Interobserver agreement in detection of "white globe appearance" and the ability of educational lectures to improve the diagnosis of gastric lesions.

BACKGROUND: White globe appearance (WGA) refers to a small white lesion of globular shape underneath cancerous gastric epithelium that can be clearly visualized by magnifying endoscopy with narrowband imaging (M-NBI). WGA has been reported to be a novel endoscopic marker that is highly specific in differentiating early gastric cancer (GC) from low-grade adenoma, and has a significantly higher prevalence in early GCs than in noncancerous lesions. However, interobserver agreement in detecting WGA and whether training intervention can improve diagnostic accuracy are unknown. METHODS: Twenty sets of M-NBI images were examined by 16 endoscopists. The endoscopists attended a lecture about WGA, and examined the images again after the lecture. Interobserver agreement in detecting WGA in the second examination and increases in the proportion of correct diagnoses and the degree of confidence of diagnoses of cancerous lesions were evaluated. RESULTS: The kappa value for interobserver agreement in detecting WGA in the second examination was 0.735. The proportion of correct diagnoses was significantly higher in the second examination compared with the first examination when WGA was present (95.5% vs 55.4%; P < 0.001), but not when WGA was absent (61.6% vs 52.7%; P = 0.190). The proportion of correct diagnoses with a high degree of confidence was significantly higher in the second examination, both with WGA (91.1% vs 29.5%; P < 0.001) and without WGA (36.6% vs 20.5%; P = 0.031). CONCLUSIONS: The detection of WGA by endoscopists was highly reproducible. A brief educational lecture about WGA increased the proportion of correct diagnoses and the degree of confidence of diagnoses of GC with WGA.

White globe appearance is a novel specific endoscopic marker for gastric cancer: A prospective study.

BACKGROUND AND AIM: White globe appearance (WGA) is a small white lesion with a globular shape that can be identified by magnifying endoscopy with narrow-band imaging (M-NBI). WGA was recently reported as a novel endoscopic marker that can differentiate between gastric cancer (GC) and low-grade adenoma. However, the usefulness of WGA for differentiating GC from non-cancerous lesions (NC), including those of gastritis, is unknown. METHODS: To compare the prevalence of WGA in GC and NC, we carried out a prospective study of 994 patients undergoing gastroscopy. All patients were examined for target lesions that were suspected to be GC. When a target lesion was detected, the presence or absence of WGA in the lesion was evaluated using M-NBI, and all target lesions were biopsied or resected for histopathological diagnosis. Primary endpoint was a comparison of WGA prevalence in GC and NC. Secondary endpoints included WGA diagnostic performance for diagnosing GC. RESULTS: A total of 188 target lesions from 156 patients were analyzed for WGA, and histopathological diagnoses included 70 cases of GC and 118 cases of NC. WGA prevalence in GC and NC was 21.4% (15/70) and 2.5% (3/118), respectively (P < 0.001). WGA diagnostic accuracy, sensitivity, and specificity for detecting GC were 69.1%, 21.4%, and 97.5%, respectively. CONCLUSIONS: WGA prevalence in GC is significantly higher than that in NC. Because WGA is highly specific for GC, the presence of WGA is useful to diagnose GC.

Can flat-type brownish microlesions in the orohypopharynx be followed up without biopsy or endoscopic resection?

BACKGROUND: Narrow-band imaging (NBI) is useful for detecting superficial oropharyngeal lesions. However, the diagnostic and treatment guidelines for NBI are not established. The aim of the present study was to evaluate the treatment strategy for these microlesions. METHODS: From October 2008 to September 2009, 68 flat-type brownish microlesions were observed in the orohypopharynx using NBI. Lesions were examined via magnifying NBI (M-NBI) and followed up without biopsy or endoscopic resection for >12 months. To clarify the characteristics, lesions were compared with the endoscopic characteristics of flat-type lesions diagnosed by biopsy and endoscopic resection as squamous cell carcinoma and high-grade intraepithelial neoplasia. RESULTS: The average diameter of the 68 lesions was 1.6 mm (range, 0.5-5 mm). At the 1-year follow up, 19 lesions had disappeared. No size increases or morphological changes wereobserved among 49 lesions followed for >1 year. At 2 years, 10 patients had dropped out and 11 lesions had disappeared. No changes were observed among 28 lesions followed for >2 years. Of the flat-type lesions as squamous cell carcinoma and high-grade intraepithelial neoplasia, a distinct border and irregular distribution of atypical vessels were observed in all cases using M-NBI. These findings were observed in two of 68 flat-type brownish microlesions during follow up. CONCLUSION: Although there is some possibility of squamous cell carcinoma or high-grade intraepithelial neoplasia, flat-type microlesions of ≤5 mm diameter in the orohypopharynx may be followed for up to 2 years without biopsy or endoscopic resection.

[Solitary pulmonary metastasis of low-grade uterine endometrial stromal sarcoma resected 31 years before].

A 74-year-old female underwent hysterectomy and bilateral ovariectomy for uterine endometrial stromal sarcoma( ESS), low grade, at another hospital 31 years previously. When the patient was admitted for pneumonia, a lung tumor was pointed out on her chest X-ray and computed tomography( CT) scan. Chest X-ray showed an oval figure shadow of about 3.5 cm in diameter in the right lower lung field.Chest CT scan revealed an irregular form tumor of 3.5 cm in diameter in the right S8 of the lung. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan identified an abnormal accumulation of FDG at the tumor site. A pulmonary metastasis of the ESS was suspected by transbronchial lung biopsy, and the patient underwent the thoracoscopic partial resection of the right lower lobe of the lung.Histologically, the tumor was diagnosed as metastasis of the ESS, low grade.

Fatal arrythmia in a young man after COVID-19 vaccination: An autopsy report.

RATIONALE: The benefits of COVID-19 mRNA vaccination are claimed to be substantial; however, vaccination-related myocarditis and pericarditis have also been observed globally, particularly among young men. In most cases, the symptoms are mild and resolve on their own; however, fatal cases have rarely been described. PATIENT CONCERNS: A healthy 40-year-old Japanese man suddenly experienced tachycardia and lost consciousness 2 days after vaccination. Continued resuscitation recovered the spontaneous heartbeat; however, the patient did not regain consciousness and died 9 days later. Electrocardiography after resuscitation showed marked ST-segment depression and incomplete right bundle branch block. Influenza antigen and polymerase chain reaction tests for SARS-CoV-2 were negative. DIAGNOSES: Fatal arrhythmia after a second COVID-19 mRNA vaccination. INTERVENTIONS: We performed an autopsy and studied the material morphologically and immunohistochemically. OUTCOMES: At autopsy, several small inflammatory foci with cardiomyocytic necrosis were scattered in the right and left ventricles, with a propensity for the right side. Some inflammatory foci were located near the atrioventricular nodes and His bundles. The infiltrating cells predominantly consisted of CD68-positive histiocytes, with a small number of CD8-positive and CD4-positive T cells. In this case, myocarditis was focal and mild, as is mostly observed following COVID-19 mRNA vaccination. However, the inflammatory foci were close to the conduction system and were considered the cause of fatal arrhythmia. LESSONS: Although the benefits of COVID-19 vaccination appear to outweigh the side effects, it should be noted that fatal arrhythmias may rarely occur, and caution should be taken if individuals, particularly young men, complain of any symptoms after vaccination.

Ureteral Metastasis of Colonic Adenocarcinoma with Enteroblastic Differentiation: A Rare Case to be Distinguished from Clear Cell Adenocarcinoma of the Urinary Tract.

Adenocarcinomas with enteroblastic differentiation are rare clear cell tumors that are positive for enteroblastic markers. Enteroblastic differentiation is particularly uncommon in colorectal adenocarcinomas. Herein, we report a case of clear cell adenocarcinoma with enteroblastic differentiation in the sigmoid colon of a 38-year-old Japanese woman that metastasized to the lower left ureter. After neoadjuvant chemotherapy, the patient underwent low anterior resection. The tumor consisted of tubular, cribriform, and focal micropapillary proliferation of clear cells immunopositive for spalt-like transcription factor 4 (SALL4), glypican 3, and alpha-fetoprotein. Six months after the colonic resection, a tumor was found in the left lower ureter, which was resected. The ureteral tumor revealed clear cell adenocarcinoma, which was identical to the colonic tumor proliferating in the ureteral mucosa. Metastatic ureteral tumors are rare. We performed a literature search and found only 50 reported cases of ureteral metastases from colorectal cancer. Of these, only 10 metastatic tumors were identified in the ureteral mucosa. No case of ureteral metastasis of clear cell colorectal adenocarcinoma or colorectal adenocarcinoma with enteroblastic differentiation has been reported. Hence, it can be challenging to distinguish them from clear cell adenocarcinoma of the urinary tract and/or clear cell urothelial carcinoma. This paper discussed the differential diagnosis of these tumors and reviewed the clinicopathological features of colorectal carcinomas metastasizing to the ureter.

Can magnifying endoscopy with narrow band imaging be useful for low grade adenomas in preoperative biopsy specimens?

BACKGROUND: In biopsy specimens with low grade adenomas, it is often difficult to identify the presence of high grade adenomas or early carcinomas and low grade adenomas preoperatively, and clear guidelines have not yet been defined for the applicability of endoscopic treatment to low grade adenomas identified in biopsy specimens. METHODS: We aimed to clarify the usefulness of magnifying endoscopy with narrow band imaging (NBI) compared to conventional white light endoscopy for diagnosing actual high grade adenomas or early carcinomas with low grade adenomas, using the VS (microvascular pattern [V] and microsurface pattern [S]) classification for low grade adenomas in biopsy specimens. The study cohort consisted of 135 patients who were diagnosed with low grade adenomas in preoperative biopsy specimens and received endoscopic submucosal dissection. RESULTS: In the elevated type of lesion, magnifying endoscopy with NBI diagnosed high grade adenomas or early carcinomas at a higher sensitivity and specificity than conventional white light endoscopy (82.4 vs. 70.6%, P = 0.391, 97.3 vs. 54.7%, P < 0.0001). In the depressed macroscopic type of lesion, magnifying endoscopy with NBI also diagnosed high grade adenomas or early carcinomas at a higher sensitivity (95.5 vs. 68.2%, P = 0.0459) than conventional white light endoscopy. Although the specificity was high, at 100%, the difference when compared to conventional white light endoscopy was not significant (100 vs. 100%, P > 0.99). CONCLUSIONS: For low grade adenomas in biopsy specimens, it is vital to take sufficient consideration of endoscopic findings and not take action based only on the biopsy results. If a decision is made using the VS classification with magnifying endoscopy with NBI, actual high grade adenomas or early carcinomas can be differentiated from low grade adenomas so that endoscopic treatment can be performed more strictly.

[A case of disseminated carcinomatosis of bone marrow treated by S-1 and cisplatin after distal gastrectomy for early gastric cancer].

Patients with bone metastasis originating from gastric cancer experience complications from DIC. They are treated with anticoagulation therapy or platelet transfusion, but their prognosis is poor. Our case was a 50-year-old male who had undergone distal gastrectomy for early gastric cancer[pT1a(M)N0M0, pStage I a]ten years previously. He was admitted to our hospital complaining of backache. As a result of his examination, he was diagnosed with disseminated carcinosis of bone marrow with DIC as a postoperative recurrence of gastric cancer. The patient was treated with combination chemotherapy of S-1 and cisplatin(S-1 80 mg/body, po, day 1-21 and cisplatin 50mg/body, iv, day 8). After one course of treatment, DIC was resolved and his pain was relieved. He survived for about nine months. S-1 and cisplatin are considered to be effective for disseminated carcinosis of bone marrow.

Verification of the eighth edition of the UICC-TNM classification on surgically resected lung adenocarcinoma: Comparison with previous classification in a local center.

BACKGROUND: The UICC 8th TNM classification of lung cancer has been changed dramatically, especially in measuring methods of T-desriptors. Different from squamous- or small-cell carcinomas, in which the solid- and the invasive-diameter mostly agree with each other, the diameter of the radiological solid part and that of pathological invasive part in adenocarcinomas often does not match. AIM: We aimed to determine radiological and pathological tumor diameters of pulmonary adenocarcinomas with clinicopathological factors and evaluate the validity of the 8th edition in comparison with the 7th edition. METHODS AND RESULTS: We retrospectively analyzed clinicopathological factors of 429 patients with surgically resected pulmonary adenocarcinomas. The maximum tumor and their solid-part diameters were measured using thin-sectioned computed tomography and compared with pathological tumor and invasive diameters. Overall survival (OS) rate was determined using the Kaplan-Meier method for different subgroups of clinicopathological factors. Akaike's information criteria (AIC) was used as a discriminative measure for the univariate Cox model for the 7th and 8th editions. Multivariate Cox regression analysis was performed to explore independent prognostic factors. Correlation coefficients between radiological and pathological diameters in the 7th and 8th editions were 0.911 and 0.888, respectively, without a significant difference. The major reasons for the difference in the 8th edition were the presence of intratumoral fibrosis and papillary growth pattern. The weighted kappa coefficients in the 8th edition were superior those in the 7th edition for both the T and Stage classifications. In the univariate Cox model, AIC levels were the lowest in the 8th edition. Multivariate analysis revealed that age, lymphovascular invasion, pT(8th), and stage were the most important determinants for OS. CONCLUSION: The UICC 8th edition is a more discriminative classification than the 7th edition. For subsolid nodules, continuous efforts are necessary to increase the universality of the measurement of solid and invasive diameters.

An Intrahepatic Cholangiocarcinoma with Focal Rhabdoid Features and SMARCA4-Deficiency.

Intrahepatic cholangiocarcinoma with rhabdoid morphology is rare, and only three case reports have been published to date, none of which discuss the genetic changes in the rhabdoid component. We present a case of intrahepatic cholangiocarcinoma with focal rhabdoid features and SMARCA4-deficiency detected using immunohistochemistry. A Japanese man in his 60s without viral hepatitis was diagnosed with an avascular tumor in the liver, measuring 4.4 cm in the greatest dimension. The tumor was mostly composed of moderately differentiated adenocarcinoma, focal poorly differentiated adenocarcinoma, and an undifferentiated rhabdoid component. Immunohistochemical analysis showed an inclusion-like staining pattern for keratin AE1/AE3 and vimentin in the rhabdoid component. BRG1/SMARCA4 was detected in the differentiated component but not in the poorly- and undifferentiated components. Our novel findings reflecting the morphological and genetic heterogeneity of intrahepatic cholangiocarcinoma and will aid the research on drugs targeting the aberrant SWItch/Sucrose NonFermentable complex.

Resection depth and layer of underwater versus conventional endoscopic mucosal resection of intermediate-sized colorectal polyps: A pilot study.

Background and study aims Curability of colorectal tumors is associated with resection depth and layer in endoscopic resection. Underwater endoscopic mucosal resection (UEMR) has not undergone sufficient histopathological evaluation. We conducted a pilot study to compare the effectiveness, including resection depth and layer, of UEMR and conventional endoscopic mucosal resection (CEMR). Patients and methods This study was a single-center, retrospective study. Patients with colorectal lesions were treated by UEMR or CEMR between January 2018 and March 2020. Eligible patients were selected from included patients in a 1:1 ratio using propensity score matching. We compared the resection depth and layer and treatment results between the UEMR and CEMR groups. Results We evaluated 55 patients undergoing UEMR and 291 patients undergoing CEMR. Using propensity score matching, we analyzed 54 lesions in each group. The proportion of specimens containing submucosal tissue was 100 % in both groups. The median thickness of the submucosal tissue was significantly greater in the CEMR group than in the UEMR group [1235 µm (95 % confidence interval [CI], 1020-1530 µm) vs. 950 µm (95 % CI, 830-1090 µm), respectively]. However, vertical margins were negative in all lesions in both groups. Conclusions Our findings suggest that the median thickness of submucosal tissue in the UEMR group was about 1,000 µm. Even though the resection depth achieved with UEMR was more superficial than that achieved with CEMR, UEMR may be a treatment option, especially for colorectal lesions ≤ 20 mm in diameter without suspicious findings of submucosal deeply invasive cancer.

[A case of pulmonary benign metastasizing leiomyoma from the uterus].

We report here a case of pulmonary benign metastasizing leiomyoma (BML) from the uterus. A 48-year-old woman was admitted to our hospital because of multiple pulmonary nodules on the chest radiograph 7 years after total hysterectomy with removal of the left ovarium for uterine leiomyoma. A specimen of the lesion obtained by a thoracoscopic lung biopsy was consistent with leiomyoma. Histological re-evaluation of the uterine myoma showed similar histology as compared with the lung tumor. Immunohistological staining for both estrogen and progesterone receptors on the lung tissue was positive. Based on these results, we diagnosed the pulmonary lesions as BML. The patient received no treatment and has shown no evidence of exacerbation of disease during 6 years of follow up.

Does previous biopsy lead to cancer overdiagnosis of superficial non-ampullary duodenal epithelial tumors?

Background and study aims We aimed to evaluate the diagnostic performance of magnifying endoscopy with narrow-band imaging (M-NBI) in superficial non-ampullary duodenal epithelial tumors (SNADETs) regarding the absence or presence of biopsy before M-NBI diagnosis. Patients and methods Clinicopathological data were retrospectively reviewed for 99 SNADETs from 99 patients who underwent endoscopic resection. The 99 tumors were divided into the non-biopsy group (32 lesions not undergoing biopsy before M-NBI examination) and the biopsy group (67 lesions undergoing biopsy before M-NBI examination). We investigated the correlation between the M-NBI diagnosis and the histopathological diagnosis of the SNADETs in both groups. Results According to the modified revised Vienna classification, 31 tumors were classified as category 3 (C3) (low-grade adenoma) and 68 as category 4/5 (C4/5) (high-grade adenoma/cancer). The accuracy, sensitivity, and specificity of preoperative M-NBI diagnoses in the non-biopsy group vs the biopsy group were 88 % (95 % confidence interval: 71.0 - 96.5) vs 66 % (51.5 - 75.5), P  = 0.02; 95 % (77.2 - 99.9) vs 89 % (76.4 - 96.4), P  = 0.39; and 70 % (34.8 - 93.3) vs 14 % (3.0 - 36.3), P  < 0.01, respectively. Notably, in the biopsy group, the specificity of M-NBI in SNADETs was low at only 14 % because we over-diagnosed most C3 lesions as C4/5. M-NBI findings might have been compromised by the previous biopsy procedure itself. Conclusions In the non-biopsy group, the accuracy of M-NBI in SNADETs was excellent in distinguishing C4/5 lesions from C3. The M-NBI findings in SNADETs should be evaluated while carefully considering the influence of a previous biopsy.

Colitis induced by Lenvatinib in a patient with advanced hepatocellular carcinoma.

Lenvatinib is a standard molecular targeted agent for the first-line treatment of unresectable hepatocellular carcinoma. Here, we report a case of colitis induced by Lenvatinib treatment in a patient with hepatocellular carcinoma. A 78-year-old man previously treated with Lenvatinib for unresectable hepatocellular carcinoma was admitted to our hospital complaining of right lateral abdominal pain without diarrhea. Our endoscopic findings showed multiple ulcers and erosions on his ascending colon, and he was diagnosed with colitis induced by Lenvatinib treatment. After the discontinuation of Lenvatinib, his colitis improved, and he resumed Lenvatinib at a lower dose. Colitis is a rare adverse event of Lenvatinib, and this is the first detailed report of colitis induced by Lenvatinib with endoscopic findings.

White globe appearance is an endoscopic predictive factor for synchronous multiple gastric cancer.

BACKGROUND: White globe appearance (WGA) is a small white lesion with a globular shape identified during magnifying endoscopy with narrow-band imaging. However, the association between WGA and synchronous multiple gastric cancer (SMGC) remains unclear. METHODS: Consecutive patients who underwent endoscopic submucosal dissection for gastric cancer (GC) between July 2013 and April 2015 at our institution were eligible for this study. We excluded patients with a history of gastric tumor or gastrectomy. Patients who had more than 2 GCs in their postoperative pathological evaluation were classified as SMGC-positive, and patients who had at least 1 WGA-positive GC were classified as WGA-positive patients. The primary outcome was a comparison of the prevalence of WGA in patients classified as SMGC-positive and SMGC-negative. Univariate and multivariate analyses were performed using the following variables: WGA, age, sex, atrophy, and Helicobacter pylori (H. pylori) status. RESULTS: There were 26 and 181 patients classified as SMGC-positive and SMGC-negative, respectively. Univariate analysis revealed that WGA-positive classification (50% vs. 23%, P=0.008) and male sex (88% vs. 66%, P=0.02) were significant factors associated with SMGC classification, while age ≥65 years (81% vs. 81%, P>0.99), severe atrophy (46% vs. 46%, P>0.99), and H. pylori positivity (69% vs. 65%, P=0.8) were not. In the multivariate analysis, only WGA-positive classification (odds ratio 2.78, 95% confidence interval 1.16-6.67; P=0.02) was a significant independent risk factor for SMGC. CONCLUSIONS: Our exploratory study showed the possibility of WGA as a predictive factor for SMGC. In cases of WGA-positive gastric cancer, careful examination might be needed to diagnose SMGC.