[Early Duodenal Cancer Resected by Using Laparoscopic and Endoscopic Assistance Surgery in a Patient with Peutz-Jeghers Syndrome].

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision. The polyp was diagnosed as well-differentiated adenocarcinoma in situ and was resected without remnants. PJS is characterized by a high incidence of malignant tumors, and lifelong surveillance for gastrointestinal and extra-gastrointestinal tumors is necessary. The incidence of duodenal cancer is not high among patients with PJS. However, surgery for advanced cancer is highly invasive. It is desirable to detect the tumors at an early stage so that they can be resected via a less invasive treatment method such as endoscopic resection or laparoscopic surgery with an endoscope.

[A Rare Case of Cronkhite-Canada Syndrome Associated with Gastric Cancer and Gastric Outlet Obstruction].

Cronkhite-Canada syndrome(CCS)is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities. We report a rare case of CCS associated with gastric cancer and gastric outlet obstruction with a review of the literature. A 75-year-old man was admitted because of frequent vomiting and hypoproteinemia. He was diagnosed with CCS due to typical clinical and laboratory findings including alopecia, nail atrophy, hypoproteinemia, and typical gastrointestinal polyposis. Upper endoscopic examination also pointed out a large gastric cancer mainly located in the antrum and the reversible pyloric obstruction caused by the gastric tumor. Biopsy of the tumor revealed tubular adenocarcinoma. Computed tomography demonstrated the dilated duodenum caused by packing of the gastric tumor. 1.5 months after prednisolone therapy, he underwent total gastrectomy with complete resection of the dilated duodenal bulb. Histological examination revealed gastric cancer(pap>tub1)classified into Stage ⅢC. Postoperative course was uneventful and he moved to another hospital. To our knowledge, including the present case, there were 20 reported cases of CCS associated with gastric cancer from Japan(1979-2022). Also, 7 cases of CCS associated with gastric outlet obstruction was reported.

AI analysis and modified type classification for endocytoscopic observation of esophageal lesions.

Endocytoscopy (EC) facilitates real-time histological diagnosis of esophageal lesions in vivo. We developed a deep-learning artificial intelligence (AI) system for analysis of EC images and compared its diagnostic ability with that of an expert pathologist and nonexpert endoscopists. Our new AI was based on a vision transformer model (DeiT) and trained using 7983 EC images of the esophagus (2368 malignant and 5615 nonmalignant). The AI evaluated 114 randomly arranged EC pictures (33 ESCC and 81 nonmalignant lesions) from 38 consecutive cases. An expert pathologist and two nonexpert endoscopists also analyzed the same image set according to the modified type classification (adding four EC features of nonmalignant lesions to our previous classification). The area under the curve calculated from the receiver-operating characteristic curve for the AI analysis was 0.92. In per-image analysis, the overall accuracy of the AI, pathologist, and two endoscopists was 91.2%, 91.2%, 85.9%, and 83.3%, respectively. The kappa value between the pathologist and the AI, and between the two endoscopists and the AI showed moderate concordance; that between the pathologist and the two endoscopists showed poor concordance. In per-patient analysis, the overall accuracy of the AI, pathologist, and two endoscopists was 94.7%, 92.1%, 86.8%, and 89.5%, respectively. The modified type classification aided high overall diagnostic accuracy by the pathologist and nonexpert endoscopists. The diagnostic ability of the AI was equal or superior to that of the experienced pathologist. AI is expected to support endoscopists in diagnosing esophageal lesions based on EC images.

[A Case Report of Perianal Paget's Disease Treated with Robot-Assisted Surgery for Positive Margins after Local Excision].

The patient is a 73-year-old man who was diagnosed with perianal Paget's disease by skin biopsy. Biopsy from the dentate line did not show any tumor cells. The patient was considered to undergo sphincter-preserving local resection and subsequently underwent the procedure. Histopathological examination of the resected specimen revealed perianal Paget's disease with a positive anorectal margin. The patient was referred to our department due to postoperative anal stenosis. On the 32nd postoperative day, a double barreled sigmoid colostomy was performed. However, considering the inability to adequately check for detect due to anorectal stenosis and the expected unfavorable anorectal function caused by sphincter- preserving re-operation, a robot-assisted abdominoperineal resection(D1)was performed 7 months after the initial surgery. Histopathological examination of the resected specimen revealed no residual tumor cells in the resected specimen. After local excision for perianal Paget's disease, the skin of the buttock becomes scarred due to skin valve formation and skin grafting, making closure of the perineal wound difficult when performing abdominoperineal resection. In robot-assisted surgery, it is relatively easy to remove the anorectal muscles from the abdominal cavity and reach the sciatico-rectal fossa, thus reducing the size of the perineal wound.

[Report of Multidisciplinary Treatment for Sisters with Li-Fraumeni Syndrome].

Li-Fraumeni syndrome(LFS)is a hereditary cancer disorder caused by germline variant in TP53 and characterized by various malignancies. Multidisciplinary treatment is needed for tumors of LFS, however, radiation therapy is a relative contraindication because of frequent development of secondary malignancy such as sarcoma in the irradiated field. Case 1: A 22- year-old woman who was diagnosed with LFS by genetic test when she developed upper rectal cancer. Her rectal tumor with marked bilateral lateral lymph node dissection was successfully removed by low anterior resection with extensive lateral lymph node dissection. She underwent resection for ovarian metastasis followed by chemotherapy and radiotherapy but subsequently died by the disease 32 months postoperatively. Case 2(elder sister of Case 1): A brain tumor was identified in the left high frontal lobe to the parietal lobe because of consciousness disorder, after the genetic diagnosis of LFS. The brain tumor was successfully resected. Histological examination revealed diffuse astrocytoma(WHO grade Ⅱ). Local recurrence was observed 46 months later, and radiation therapy was performed. Six months have passed since radiation therapy, no exacerbation of local recurrence has been observed.

[A Case of Curative Resection of a Retroperitoneal Liposarcoma].

A 55-year-old woman had been admitted to a hospital with abdominal bloating. Retroperitoneal liposarcoma was suspected and diagnosed as not resectable. She was then referred to our hospital with dyspnea and difficulties with movement due to the huge mass. An abdominal CT revealed a large mass originating in the left retroperitoneum. The tumor occupied most of the abdominal cavity, resulting in the displacement of her organs. However, there was no evidence of infiltration of the tumor into the aorta and inferior vena cava. Under a provisional diagnosis of retroperitoneal liposarcoma, a surgical resection was undertaken. The resected specimen had a maximum diameter of 48 cm and weighed 14 kg. Histopathological examination revealed a differentiated liposarcoma. The patient remains alive 6 months after the operation, without recurrence.

[A Case of Malignant Peripheral Nerve Sheath Tumor of the Anus Resected by Robot Assisted-APR].

An 81-year-old female visited a local hospital with complaints of anal pain. A tumor was found on the right side of her anus, and the histopathological diagnosis was a non-epithelial malignant tumor. Therefore, the patient was referred to our hospital. Result of imaging inspection revealed that the tumor had invaded the lower rectum, but had not distantly metastasized. Based on the findings of another biopsy, the patient was diagnosed with a malignant peripheral nerve sheath tumor (MPNST). Robot-assisted abdominoperineal resection(D1)was performed, and the lesion was resected without any pathological remnants. During the postoperative period, the patient developed perineal wound infection. Subsequently, the patient was discharged from the hospital on postoperative day 10. At the 6-month postoperative follow-up, no recurrence was noted. Most MPNSTs occur in the limbs, trunk, and neck. MPNST in the primary gastrointestinal tract or in the vicinity of the gastrointestinal tract is relatively rare, and in principle, combined resection of the intestinal tract is required for surgical treatment. Here, we report a case of MPNST that occurred near the anus and infiltrated to the lower rectum and was completely resected by robot-assisted abdominoperineal resection.

Comprehensive analysis of DNA mismatch repair-deficient gastric cancer in a Japanese hospital-based population.

BACKGROUND: The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated. METHODS: Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary gastric cancers of 513 consecutive patients. Genetic and/or epigenetic alterations of the MMR genes were also investigated. RESULTS: Loss of expression of one or more MMR proteins was observed in 58 patients (11.3%); 54 patients showed loss of MLH1/PMS2, 3 patients showed loss of MLH1/PMS2/MSH6 and 1 patient showed loss of PMS2 alone. Among these 58 patients, 55 showed hypermethylation of the promoter region of MLH1. Genetic testing revealed that the remaining three patients had Lynch syndrome (n = 1) or Lynch-like syndrome (n = 2). A total of 15 patients (25.9% of all patients with dMMR gastric cancer and 2.9% of all patients with gastric cancer), including 11 patients with stage I-III dMMR gastric cancer who had recurrence and 4 patients with stage IV dMMR gastric cancer, are potential candidates for the use of anti-PD-1 blockades. CONCLUSIONS: This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer.

Clinical outcomes of gastric tube reconstruction following laparoscopic proximal gastrectomy for early gastric cancer in the upper third of the stomach: experience with 100 consecutive cases.

BACKGROUND: Gastric tube reconstruction is a form of esophagogastrostomy performed after laparoscopic proximal gastrectomy (LPG). It is a simple and safe technique, but it may cause reflux esophagitis (RE) and impair postsurgical QOL. For several years, we have developed the gastric tube reconstruction and performed it on more than 100 patients. This study aimed to determine whether gastric tube reconstruction can be a feasible choice after LPG in regard to surgical safety and postoperative nutritional status. METHODS: The subjects consisted of 171 patients who underwent LPG (n = 102) or laparoscopic total gastrectomy (LTG) (n = 69). We compared the two groups in terms of surgical outcomes, incidence rate of RE, and nutritional status including postoperative weight loss and hemoglobin levels. RESULTS: There were no significant differences with regard to the surgical duration and blood loss between the two groups. The incidence of RE was not significantly higher with LPG than with LTG (16.7% vs. 10.1%, respectively; P = 0.07). Later than 2 years and 6 months after surgery, the body weight percentage of preoperative body weight in the LPG group was significantly higher than that in the LTG group. Hemoglobin and ferritin levels in the LPG group were significantly higher than those in the LTG group, later than one after surgery. The overall survival rates were similar between the two groups (5-year survival rates: 97.1% vs. 94.2% in the LPG and LTG groups, respectively; P = 0.69). CONCLUSIONS: Gastric tube reconstruction after LPG is simple and had better outcomes than LTG in terms of postoperative nutritional status.

Migrating contractions of the afferent and Roux limbs show peristaltic movement independently of each other in conscious dogs after Roux-en-Y reconstruction after distal gastrectomy.

PURPOSE: The Roux-en-Y (RY) procedure is used frequently for surgical reconstruction after gastrectomy. However, a minority of patients suffer a serious motility disorder of the Roux and afferent limb postoperatively. We conducted this study to clarify the association between the motility and peristaltic direction of two limbs in conscious dogs. METHODS: We performed distal gastrectomy on five dogs and implanted seven force transducers on the serosal surfaces of the remnant gastric body and afferent and Roux limbs. We then analyzed the electric signals from these force transducers. RESULTS: Migrating contractions were observed in the two limbs, but not in the gastric remnant body. Migrating contractions in the forward direction propagated independently from the most proximal side in each limb. There was no propagation of contraction across the jejunojejunostomy between the two limbs. CONCLUSIONS: Each proximal part of the Roux and afferent limbs has an independent motility pacemaker in conscious dogs after gastrectomy with RY reconstruction.

[A Case of Papillary Carcinoma of Thyroid Associated with Familial Adenomatous Polyposis in a Younger Woman].

Familial adenomatous polyposis(FAP)is an autosomal dominantly inherited disorder, and the result of a germ line variant in the adenomatous poplyposis coli(APC)gene. FAP can be associated with various extracolonic lesions including thyroid cancer, which frequently occurs in women. We report the case of a 15-year-old woman diagnosed as FAP with multiple thyroid papillary carcinomas. Her mother had been treated for FAP with colorectal cancer and thyroid cancer in our department. Multiple tumors with a maximum diameter of 17 mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. She was diagnosed with FAP because of multiple polyps on colonoscopy. We performed a subtotal thyroidectomy. Pathological findings revealed a cribriform-morular variant of papillary thyroid carcinoma. We report a rare case of papillary carcinoma of thyroid associated with FAP in a younger woman.

[Conversion Surgery following Second-Line Chemotherapy for Unresectable Gastric Cancer].

We retrospectively analyzed clinicopathological and survival data of 8 patients with unresectable gastric cancer who underwent conversion surgery(CS)following second-line chemotherapy from April 2013 to December 2020. There were 7 males and 1 female patients with a median age of 69(64-76)years old. Five patients had 1 unresectable factor, 2 had 2 unresectable factors, and 1 had 3 unresectable factors. All patients achieved R0 resection. The median survival time(MST) of patients with CS following second-line chemotherapy was significantly longer than that without CS(73.4 vs 12.3 months, respectively). The MST of patients with CS following first-line chemotherapy was significantly longer than that without CS (22.9 vs 12.3 months, respectively). This study suggested that CS following first- or second-line chemotherapy may improve survival duration for unresectable gastric cancer.

[Two Cases of Esophageal Neuroendocrine Carcinoma That Were Successfully Controlled by Multi-Modality Therapy].

Esophageal neuroendocrine carcinoma is extremely rare, and its treatment strategy has not been established. We report 2 cases esophageal neuroendocrine carcinoma. Case 1: A 74-year-old man was diagnosed as having esophageal neuroendocrine carcinoma(clinical T3N4M0, Stage Ⅳa). He received 60 Gy of radiation therapy with etoposide(100 mg/m2)plus cisplatin(80 mg/m2). No recurrence has been detected 1 year after treatment. Case 2: A 78-year-old man was diagnosed as esophageal neuroendocrine carcinoma(clinical T3N0M0, Stage Ⅱ). He underwent esophagectomy with 3 field lymph nodes dissection. Adjuvant chemotherapy was administered with irinotecan(60 mg/m2)plus cisplatin(60 mg/m2). After chemotherapy, he survived 1 year without recurrence.

[Three Cases of Conversion Surgery for Unresectable Gastric Cancer with Multiple Liver Metastases].

We herein report 3 cases of advanced gastric cancer with multiple liver metastases who was successfully treated with systemic chemotherapy and underwent conversion surgery with liver resection. There were 2 males and 1 female patients with a range 68 to 74 years of age. Two patients received S-1 plus oxaliplatin therapy and 1 received S-1 plus cisplatin therapy. All patients survived after 5-49 months postoperatively.

[Changes in Renal Function and Feasibility of Adjuvant Chemotherapy for Colorectal Cancer Patients with Diverting Ileostomy after Ileal Pouch-Anal Anastomosis].

We investigated changes in estimated glomerular filtration rate(eGFR)in 11 colorectal cancer patients(6 familial adenomatous polyposis, 5 ulcerative colitis)who underwent restorative proctocolectomy with ileal pouch-anal anastomosis(IPAA) and diverting ileostomy(DI), the tolerability and adverse events of adjuvant chemotherapy(ACT)in 4 cases. After IPAA, eGFR decreased significantly(p=0.02)and did not return to the preoperative level even after stoma closure(p<0.01). mFOLFOX6 was selected as the regimen in 4 candidates, and no significant changes in eGFR after ACT were observed. The relative dose intensity of oxaliplatin was 91.7%, and no gastrointestinal adverse events of Grade 3 or higher were observed. Although in a small number of cases, mFOLFOX6 as ACT after IPAA and DI may be feasible.

[Idea of Treatment Method for Upper and Lower Rectal Cancer Avoiding Irradiation to Internal and External Sphincter].

BACKGROUND: Preoperative chemoradiotherapy(CRT)followed by total mesorectal excision(TME)is used for locally advanced rectal cancer, but it can induce postoperative anorectal function. The primary objective of this study is to confirm the efficacy and safety of preoperative CRT and TME without irradiation to the internal and external sphincter muscles. SUBJECTS AND METHODS: Patients were eligible for this study if they met the following inclusion criteria: histologically proven rectal cancer, clinical T3T4N0-2 disease, and a distance between anal margin of tumor and the rental line is more than 2 cm. Twelve patients who underwent preoperative CRT and TME between 2013 and 2017 were enrolled. The primary endpoint was completion rate of sphincter-preserving surgery. RESULTS: All patients completed preoperative CRT without Grade 3 or higher adverse effect. Sphincter-preserving surgery was performed in all cases. The 5-year disease-free survival rate was 46.7%, and the local recurrence-free survival rate was 75%, and the overall survival rate was 90.9%. CONCLUSION: It is suggested that preoperative CRT and TME without irradiation to the internal and external sphincter muscles is effective and safe therapy for locally advanced rectal cancer.

[A Case of Synchronous Gallbladder Metastasis Originating from Advanced Gastric Cancer].

Gallbladder metastasis from gastric cancer is often found accidentally during postoperative pathological examinations, and its preoperative diagnosis is very difficult. There are a few reports in diagnostic imaging, and it is well known to have a very poor prognosis. There have been 13 reports on gallbladder metastasis from gastric cancer in the Japanese literature. Among the 13 reports, 10 cases were diagnosed with gallbladder metastasis synchronously and only 1 case was diagnosed as gallbladder metastasis before surgery. One case was reported as hematogenous metastasis, and 9 cases were reported as lymphoid metastasis. In total, 7 patients died, all within the first year after surgery. We experienced a case of synchronous gallbladder metastasis from gastric cancer.

[A Family of Attenuated Familial Adenomatous Polyposis].

The proband was a 49-year-old woman who had undergone total colectomy, ileorectostomy, and bilateral ovariectomy for the treatment of cecal(T3N0)and sigmoid colon(T4a, N2b, M1c2[Ova], Stage Ⅳc)cancers. Pathological findings revealed 6 adenomas and 2 adenocarcinoma-in-adenomas in the right colon, other than advanced colon cancers. She had a family history of colorectal cancer meeting the Amsterdam Criteria I, but none of her relatives had definite polyposis. Considering the possibility of Lynch syndrome, the microsatellite-instability test and immunohistochemistry(IHC)examination of the mismatch repair protein were performed, leading to the results of microsatellite stable and proficient mismatch repair protein expression. Therefore, we performed the multigene panel test containing 26 genes using the next-generation sequencing technology. In the APC(5q22.2)gene, a pathogenic variant(exon 12 c.994C>T/p.Arg332*)was identified, leading to a diagnosis of attenuated familial adenomatous polyposis(AFAP). After disclosure of the results to the proband, the single-site variant analysis was performed on her 3 daughters. In her second and third daughters, the same variant was confirmed, and laparoscopic total colectomy was performed 23 and 35 months after the disclosure of the genetic analysis results, respectively. Currently, we are conducting periodical surveillance for the residual rectum.

[A Family with Lynch Syndrome Diagnosed after a Proband of Elderly Multiple Colorectal Cancers].

The proband was a 77-year-old man who had been admitted to a local hospital for fecal occult blood. He was diagnosed with descending colon carcinoma, T4a, N1, M0, Stage Ⅲb, and rectal adenoma. He had undergone surgeries for rectal cancer at 52 years of age and cecum colon cancer at 57 years of age. Regarding his family history, 5 first-degree and 3 second- degree relatives had a history of gastrointestinal and gynecological cancers, thus meeting 2 of the 5 criteria of the revised Bethesda guidelines. The microsatellite-instability(MSI)test performed using preoperative biopsy tissues demonstrated high-frequency MSI(MSI-H). Hartmann's procedure was performed for MSI-H colon cancer under a strong suspicion of Lynch syndrome. Pathological findings were consistent with descending colon carcinoma, tub2, pT3, pN0, M0, pStage Ⅱa. He was then referred to our hospital. We performed the immunohistochemistry(IHC)analysis of the mismatch repair protein using surgical specimens. The IHC analysis revealed defective expression of the MSH2/MSH6 protein. We found a pathogenic variant in the mismatch repair gene, MSH2(c.1510+2T>G), through genetic testing and finally diagnosed the patient with Lynch syndrome. After disclosure of the results to the proband, 7 relatives underwent genetic testing for the MSH2 variant. Four relatives had the same variant and were also diagnosed with Lynch syndrome. They subsequently underwent surveillance for Lynch syndrome-associated cancers. In 2 variant carriers with a history of early colorectal cancer, an early colon cancer was identified and successfully resected endoscopically. Surveillance for Lynch syndrome-associated cancer is ongoing for the proband and variant carriers.

[A Case of Advanced Recurrent Colorectal Cancer with Complete Response to Pembrolizumab Chemotherapy].

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