastrectomy with lymph node dissection was considered excessively invasive. Therefore, closed LECS was performed. Postoperative pathological diagnosis was pT1b2(SM2), pPM0, pDM0, Ly1c, v1a. Closed LECS could be useful therapeutic option for early gastric cancer.

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.

APC germline variant analysis in the adenomatous polyposis phenotype in Japanese patients.

BACKGROUND: Familial adenomatous polyposis (FAP), an autosomal dominant disorder characterized by multiple colonic polyps, is caused by a germline pathogenic variant of the APC gene. However, this variant is not detected in up to 30% of patients with the adenomatous polyposis phenotype. METHODS: We performed next-generation sequencing (NGS) to identify the causative genes in FAP patients with 10 or more polyps. For patients in whom the APC germline variant was not able to be identified, we screened for APC mosaicism using high-coverage NGS of APC with DNA from leucocytes and/or frozen tissue. RESULTS: The pathogenic APC germline variant was found in 93.3%, 71.6%, and 17.1% of patients with profuse-type polyposis, sparse-type polyposis, and oligo-polyposis, respectively. The APC germline variant detection rate in patients with FAP-related diseases was 69.7% for fundic gland polyposis, 79.7% for duodenal adenoma, 94.7% for desmoid tumor, and 71.4% for thyroid cancer, with increasing numbers of extracolonic lesions associated with an increasing APC germline variant detection rate. A mosaic test detected nine patients with APC mosaicism. A comparison of APC-associated polyposis with APC mosaicism showed that patients with APC mosaicism had a low frequency of duodenal adenoma and a family history of colonic polyposis. CONCLUSIONS: We determined the detection rate of the APC germline variant by phenotype and identified APC mosaicism. Genetic testing of FAP patients is important because it can help with surgical decision-making, monitoring, and genetic counseling. Furthermore, genetic testing by NGS proved to be an effective method of detecting APC germline variants.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer.

Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.

Nutritional assessment and surgical outcomes in very elderly patients undergoing pancreaticoduodenectomy: a retrospective study.

PURPOSE: To evaluate and compare the nutritional factors and clinical outcomes of pancreaticoduodenectomy between elderly and non-elderly patients. METHODS: This retrospective study evaluated 122 consecutive patients who underwent pancreaticoduodenectomy from April 2008 to April 2020. Preoperative and postoperative nutritional factors (prognostic nutritional index), complication rates, and survival rates were compared between the elderly (≥ 80 years) and non-elderly (< 80 years) patient groups. Changes in nutrition markers were evaluated before surgery to 1 year after surgery. RESULTS: A total of 20 elderly patients (16.4%) and 102 non-elderly patients (83.6%) underwent pancreaticoduodenectomy. Elderly patients had a significantly lower preoperative prognostic nutritional index than did non-elderly patients. At 3 months postoperatively, elderly patients had a lower albumin level and prognostic nutritional index. The median length of hospital stay was significantly longer (39.9 vs. 27 days, P = 0.004), the rate of death due to other diseases was higher, and the overall survival rate was significantly lower (1-/3-/5 year overall survival rates: 78.1%/26.7%/13.3% vs. 87.1%/54.4%/46.7%; log-rank test, P = 0.003) in the elderly group than in the non-elderly group. CONCLUSIONS: The results suggest that careful patient selection and optimal perioperative care are necessary to determine whether pancreaticoduodenectomy is indicated for elderly patients.

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study.

PURPOSE: We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. METHODS: Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. RESULTS: A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). CONCLUSIONS: Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.

Adequacy evaluation of the annual colonoscopic surveillance and individual difference of disease phenotypes in Lynch syndrome.

BACKGROUND: Regular endoscopic surveillance for Lynch syndrome is reported to reduce colorectal cancer (CRC)-related mortality. However, the appropriate surveillance intervals are still unclear. We evaluated the adequacy of annual colonoscopy and investigated the differences in tumor occurrence rates between individual patients. METHODS: In total, 25 patients with Lynch syndrome who underwent colonoscopic surveillance between 2007 and 2016 at the Iwakuni Clinical Center were included. We retrospectively investigated the surveillance frequency and the clinical features associated with tumor development. RESULTS: Colonoscopic surveillance was performed every 397 days on average. A total of 101 tumors, including 8 intramucosal carcinomas and 15 carcinomas, were observed within the study period. Annual colonoscopy detected six malignancies, including a carcinoma requiring surgery. Tumor incidence was associated with tumor existence in the initial colonoscopies (P = 0.018). Patients with a tumor occurrence rate of 0.4 tumors per year during our observation period were significantly more likely to have malignancies detected during regular surveillance than patients who had a lower occurrence rate (P < 0.001). Malignancy occurrence rate was strongly associated with tumor occurrence rate (P < 0.001, R2 = 0.44). CONCLUSIONS: Annual colonoscopic surveillance for Lynch syndrome patients was effective in reducing the risk of CRC progression, but was insufficient to completely avoid surgery. Because the tumor occurrence rate differed substantially between individuals, more intensive surveillance was required for high-risk patients.

Oxaliplatin-induced increase in splenic volume: experiences from multicenter study in Japan.

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.

The Late Phase/Early Phase Ratio of Pancreatic CT Values as a Novel Predictor of Pancreatic Fistula after Distal Pancreatectomy.

Post-operative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). In this retrospective study, we reviewed the data from patients who underwent DP between 2008 and 2019 in our institute to determine whether the late phase/early phase ratio (L/E ratio) by preoperative computed tomography (CT) scan in the pancreas could predict POPF occurrence after DP. We examined the relationship between preoperative or intraoperative factors and the occurrence of POPF after DP using statistical methods in 23 males and 21 females with a mean age of 73. The mean L/E ratio was significantly lower in the POPF group than the non-POPF group (p=0.035). The L/E ratio had moderate diagnostic accuracy, with a calculated optimal cutoff value of 0.77. In univariate analysis, a significant association was noted between POPF and stump thickness ≥ 16.9, body mass index ≥ 27.5, and L/E ratio ≤ 0.77. In the multivariate analysis, the L/E ratio (odds ratio, 5.96; p=0.036) was an independent risk factor for POPF. Our findings suggest that the pancreatic L/E ratio may predict the occurrence of POPF after DP. This measure may be useful in preoperative risk stratification, patient counseling, and perioperative patient management, improving clinical outcomes after DP.

Solitary Cardiac Metastasis of Hepatocellular Carcinoma.

Cardiac metastasis originating from hepatocellular carcinoma (HCC) is a rare condition with a poor prognosis. No therapeutic standards for cardiac metastasis originating from HCC have been established. At 19 months after a curative hepatectomy, a 64-year-old Japanese hepatitis B virus-positive male patient experienced solitary cardiac metastasis originating from HCC. The cardiac tumor was discovered in the right ventricle. The patient received three courses of radiotherapy and chemotherapy and survived > 3 years after the initial diagnosis of cardiac metastasis. His case demonstrates that radiotherapy combined with chemotherapy can be an effective treatment for cardiac metastasis.