Optimizing Organ-Preservation Strategies Through Chemotherapy-Based Selection in Esophageal Squamous Cell Carcinoma: Results From the CROC Multi-Institutional Phase 2 Clinical Trial.

PURPOSE: This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Chemotherapy-naïve patients with resectable ESCC (stage IB-III, Union for International Cancer Control, International Cancer Control seventh edition) were eligible for the study. All patients received 3 cycles of docetaxel, cisplatin, and 5-FU (DCF) therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every 3 weeks). Remarkable response was defined as a reduction in the tumor to T1, metastatic lymph nodes <1 cm on the short axis, and downstaging to stage IA after 3 cycles of DCF therapy. Remarkable responders then underwent dCRT, which included 2 courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1 to 4, repeated every 4 weeks, along with 50.4 Gy of concurrent radiation therapy. The primary endpoint was 1-year progression-free survival in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival. RESULTS: Of the 92 patients registered, 90 were analyzed. A remarkable response to 3 courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range, 1-85 months), the 1-year progression-free survival was 89.8% (95% confidence interval [CI], 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and esophagectomy-free survival rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after 2 courses of DCF therapy was significantly associated with OS (P = .0049). CONCLUSIONS: In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with 3 courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.

Correlation of multiple endpoints in the first-line chemotherapy of advanced gastric cancer: Pooled analysis of individual patient data from Japanese Phase III trials.

BACKGROUND: Individual-level surrogates are important for management in patients treated for advanced gastric cancer (AGC). This study aimed to comprehensively investigate the correlation of multiple clinical endpoints in the first-line chemotherapy of AGC. METHODS: Individual patient data (IPD) were collected from four Japanese Phase III trials comparing S-1-based first-line chemotherapies (SPIRITS, START, GC0301/TOP-002, and G-SOX trials). Patients without Response Evaluation Criteria in Solid Tumors (RECIST)-based radiological assessments were excluded. Spearman's rank correlation coefficient was tested for correlation among overall survival (OS), progression-free survival (PFS), and postprogression survival (PPS). OS, PFS, and PPS were compared between responders (best response: complete response or partial response) and nonresponders (best response: stable disease or progressive disease). RESULTS: The study included a total of 1492 patients. Eighty percent of the patients (n = 1190) received subsequent chemotherapies after the failure of each trial's treatment protocol. PFS moderately correlated with OS (Spearman correlation coefficient = 0.66, p < 0.005), whereas the correlation between PPS and OS was strong (Spearman correlation coefficient = 0.87, p < 0.005). Responders had significantly longer OS (median, 17.7 vs. 9.1 months, p < 0.005), PFS (median, 6.9 vs. 2.8 months, p < 0.005), and PPS (median, 10.5 vs. 6.0 months, p < 0.005) than nonresponders. CONCLUSIONS: Our results reacknowledged the mild surrogacy of PFS and importance of postprogression treatments in patients with AGC receiving first-line chemotherapy. Consistent longer survival outcomes in better RECIST categories suggested that tumor response might be a useful individual-level surrogate.

Detection of Kita-Kyushu Lung Cancer Antigen-1, a Cancer/Testis Antigen, in the Stomach Close to a Cancerous Condition.

Background: Kita-Kyushu lung cancer antigen-1 (KK-LC-1), encoded by CT83, is a cancer/testis antigen (CTA) and an attractive target for immunotherapy. Our previous study demonstrated frequent CT83 expression in gastric cancers (GCs) and non-tumor sites of the stomach with tumors. Additionally, there was a correlation with Helicobacter pylori (Hp) infection. Since it currently remains unclear whether KK-LC-1 is expressed in the stomach without GC, this study investigated KK-LC-1 expression in non-GC stomach. Methods: We investigated differences in CT83 gene expression at non-tumor sites of stomachs with or without tumors in 118 GC patients and 115 non-GC patients. Fisher's exact test was used for statistical analyses. Results: CT83 expression was detected in 77% of non-tumor sites in stomachs with tumors, which was significantly higher than in stomachs without tumors (7%, p < 0.0001). All patients with CT83 expression at non-tumor sites of their stomachs without tumors carried Hp. Conclusion: CT83 appears to be rarely expressed in the atrophic stomach, and furthermore, a part of patients positive for its expression will develop GC in the future, suggesting that CT83 expression is a useful marker for predicting GC.

Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells.

OBJECTIVE: The concept of BRCAness has been proposed as a homologous recombination repair dysfunction triggered by a genetic defect in the BRCA pathway including the BRCA1/2 mutations. A certain number of pancreatic ductal adenocarcinoma (PDAC) patients have BRCAness. However, a large-scale analysis of BRCAness in PDAC has not been performed. In addition, no basic studies have examined the significance of BRCAness in PDAC cell lines. METHODS: Ninety-two patients who underwent surgery for PDAC were enrolled. Formalin-fixed and paraffin-embedded specimens of resected PDACs were used to analyze BRCAness by multiplex ligation-dependent probe amplification. We also analyzed BRCAness in pancreatic cancer cell lines and the sensitivity to cisplatin and olaparib using a colony formation assay. RESULTS: Of the 92 patients with PDAC, 6 were detected to have BRCAness-positive PDAC (6.5%). No significant differences in overall survival and progression-free survival were observed between the BRCAness-positive and BRCAness-negative groups. One PDAC cell line, KP-2, was positive for BRCAness and was more sensitive to cisplatin and olaparib than the BRCAness-negative cell lines. CONCLUSIONS: Our results revealed that a considerable number of PDACs are positive for BRCAness, suggesting that BRCAness status could be a useful biomarker for selecting anticancer treatments for advanced or relapsed PDAC.

Endoscopic re-intervention after stent-in-stent versus side-by-side bilateral self-expandable metallic stent deployment.

BACKGROUND AND AIM: Endoscopic bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is widely performed; however, re-intervention after recurrent biliary obstruction (RBO) is often challenging. We compared stent-in-stent (SIS) and side-by-side (SBS) SEMS placement for MHBO considering re-intervention for RBO. METHODS: One hundred five consecutive patients with MHBO who underwent endoscopic bilateral SEMS placement in our hospital and its affiliated institutions were enrolled in this study; 75 patients underwent partial SIS deployment between December 2005 and December 2012; and 30 underwent SBS deployment between January 2013 and March 2019. Initial treatments and re-interventions in each group were retrospectively evaluated. RESULTS: Technical success rate (92% vs 100%, P = 0.179), procedure duration (46 vs 35 min, P = 0.382), functional success rate (97.1% vs 100%, P = 1.00), complication rate (24.6% vs 20.0%, P = 0.797), time to RBO (260 vs 312 days; Gray test, P = 0.815), and rate of RBO (59.4% vs 70.0%, P = 0.371) were not significantly different between the SIS and SBS groups. However, bilateral re-stenting with plastic stents through SEMS was successful in 63.4% of patients in the SIS group compared with 100% of patients in the SBS group (P = 0.0013). Median time to RBO upon first re-stenting with a plastic stent was 75 days (range, 11-195 days). CONCLUSIONS: Endoscopic re-stenting after RBO was significantly more successful in the SBS group than in the SIS group. SBS method is suitable for MHBO considering revisionary stent placement.

New image-processing technology for endoscopic ultrasound-guided fine-needle aspiration biopsy specimen evaluation in patients with pancreatic cancer.

Objectives: We evaluated the usefulness of a newly developed system with which the total amount of whitish cores in endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) samples is automatically calculated (automated multiband imaging system [AMUS]). Methods: From 30 prospectively enrolled patients suspected of having pancreatic cancer, four EUS-FNAB specimens per patient were obtained. Following AMUS calculations, two specimens were prepared after stereomicroscopy-guided manual division into whitish and reddish sections (isolation group), and the other two were prepared without such division (no-isolation group). The relation of the AMUS results pertaining to the length of the manually measured whitish cores (stereo-microscopically visible white core [SVWC]) and the sample suitability for pathologic evaluation were analyzed. Results: Histological diagnostic accuracy was 90%; median SVWC length, 14 mm; and median area of whitish core calculated using the AMUS, 13 mm2. The SVWC length correlated with whitish core amount (ρ = 0.83, p < 0.01) and adequacy score (ρ = 0.50, p < 0.01). The whitish core amount correlated with the adequacy score (ρ = 0.40, p < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.84 (p < 0.01; cutoff ≥ 8 mm2, sensitivity 92.5%). Subgroup analysis (isolation vs. no-isolation group) revealed no significant between-group differences in the median histological adequacy (p = 0.27) or tumor cell content ratio (p = 0.28). The median scores for degree of blood contamination were significantly lower in the isolation group than in the no-isolation group (p < 0.01). Conclusion: AMUS is a simple on-site verification procedure for determining the appropriate sampling tissue quantity for high diagnostic accuracy.

Usefulness of the automated multiband imaging system for EUS-FNA biopsy specimen evaluation in patients with upper gastrointestinal subepithelial lesions.

Background and Objectives: Sample isolation processing by stereomicroscopy (SIPS) was recently introduced as an alternative to rapid on-site cytologic evaluation and showed high accuracy for use in pathologic diagnoses. SIPS is a useful, but slightly complicated procedure; therefore, a new, more straightforward method for the objective estimation of the core tissue amount required during the sampling is desirable. We evaluated the usefulness of the automated multiband imaging system (AMUS) for calculating whitish core amounts in EUS-FNA biopsy (EUS-FNAB) samples from patients with subepithelial lesions (SELs). Methods: Four EUS-FNAB specimens per patient were obtained from 20 patients with upper gastrointestinal SELs. The correlation between the whitish core amount calculated by AMUS, length of the manually measured whitish cores (stereomicroscopically visible white core [SVWC]), and sample suitability for pathologic evaluation were analyzed. Results: We identified 13 patients with gastrointestinal stromal tumors, five with leiomyomas, one with a schwannoma, and one with an ectopic pancreas. The histological diagnostic accuracy was 100%, median SVWC length was 9 mm, and median whitish core area, calculated using AMUS, was 10 mm2. SVWC length correlated with whitish core amount (ρ = 0.81, P < 0.01) and adequacy score (ρ = 0.54, P < 0.01). Whitish core amount correlated with adequacy score (ρ = 0.54, P < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.83 (P < 0.01; cutoff ≥4 mm2, sensitivity 98.4%). Conclusions: AMUS, a simple on-site verification instrument, is an alternative to SIPS for determining the appropriate SEL tissue sampling quantity with high diagnostic accuracy.

The role of thromboxane prostanoid receptor signaling in gastric ulcer healing.

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A2 (TXA2 ) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA2 in gastric ulcer healing using TXA2 receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA2 synthase inhibitor OKY-046 and the TXA2 receptor antagonist S-1452 compared with vehicle-treated mice. TPKO showed delayed gastric ulcer healing compared with wild-type mice (WT). The number of microvessels and CD31 expression were lower in TPKO than in WT mice, and TPKO suppressed the expression of transforming growth factor beta (TGF-ß) and vascular endothelial growth factor A (VEGF-A) in areas around gastric ulcers. Immunofluorescence assays showed that TGF-ß and VEGF-A co-localized with platelets. Gastric ulcer healing was significantly reduced in WT mice transplanted with TPKO compared with WT bone marrow. These results suggested that TP signalling on platelets facilitates gastric ulcer healing through TGF-ß and VEGF-A.

CD109 expression in tumor cells and stroma correlates with progression and prognosis in pancreatic cancer.

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

A case of pancreatic neuroendocrine carcinoma with a favorable clinical response to pembrolizumab.

A 76-year-old man with epigastric pain developed 1 month earlier was referred to our department for additional screening and treatment after abdominal ultrasound revealed a mass shadow in the pancreatic head and liver. Blood biochemistry revealed signs of mild jaundice and hepatic dysfunction. Abdominal contrast-computed tomography revealed an irregular hypodense mass with poor enhancement in the pancreatic head and several hypodense nodules in the liver. Endoscopic examination revealed duodenal infiltration signs. The biopsied duodenal mucosa contained atypical cells with high nuclear-to-cytoplasmic ratios; the cells stained positive for CD56, chromogranin, and synaptophysin, and the Ki-67 index was 90%. Accordingly, pancreatic neuroendocrine carcinoma (PanNEC) was diagnosed. Platinum-based chemotherapy (6 courses) and streptozotocin (10 courses) were adopted as the first- and second-line regimens, respectively. However, the patient showed progressive disease (PD). Pembrolizumab was added as a third-line regimen (13 courses) after confirming PanNEC with high microsatellite instability (MSI-high). Despite a temporary partial response (PR), the patient showed PD by the end of the 13 courses and died 1 year and 7 months after diagnosis. Although there is no established PanNEC therapy, those with MSI-high may respond favorably to pembrolizumab. Therefore, we should ascertain the MSI status of any PanNEC in routine practice.

Prospective study for an independent predictor of prognosis in liver cirrhosis based on the new sarcopenia criteria produced by the Japan Society of Hepatology.

AIM: There are limited data from prospective studies showing the clinical usefulness of the new criteria for sarcopenia in liver disease produced by the Japan Society of Hepatology. Therefore, we aimed to evaluate the clinical usefulness of this new criteria for prognosis in cirrhotic patients. METHODS: This prospective study was performed at six centers. The 300 enrolled patients, aged more than 20 years with liver cirrhosis, were evaluated over a 3-year period for skeletal muscle mass index and grip strength. Sarcopenia was defined according to the Japan Society of Hepatology criteria by grip strength and computed tomography-based skeletal muscle mass index values. We investigated the correlation between sarcopenia and the survival rate of cirrhotic patients. RESULTS: Among the 300 assessed patients there were 99 (33%) patients with sarcopenia. The number of deaths in the sarcopenia and non-sarcopenia groups was 34 (34.3%) and 38 (18.9%), respectively (p = 0.002). Multivariate analysis confirmed that sarcopenia, decompensated phase, albumin-bilirubin grade, and hepatocellular carcinoma (HCC) stage 3/4 were independent factors correlated with death in patients with liver cirrhosis during the observation period. The interaction between sarcopenia and the presence of HCC was statistically significant (p < 0.001), and the presence of HCC had the highest hazard ratio of 6.665 for deaths in cirrhotic patients when non-sarcopenia and the absence of HCC were used as references. CONCLUSIONS: The new Japan Society of Hepatology criteria for sarcopenia are accurate predictors of poor prognosis in patients with liver cirrhosis.

A case of immune checkpoint inhibitor-associated myocarditis after initiation of atezolizumab plus bevacizumab therapy for advanced hepatocellular carcinoma.

In November 2020, atezolizumab plus bevacizumab became available for the treatment of hepatocellular carcinoma (HCC), and its efficacy is expected as a new treatment option for HCC. However, the occurrence of immune-related adverse events (irAEs) associated with the administration of immune checkpoint inhibitors is a major concern in clinical practice. We reported a case of irAE-induced myocarditis after the treatment for HCC. Based on the symptoms and echocardiographic findings, we suspected irAE-induced myocarditis and acute heart failure, and the patient was admitted to the hospital for further investigation and treatment. From starting the patient on therapy with methylprednisolone succinate sodium, the laboratory data and symptoms tended to improve. The patient was discharged to home on the 25th day of treatment. Because the number of patients with irAE myocarditis is expected to increase in clinical practice in the near future, further accumulation and investigation of cases are necessary.

Cartilage-hair Hypoplasia Complicated with Liver Cirrhosis Due to Chronic Intrahepatic Cholestasis.

We herein report a rare case of cartilage-hair hypoplasia (CHH) complicated with liver cirrhosis. A 20-year-old Japanese man with CHH was found incidentally to have liver cirrhosis and an esophageal varix. This patient had been treated for infections due to immunodeficiency since early childhood. He ultimately died of liver failure at 31 years of age. An autopsy revealed an abnormality of the interlobular bile ducts and intrahepatic cholestasis. Liver cirrhosis was thought to have been caused by chronic intrahepatic cholestasis due to biliary duct hypoplasia and changes in the intestinal microbiome. Therefore, CHH may cause biliary cirrhosis due to multiple effects.

Histopathological comparison of aspiration and biopsy needles in endoscopic ultrasound-guided tissue acquisition in patients with subepithelial lesions.

BACKGROUND: Information on whether a fine-needle biopsy (FNB) needle can improve histopathological specimen quality or the amount of core tissue collected in the diagnosis of subepithelial lesions (SELs) remains insufficient. In this study, we aimed to compare the procedure outcomes and adequacy of histopathological specimens of fine-needle aspiration (FNA) and FNB needles in endoscopic ultrasound-guided tissue acquisition (EUS-TA) using sample isolation processing by stereomicroscopy (SIPS) in patients with SELs. METHODS: We performed a retrospective comparison of SEL cases registered in two previously conducted prospective studies. Of 61 cases, we identified 56 cases of SELs that involved the muscularis propria layer. Of these, 27 patients who underwent EUS-TA using a 22-gauge FNA needle between July 2016 and December 2017, and 29 patients who underwent the procedure using a 22-gauge FNB needle between March 2018 and January 2019 were included in the FNA and FNB group, respectively. RESULTS: Patient background characteristics did not differ between the groups. The technical success rate was 100% in both groups. The median adequacy score was significantly higher in the FNB group than in the FNA group (P < .01). The histological diagnosis showed no significant difference in the accuracy rate between the groups. CONCLUSIONS: In EUS-TA using the SIPS procedure to target SELs derived from the muscularis propria layer, FNB needles collect more core tissues and significantly improve histopathological specimen quality compared with FNA needles. When combined with SIPS, a high tissue diagnosis rate may be obtained regardless of the type of puncture needle used.

Usefulness of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients: a single-center retrospective cohort study.

BACKGROUND: The effectiveness of endoscopic treatment for superficial esophageal squamous cell carcinoma in the elderly is unclear. METHODS: We retrospectively studied efficacy and safety of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in 358 patients at our hospital from July 2005 to December 2018. Patients were divided into elderly (≥75 years) and young (≤74 years) groups. Efficacy was evaluated based on overall survival and disease-specific survival, whereas safety was investigated based on the frequency of endoscopic submucosal dissection-related adverse events. RESULTS: The median observation period was 50 months. The elderly group comprised 111 patients, and young group comprised 247 patients. In the elderly and young groups, 76 (68.5%) and 159 (64.4%) underwent curative resection (P = 0.450), 8 (7.2%) and 34 (13.8%) underwent non-curative resection plus additional treatment and 12 (10.8%) and 15 (6.0%) underwent follow-up, respectively. The frequency of additional treatment for non-curative resection was significantly lower in the elderly group (P = 0.023). The 3-year overall survival of the elderly and young groups was 85.6 and 94.1%, respectively (P = 0.003). The 3-year disease-specific survival of the elderly and young groups was 98.4 and 98.5% (P = 0.682), respectively. The frequency of endoscopic submucosal dissection-related adverse events did not differ significantly between the groups (P = 0.581). The Charlson Comorbidity Index ≥2 was an independent prognostic factor for survival in the elderly group (P = 0.010; hazard ratio, 5.570; 95% confidence interval, 1.519-20.421). CONCLUSIONS: Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients is as safe as that for young patients. The evaluation of Charlson Comorbidity Index was considered to help estimate the prognosis of elderly patients.

A management of neutropenia using granulocyte colony stimulating factor support for chemotherapy consisted of docetaxel, cisplatin and 5-fluorouracil in patients with oesophageal squamous cell carcinoma.

BACKGROUND: An exploratory study was designed to evaluate the efficacy of granulocyte colony stimulating factor support for chemotherapy consisting of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer. METHODS: The inclusion criteria were as follows: (1) oesophageal squamous cell carcinoma, (2) a schedule to receive three courses of induction chemotherapy (docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, 5-fluorouracil 750 mg/m2 days 1-5, every 3 weeks), (3) stage IB-III, (4) 20-75 years old, (5) 0-1 performance status, (6) preserved organ functions and (7) written informed consent. The endpoints were to evaluate the efficacy of granulocyte colony stimulating factor support including secondary prophylactic usage for docetaxel, cisplatin and 5-fluorouracil chemotherapy. Patients who previously had 'febrile neutropenia', or 'Grade 3 or 4 infection accompanied by grade 3 or 4 neutropenia' prophylactically received granulocyte colony stimulating factor support from day 7. RESULTS: A total of 91 patients were included in the analysis. Granulocyte colony stimulating factor support was given to 81.3%. The incidence of grade 4 neutropenia and febrile neutropenia were 81.3 and 32.9%, respectively. The dose of anticancer agents was reduced in 48.4%. There were no treatment-related deaths. The relative dose intensity of docetaxel, cisplatin and 5-fluorouracil were 92.7 ± 9.8%, 86.0 ± 15.6% and 91.8 ± 10.0%, respectively. In the secondary prophylactic granulocyte colony stimulating factor support group, the neutrophil count significantly increased between day 7 and day 13 as compared with the non-prophylactic granulocyte colony stimulating factor support group (P < 0.05 for each day). CONCLUSIONS: Granulocyte colony stimulating factor support including secondary prophylactic usage may be feasible for maintaining the intensity of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer.

Evaluation of the usefulness of upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist in patients with Hypopharyngeal cancer.

OBJECTIVE: The aim of this retrospective study is to evaluate the usefulness of upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist in patients with hypopharyngeal cancer to assess the risk. METHODS: The study group comprised 41 patients with untreated hypopharyngeal cancer that was precisely diagnosed by an otolaryngologist using upper gastrointestinal endoscopy and the ValsamouthⓇ at our hospital from January 2016 to December 2017. With upper gastrointestinal endoscopy and the ValsamouthⓇ, the oral cavity, oropharynx, larynx, hypopharynx, and esophagus were observed in this order. Narrow-band imaging, and subsequently, white-light observation were performed. At the hypopharynx, vocalization, and subsequently, the Valsalva maneuver were performed. After observing the esophagus, Lugol chromoendoscopy of the esophagus was performed. RESULTS: The mean age of the 38 men and 3 women included in the study was 69.7 ± 10.0 years (range, 51-94 years). As for the T category of hypopharyngeal cancer, T1 cancer was observed in 9 patients, T2 cancer in 14, T3 cancer in 11, and T4 cancer in 7. With vocalization, the grade of visualization in the hypopharynx was 1 in 30 patients (73.2%), 2 in 11 patients (26.8%), and 3 or more in 0 patients (0.0%). With the Valsalva maneuver, the grade of visualization in the hypopharynx was 1 in 1 patient (2.4%), 2 in 15 patients (36.6%), 3 in 8 patients (19.5%), 4 in 11 patients (26.8%), and 5 in 6 patients (14.6%). The grade of visualization in the hypopharynx on average was 1.27 after vocalization and 3.15 after the Valsalva maneuver (p < 0.001). With vocalization, the percentage of patients in whom the entire image of hypopharyngeal cancer could be observed was 0.0% for grade 1 and 18.2% for grade 2. With the Valsalva maneuver, the percentage of patients in whom the entire image of hypopharyngeal cancer could be observed was 0.0% for grade 1, 40.0% for grade 2, 50.0% for grade 3, 86.1% for grade 4, and 100% for grade 5. Synchronous esophageal cancers were detected in 17.1% (7/41) of the patients. The grade of Lugol-voiding lesions was A in 5.6%, B in 52.8%, and C in 41.7%. CONCLUSION: The examination with upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist is feasible in patients with hypopharyngeal cancer. This procedure can detect synchronous esophageal cancer, allowing the risk of metachronous cancer in the head and neck or the esophagus to be recognized after the treatment.

Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer.

PURPOSE: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). RESULTS: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). CONCLUSIONS: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

Pancreatic Schwannoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration.

A schwannoma is a tumor originating from Schwann cells. It is occasionally observed in the abdominal viscera in the form of a submucosal tumor derived from the gastric or duodenal muscularis propria. To date, only a few studies have reported on pancreatic schwannomas. Furthermore, very few patients are preoperatively diagnosed with pancreatic schwannoma because of the lack of established imaging characteristics distinguishing this type of schwannoma from other conditions. We herein report the first English publication of pancreatic schwannoma in which surgery was avoided because a pathological diagnosis was made solely on the basis of endoscopic ultrasound-guided fine-needle aspiration findings.