Naoki Asayama

Endoscopic submucosal dissection as total excisional biopsy for clinical T1 colorectal carcinoma.

Background/Aims: Only the depth of submucosal invasion can be estimated prior to determining the indications for endoscopic submucosal dissection (ESD) as a curative treatment for colorectal carcinoma (CRC). Here we evaluated the outcomes of ESD for clinical T1 CRCs. Methods: Of 660 patients who underwent ESD for CRC at the Hiroshima University Hospital between June 2003 and December 2013, we examined the outcomes of 37 (6%; 26 men, 11 women; mean age ± SD, 68 ± 12 years) who underwent ESD as total excisional biopsy for various reasons, in spite of an endoscopic diagnosis of T1 CRC. Results: The mean lesion size was 25 ± 14 mm; 14 lesions were protruding and 23 were superficial. The en bloc resection rate was 100% (37/37). The histological en bloc resection rate was 92% (34/37). ESD resulted in a positive vertical margin in 3 cases. Deep submucosal invasion was seen in 3 cases, 2 of which had severe submucosal fibrosis. Although severe submucosal fibrosis was not found in other cases, pathologic examination of the deepest invasive portion of the tumor revealed poorly differentiated adenocarcinoma. The rates of post-ESD bleeding and perforation were 8% (3/37) and 5% (2/37), respectively. All patients recovered under conservative therapy. No cases of recurrence were noted in patients without additional surgical resection when the lesions satisfied the curative conditions listed in the 2014 Japanese Society for Cancer of the Colon and Rectum guidelines. Conclusion: En bloc resection by ESD as total excisional biopsy for clinical T1 CRC is a highly effective treatment and establishes a precise histological diagnosis.

Towards safer and appropriate application of endoscopic submucosal dissection for T1 colorectal carcinoma as total excisional biopsy: Future perspectives

According to the Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for the Treatment of Colorectal Cancer, cases with T1 colorectal carcinoma should be considered for additional colectomy with lymph node dissection when histologically complete en bloc resection is endoscopically carried out and when one of the four risk factors listed below is present. These four risk factors are: (i) submucosal (SM) invasion depth ≥1000 μm; (ii) positive vascular invasion; (iii) poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous carcinoma; and (iv) grade 2/3 budding at the deepest part of SM invasion. However, the probability of lymph node metastasis is extremely low if none of these risk factors are present, with the exception of SM invasion depth ≥1000 μm. Consequently, it is assumed that there will be an increasing number of cases where no additional surgery is done, or cases of moderate invasive carcinoma in which endoscopic treatment is carried out to achieve an excisional biopsy, for which complete resection is applicable. In these cases, the preoperative diagnosis, resection techniques such as endoscopic submucosal dissection, features of resected specimens, and the accuracy of pathological diagnosis are all extremely important.

Clinical impact and characteristics of the narrow-band imaging magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

BACKGROUND AND AIMS The Japan NBI Expert Team (JNET) was established in 2011 and has proposed a universal narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors. The aim of this study was to evaluate the clinical usefulness of the JNET classification for colorectal lesions. METHODS We analyzed 2933 colorectal lesions, which were diagnosed by NBI magnifying observation before endoscopic treatment or surgery. The colorectal lesions consisted of 136 hyperplastic polyps/sessile serrated polyps (HPs/SSPs), 1926 low-grade dysplasia (LGD), 571 high-grade dysplasia (HGD), 87 superficial submucosal invasive (SM-s) carcinomas, and 213 deep submucosal invasive (SM-d) carcinomas. We evaluated the relationship between the JNET classification and the histologic findings of these lesions. RESULTS The sensitivity, specificity, positive and negative predictive values, and accuracy of Type 1 lesions for the diagnosis of HP/SSP were, respectively, 87.5%, 99.9%, 97.5%, 99.4%, and 99.3%; of Type 2A lesions for the diagnosis of LGD were 74.3%, 92.7%, 98.3%, 38.7%, and 77.1%; of Type 2B lesions for the diagnosis of HGD/SM-s carcinoma were 61.9%, 82.8%, 50.9%, 88.2%, and 78.1%; for Type 3 lesions for the diagnosis of SM-d carcinoma were 55.4%, 99.8%, 95.2%, 96.6%, and 96.6%, respectively. CONCLUSIONS Types 1, 2A, and 3 of the JNET classification were very reliable indicators for HP/SSP, LGD, and SM-d carcinoma, respectively. However, the specificity and positive predictive value of Type 2B were relatively lower than those of others. Therefore, an additional examination such as pit pattern diagnosis using chromoagents is necessary for accurate diagnosis of Type 2B lesions.

Factors Associated with Esophageal Candidiasis and Its Endoscopic Severity in the Era of Antiretroviral Therapy

Background Candidia esophagitis (CE) is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART) era. Methodology/ Principal Findings A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI) endoscopy were analyzed. Sexual behavior, CD4+ count, HIV-RNA viral load (VL), history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsis grade I/II) or severe (grade III/IV). Of the 733 subjects, 62 (8.46%) were diagnosed with CE (mild, n = 33; severe, n = 29). Of them, 56.5% (35/62) had no GI symptoms, 30.6% (19/62) had CD4 + ≥200 cells/μL, and 55.3% (21/38) had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4+ counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds). Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29) had no GI symptoms and 44.4% (8/18) had no oral candidiasis. Median CD4+ counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04). Conclusions Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.

Endoscopic features and management of diminutive colorectal submucosal invasive carcinoma.

The vast majority of diminutive (∼5 mm) colorectal tumors consist of a very low prevalence of advanced neoplasia, and a predict‐resect‐and‐discard policy has been proposed recently in Western countries. The histology of some diminutive colorectal tumors reveals carcinoma, not adenoma, although the frequency is relatively low. Clarifying the endoscopic features of diminutive submucosal invasive colorectal carcinoma (CRC) during colonoscopy is important for managing diminutive lesions.

Predictive Clinical Factors in the Diagnosis of Gastrointestinal Kaposi's Sarcoma and Its Endoscopic Severity

Background The diagnosis of gastrointestinal (GI) involvement in Kaposis sarcoma (KS) is important to make because the need for treatment depends on the extent of the disease. Moreover, severe GI lesions can cause serious complications. Endoscopy with biopsy is an extremely useful method to diagnose GI-KS. However, determining the indications for endoscopy is difficult because KS can occur without GI symptoms or cutaneous KS. This study sought to clarify predictive clinical factors for GI-KS and its severity on endoscopy. Methodology/Principal Findings A total of 1,027 HIV-infected patients who underwent endoscopy were analyzed. Sexual behavior, CD4 count, HIV RNA, history of highly active antiretroviral therapy (HAART), GI symptoms, and cutaneous KS were assessed. Endoscopic severity including bulky tumor, ulceration, and number of lesions were evaluated. Thirty-three patients had GI-KS and 46 patients cutaneous KS. Among the GI-KS patients, 78.8% (26/33) had no GI symptoms and 24.2% (8/33) had no cutaneous KS. Univariate analysis identified men who have sex with men (MSM), CD4 <100 cells/µL, HIV RNA ≥10,000 copies/mL, no history of HAART, and cutaneous KS were significantly associated with GI-KS. Among these factors, cutaneous KS was closely related to GI-KS on multivariable analysis. Among patients without cutaneous KS, MSM and CD4 count <100 cells/µL were the only independent clinical factors related to GI-KS. Bulky tumor was significantly associated with CD4 <100 cells/µL and large number of lesions was significantly associated with HIV-RNA ≥10,000 copies/mL. Conclusions To diagnose GI-KS, clinical factors need to be considered before endoscopy. The presence of GI symptoms is not useful in predicting GI-KS. MSM and CD4 count <100 cells/µL are predictive factors among patients without cutaneous KS. Caution should be exercised especially in patients with low CD4 counts or high HIV viral loads as they are more likely to develop severe GI-KS lesions.

Impact of HIV infection on colorectal tumors: a prospective colonoscopic study of Asian patients.

Background:Non-AIDS defining cancer has recently become a major problem in HIV-infected patients. Little has been reported on whether HIV infection is a risk factor for colorectal adenoma, especially in Asians. Methods:The study was conducted under a prospective cross-sectional design and included all adults who underwent colonoscopy. Subjects were matched by age and sex to compare the prevalence of colorectal adenoma, adenocarcinoma, polyps, and other tumors. Detailed risk factors were assessed, including lifestyle habits, medications, comorbidities, gastrointestinal symptom rating scale, HIV-associated factors, and human papillomavirus infection. To evaluate the effects of HIV infection on adenoma, the odds ratio (OR) was estimated by multivariate logistic regression. Results:A total of 177 HIV-infected patients and 177 controls were selected for analysis. No significant difference was noted in the prevalence of adenoma (n = 29 vs. 40, P = 0.14). Multivariate analysis adjusted by baseline demographics and risk factors showed that HIV is not associated with increased risk of adenoma (adjusted OR = 0.66, P = 0.16). Kaposi’s sarcoma was more common in HIV-infected patients (n = 6 vs. 0, P = 0.03). Among HIV-infected patients, advanced age was an independent and significant risk factor for adenoma (adjusted OR = 2.28, P < 0.01). CD4 count, HIV-RNA, history of antiretroviral treatment, and oncogenic human papillomavirus infection were not risk factors for adenoma. Conclusions:HIV infection was not identified as risk for adenoma in Asian patients. However, advanced age was independently associated with increased risk of adenoma. HIV-infected patients should not miss screening opportunity for colorectal adenoma and other gastrointestinal malignancies.

Clinical usefulness of a single-use splinting tube for poor endoscope operability in deep colonic endoscopic submucosal dissection

Background and study aims: Poor endoscope operability remains a significant challenge during colorectal endoscopic submucosal dissection (ESD). We retrospectively evaluated the experience and clinical usefulness of a new single-use splinting tube in deep colonic ESD in the setting of poor scope operability. Patients and methods: Among 691 patients with colorectal tumors treated with ESD at Hiroshima University Hospital between November 2009 and July 2015, we analyzed 20 consecutive patients who underwent deep colonic ESD using a single-use splinting tube because of poor scope operability. Poor operability was defined as paradoxical movement of the endoscope, poor control with adhesions, and lesion motion with heartbeat or breathing. Technical and clinical success rates and adverse events were assessed. Results: Paradoxical movement and poor control with adhesions were improved in all cases using the single-use splinting tube. The en bloc resection rate was 95 % (19/20) and histological en bloc resection rate was 100 % (20/20). There were no complications related to use of the splinting tube. Conclusions: Use of a single-use splinting tube helped to overcome poor scope operability in deep colonic ESD.

Assessment of Antigenemia Assay for the Diagnosis of Cytomegalovirus Gastrointestinal Diseases in HIV-Infected Patients

We conducted a single-center prospective study to evaluate the utility of cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV-gastrointestinal disease (GID). The study subjects were HIV-infected patients with CD4 count ≤200 μL/cells who had undergone endoscopy. A definite diagnosis of CMV-GID was made by histological examination of endoscopic biopsied specimen. CMV antigenemia assay (C10/C11 monoclonal antibodies), CD4 count, HIV viral load, history of HAART, and gastrointestinal symptoms as measured by 7-point Likert scale, were assessed on the same day of endoscopy. One hundred cases were selected for analysis, which were derived from 110 cases assessed as at high-risk for CMV-GID after endoscopy screening of 423 patients. Twelve patients were diagnosed with CMV-GID. Among the gastrointestinal symptoms, mean bloody stool score was significantly higher in patients with CMV-GID than in those without (2.5 vs. 1.7, p=0.02). The area under the receiver-operating characteristic curve of antigenemia was 0.80 (95%CI 0.64-0.96). The sensitivity, specificity, positive likelihood ratio (LR), and negative LR of antigenemia were 75.0%, 79.5%, 3.7, and 0.31, respectively, when the cutoff value for antigenemia was ≥1 positive cell per 300,000 granulocytes, and 50%, 92.0%, 5.5, and 0.55, respectively, for ≥5 positive cells per 300,000 granulocytes. In conclusion, CMV antigenemia seems a useful diagnostic test for CMV-GID in patients with HIV infection. The use of ≥5 positive cells per 300,000 granulocytes as a cutoff value was associated with high specificity and high positive LR. Thus, a positive antigenemia assay with positive endoscopic findings should allow the diagnosis of CMV-GID without biopsy.

Polyglycolic acid sheet application for intractable acute hemorrhagic rectal ulcer

Acute hemorrhagic rectal ulcer is commonly encountered in elderly patients with severe comorbidities. The bleeding form the ulcer is potentially life-threatening. Takimoto et al. reported a novel endoscopic tissue shielding method using polyglycolic acid sheets (Neoveil; Gunze, Kyoto, Japan) and fibrin glue (Beriplast P Combi-Set; CSL Behring Pharma, Tokyo, Japan). A 57-year-old woman presented with acute precordial pain and was diagnosed with acute type A aortic dissection, for which she underwent emergency surgery. She had a history of hypertension and chronic kidney disease with dialysis. She unexpectedly developed a large amount of rectal bleeding 10 days after the operation with hypovolemic shock. Colonoscopy (CS) revealed a semicircular rectal ulcer with spurting bleeding. Although coagulation using hemostatic forceps was performed (Fig. 1a), re-bleeding occurred. Repeat CS identified another bleeding point on the ulcer. Ultimately, endoscopic hemostasiswas performed 19 times over 2months, but definitive hemostasis could not be achieved. Total parenteral nutrition was administered during the fasting period.