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.

Detection of pharyngeal cancer in the overall population undergoing upper GI endoscopy by using narrow-band imaging: a single-center experience, 2009-2012.

BACKGROUND: Nonmagnifying observation by using narrow-band imaging (NBI) is useful for detecting pharyngeal lesions. Magnifying observation by using NBI can distinguish between cancerous and noncancerous lesions and is therefore useful for the early detection of pharyngeal cancer. OBJECTIVE: To evaluate the usefulness of observation of the pharynx by using NBI in the overall population undergoing upper GI endoscopy. DESIGN: Retrospective study. SETTING: Single tertiary referral center. PATIENTS: A total of 11,050 upper GI endoscopies between January 2009 and December 2012. INTERVENTIONS: Observation of the pharynx by using NBI. MAIN OUTCOME MEASURES: The rate of detection of pharyngeal cancer, the rates of detection according to the reason for endoscopy, and the types of cancers detected. RESULTS: Thirty-eight cancerous lesions were detected in 29 patients (0.26%, 29/11,050). The rate of detection of pharyngeal cancer was significantly higher in patients with a history of head and neck cancer (9.7%, 3/31) or a history of esophageal cancer (3.5%, 10/282). In patients undergoing endoscopy for screening, pharyngeal discomfort, and a history of gastric cancer, the rates of detection of pharyngeal cancer were 0.11% (10/8872), 1.1% (3/265), and 0.19% (3/1600), respectively. Two patients (6.9%) were female. One had a history of esophageal cancer, and the other had pharyngeal discomfort. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Observation of the pharynx by using NBI in patients with previous head and neck cancer or esophageal cancer or who have pharyngeal discomfort is very important. Moreover, pharyngeal cancer was certainly found in the male patients undergoing screening endoscopy, although the rate was lower.

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.

[An autopsy case of pulmonary tumor thrombotic microangiopathy that occurred during chemotherapy for gastric cancer].

A man in 60s underwent total gastrectomy for advanced gastric cancer with para-aortic lymph node metastases. Although postoperative chemotherapy decreased the metastases, he was subsequently admitted with progressive respiratory distress. Pulmonary hypertension and right-sided heart failure developed, and he died of sudden cardiopulmonary arrest 30 hours after admission. Autopsy revealed widespread tumor embolism, fibrocellular intimal proliferation, and thrombus formation in the small arteries, consistent with a diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM) associated with gastric cancer. Although PTTM a rare clinicopathological entity that causes severe pulmonary hypertension, it should be considered as a differential diagnosis for acute dyspnea or pulmonary hypertension in patients with carcinoma, regardless of clinical improvement.

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.

Solitary pleural metastasis in rectal cancer.

Pleural metastasis in rectal cancer is often due to secondary invasion or dissemination from intrapulmonary metastases. To date, there are no reports on solitary pleural metastasis. Here, we report a rare case of lower rectal cancer that recurred as pleural metastasis 4 years after surgical resection of the primary tumor. He was a 65-year-old man who visited our department with an abnormal shadow on his chest X-ray. He had a history of lower rectal cancer and had undergone laparoscopic low anterior resection of the rectum and bilateral lymph node dissection after neoadjuvant chemotherapy. Pathological ypT3N1M0 stage IIIA tumor was diagnosed, and adjuvant chemotherapy was administered. According to the computed tomography scan, a pleural tumor or pulmonary metastasis was suspected. Thoracoscopic partial resection of the lung and a partial pleurectomy were performed for diagnostic and therapeutic purposes. Histopathological examination revealed a highly differentiated tubular adenocarcinoma, consistent with metastatic rectal cancer. The nodule arose from the visceral pleura and invaded the parietal pleura with few malignant cells in the lung parenchyma. The lesion was surgically resected. However, 3 months after the second surgery, tumor recurrence with pleural dissemination was observed, and chemotherapy was initiated.

[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.

Epithelial-mesenchymal transition induced by biliary innate immunity contributes to the sclerosing cholangiopathy of biliary atresia.

Infections of Reoviridae consisting of a double-stranded RNA (dsRNA) genome and the biliary innate immune response to dsRNA are implicated in the aetiopathogenesis of biliary atresia (BA). Epithelial-mesenchymal transition (EMT) has recently been proposed as a mechanism behind the sclerosing cholangitis in BA. We hypothesized that the innate immune response to dsRNA in biliary epithelial cells plays an important role in peribiliary fibrosis via biliary EMT. Experiments using cultured human biliary epithelial cells revealed that stimulation with poly(I : C) (a synthetic analogue of viral dsRNA) increased the expression of basic fibroblast growth factor (bFGF, an EMT-inducer), S100A4 (a mesenchymal marker) and Snail (a transcriptional factor), and decreased that of epithelial markers (biliary-type cytokeratin 19 and E-cadherin) and Bambi (TGF-beta1 pseudoreceptor). The expression of TGF-beta1 (EMT-inducer) and vimentin (a mesenchymal marker) was not affected by poly(I : C). Both EMT-inducers, bFGF and TGF-beta1, evoked a decrease and increase in the expression of the epithelial markers and of vimentin respectively, and the expression of Bambi was down-regulated on stimulation with bFGF. Combined treatment with bFGF and TGF-beta1 quickly and completely induced a transformation of morphology as well as change from epithelial to mesenchymal features in cultured biliary epithelial cells. Immunohistochemistry revealed that biliary epithelial cells lining extrahepatic bile ducts and peribiliary glands in BA frequently show a lack of epithelial markers and an aberrant expression of vimentin. Moreover, the biliary epithelium showing sclerosing cholangitis expressed bFGF accompanied by bFGF-positive mononuclear cells. In conclusion, the EMT may contribute to the histogenesis of sclerosing cholangiopathy, and the biliary innate immune response to dsRNA viruses induces biliary epithelial cells to undergo EMT via the production of bFGF and the increased susceptibility to TGF-beta1 caused by the down-regulation of Bambi expression.

An Autopsy Case of Idiopathic Pleuroparenchymal Fibroelastosis with Left Vocal Cord Paralysis and a Rapid Deterioration without an Acute Exacerbation.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a generally slow-progressing rare disorder of unknown etiology. The direct cause of death in cases of IPPFE is rarely investigated. We experienced an autopsy case of a Japanese man with IPPFE and found aspiration pneumonia to be the major trigger of death. The individual had left vocal cord paralysis at admission, which may have contributed to aspiration pneumonia, and which probably was affected by the fibrous adhesion of the left apex of the chest wall resulting from IPPFE. The prevention of aspiration pneumonia is important for maintaining the respiratory function, especially in IPPFE patients with repeated pneumothorax.

Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis.

AIM: Serum antinuclear antibodies (ANA) are occasionally noted in patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH. METHODS: We compared clinicopathological features in patients with ANA-positive NASH (n = 35) and ANA-negative NASH (n = 36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. RESULTS: ANA-positive NASH was significantly associated with female gender (P = 0.005), high degree of portal inflammation (P = 0.039), interface activity (P = 0.036) and hepatocellular ballooning (P = 0.0008). In addition, ANA of high titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (P = 0.02). The degree of steatosis wais rather mild in the high-titer ANA group(P = 0.01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in the portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. CONCLUSION: These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanism may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis.

[Squamous cell carcinoma of the bladder treated with a new combined chemotherapy regimen, intraarterial nedaplatin and pirarubicin plus intravenous methotrexate and vincristine--second case report in Japan].

We report our second patient treated successfully with a new combined chemotherapy regimen of intra-arterial pirarubicin and nedaplatin plus intravenous methotrexate and vincristine for squamous cell carcinoma (SCC) of the bladder. A 57-year-old man consulted our hospital in September 2005 for treatment of bladder tumors diagnosed in another hospital. Magnetic resonance imaging (MRI) showed an extravesical invasive tumor on the anterior wall of the bladder, and clinical stage T2bN0M0 was diagnosed. Transurethral cold-cup biopsy was performed, and pathological examination revealed SCC. After he received two courses of this new combined intra-arterial chemotherapy regimen using nedaplatin, tumors were detected in MRI and cystoscopy. We performed partial cystectomy in January 2006. Postoperative pathological examination revealed no tumor cells (pathological CR). There were no severe adverse reactions by this chemotherapy regimen. He has been alive without evidence of disease.