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Transactivation response DNA‐binding protein 43 kDa (TDP‐43) is a key protein of sporadic amyotrophic lateral sclerosis (ALS), and phosphorylated form of TDP‐43 (p‐TDP‐43) is a major pathological protein that accumulates in sporadic ALS. p‐TDP‐43 is found not only in primary motor neurons, but often propagates to non‐motor systems as well. However, pallido‐nigro‐luysian (PNL) degeneration (PNLD) is rarely associated with ALS. We describe here a 68‐year‐old ALS patient presenting severe PNLD. He had difficulty walking due to poor movement of his right leg, and was diagnosed as having Parkinson’s disease because of akinesia. About 2 years after onset, weakness of his left hand and leg led to a diagnosis of ALS. Tube feeding and non‐invasive positive‐pressure ventilation were initiated. He died of respiratory failure at the age of 71. There was no family history of either neurological disorders or dementia. Neuropathological examination revealed severe loss of neurons and gliosis in the PNL system in addition to the upper and lower motor neuron system. p‐TDP‐43 pathology was widespread in the PNL and motor neuron systems and also in the amygdala and hippocampus where no significant gliosis or neuronal loss was detected. Synuclein pathology was not observed in the investigated areas. Immunoblot analysis of p‐TDP‐43 C‐terminal fragments showed a type B band pattern consistent with sporadic ALS. This is the first case of ALS with PNLD, in which p‐TDP‐43 distribution was widespread in the hippocampal formation (Nishihira type 2 and Brettschneider stage 4), and the type B immunoblot pattern was confirmed. Our case indicated that the PNL system can be involved in the disease process in sporadic ALS cases, although rarely. We also reviewed previous autopsy cases of ALS with PNLD to clarify the clinicopathological features. [ABSTRACT FROM AUTHOR]

In order to investigate cell kinetics and cell cycle regulator protein expression with reference to the growth pattern of early gastric carcinomas (EGCs), we evaluated a total of 240 EGCs with submucosal invasion clinicopathologically and 106 submucosal invasive lesions immunohistochemically. The incidence of lymph node metastasis was relatively high (36.4%) in the superficially spreading growth (SUP) type tumors whereas the penetrating growth (PEN) type had a low incidence (5.7%, P < 0.001) and correlated with submucosal tumor size. Ki67 labeling was lower in submucosal areas of the SUP-type tumors (median, 37.3%) than the PEN-type tumors (51.0%, P < 0.001). ssDNA labeling in the lamina propria, indicative of apoptotic activity, was higher in the SUP-type tumors (0.55%) than in PEN-type (0.30%, P < 0.01) lesions. The expression of cell cycle regulator p21WAF1/CIP1 was lower in the SUP-type tumors (lamina propria 15.6%, submucosa 2.6%) than in PEN-type tumors (lamina propria 26.5%, submucosa 4.4%, P < 0.05–0.001). In conclusion, differences in cell kinetics and p21WAF1/CIP1 expression might influence the growth pattern of EGCs. The SUP-type EGC, characterized by high apoptotic in the lamina propria and low proliferative activities in the submucosa, is associated with frequent lymph node metastasis, suggesting a strong correlation between tumor size in the submucosa and metastatic potential. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Narrow-band imaging combined with magnified endoscopy has enabled the detection of superficial squamous cell carcinoma of the head and neck (SSCCHN) that has been resected with minimally invasive treatment, preserving vocalization and swallowing functions. However, risk factors of lymph node metastasis (LNM) must be identified, as some patients with LNM have a poor prognosis. From an initial 599 patients with 700 lesions who underwent trans-oral surgery in 27 Japanese hospitals (a nationwide registration survey), we enrolled 541 patients with 633 SSCCHNs, as indicated by central pathological diagnoses. All pathological specimens for each patient were examined using 20 pathological factors that are thought to affect the LNM of SSCCHN. In all, 24 (4.4%) of the 568 SSCCHNs exhibited LNM, and all 24 had at least one solitary nest of epithelial neoplastic cells present in the stroma, clearly separated from the intraepithelial carcinoma. Multivariate analysis also showed that tumor thickness (p = 0.0132, RR: 7.85, 95% confidence interval [CI]: 1.54-40.02), and an INFc pattern classified as infiltrating growth (INF) with unclear boundaries between tumor and non-tumor tissues (p = 0.0003, RR: 14.47, 3.46-60.46), and tumor budding (p = 0.0019, RR: 4.35, CI: 1.72-11.01) were significantly associated with LNM. Solitary nests may be indicative of LNM. In addition, tumor thickness was revealed to be a risk factor for LNM in SSCCHNs using pT factors that do not include an invasion depth element because of the anatomical absence of the muscularis mucosae., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

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., Competing Interests: Declaration of Competing Interest The authors report no potential conflicts of interest relevant to this manuscript., (Copyright © 2020 Oto-Rhino-Laryngological Society of Japan Inc. Published by Elsevier B.V. All rights reserved.)

We report a case of unresectable locally advanced pancreatic cancer successfully resected after gemcitabine(GEM)plus nab-paclitaxel(PTX)treatment. A 68-year-old man was referred to our institution with jaundice. We diagnosed pancreatic head cancer using computed tomography(CT)and endoscopic retrograde cholangiopancreatography. We initially diagnosed it as locally advanced unresectable pancreatic cancer because of extensive invasion to the portal vein. GEM plus nab- PTX was administered to the patient as systemic chemotherapy. After 9 courses of chemotherapy, a CT scan revealed that the tumor had significantly reduced in size and range of portal vein invasion. Therefore, we performed pancreaticoduodenectomy with resection of the portal vein and achieved R0 resection. Currently, the patient is alive without recurrence. Therefore, conversion surgery after treatment with GEM plus nab-PTX chemotherapy for unresectable pancreatic cancer should be considered.

L-Type amino acid transporter 1 (LAT1) is one of the major amino acid transporters. High levels of LAT1 expression have been reported in various tumors, which can act as a novel prognostic marker. Previously, we demonstrated that LAT1 is highly expressed in advanced gastric carcinoma with lymph node metastasis, and proposed that LAT1 is an independent prognostic factor in non-scirrhous gastric carcinoma. The aim of the present study was to investigate the relationship between LAT1 expression and the size of lymph node metastatic lesions in gastric carcinoma. LAT1 and Ki-67 expression was immunohistochemically analyzed in 64 cases of advanced gastric carcinoma with lymph node metastasis. LAT1 expression in the metastatic lymph nodes was correlated with that in the primary lesions. The high LAT1 expression group showed a larger size of metastatic lesion and a higher Ki-67 labeling index than the low LAT1 expression group. LAT1 expression had a weak association with Ki-67 labeling index and tumor diameter of lymph nodes. These results suggest that LAT1 expression is associated with disease progression in gastric carcinoma. We proposed that LAT1 could be a potential therapeutic target for gastric carcinoma cases with large lymph node metastasis., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Dysregulated expression of L-type amino acid transporter 1 (LAT1), which transports large neutral amino acids, is a characteristic of various human cancers and possibly offers a molecular target for chemotherapy. LAT2, in contrast, shows lower expression in neoplasms. LAT1 is presumed to be a biomarker of many cancers, suggesting a kind of oncoprotein. However, no precise analysis of LAT1 and LAT2 expression has been performed in systemic normal tissues. To see characteristics of LAT1 and LAT2, immunohistochemical expression of LAT1 and LAT2 was assessed and compared in normal human systemic organs and tissues from 3 adults, 3 children and 3 fetuses in the present study. Cardiac muscles, hepatocytes, thymic epithelial cells and primitive neuroectodermal cells in fetus were positive with LAT1, whereas no expression was found in the respective adult tissues, indicating an aspect of oncofetal protein. In adult tissues, LAT1 was found to be expressed proximal to proliferative zones in gastrointestinal mucosa by double immunostaining of LAT1 and Ki-67. Testicular Sertoli cells, ovarian follicular cells, and pancreatic islet cells showed strong expression. Although the systemic capillary endothelium did not express LAT1, but did express LAT2, capillaries corresponding to the blood-brain, blood-follicle, and blood-retinal barriers demonstrated strong LAT1 immunoreactions. In conclusion, LAT1 was expressed in gonad tissues and several kinds of cells having special functions, as well as being discovered to be an aspect of oncofetal protein. In addition, ubiquitous LAT2 expression was confirmed immunohistochemically in systemic tissues, indicating constitutional function.

Pulmonary tumor thrombotic microangiopathy (PTTM), characterized by widespread fibrocellular intimal proliferation of the small pulmonary arteries and arterioles in patients with metastatic carcinomas, has been reported in only few cases. In childhood, gastrointestinal tumors represent less than 5% of pediatric neoplasms, and carcinomas within this subgroup have been very rarely described, in particular those arising in the stomach. We report on a case of a microscopic gastric signet-ring cell carcinoma identified by serial step sections through the entire stomach at autopsy. The patient was a 17-year-old high school student with severe dyspnea and marked pulmonary hypertension due to PTTM. Although the combination of PTTM with gastric cancer is very rare in childhood, it should be considered in the differential diagnosis of primary pulmonary hypertension and progressive respiratory failure, as indicated by a review of previously reported cases.