A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

[Curative Resection of Sigmoid Colon Cancer with Multiple Liver Metastases by Long-Term Multidisciplinary Treatment].

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.

Vascular Anomaly Associated with Ectopic Pancreas in the Pylorus.

The ectopic pancreas is a relatively rare congenital condition, defined as pancreatic tissue lacking anatomical or vascular continuity with the normal pancreatic body. The ectopic pancreas is most frequently found in the stomach, usually asymptomatic and discovered incidentally. We report the case of a 72-year-old man who was diagnosed with cancer in the gastric vestibule. Distal gastrectomy was performed, and 3 cm of the ectopic pancreas was found on the anterior surface of the pylorus intraoperatively. The gastroduodenal artery was not found by approaching the inferior border of the pancreas but by following the branches from the common hepatic artery. Posterior view CT confirmed that the GDA terminated in the ectopic pancreas. An ectopic pancreas may be associated with vascular anomalies. Clinicians must consider the possibility of vascular anomalies when operating on patients with an ectopic pancreas. If the gastroduodenal artery cannot be found intraoperatively, identification should be attempted by following the common hepatic artery.

Modified Socratic Method (planned and executed by Takada) for medical education: Grade II Acute Cholecystitis of Tokyo Guidelines 2018 as an example case.

BACKGROUND: Socratic method, which is an educational method to promote critical thinking through a dialogue, has never been practiced in a large number of people at the academic societies. METHODS: Modified Socratic method was performed for the first time as an educational seminar using an example case of moderate acute cholecystitis based on the evidence described in Tokyo Guidelines 2018. We adopted a method that Takada had been modifying for many years: the instructor first knows the degree of recognition of the audience, then the instructor gives a lecture in an easy-to-understand manner and receives questions from the audience, followed by repeated questions and answers toward a common recognition. RESULTS: Using slides, video, and an answer pad, 281 participants including the audience, instructors and moderators came together to repeatedly ask and answer questions in the five sessions related to the case scenario. The recognition rate of the topic of Critical View of Safety increased significantly before vs after this method (53.0% vs 90.3%). The seminar had been successfully performed by receiving a lot of praise from the participants. CONCLUSION: This educational method is considered to be adopted by many academic societies in the future as an effective educational method.

[Usefulness of Mohs Paste Against Breast Cancer with Skin Invasion].

We report with the addition of literature because we have experienced 3 cases of locally advanced breast cancer with skin invasion that have alleviated symptoms and improved quality of life by using Mohs paste. In Case 1, Mohs paste reduced exposed tumors, exudation, and bleeding. In Case 2, bleeding, which had been the cause of the marked anemia, was controlled, and tumor shrinkage and epithelialization were observed. Case 3 had a poor prognosis due to systemic metastasis, but the QOL improved for a certain period of time as exudation, bleeding, and foul odor were controlled. From the viewpoint of palliative care, Mohs paste is a safe and effective treatment method against various symptoms such as large amounts of exudation, bleeding, and foul odor caused by breast cancer skin invasion, and depending on the case, prognosis can be expected to be extended by shrinking the tumor. The cooperation of not only doctors but also palliative care teams including pharmacists and nurses is essential for use.

[A case of gastric perforation that occurred during the incubation period for infectious mononucleosis in an adolescent patient].

A 17-year-old young man visited our hospital because of severe upper abdominal pain and was diagnosed with acute peritonitis caused by gastrointestinal perforation. Emergent surgical treatment was performed, and the perforated lesion of the stomach was repaired. He recovered and was discharged without any complication at 14 days postoperatively. However, he had intermittent fever 2 days after discharge and visited our hospital again. He was diagnosed with infectious mononucleosis (IM), derived from Epstein-Barr virus (EBV) initial infection, on biochemical examination that was positive for anti-EBV VCA-IgG and negative for EBV nuclear antigen, although he was ameliorated conservatively. This pathophysiology raised a possibility that EBV infection had induced acute gastritis or gastric ulcer leading to the penetration of the stomach. Six weeks postoperatively, esophagogastroduodenoscopy showed a gastric ulcer in the vestibular part of the stomach. Pathologic examination of the stomach revealed mucosal erosion with B-cell infiltration into the lamina propria;however, Epstein-Barr viral infection was unclear by EBV-encoded small RNA in situ hybridization. Here, we report a rare case of gastric perforation that occurred during the incubation period of IM with a review of the relevant literature.

[A Case of Duodenal Adenocarcinoma in the Third Portion Treated with Partial Duodenectomy].

A 85-year-old man was admitted due to vomiting. Abdominal CT showed the remarkable expansion of the stomach and the stenotic lesion in the third portion of the duodenum. Duodenal endoscopy showed a circular tumor of the third potion of the duodenum, and biopsy disclosed tubular adenocarcinoma. Operation was performed on the basis of a diagnosis of primary duodenal cancer of the third portion. Liver metastasis, peritoneal dissemination, and apparent lymph node enlargement were not observed. The tumor was present in the third portion of the duodenum and partial duodenectomy was performed. Reconstruction was achieved by side to side anastomosis of the duodenum and the jejunum. Histopathological diagnosis was well differentiated tubular adenocarcinoma, SS, ly1, v1. Primary duodenal cancer is a relatively rare disease, and there are few cases of third portion. If pancreatic invasion and lymph node metastasis are not observed as in this case, it is necessary to examine the indication of partial duodenectomy.

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.

[A Case of Unresectable Recurrent Colorectal Cancer with Regorafenib Treatment and Long-Term Survival].

This paper reports a case in which the patient has survived for 5 years and 6 months after recurrence of colorectal cancer by chemotherapy, and especially in regorafenib as fourth-line therapy has obtained stable disease(SD)for 2 years and 6 months. A man in his 70s underwent left hemicolectomy in the diagnosis of descending colon cancer. Four years and 4 months after the operation, abdominal CT revealed paraaortic lymph node metastasis. When SOX plus bevacizumab was performed as first-line therapy, partial response(PR)was obtained, and PR was maintained for a long time. After progressive disease(PD), IRIS was performed as second-line therapy, but the effect was not obtained. Panitumumab was started as third-line therapy, and PR was temporarily recognized, but since it became PD again, regorafenib was introduced as fourth- line therapy. After regorafenib administration, reduction of paraaortic lymph nodes and lowering of CEA are recognized, and long SD can be maintained. This case can be said to be 1 case in which the usefulness of regorafenib was shown as a salvage- line for unresectable colorectal cancer.

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report.

BACKGROUND: Therapy targeting programmed death-1 or programmed death-1 ligand-1 (PD-1/PD-L1) has been developed for various solid malignant tumors, such as melanoma and non-small-cell lung cancer (NSCLC), but this approach has little effect in the treatment of pancreatic cancer. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare pancreatic malignancy having unique morphology and is considered a variant of pancreatic ductal adenocarcinoma (PDAC). Although UCOGC has been reported to have better prognosis than conventional PDAC, the optimal treatment for UCOGC with distant metastases has not been determined. CASE PRESENTATION: A 66-year-old man was initially diagnosed with NSCLC with multiple intrapulmonary metastases and abdominal lymph node metastasis in the tail of the pancreas, and bronchial biopsy and diagnostic imaging were performed. Pathologic examination of the lung showed poorly differentiated adenocarcinoma cells expressing epithelial marker and PD-L1. Therefore, pembrolizumab monotherapy for NSCLC was given. The pulmonary lesions shrank markedly and were in complete remission after 8 months of anti-PD-1 therapy, though no therapeutic effect was observed in the pancreatic site. Distal pancreatectomy was then performed, and histopathological examination showed that the tumor was UCOGC originating from the pancreas. The histologic findings of the resected specimen mimicked those of the lung biopsy specimen, leading to the final assessment that the lung tumors were metastatic foci that migrated from the UCOGC, and only the metastatic lesions benefited from pembrolizumab therapy. CONCLUSION: Immune checkpoint inhibitors have limited therapeutic effects on primary lesions of pancreatic cancer, but they may exert antitumor effects on pulmonary metastases of UCOGC.

[A Case of Intraductal Papillary Mucinous Carcinoma of the Pancreas Extending Widely within the Pancreas Resected by Total Pancreatectomy].

A 78-year-old woman visiting our hospital with the chief complaint of abdominal pain was diagnosed with ischemic colitis. CT pointed out pancreatic enlargement, so detailed pancreatic examination was conducted in parallel with treatment. In enhanced CT and MRI, the main pancreatic duct significantly extended over the entire length, and mural nodules scattered in the main pancreatic duct were observed. It was diagnosed with main duct intraductal papillary mucinous neoplasm (IPMN), which is likely to be intraductal papillary mucinous carcinoma(IPMC), and total pancreatectomy was performed. Pathological findings showed diffuse dilation of the main pancreatic duct, non-invasive IPMC progressed over approximately the entire length of the main pancreatic duct, mucinous carcinoma-tubular adenocarcinoma was widely infiltrated in pancreatic tissues around mural nodules. The cancer remained in the pancreas and was eventually diagnosed with IPMC, invasive, pT2, pN0, and pStage ⅠB. This case was an IPMN with high-risk stigmata, and it was an adaptive case of total pancreatectomy because mural nodules extended to the entire pancreas. In recent years, total pancreatectomy has come to be expected good results by the progress of diabetes treatment and the development of pancreatic enzyme agents, it is necessary to carefully judge each case for adaptation.

[Multimodal Therapy for Stage â £ Gallbladder Carcinoma Achieved Long-Term Survival-A Case Report].

A 75-year-old man with a chief complaint of abdominal pain visited our hospital and was diagnosed with Stage Ⅳ gallbladder carcinoma that infiltrated the transverse colon with distant lymph node metastases. He received gemcitabine plus cisplatin chemotherapy, which led the primary lesion to shrink. However, transverse colon obstruction occurred, and semi- urgent right hemicolectomy and extended cholecystectomy were performed. A year and 2 months after first diagnosis, an inferior pancreatic head lymph node swelling was detected. Chemoradiotherapy was performed using S-1, and the lymph node swelling was reduced. Despite continuous S-1 therapy, the lymph node gradually started to swell again, which led to duodenum obstruction by compression. He underwent gastrojejunal bypass; however, his general condition gradually worsened, and he died 2 years and 6 months after the first diagnosis. Even in cases of unresectable gallbladder carcinoma, multimodal therapy, such as surgery, chemoradiotherapy, and palliative gastrointestinal bypass, may archive a long prognosis of 2 years and 6 months.

[A Case of Resection of Intraductal Papillary Mucinous Carcinoma Detected Due to Acute Pancreatitis].

A 67-year-old man visiting our hospital with the chief complaint of sudden upper abdominal pain was diagnosed with acute pancreatitis. Based on computed tomography findings, intraductal papillary mucinous neoplasm(IPMN)was suspected as the cause of the pancreatitis and detailed examination was conducted following its alleviation. Endoscopic retrograde and magnetic resonance cholangiopancreatography showed marked dilation of the main pancreatic duct, with a mural nodule inside the main pancreatic duct at the pancreatic head. Main duct IPMN was diagnosed and pancreaticoduodenectomy was performed 3 months after the onset of acute pancreatitis. The histopathological findings showed a tumor proliferating in a mold pattern in the lumen of the dilated main pancreatic duct, resulting in a diagnosis of intraductal papillary mucinous carcinoma(IPMC). The presence of IPMN should be considered as a cause of acute pancreatitis; if findings suggestive of IPMN are found on imaging, detailed examinations and treatment are needed in consideration of the potential for malignancy following alleviation of pancreatitis.

[Short-Term and Long-Term Outcomes of Colonic Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer].

We examined the short-term and long-term outcomes in 50 patients who underwent stenting as a bridge to surgery(BTS) for obstructive colorectal cancer. The patients comprised 30 men and 20 women, with a mean age of 74.0 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.4 days. No serious complications related to stenting occurred. Colonoscopy after stenting was important for the preoperative diagnosis of coexisting lesions and planning of the extent of resection. Elective and one-stage surgeries could be performed in all patients after stenting. Regarding long-term outcomes, the 5-year overall survival rate and disease-free survival rate in the BTS patients with Stage Ⅱ plus Ⅲ cancer were 73.1% and 55.7%, respectively. The results of this study suggest that BTS for obstructive colorectal cancer is an effective treatment strategy for not only short-term but also long-term outcomes.

[A Case of Advanced Gallbladder Cancer with Paraaortic Lymph Node Metastases Successfully Treated by Chemotherapy and Conversion Surgery].

The patient was a 76-year-old man who was admitted to our hospital with a diagnosis of ileus. A gallbladder tumor was found incidentally on CT, and it was diagnosed as gallbladder cancer. Enlargement of multiple lymph nodes, including the paraaortic lymph nodes, was observed, and PET-CT further showed FDG uptake in the lymph nodes. Based on these findings, the patient was diagnosed with Stage ⅣB gallbladder cancer with paraaortic lymph node metastases. Since surgical resection was not possible, chemotherapy with gemcitabine and cisplatin(GEM plus CDDP)was started. After completion of 4 courses of GEM plus CDDP, the enlarged lymph nodes were decreased in size on CT, and there was no FDG uptake on PET-CT. These findings indicated downstaging to Stage Ⅱ; thus, conversion surgery with extended cholecystectomy and lymph node dissection was performed. The pathological diagnosis confirmed that the patient had Stage Ⅱ cancer(pT2N0M0). A case of unresectable gallbladder cancer that was treated with GEM plus CDDP and subsequent conversion surgery is reported, along with a literature review.

[Four Cases of Ileocolic Intussusception Associated with Malignant Lymphoma of the Ileum].

We report the cases we encountered in our department involving 4 patients with malignant ilial lymphoma that caused ileocolic intussusception. The patients were 2 male and 2 female, aged 65-76 years. All patients' chief complaint was abdominal pain. Computed tomography revealed target signs characteristic of intussusception. Colonoscopy showed a tumor that escaped into the colon, leading to the diagnosis of ileocolic intussusception due to an ileal tumor. However, definitive diagnosis could not be achieved from biopsy. Thus, ileocecal resection or right hemicolectomy was performed. Macroscopically, all tumors were polypoid type and were present within 25 cm from the valve of Bauhin. Histological diagnoses were diffuse large B-cell lymphoma(DLBCL)in 2 patients, T-cell lymphoma in one, and follicular lymphoma in one. Postoperative chemotherapy was performed in patients with DLBCL and T-cell lymphoma. Tumors are commonly the cause of intussusception in adults; therefore, emergent surgery is imperative. When malignant lymphoma is diagnosed, a multidisciplinary approach that includes postoperative chemotherapy is necessary.

[A Case of Retroperitoneal Liposarcoma That Required Three Times Surgical Resections during Four Years].

The patient was a 64-year-old man, who had undergone surgical resection for a right retroperitoneal giant tumor. The histopathological diagnosis was a well-differentiated liposarcoma. Two years and 4 months after the initial surgery, 3 recurrent lesions were found on the dorsal side of the colon hepatic flexure, and resection was performed. One year and 1 month after the secondary surgery, the tumor recurred again, and invaded the right abdominal wall and right transverse colon. Tumor was completely resected macroscopically. All resected tumors were well-differentiated liposarcoma. There have not been any signs of recurrence until 1 year and 6 months after the last operation. For retroperitoneal liposarcoma, complete surgical resection is the only established treatment, but the tumor often recurs. Aggressive resection against recurrent cases is known to contribute to life prognosis, but there is a possibility of the degeneration to a highly malignant dedifferentiated tumor while recurrence is repeated. Therefore, sufficient follow-up observation is needed.

[Results of Preoperative Colon Stent Placement for Obstructive Colorectal Cancer].

We examined short-term outcomes in 34 patients who had stenting as a bridge to surgery(BTS)for obstructive colorectal cancer during the 5-year period between April 2012 and March 2017.T he patients were 22 men and 12 women with a mean age of 72.6 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.5 days.No serious complications related to stenting occurred.Elective surgery could be performed in all patients after stenting.The mean number of days to surgery was 24.7 days.Laparoscopic surgery was performed in 14 patients.Postoperative complications included minor leakage in 1 patient, an abdominal wall abscess due to tumor invasion of the abdominal wall in 1 patient, and heart failure and pneumonia, as serious complications, in 1 patient each.Colorectal stenting in patients with obstructive colorectal cancer is a safe and relatively simple procedure.This is an effective treatment strategy in which preoperative colorectal decompression enables a one-stage resection.

[Findings from Total Colonoscopy in Obstructive Colorectal Cancer Patients Who Underwent Stent Placement as a Bridge to Surgery(BTS)].

We clinically investigated 34 patients with obstructive colorectal cancer who underwent placement of a colonic stent as a bridge to surgery(BTS), focusing on endoscopic findings after stent placement.Twenty -nine patients(85.3%)underwent colonoscopy after stent placement, and the entire large intestine could be observed in 28(96.6%).Coexisting lesions were observed in 22(78.6%)of these 28 patients.The lesions comprised adenomatous polyps in 17 patients(60.7%), synchronous colon cancers in 5 patients(17.9%), and obstructive colitis in 3 patients(10.7%), with some overlapping cases.All patients with multiple cancers underwent one-stage surgery, and all lesions were excised at the same time.Colonoscopy after colonic stent placement is important for preoperative diagnosis of coexisting lesions and planning the extent of resection. These considerations support the utility of colonic stenting for BTS.

[Long-Term Complete Response by S-1 Chemotherapy for Gastric Cancer with Para-Aortic Lymph Node Metastases].

We describe a 67-year-old man with long-term CR by S-1 chemotherapy for gastric cancer with para-aortic lymph node metastases after reduction surgery. The patient presented at our hospital with epigastric pain. He was diagnosed with gastric cancer with para-aortic lymph node metastases. We performed gastrectomy and D1 lymphadenectomy without any resection of the para-aortic lymph node metastases. We treated the patient with oral S-1 chemotherapy. The initial treatment schedule was 100mg/body/day, twice daily for 4weeks with 2weeks of rest. Grade 1 neutropenia developed at the end of the second course of treatment. The regimen was changed to 2 weeks of administration, with 1 week of rest. The para-aortic lymph node metastases immediately responded to the chemotherapy. Abdominal CT showed almost complete regression of the lymph node metastases 10 months postoperatively. The patient has received S-1 chemotherapy and remained in remission for more than 5 years 6 months.