Magnifying colonoscopy as a non-biopsy technique for differential diagnosis of non-neoplastic and neoplastic lesions

瞄准：为了澄清与放大结肠镜检查观察的粘膜地窟模式是否对可行，把非肿瘤的息肉与肿瘤的息肉区分开来。方法：从通过 2000 年 3 月的 1999 年 6 月，有 210 损害的 180 个连续病人与放大结肠镜诊断了(CF-200Z，天堂光有限公司，东京，日本) 被注册。有 0.2% 靛青洋红染料的放大和多彩石印版内视镜检查法为粘膜地窟观察被用于每损害。损害出现打字我和 II 地窟模式被活体检视组织学地认为非肿瘤、检验，而损害证明到 V 地窟模式的类型 III 被移开内视镜的联盟者或通过手术。内视镜的诊断和 histologic 诊断的关联然后被调查。结果：在内视镜检查法， 24 损害证明我或 II 坑模式，和 186 损害显示出的一种类型打 III 到 V 坑模式。与 histologic 检查， 26 损害作为非肿瘤的息肉被诊断，并且 184 损害作为肿瘤的息肉被诊断。全面诊断精确性是 99.1%(208/210 ) 。敏感和特性是 92.3%(24/26 ) 并且 99.8%(184/186 ) 分别地。结论：放大结肠镜检查能作为一种非活体检视技术被使用区分肿瘤、非肿瘤的息肉。

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.

Pneumoscrotum: A rare manifestation of perforation associated with therapeutic colonoscopy

Pneumoscrotum is uncommon and also rarely reported as a complication associated with colonic perforation. A case of colonic perforation in delayed fashion associated with EMR, revealed by pneumoscrotum, is reported and the associated literatures are reviewed. A 52-year-old male received piecemeal EMR for a laterally spreading tumor 35 mm in size in our hospital. He complained of enlargement of the scrotum and revisited our hospital the day after the procedure. A diagnosis of pneumoscrotum was made, and as most such cases have been reported to be associated with pneumoperitoneum, colonic perforation was suspected. Free air but no fluid collection was found by abdominal computed tomography, and delayed colonic perforation was diagnosed. However, as there were no clinical signs of peritoneal irritation,conservative treatment was administered and the patient recovered uneventfully. Pneumoscrotum could be a sign of colonic perforation after EMR, and treatment should be carefully chosen.

Primary signet-ring cell carcinoma of the colon at early stage: A case report and a review of the literature

经历了外科到将切除的一个 67 岁的人多重胃的癌症 4 年以前，为监视结肠镜检查访问了我们的医院。揭示的结肠镜检查一变色，在直径的 7 公里，有在结肠左曲附近的横向的冒号的中央消沉的提高公寓的损害。尽管内视镜检查法和钡灌肠的调查结果粘膜下层侵略是暗示的，病人选择了经历内视镜的粘膜切除术。resected 标本的病理学的检查揭示了图章戒指房间癌和积极外科的边缘。第二个手术被动，并且到淋巴结的剩余肿瘤或转移都没在 resected 标本被发现。由在一个早阶段检测并且对待的图章戒指房间癌组成的三原色表面的癌症是极其稀罕的。我们在场一个盒子和评论文学。

Study protocol of the Asian XELIRI ProjecT(AXEPT):a multinational,randomized,non-inferiority,phase Ⅲ trial of second-line chemotherapy for metastatic colorectal cancer, comparing the eicacy and safety of XELIRI with or without bevacizumab versus FOLFIRI w

Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.

Incidence and localization of lymphoid follicles in early colorectal neoplasms

AIM: To investigate the incidence and localizations of lymphoid follicles (LFs) in early colorectal neoplasms in human beings.METHODS: From July 1992 to September 1999, a total of 1 324 early colorectal neoplasms were removed endoscopically or surgically at our hospital; 1 031 (77.9%)were available for analysis in this study. Localization of LFs was defined histologically: as submucosal LFs, if located under the muscularis mucosa; and as intramucosal LFs, if located across or oyer the muscularis mucosa.RESULTS: Histologically, the materials included 903intramucosal neoplasms and 128 submucosal cancers.Overall incidence of LFs was 27.2% (280/1 031). The incidence of LFs was significantly higher in females (33.6% vs 24.9%,P=0.0064), the right-sided colon (32.2% vs 25.6%, P=0.0403) and in flat or depressed type lesions (34.6% vs 25.2%, P＜0.0001)as compared to males, left-sided colon and protruding type lesions, respectively. The incidences of intramucosal neoplasms and submucosal cancers were 24.3% and 43.8%, respectively (P＜0.0001). Localizations of LFs (intramucosal LF/submucosal LF) in depressed, flat,and protruding types were 1/24, 14/36, and 131/74,respectively.CONCLUSION: The incidence of LFs in early human colorectal neoplasms significantly differs by gender,location, macroscopic type, and histology. Moreover,localization significantly differs by macroscopic type.

Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

Tumor biopsy and patient enrollment in clinical trials for advanced hepatocellular carcinoma

Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.

PhaseFIT:live-organoid phase-fluorescent image transformation via generative AI

Organoid models have provided a powerful platform for mechanistic investigations into fundamental biological processes involved in the development and function of organs.Despite the potential for image-based phenotypic quantification of organoids,their complex 3D structure,and the time-consuming and labor-intensive nature of immunofluorescent staining present significant challenges.In this work,we developed a virtual painting system,PhaseFIT(phase-fluorescent image transformation)utilizing customized and morphologically rich 2.5D intestinal organoids,which generate virtual fluorescent images for phenotypic quantification via accessible and low-cost organoid phase images.This system is driven by a novel segmentation-informed deep generative model that specializes in segmenting overlap and proximity between objects.The model enables an annotation-free digital transformation from phase-contrast to multi-channel fluorescent images.The virtual painting results of nuclei,secretory cell markers,and stem cells demonstrate that PhaseFIT outperforms the existing deep learning-based stain transformation models by generating fine-grained visual content.We further validated the efficiency and accuracy of PhaseFIT to quantify the impacts of three compounds on crypt formation,cell population,and cell stemness.PhaseFIT is the first deep learning-enabled virtual painting system focused on live organoids,enabling large-scale,informative,and efficient organoid phenotypic quantification.PhaseFIT would enable the use of organoids in high-throughput drug screening applications.

Looking for the right TNM staging system for pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors(panNETs)represent a rare subgroup of neuroendocrine neoplasms(NENs)which showed an impressive increase of incidence over the last decade(1).As over the same period particularly low stage and low grade NETs had the highest increase it is plausible that small(e.g.,