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.

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.

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.

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.

[A Case of Inverted LECS for GIST Near the Pylorus Ring].

Laparoscopy and endoscopy cooperative surgery(LECS)is a surgical procedure to avoid excessive resection of the gastrointestinal wall and preserve its function. For gastrointestinal stromal tumors(GIST)near the cardia and pylorus ring, the function of the cardia and pylorus can be preserved by minimum excision and hand-sewn suture closures. Here, we report a case successfully treated with inverted LECS for GIST near the pylorus ring. The patient was a 58-year-old male. Upper gastrointestinal endoscopy had revealed a 45 mm sized SMT near the pylorus ring. Biopsy by EUS-FNA indicated gastric GIST. The tumor was separated from the pylorus ring and inverted LECS was performed. The defect was closed with hand-sewn sutures, forming an L-shape. The postoperative course was good and he was discharged from hospital 10 days after surgery. It is considered that devising the direction of closure by means of the LECS procedure can preserve the pyloric function without passage obstruction or stasis, even for gastric GIST near the pylorus ring.

[Unresectable Advanced HER2-Positive Gastric Cancer Leading to a Perforation during Chemotherapy with Trastuzumab plus Paclitaxel].

The patient was a 70s female with gastric cancer. CT and PET scans revealed metastases of para-aortic lymph nodes, hepatoduodenal ligament lymph nodes, and left supraclavicular lymph nodes. She was diagnosed with T4a, N2, M1(LYM), and cStage ⅣB and was given chemotherapy with paclitaxel due to chronic kidney disease and trastuzumab treatment. We planned to perform radical gastrectomy with lymph node dissection due to the disappearance of FDG uptake except for primary gastric cancer on PET scans 5 months after chemotherapy. However, the patient developed pan-peritonitis due to gastric cancer perforation; therefore, emergency distal gastrectomy with Billroth Ⅱ reconstruction was performed. She received chemotherapy(only trastuzumab)after getting discharged. Reports about gastric cancer perforation during chemotherapy using trastuzumab are rare. We should consider the possibility of perforated gastric cancer during chemotherapy and optimal surgical procedures, including the extent of lymph node dissection in the case of Stage Ⅳ gastric cancer.

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.

[A Case of Laparoscopic Subtotal Gastrectomy with a Very Small Remnant Stomach in an Elderly Patient with Multiple Malignant Gastric Tumors].

An 85-year-old man was referred to our hospital for anemia. Upper gastrointestinal endoscopy showed 6 malignant gastric lesions. Abdominal CT showed a primary tumor. We treated early gastric cancer at the upper stomach with endoscopic submucosal dissection(ESD)to avoid total gastrectomy. We then performed laparoscopic subtotal gastrectomy with a very small remnant stomach. In elderly patients with multiple gastric cancer, it is useful to combine ESD with laparoscopic subtotal gastrectomy with a very small remnant stomach.

[A Case of Colon Cancer with Suspected DPD Deficiency Causing Severe Adverse Effects following Adjuvant Chemotherapy with Capecitabine].

The present study reports a case of colon cancer in a 76-year-old female who underwent laparoscopic right colectomy. Pathological findings revealed pT3(SS), pN2a, cM0, and pStage Ⅲb. Hence, we administered adjuvant chemotherapy with capecitabine. On day 18, she was urgently hospitalized because of severe oral mucositis(grade 3), diarrhea(grade 3), and leukocytopenia(grade 4). Furthermore, the patient experienced DIC, which gradually improved through intensive conservative treatment. From the clinical course, we suspected that the severe adverse effects were caused due to a deficiency of DPD. We were able to save the patient through early treatment.

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.

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.

[A Case of Laparoscopic Distal Gastrectomy for Gastric Cancer with Common Hepatic Artery Anomaly].

A 67-year-old woman with upper abdominal pain was referred to our hospital. Upper gastrointestinal endoscopy revealed a type 3 gastric cancer at the greater curvature of the angular notch. Abdominal CT helped detect the primary tumor. Multi-detector-row computed tomography(MDCT)and 3D-CT angiography revealed a vascular anomaly in which the left gastric and splenic arteries formed the common trunk. The common hepatic and superior mesenteric arteries formed the common trunk. We performed a laparoscopic distal gastrectomy with D2 lymph node dissection. During suprapancreatic lymph node dissection, the surface of the portal vein was difficult to expose toward the left side because the portal vein joined the splenic and superior mesenteric veins on the caudal side. Therefore, the No. 8a lymph nodes were dissected along the anterior hepatic plexus. In cases of common hepatic artery anomaly, identifying the anterior hepatic plexus is useful for the dissection of the suprapancreatic lymph nodes.

[A Case of Surgery for Transversal Colon Cancer with Intestinal Malrotation -Visualizing Method of Blood Flow in the Fluorescence Navigation Period].

BACKGROUND: Anastomotic blood flow evaluation using the fluorescence method with indocyanine green(ICG)is expected to decrease the risk of anastomotic leakage in colorectal cancer surgery. The fluorescence method is considered to be also useful for assessing arterial divergence patterns in patients with special anatomical features. We report a case of transverse colon cancer with intestinal malrotation treated with laparoscopic surgery using the ICG fluorescence method. CASE: A 62- year-old woman who was diagnosed as having transverse colon cancer with intestinal malrotation underwent a laparoscopic transverse colon resection with D3 lymph node dissection. We identified the ileocolic artery and middle colic artery (MCA)after the ICG injection and the severed MCA during lymphadenectomy. We made a final diagnosis of pT2N0M0, pStage Ⅰ. CONCLUSION: The fluorescence method was useful for assessing the arterial divergence pattern in a patient with a special anatomical feature. However, the ICG fluorescence method had some problems, including visualizing blood flow for only a short time and poorly transmitting the dye through thick fat.

Detection of circulating microRNAs with Ago2 complexes to monitor the tumor dynamics of colorectal cancer patients during chemotherapy.

Because of the different forms of circulating miRNAs in plasma, Argonaute2 (Ago2)-miRNAs and extracellular vesicles (EV-miRNAs), we examined the two forms of extracellular miRNAs in vitro and developed a unique methodology to detect circulating Ago2-miRNAs in small volumes of plasma. We demonstrated that Ago2-miR-21 could be released into the extracellular fluid by active export from viable cancer cells and cytolysis in vitro. As miR-21 and miR-200c were abundantly expressed in both metastatic liver sites and primary lesions, we evaluated Ago2-miR-21 as a candidate biomarker of both active export and cytolysis while Ago2-miR-200c as a biomarker of cytolysis in plasma obtained from colorectal cancer (CRC) patients before treatment and in a series of plasma obtained from CRC patients with liver metastasis who received systemic chemotherapy. The measurement of Ago2-miR-21 allowed us to distinguish CRC patients from subjects without CRC. The trend in ΔCt values for Ago2-miR-21 and -200c during chemotherapy could predict tumor response to ongoing treatment. Thus, capturing circulating Ago2-miRNAs from active export can screen patients with tumor burdens, while capturing them from passive release by cytolysis can monitor tumor dynamics during chemotherapy treatment.

Safety of Surgical Treatment for Elderly Patients with Gallbladder Carcinoma.

Gallbladder carcinoma (GBC) is a common malignancy with a poor prognosis. With the average life expectancy increasing globally, the incidence of GBC is predicted to increase as well. We investigated the safety and feasibility of surgical treatment for elderly patients with GBC. We retrospectively compared clinical pathological data and treatment outcomes in 45 consecutive GBC patients (23 patients ≥ 75 years [elderly group] and 22 patients < 75 years [younger group]) who underwent curative resection at the Iwakuni Center from January 2008 to December 2017. The proportion of preoperative comorbidities and anticoagulant use was significantly higher in the elderly group. The American Society of Anesthesiologists score was higher in the elderly versus the younger group, and the elderly group had significantly shorter operation times. Reduced activities of daily living was more common in the elderly versus younger group. The percentage of radical resection and overall 3-year survival (66.6% younger vs. 64.4% elderly) were similar between the groups. Controlling Nutritional Status (CONUT) score ≥ 3 and R0 resection were identified as prognostic factors for overall survival rate among all patients. After careful patient selection.

Metachronous colorectal carcinoma with massive submucosal invasion detected by annual surveillance in a Lynch syndrome patient: a case report.

BACKGROUND: Lynch syndrome is the most common form of hereditary colorectal carcinoma. It is characterized by the presence of germline mutations in DNA mismatch repair genes. Mutation carriers have a lifetime risk of developing colorectal carcinoma of approximately 80%. Current treatment guidelines recommend periodic surveillance for colorectal carcinoma in patients with Lynch syndrome. However, the optimal interval between colonoscopies has not yet been determined. CASE PRESENTATION: We describe a 54-year-old man with Lynch syndrome who was undergoing annual colonoscopy surveillance for the development of colorectal carcinoma. At 54, 57, 59, and 60 years old, a colonoscopy showed high-grade dysplasia and adenoma. Therefore, endoscopic mucosal resection was performed. At 61 years old, a colonoscopy showed metachronous colorectal carcinoma with massive submucosal invasion. He subsequently underwent laparotomy for colorectal carcinoma. CONCLUSIONS: Annual surveillance using colonoscopy can detect colorectal carcinoma at an early stage, leading to reduced mortality. However, some patients might require a laparotomy, as was the case here. More frequent colonoscopic surveillance might be necessary to avoid surgery for colorectal carcinoma in Lynch syndrome patients with multiple risk factors for interval cancer.

Preoperative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Cholecystectomy and the Usefulness of the 2013 Tokyo Guidelines.

To identify predictive factors for conversion from laparoscopic cholecystectomy (LC) to open cholecystectomy performed for mixed indications as an acute or elective procedure. We retrospectively analyzed the data of 236 consecutive cases of LC performed in our department between January 2012 and January 2015, and evaluated preoperative risk factors for conversion and the usefulness of the 2013 Tokyo guidelines (TG2013) for diagnosing acute cholecystitis. The conversion rate in our series was 8% (19/236 cases). The following independent predictive factors of conversion were identified (p≤0.04): previous upper abdominal surgery (odds ratio (OR), 14.6), pericholecystic fluid (OR, 10.04), acute cholecystitis (OR, 7.81), and emergent LC (OR, 15.8). Specifically for patients with acute cholecystitis defined using the 2013 Tokyo guidelines, use of an antiplatelet or anticoagulant drug for cardiovascular disease (p=0.043), previous upper abdominal surgery (p<0.031) and a resident as operator (p=0.041) were predictive factors. The risk factors for conversion identified herein could help to predict the difficulty of the procedure and could be used by surgeons to better inform patients regarding the risks for conversion. The TG2013 can be an effective tool for diagnosing acute cholecystitis to make informed clinical decisions regarding the optimal procedure for a patient.

Risk of gastric adenoma and adenocarcinoma in patients with familial adenomatous polyposis in Japan: a nationwide multicenter study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) have an increased risk of developing gastric neoplasms. However, the clinical course of FAP with these gastric lesions has not yet been fully clarified. The present study aimed to clarify the changes in the incidence risk of developing gastric adenoma or gastric cancer during the lifespan of patients with FAP. METHODS: Four hundred forty-three patients with data regarding gastric adenoma and gastric cancer retrospectively registered in a nationwide Japanese multicenter study were enrolled. The cumulative incidences and hazard rates (HRs) of gastric neoplasms were evaluated. RESULTS: The cumulative incidence rates in 50-year-old patients with FAP were 22.8% for gastric adenoma and 7.6% for gastric cancer, respectively. No significant association was found between gastric neoplasms and the colonic phenotype. The peak age for the HR of gastric adenoma was 65 years, with the highest HR (0.043). Regarding the incidence of gastric cancer, the HR increased moderately up to the age of 40 years, but the increase accelerated from the age of 50 years (HR = 0.0067). CONCLUSION: Careful surveillance of the upper gastrointestinal tract in elderly patients with FAP, such as shortening the interval of follow-up according to age, may be helpful for early diagnosis of gastric cancer.