[Development of Cancer of the Remnant Colorectal Segment after Ileal-Pouch Anal Anastomosis/Ileorectal Anastomosis in Patients with Familial Adenomatous Polyposis].

PURPOSE: This retrospective study was performed to investigate the recent trend of occurrence of cancer of the remnant colorectal segment(RCRS)after ileal-pouch anal anastomosis(IPAA)/ileorectal anastomosis(IRA)and to consider the optimal surveillance methods in patients with familial adenomatous polyposis(FAP)undergoing(procto)colectomy. PATIENTS AND METHODS: The subject was a total of patients with FAP undergoing IPAA or IRA between 2005 and 2022. Clinicopathological data were extracted from medical charts and analyzed. Cumulative incidence of cancer in the RCRS and overall survival after treatment of such tumors were calculated by the Kaplan-Meier method. RESULTS: There were 45 male and 56 female. IPAA was performed in 49 patients(hand-sewn; n=33, stapled; n=16)and IRA was performed in 52 patients. The median age at initial colorectal surgery was 32 years old(range, 13-66 years old). Median postoperative follow-up was 11 years(range, 1-48 years). Eighty-one patients were confirmed to have pathogenic variant of APC by genetic test. The cumulative incidence of cancer of the RCRS did not differ between patients undergoing IPAA and those undergoing IRA(p= 0.73, 4.1% versus 1.9% at 10 years). The cumulative 5-year overall survival rate after additional surgery for the tumor of RCRS was 82%. CONCLUSION: This study has several limitations due to single institutional retrospective study with small cases and non-standardized postoperative endoscopic surveillance. However, our results seem to show satisfactory oncological outcomes of patients with FAP in terms of the control of cancer of the RCRS under postoperative periodic surveillance, regardless of the type of colorectal resection.

[A Case of Transverse Colon Cancer Associated with Lynch Syndrome with Excellent Response to Pembrolizumab].

A 47-year-old woman diagnosed with transverse colon cancer with liver, peritoneal, and lymph node metastases was admitted. Modified FOLFOX6(mFOLFOX6)regimen was given as a first line chemotherapy and was followed by pembrolizumab after 1 cycle of the mFOLFOX6, because microsatellite instability(MSI)test of the tumor showed high-frequency MSI. Because of the transverse colon obstruction after 2 cycles of pembrolizumab, she underwent right hemicolectomy. Histological examination of the resected specimen revealed no residual tumor cells in the primary tumor and reginal lymph nodes. Immunohistochemistry for mismatch repair proteins(IHC-MMR)showed loss of MSH2 and MSH6 expression. Genetic test identified a MSH2 pathogenic variant leading to the diagnosis of Lynch syndrome. The present case shows the importance of MSI test or IHC-MMR before the treatment of metastatic colorectal cancer.

[Complete Response to Immune Checkpoint Inhibitors in Unresectable Gastric Cancer-A Report of Five Cases].

Immune checkpoint inhibitors(ICIs)are widely used for the treatment of unresectable gastric cancer. We treated approximately 70 patients with ICIs. ICI treatment with pembrolizumab was administered for MSI-high cases and nivolumab for MSS cases in the second- or third-line chemotherapy. We observed 5 cases of complete response. Among these, 2 patients presented with liver metastases, 2 with peritoneal disseminations, and 1 with pulmonary metastasis. In 1 patient, the primary tumor invaded the diaphragm and descending aorta; whereas, in another patient the primary tumor invaded the pancreas and liver. All patients had progressive disease after first-line chemotherapy.

[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.

Endocytoscopic Observation of Esophageal Lesions: Our Own Experience and a Review of the Literature.

This review outlines the process of the development of the endocytoscope (EC) with reference to previously reported studies including our own. The EC is an ultra-high-magnification endoscope capable of imaging at the cellular level. The esophagus is the most suitable site for EC observation because it is amenable to vital staining. The diagnosis of esophageal lesions using EC is based on nuclear density and nuclear abnormality, allowing biopsy histology to be omitted. The observation of nuclear abnormality requires a magnification of ×600 or higher using digital technology. Several staining methods have been proposed, but single staining with toluidine blue or methylene blue is most suitable because the contrast at the border of a cancerous area can be easily identified. A three-tier classification of esophageal lesions visualized by EC is proposed: Type 1 (non-cancerous), Type 2 (endocytoscopic borderline), and Type 3 (cancerous). Since characteristic EC images reflecting pathology can be obtained from non-cancerous esophageal lesions, a modified form of classification with four additional characteristic non-cancerous EC features has also been proposed. Recently, deep-learning AI for analysis of esophageal EC images has revealed that its diagnostic accuracy is comparable to that of expert pathologists.

Recent trends in the morbidity and mortality in patients with familial adenomatous polyposis: a retrospective single institutional study in Japan.

BACKGROUND: This study aimed to assess current trends in morbidity and mortality among patients with familial adenomatous polyposis (FAP). These data can be used for optimal surveillance and management of such patients. METHODS: Data (November 2001 and April 2020) of genetically confirmed patients with FAP (n = 87) and their first-degree relatives with FAP phenotype (n = 20) were extracted from the Saitama Medical Center database. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were estimated using indirect method. RESULTS: Overall, 46 men and 61 women were included; the median age at FAP diagnosis was 28.0 years for both. The SMR for all causes of death was 47.7 (95% confidence interval [CI] 19.1-98.2) in women and 26.5 (95% CI 9.73-57.8) in men. The SIR for colorectal cancer (CRC) was 860 (95% CI 518-1340) in women and 357 (95% CI 178-639) in men. The SMR for CRC was 455 (95% CI 93.7-1330) in women and 301 (95% CI 62.0-879) in men. Thirteen patients died during the observation period, and CRC was the leading cause of death (46%). Other causes of death included desmoid tumor (n = 2), small intestinal cancer (n = 2), ovarian cancer (n = 1), duodenal cancer (n = 1), and sepsis (n = 1). CONCLUSIONS: The mortality ratio, estimated using SMR, remained high. CRC was the leading cause of death, whereas almost half of the causes of deaths were extra-colonic tumors. Life-long management of extra-colonic diseases may improve the prognosis in these patients.

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 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.

[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.

[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.

[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.

[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.

[A Case of Carcinoma of the Ileostomy Site Associated with Familial Adenomatous Polyposis-Report of a Case].

We report a rare carcinoma of the permanent ileostomy site developing 20 years or more after total proctocolectomy (TPC)in a 65-year-old woman with familial adenomatous polyposis(FAP). She underwent TPC for rectal cancer associated with FAP in her 40th at other institution. She also underwent pancreas-sparing total duodenectomy for duodenal mucosal cancer associated with severe duodenal polyposis at 59 years at our institution. She was referred to our hospital again complaining of the mass of the ileostomy site, 10 cm in diameter. Though biopsy revealed no definite malignancy, serum CA19-9 was elevated(98 U/mL), leading to a preoperative diagnosis to be ileal carcinoma. The involved bowel was widely resected. Histological examination demonstrated Stage ⅡA ileal carcinoma. Postoperative course was uneventful and she is well without recurrence 7 months after the ileal resection. This case seems valuable in that long-term surveillance including ileal carcinoma is important in the management of FAP patients whose colorectal cancer and duodenal cancer have been already well controlled.

[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.

Endocytoscopic observation with methylene blue staining for duodenal neoplasms associated with familial adenomatous polyposis.

Duodenal cancer is a leading cause of death after colectomy in patients with familial adenomatous polyposis (FAP). Detailed endoscopic evaluation of duodenal lesions with potential for carcinoma development is therefore mandatory. Here we investigated the features of duodenal lesions in FAP patients using an endocytoscopy system (ECS). We retrospectively reviewed duodenal lesions in 15 cases of FAP using an ECS (GIF-H290EC) with methylene blue (MB) as the vital dye. With reference to the Spigelman classification, we investigated the number of lesions using white light (WL), narrow-band imaging (NBI), and MB staining. Using the maximum magnification power of the ECS we investigated the histology (duct openings or finger-like projections) and grade of dysplasia (presence or absence of enlarged oval-shaped nuclei) of the lesions. The number of duodenal lesions increased in ascending order of WL, NBI, and MB (P < 0.05). Among 51 MB-unstained lesions, 46 (90.2%) were proven to be duodenal neoplasms histologically. Duct openings were seen in 90.2% of tubular adenomas and tubulovillous adenomas. Finger-like projections were seen in 33.3% of tubular adenomas and in 88.2% of tubulovillous adenomas. Enlarged oval-shaped nuclei were observed in 100% of duodenal cancers, 33.3% of high-grade adenomas, and 9.4% of low-grade adenomas. MB staining allows more accurate detection of duodenal neoplasms in comparison to conventional WL and NBI observation. In cases of FAP, use of the maximum magnification power of the ECS may allow selection of lesions with high malignant potential.

[Does Colonic Stenting Affect the Long-Term Prognosis of Colorectal Cancer ?]

The impact of colonic stenting on long-term prognosis has not yet been clarified. We compared background factors, progression-free survival, and overall survival between patients with stents(stent group)who underwent surgery after colonic stenting as a bridge to surgery and patients without stents(non-stent group)who underwent emergency surgery for left-sided colorectal cancer ileus. There was no difference between the 2 groups in the induction of adjuvant chemotherapy, but the use of oxaliplatin-base was highly introduced in the stent group(p=0.03). The 5-year DFS rates were 55.1% and 70.3%(p=0.21)and the 5-year OS rates were 90.7%and 70%(p=0.35)in the stent and non-stent groups, respectively. In the present study, colon stent placement did not affect long-term prognosis.

Pre-operative Evaluation of Lateral Pelvic Lymph Node Metastasis in Lower Rectal Cancer: Comparison of Three Different Imaging Modalities.

OBJECTIVES: The pre-operative diagnostic value of detecting lateral pelvic lymph node (LPLN) metastasis with magnetic resonance imaging, multidirectory computed tomography, and positron emission tomography/computed tomography was investigated in lower rectal cancer patients. METHODS: We retrospectively evaluated, using the three different modalities, the metastatic status of LPLNs in four regions, including both the internal iliac and the obturator, in 46 patients affected by lower rectal cancer patients who underwent LPLN dissection. The size inclusion criterion for LPLN metastasis was set at 6 mm in the short axis diameter. Histological examination was performed for determining the false positive and negative rate of LPLNs metastasis detection. RESULTS: Among 184 LPLNs regions, 17 (9%) were positive for metastasis. The region-based sensitivity, specificity, and accuracy rate did not differ among the three tested diagnostic modalities. Moreover, a significant increase in these rates could not be observed when the modalities were combined. Of 184 regions, 8 (4.4%) were false negative, whereas 2 (1.1%) were false positive. The histological pattern of metastatic regions did not differ in 8 false negative LPLNs. CONCLUSIONS: Each modality had a similar detection power for LPLNs metastasis, with a cut-off value at 6 mm in the short axis diameter. However, the sensitivity of all the modalities was slightly low, along with the number of false negative LPLNs. Further reduction of the false negative rate with these modalities may be difficult because of an inherent limitation of current imaging technologies to accurately detect lymph node metastases.