[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.

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors.

Introduction: Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method. Methods: In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression. Results: PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group. Conclusion: Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.

Gastric Emptying is Accelerated in Patients With Gastric Tube Reconstruction Following Laparoscopic Proximal Gastrectomy.

BACKGROUND: Laparoscopic proximal gastrectomy (LPG) is an attractive option for the treatment of early gastric cancer in the upper third of the stomach. No optimal method of reconstruction after LPG has been established because of problems associated with postoperative reflux. Gastric tube reconstruction, a type of esophagogastrostomy, is a simple procedure, but it is associated with a high frequency of reflux esophagitis (RE). We investigated the relationship between RE and gastric emptying, along with nutritional parameters. SUBJECTS AND METHODS: We compared gastric emptying in patients who had undergone curative LPG with gastric tube reconstruction for gastric cancer with that of patients after total gastrectomy (TG), distal gastrectomy (DG) and of healthy volunteers and patients after DG. The LPG group was divided into an RE LPG-RE (+) group and a non-reflux esophagitis (non-RE) an LPG-RE (-) group, and we compared gastric emptying and indices of nutrition, such as body weight and laboratory findings, between those among LPG-RE (+), LPG-RE (-), and TG groups. RESULTS: The time lag between ingestion and peak 13 CO 2 expiration (T lag) in the healthy volunteer group was significantly shorter in the LPG group longer than those in the healthy volunteer LPG group and TG group. The T lag was significantly shorter in the RE LPG-RE (+) group than in the non-RE LPG-RE (-) group. The percentage change in body weight percentage in the non-RE LPG-RE (-) group was significantly larger than that in the RE LPG-RE (+) group at 12 months after surgery. Both the serum albumin and hemoglobin levels in the non-RE LPG-RE (-) tended to be preserved compared with those in the RE LPG-RE (+) group and TG group. CONCLUSIONS: Gastric emptying was accelerated after LPG, and was associated with RE. Our data suggest that RE could be associated with body weight loss after LPG.

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.

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.

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.

[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.

Wnt-induced, TRP53-mediated Cell Cycle Arrest of Precursors Underlies Interstitial Cell of Cajal Depletion During Aging.

BACKGROUND & AIMS: Gastric dysfunction in the elderly may cause reduced food intake, frailty, and increased mortality. The pacemaker and neuromodulator cells interstitial cells of Cajal (ICC) decline with age in humans, and their loss contributes to gastric dysfunction in progeric klotho mice hypomorphic for the anti-aging Klotho protein. The mechanisms of ICC depletion remain unclear. Klotho attenuates Wnt (wingless-type MMTV integration site) signaling. Here, we examined whether unopposed Wnt signaling could underlie aging-associated ICC loss by up-regulating transformation related protein TRP53 in ICC stem cells (ICC-SC). METHODS: Mice aged 1-107 weeks, klotho mice, APCΔ468 mice with overactive Wnt signaling, mouse ICC-SC, and human gastric smooth muscles were studied by RNA sequencing, reverse transcription-polymerase chain reaction, immunoblots, immunofluorescence, histochemistry, flow cytometry, and methyltetrazolium, ethynyl/bromodeoxyuridine incorporation, and ex-vivo gastric compliance assays. Cells were manipulated pharmacologically and by gene overexpression and RNA interference. RESULTS: The klotho and aged mice showed similar ICC loss and impaired gastric compliance. ICC-SC decline preceded ICC depletion. Canonical Wnt signaling and TRP53 increased in gastric muscles of klotho and aged mice and middle-aged humans. Overstimulated canonical Wnt signaling increased DNA damage response and TRP53 and reduced ICC-SC self-renewal and gastric ICC. TRP53 induction persistently inhibited G1/S and G2/M cell cycle phase transitions without activating apoptosis, autophagy, cellular quiescence, or canonical markers/mediators of senescence. G1/S block reflected increased cyclin-dependent kinase inhibitor 1B and reduced cyclin D1 from reduced extracellular signal-regulated kinase activity. CONCLUSIONS: Increased Wnt signaling causes age-related ICC loss by up-regulating TRP53, which induces persistent ICC-SC cell cycle arrest without up-regulating canonical senescence markers.

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.

[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 prospective pilot study of an elemental nutritional supplement for prevention of oral mucositis during S-1 adjuvant chemotherapy for gastric cancer.

PURPOSES: Oral mucositis is one of the most common reasons for discontinuation of S-1 adjuvant chemotherapy after radical gastrectomy. Some studies suggest that nutritional support with amino acids may improve oral mucositis. We conducted a prospective, randomized clinical trial of patients who underwent adjuvant chemotherapy for gastric cancer to examine whether an oral elemental diet prevents chemotherapy associated oral mucositis and body weight loss. METHODS: Patients were randomly assigned to a group consuming Elental® (the treatment group, n = 11) or a control diet group (n = 11). Patients in the treatment group consumed one pack of Elental® per day during adjuvant chemotherapy. The primary endpoint was the presence and grade of oral mucositis. Secondary endpoints included adherence to Elental® based on the doses recorded in a diary, changes in nutrition parameters, and frequency and severity of adverse events. RESULTS: The incidence of oral mucositis was significantly lower in the treatment group (9.1%) than in the control group (27.3%). The median body weight loss in the treatment group was significantly smaller than that in the control group (P = .015). According to Kaplan-Meier estimates the treatment group was significantly associated with high cumulative S-1 continuation rates (log-rank P = .047). CONCLUSION: We conclude that the amino-acid-rich elemental diet Elental® may be useful as a countermeasure for S-1 adjuvant chemotherapy-induced mucositis.

[A Case of Peritoneal Metastasis of Appendiceal Mucinous Carcinoma Successfully Managed by Multidisciplinary Treatment].

There is no established treatment for appendiceal mucinous adenocarcinoma. When this condition is complicated by pseudomyxoma peritonei(PMP), multidisciplinary treatment is often administered. A 40-year-old woman was diagnosed with right ovarian cancer for which laparotomy was performed. At the time of laparotomy, we considered the tumor to be an appendiceal carcinoma infiltrating the right ovary and performed ileocecal resection with lymph node dissection(D3)and right salpingo-oophorectomy. The pathological diagnosis was stage pT3, pN0, pM0, pStage Ⅱ mucinous adenocarcinoma of the appendix. Fourteen months later, the patient underwent abdominal total hysterectomy and left salpingo-oophorectomy because a CT scan suggested recurrence in the uterus, left fallopian tube, and ovary. Seventeen months after the second operation, despite adjuvant chemotherapy, CT revealed a peritoneal nodule in the pelvic cavity. Therefore, we administered chemotherapy comprising 5 lines for 32 months, which resulted in failure. CT showed an enlarged tumor and ascites and the patient became terminally ill. We repeatedly performed cytoreduction surgery and intraperitoneal chemotherapy, which improved her QOL. One year after discharge, abdominal CT showing an abdominal wall and intraperitoneal mass. We performed again cytoreduction surgery and intraperitoneal chemotherapy. Her postoperative course is good and she is currently an outpatient.

[The Outcome of Preoperative Chemoradiotherapy for Advanced Lower Rectal Cancer-The Possibility of an Omission of the Lateral Dissection].

The objective of this study was to evaluate the outcomes of selective LPLN dissection(LPLD)based on pretreatment imaging in patients with advanced low rectal cancer treated with pre-operative CRT. We reviewed 32 patients without suspected LPLN metastasis based on the MDCT or MRI results before CRT. These patients underwent total mesorectal excision (TME)without LPLD. The clinical characteristics and oncological outcomes were examined. In all cases, the per-protocol treatments were completed. Tumor recurrence occurred in 14 patients at the liver(3 cases), the lung(7 cases)and the local sites(4 cases). Of the 4 cases with pelvic recurrence, no recurrence was found in the lateral lymph node area. Under the condition that pre-operative chemoradiotherapy is to be performed for advanced lower rectal cancer with negative lateral lymph node metastasis, a lateral dissection could be omitted.

[A Case of Low-Grade Appendiceal Mucinous Neoplasm Complicated by Pseudomyxoma Peritoneri Successfully Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy].

We experienced a case of low-grade appendiceal mucinous neoplasm complicated by pseudomyxoma peritonei that was successfully treated with cytoreductive surgery and early postoperative intraperitoneal chemotherapy. The patient was a 26- year-old man with massive ascites and a swollen appendix on the computed tomography(CT). The appendix was a cystic mass of 5 cm in size. The entire parietal peritoneum, omentum, stomach, spleen, gall bladder, and entire colon were covered with numerous mucous nodules. Total colectomy, total gastrectomy, splenectomy, cholecystectomy, total omentectomy, parietal peritonectomy, ileostomy, and intraperitoneal irrigation were performed. The pathological diagnosis was low-grade appendiceal mucinous neoplasm. Postoperative intraperitoneal chemotherapy with cisplatin and mitomycin C was performed. A residual tumor was found on the dorsal side of the hepatoduodenal ligament 3 months postoperation on the CT. The residual tumor was successfully excised via a concomitant resection of the hepatic caudate lobe. Postoperative intraperitoneal chemotherapy was then performed. No recurrence was found at 8 months postoperation. The addition of early postoperative intraperitoneal chemotherapy improved the patient's quality of life in a short period. This could be one of the treatment options.