Impact of computer-aided characterization for diagnosis of colorectal lesions, including sessile serrated lesions: Multireader, multicase study.

OBJECTIVES: Computer-aided characterization (CADx) may be used to implement optical biopsy strategies into colonoscopy practice; however, its impact on endoscopic diagnosis remains unknown. We aimed to evaluate the additional diagnostic value of CADx when used by endoscopists for assessing colorectal polyps. METHODS: This was a single-center, multicase, multireader, image-reading study using randomly extracted images of pathologically confirmed polyps resected between July 2021 and January 2022. Approved CADx that could predict two-tier classification (neoplastic or nonneoplastic) by analyzing narrow-band images of the polyps was used to obtain a CADx diagnosis. Participating endoscopists determined if the polyps were neoplastic or not and noted their confidence level using a computer-based, image-reading test. The test was conducted twice with a 4-week interval: the first test was conducted without CADx prediction and the second test with CADx prediction. Diagnostic performances for neoplasms were calculated using the pathological diagnosis as reference and performances with and without CADx prediction were compared. RESULTS: Five hundred polyps were randomly extracted from 385 patients and diagnosed by 14 endoscopists (including seven experts). The sensitivity for neoplasia was significantly improved by referring to CADx (89.4% vs. 95.6%). CADx also had incremental effects on the negative predictive value (69.3% vs. 84.3%), overall accuracy (87.2% vs. 91.8%), and high-confidence diagnosis rate (77.4% vs. 85.8%). However, there was no significant difference in specificity (80.1% vs. 78.9%). CONCLUSIONS: Computer-aided characterization has added diagnostic value for differentiating colorectal neoplasms and may improve the high-confidence diagnosis rate.

[R0 Resection following Chemotherapy for Colon Cancer Liver Metastasis Close to the Inferior Vena Cava and Hepatic Vein Confluence-A Case Report].

A 78-year-old man was diagnosed with sigmoid colon cancer, and laparoscopic sigmoidectomy was performed. On pathological examination, he was diagnosed with RAS-wild type sigmoid colon cancer with regional lymph node metastasis (T3, N1, M0, Stage ⅢB[Union for International Cancer Control 8th edition]). Computed tomography revealed S8 and S7 liver metastasis, 3 months after the initial surgery. The location of the S8 tumor was close to the inferior vena cava(IVC), right hepatic vein(RHV)and segment Ⅷ hepatic vein(V8). He was administered cetuximab plus modified FOLFOX6. After 6 courses of chemotherapy, the S8 and S7 liver tumor shrank. S8 plus 4 plus 1 and S7 partial hepatectomy was performed and R0 resection was achieved. The RHV and V8 were resected, while right superficial and middle hepatic veins were preserved. An IVC invasion was not observed. He was administered 12 courses of adjuvant modified FOLFOX6. After the partial hepatectomy, he has been followed up for 1.5 years with no recurrence.

[Long-Term Disease Control with Capecitabine plus Bevacizumab Therapy for an Elderly Patient with Unresectable Colon Cancer-A Case Report].

An 83-year-old man visited our hospital with liver tumors detected by abdominal ultrasonography. On investigation, he was diagnosed with sigmoid colon cancer with metastasis in the supraclavicular lymph node, liver, and para-aortic lymph node(T3N1M1b, Stage ⅣB[Union for International Cancer Control 8th edition]). He was administered combination therapy with capecitabine and bevacizumab owing to the increased age and Eastern Cooperative Oncology Group performance status score of 1. After 8 courses of chemotherapy, the primary tumor and liver metastases shrank. As he developed Grade 2 hand-foot syndrome, the dose of capecitabine was decreased to 75%(1,500 mg/m2)from the 11th course and to 50% (1,000 mg/m2)from the 31st course. Until 2 years after initiation of the chemotherapy, the patient showed progression-free survival. Heparinoid-containing moisturizer and steroid ointment were administered for treatment of hand-foot syndrome. This report suggests that capecitabine plus bevacizumab therapy can maintain the quality of life and is safe with dose reduction and treatment of adverse reactions for elderly patients with colon cancer.

Sessile serrated adenoma/polyp showed rapid malignant transformation in the final 13 months.

Based on the concept of the adenoma-carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype-positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers.

[A Case of Small Bowel Perforation Caused by Malignant Lymphoma after Methotrexate Therapy for Rheumatoid Arthritis].

A 73-year-old woman had a history of medication, including methotrexate for rheumatoid arthritis, for 5 years. She had chronic epigastralgia for 2 weeks and found to have multiple submucosal tumors on upper gastrointestinal endoscopy in another hospital. She had a strong abdominal pain thereafter and diagnosed as having gastrointestinal perforation on the basis of CT scans. Abdominal examination revealed disseminated peritonitis, and emergency laparoscopic surgery was performed on the day of admission. A 1 cm perforation of the ileum was identified, and a 5 cm mass of the mesentery near the perforation was also identified. Small bowel partial resection, including both lesions, was performed. From the intraoperative findings, methotrexate-associated lymphoproliferative disorders(MTX-LPD)was suspected, and methotrexate was discontinued after the surgery. At a later date, the pathological result from both the surgical specimen and upper gastrointestinal endoscopy was diffuse large B cell lymphoma(DLBCL). CT scan, PET-CT scan, and upper gastrointestinal endoscopy were performed 1-2 months after surgery, and no tumor was identified. Currently, 6 months after the surgery, the patient is still alive without any progression of the lymphoma.

[Trastuzumab Combination Chemotherapy Followed by R0 Resection for Locally Advanced Human Epidermal Growth Factor Receptor 2-Positive Gastric Cancer-A Case Report].

A man in the 60s visited our hospital with the complaints of epigastralgia and weight loss. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2(HER2)-positive gastric cancer with invasion to the pancreas (T4b[pancreas], N2, M0, Stage ⅣA[Union for International Cancer Control 8th edition]). Preoperatively, he was administered a chemotherapeutic regimen of S-1 and cisplatin plus trastuzumab. After 2 courses of chemotherapy, computed tomography revealed invasion to the abdominal wall and pyloric stenosis; however, invasion to the pancreas was obscured, and the lymph node metastases had shrunk. He underwent laparoscopic gastro-jejunostomy. After 4 courses of chemotherapy, his condition was considered stable. A laparoscopic distal gastrectomy was performed together with resection of the abdominal wall invasion. The pathological stage was pT4b(abdominal wall), pN0, M0, Stage ⅢA, and R0 resection was achieved. The patient was administered 4 courses of adjuvant capecitabine plus oxaliplatin therapy and 4 courses of capecitabine monotherapy. He has been followed-up for 1.5 years since the curative resection and has not developed recurrences. This case suggests the usefulness of multimodal therapy for locally advanced gastric cancer.

[A Case of Extrahepatic Bile Duct Carcinoid Tumor Involving Diagnostic Difficulties].

A patient in his 60s had undergone laparoscopic anterior resection for the treatment of carcinoma of the rectum in February 2016. Histopathologic examination revealed the lesion as a pT2(MP)n(-)M0, fStage Ⅰrectal cancer. One year post-surgery, contrast-enhanced computed tomography(CT)revealed enhancement of parts of the intrapancreatic distal bile ducts. Magnetic resonance cholangiopancreatography(MRCP)showed filling defects at the same site. Magnetic resonance imaging( MRI)with an endorectal coil(ERC)was then performed to identify reproducible bile duct filling defects. Neither cytology nor biopsy yielded any findings that definitely indicated malignancy. Intraductal ultrasonography(IDUS)led to the suspicion of a nonepithelial tumor or an enlarged lymph node. Repeated biopsies via ERC were performed based on the absence of evidence of malignancy and revealed the presence of some atypical cells within the lesions. Although no definitive diagnosis could be made, the patient was scheduled for surgery in June 2017 after obtaining his consent. Upon taping of the common bile duct during surgery, a tumor was palpable on the dorsal aspect of the pancreas. The bile duct tumor was completely excised and submitted for intraoperative diagnosis; the pancreatic dorsal aspect appeared to be totally split. There was no evidence of atypia in the neoplasm, which was therefore considered to be benign; however, malignancy could not be completely ruled out because the patient had presented with elevated serum levels of carbohydrate antigen(CA)19-9 once before the operation. After intraoperative consultation with the patient's family members, who were reluctant to provide consent for pancreaticoduodenectomy, we completed the operation with resection of the bile duct tumor, followed by choledochojejunostomy. The tumor was found to be chromogranin A(+), cluster of differentiation(CD)56(+/-), CA19-9(+, solely ductal structure), carcinoembryonic antigen(CEA)(+, solely ductal structure), and intranuclear p53(-), with an MIB- 1 index of<2%. With regard to neuroendocrine markers, a region that could potentially have been a carcinoid tumor, based on the findings on hematoxylin and eosin(HE)staining, and a lumenized superficial region showed positivity in toto. Therefore, the lesion as a whole was diagnosed as a G1 carcinoid neuroendocrine tumor(NET). However, the superficial lumenized layer was positive for both CA19-9 and CEA; therefore, the tumor was thought to concurrently have epithelial characteristics. The lateral stumpwas negative, while the status of the ablated region remained unclear. After discussing the histopathologic examination results with the patient and his family members, the patient's follow-upwas decided to consist of periodic checkups without any further surgical intervention. The patient has since remained free of recurrence. Carcinoid tumor of the bile duct is extremely rare but should be considered in cases involving bile duct tumors that show enhancement on imaging prior to surgery and for which no definitive diagnosis can be established despite repeated biopsy explorations.

[Pathological Complete Response Following Chemotherapy for Sigmoid Colon Cancer with Para-Aortic Lymph Node Metastasis-A Case Report].

A man in his 50s visitedour hospital with complaints of frequent urination, painful micturition, macrohematuria, and weight loss. On examination, he was diagnosed with RAS-wild-type sigmoid colon cancer invading the urinary bladder, ureter, andexternal iliac artery, with para-aortic lymph node metastasis(T4b, NX, M1a, Stage ⅣA according to the Union for International Cancer Control 8th edition guidelines)andsigmoid -vesical fistula. Thus, sigmoidcolostomy was performed. Postoperatively, S-1 plus oxaliplatin was administered. After 3 courses of chemotherapy, the primary tumor and para-aortic lymph node metastases shrunk. Moreover, after 8 courses of chemotherapy, further shrinkage of the primary tumor and paraaortic lymph node metastases was confirmed; however, tumor markers in the blood increased. Therefore, the patient received 3 additional courses of S-1 plus oxaliplatin plus cetuximab, which resultedin complete response. Sigmoidectomy, partial cystectomy, ureterectomy, resection of the external iliac artery, andreconstruction using a prosthetic vascular graft were performed. Subsequent pathological examination revealed no viable cancer cells(pathological response), achieving R0 resection. The patient has been followedup for 2.5 years after the curative resection, with no recurrence.

[A Case of Complete Response to Computed Tomography-Guided Celiac Plexus Neurolysis of Pain Associated with Postoperative Recurrence of Colon Cancer].

The patient was a man in his 40s, who had undergone laparoscopic ileocecal resection with lymph node dissection(D3)for cecal cancer in January 2012. Histopathological examination of the resected specimens had revealed StageⅡ primary tumor with subserosal invasion and positive metastasis in 1-3 regional lymph nodes(pT2[SS]n1[+]). The pathological stage was Ⅲa(fStage Ⅲa), and the tumor showed RAS gene mutation. The patient was administered 5 cycles of postoperative adjuvant chemotherapy with oral tegafur/uracil(UFT)in combination with calcium folinate(UZEL). Abdominal computed tomography( CT)performed 1.5 years postoperatively revealed liver metastasis, and a laparoscopic partial hepatectomy was performed in August 2015. In addition, a node in the greater omentum, located in the inferior surface of the liver, was also resected. Histopathological examination of the resected specimens revealed peritoneal metastasis, based on the identification of the same type of adenocarcinoma as the colon cancer. The patient was given 8 cycles of adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Then, he presented with colonic ileus, caused by recurrent dissemination, and underwent a laparoscopic transverse colectomy in October 2015. Multiple perineal disseminations were found intraoperatively, and chemotherapy was initiated with irinotecan plus tegafur/gimeracil/oteracil(S-1)plus bevacizumab(IRIS/BV)for the recurrent and unresectable disease. After 27 cycles of this regimen, lung metastasis was detected; in addition, progression of the para-aortic node metastasis around the celiac plexus was also observed, and the patient was considered as having pro- gressive disease(PD). Treatment with trifluridine/tipiracil(TAS102)was started in September 2017. Prior to the initiation of this regimen, the dose of opioid rescue medication previously started for back and abdominal pain was rapidly increased. Accordingly, the base dose was increased, but the pain could not be controlled, and the major pain was consistently located along the area of innervation in the celiac plexus. Therefore, celiac plexus neurolysis(CPN)was performed as a local therapy. A CT-guided injection technique was used to administer urografin, bupivacaine, and absolute ethanol to complete the procedure. The patient was discharged without major complications, and the base opioid dose was gradually reduced. Since the patient did not require any rescue medication during daytime on some days, the reduction of the base opioid dose was significantly effective in improving the patient's quality of life(QOL). In patients with pain possibly caused by metastasis to the para-aortic nodes, this local therapy technique may be considered.

[A Case of Phrenic Nerve Paralysis During Adjuvant Chemotherapy for Rectal Cancer].

A man aged 66 years presented with pneumaturia as a major complaint. Cancer of the sigmoid colon with infiltration to the urinary bladder was diagnosed and the patient underwent colectomy of the sigmoid colon and partial cystectomy of the bladder in May 2015. Histopathologic examinations revealed pT4b, Si(bladder), pN(-), cM0, fStage II . Because intestinal sub-obstruction and lymphatic invasion were present, CapeOX was administered as an adjunctive chemotherapy for the high-risk Stage II cancer. Because Grade 2 peripheral neuropathy appeared as a side effect, the dose was decreased to 80% from the 3 cycle. After the 7 cycle, cough and disturbed breathing appeared. The chest CT scans did not reveal drug-induced interstitial pneumonia, but indicated an elevated right diaphragm and zosteroid changes in the medial lobe of the right lung due to discoid atelectatic condition. The Grade 1 respiratory symptoms were mild, and the lung field was considered to exhibit no problems. Thus, the 8 cycle was administered. The symptoms disappeared after about 2 weeks following completion of oral administration of capecitabine. The diaphragm also recovered to its original height. In the attached document, the frequency is unknown and "dyspnea" is written for L-OHP and capecitabine, respectively. It is unknown whether phrenic nerve paralysis occurs. However, because other organic lesions were absent and the symptoms appeared during chemotherapy, the possibility is not deniable. At present, 2 years postoperatively, recurrent lesions in the mediastinum and recurrent respiratory difficulties are absent. Generally, although phrenic nerve paralysis is not considered to be a specific side effect, it was considered that for respiratory difficulties, CT reveals not only the affected condition in the lung fields, but is also useful for detection.

[Patients' reaction to pharmacists wearing a mask during their consultations].

  This study sought to determine the effect of pharmacists wearing a mask on the consultation intention of patients who do not have a trusting relationship with the pharmacists. We conducted a questionnaire survey of customers at a Tokyo drugstore in August 2012. Subjects answered a questionnaire after watching two medical teaching videos, one in which the pharmacist was wearing a mask and the other in which the pharmacist was not wearing a mask. Data analysis was performed using a paired t-test and multiple logistic regression. The paired t-test revealed a significant difference in 'Maintenance Problem' between the two pharmacist situations. After excluding factors not associated with wearing a mask, multiple logistic regression analysis identified three independent variables with a significant effect on participants not wanting to consult with a pharmacist wearing a mask. Positive factors were 'active-inactive' and 'frequency mask use', a negative factor was 'age'. Our study has shown that pharmacists wearing a mask may be a factor that prevents patients from consulting with pharmacist. Those patients whose intention to consult might be affected by the pharmacists wearing a mask tended to be younger, to have no habit of wearing masks preventively themselves, and to form a negative opinion of such pharmacists. Therefore, it was estimated that pharmacists who wear masks need to provide medical education by asking questions more positively than when they do not wear a mask in order to prevent the patient worrying about oneself.