A Case Report of Neoadjuvant Gemcitabine Plus Cisplatin for Locally Advanced Unresectable Ampulla of Vater Carcinoma.

INTRODUCTION: Ampulla of Vater carcinoma (AVC) with para-aortic node (PAN) metastasis is considered unresectable and is equivalent to distant metastasis, contributing to poor outcomes. CASE PRESENTATION: A 60-year-old man was referred to our hospital and was diagnosed with an unresectable ampulla of Vater carcinoma that had metastasized to the para-aortic nodes. The patient received a systemic chemotherapy regimen comprising a combination of gemcitabine and cisplatin. Following five cycles of treatment, imaging studies revealed a significant reduction in the primary tumor and para-aortic node metastasis, rendering detection difficult. Pancreatoduodenectomy with para-aortic node dissection was performed as a radical surgery. Upon pathological examination, no residual tumors were identified in the resected specimen, indicating that the systemic chemotherapy achieved a complete pathological response. The postoperative course of the patient was uneventful, and he was discharged on the 25th postoperative day. The patient was followed up as an outpatient and remained stable without any recurrence for two months after surgery. CONCLUSION: Neoadjuvant chemotherapy with gemcitabine and cisplatin was useful for downstaging the ampulla in patients with Vater carcinoma. This finding may help physicians manage patients with similar presentations.

Cytological scoring for pancreatic specimens obtained by endoscopic ultrasound-guided fine needle aspiration.

OBJECTIVE: Cytological diagnosis of pancreatic specimens obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often challenging because of the small sample size or well-differentiated adenocarcinoma with weak cytological atypia. Therefore, the sensitivity and specificity of cytological diagnosis for pancreatic cancer should be improved. Hence, we aimed to clarify the utility of cytological scoring to distinguish malignant from benign lesions for cytological diagnosis of pancreatic EUS-FNA specimens. METHODS: Seven reviewers, including four cytotechnologists and three medical doctors, evaluated 20 morphological indices in pancreatic specimens obtained by EUS-FNA (malignant, n = 111; benign, n = 31). Statistical analyses were performed using Fisher's exact test, logistic regression analysis, the area under the receiver operating characteristic curve, and Youden index. RESULTS: Among the 20 indices, there was a high incidence rate (>40%) of the following 13 indices in malignant cases: irregular structure, hyperchromatic nucleus, irregular cell polarity, unclear cell boundaries, nuclear membrane thickening, anisonucleosis, overlapping, irregular nuclei, high nuclear-cytoplasmic ratio, binding decline, the simultaneous appearance of malignant and benign cells, enlarged nucleoli, and background necrosis. When we diagnosed pancreatic specimens using these 13 cytological indices, the cut-off value of 8/9 showed the highest Youden index (0.950) as well as high sensitivity and specificity in distinguishing malignant from benign specimens (98% and 97%, respectively). CONCLUSION: Thirteen cytological indices showed high sensitivity and specificity in differentiating malignant and benign lesions using pancreatic EUS-FNA samples. All 13 indices were important for diagnosing malignancy in the pancreatic cytology smear of EUS-FNA. Further validation studies are required.

Clinicopathological characteristics of gastric cancer with carbohydrate antigen 19-9 expression occurring in elderly individuals: An autopsy study.

The clinicopathological significance of carbohydrate antigen 19-9 (CA19-9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19-9 in GC utilizing autopsy cases. We examined the expression of CA19-9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19-9 levels and clinicopathological variables or complications. We also investigated whether fucosyltransferases 2 and 3 (FUT2/3) allelic variants influence CA19-9 expression in GC. Compared to GC cases with negative CA19-9 expression (tCA19-9-N), those with positive CA19-9 expression (tCA19-9-P) demonstrated significant differences in characteristic features such as lymph node and distant organ metastases, lymphatic and venous permeation, and higher Tumor, Node, Metastasis (TNM) stages. Moreover, compared to GC cases with low serum CA19-9 levels (sCA19-9-L), those with high serum CA19-9 levels (sCA19-9-H) were related to venous permeation, higher proportion of lymph node and distant organ metastases, and higher TNM stages. Both tCA19-9-P GC and sCA19-9-H GC cases were significantly associated with coagulation abnormalities. sCA19-9-H GC cases correlated significantly with MUC1 and MUC5AC expression. FUT2/3 genotypes were not associated with CA19-9 expression in GC. These results suggest that CA19-9 can predict the risk of lymph node and distant metastases as well as of coagulation abnormalities.

Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men.

CONTEXT: Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths. OBJECTIVE: To compare the telomere lengths of adrenocortical and adrenal medullar cells between men and women from infancy through older adulthood. METHODS: Adrenal glands of 30 male (aged 0 to 100 years) and 25 female (aged 0 to 104 years) autopsied subjects were retrieved from autopsy files. Using quantitative fluorescence in situ hybridization, relative telomere lengths were determined in the parenchymal cells of the 3 adrenocortical zones and medulla. Age-related changes in the weight of adrenal glands were also investigated. MAIN RESULTS: Older male subjects (aged 65 years or older) had significantly shorter telomere lengths in zona fasciculata (ZF) cells compared to the corresponding female subjects. In men, older subjects exhibited a significant age-related reduction in adrenal weight; however, no age-related changes in adrenal weight were detected in women. CONCLUSION: Telomere attrition of ZF cells was correlated with adrenal weight reduction in older men but not in older women, suggesting a decreased number of ZF cells in older men. This may help us understand the possible biological mechanisms of sex difference in longevity of humans.

Correlation Between Differentiation of Adrenocortical Zones and Telomere Lengths Measured by Q-FISH.

CONTEXT: Adrenocortical zonation is associated with a markedly complex developmental process, and the pathogenesis and/or etiology of many disorders of adrenocortical zonal development have remained unknown. Cells from the three adrenocortical zones are morphologically and functionally differentiated, and the mature stage of cell development or senescence has been recently reported to be correlated with telomere length. However, the telomere length of each adrenocortical zonal cell has not yet been studied in human adrenal glands. OBJECTIVE: We aimed to study the telomere lengths of adrenocortical parenchymal cells from three different zones of the adrenal glands present during childhood, adolescence, and adulthood. METHODS: Adrenal glands of 30 autopsied subjects, aged between 0 and 68 years, were retrieved from pathology files. The normalized telomere to centromere ratio (NTCR), an index of telomere length, was determined in the parenchymal cells of the zona glomerulosa, zona fasciculata, and zona reticularis (ZR), using quantitative fluorescence in situ hybridization. RESULTS: NTCR of ZR cells was the longest, followed in decreasing order by that of zona glomerulosa and zona fasciculata cells in subjects aged 20 to 68 years, but no substantial differences in NTCR were detected among these three zones in the group <20 years of age. NTCR of ZR increased with age in subjects aged 20 to 68 years, whereas no important age-dependent changes in NTCR were detected in the group <20 years of age. CONCLUSION: The telomere lengths for three zones in adrenal cortex were correlated with their differentiation in adulthood but not in childhood and adolescence.

Acute Liver Failure Associated with Influenza A Virus Infection: an Autopsy Case Report.

An 84-year-old man with chronic renal failure, anemia, and diabetes was admitted for hemodialysis initiation. His vital signs were stable until the eighteenth hospital day, before acquiring an influenza A virus infection. Three days later, he died of septic shock with severe liver impairment. His leukocyte count, prothrombin time (PT-INR), and liver enzyme levels such as aspartate transaminase and alanine aminotransferase, were significantly increased. Hypercytokinemia was also observed. Autopsy revealed bilateral diffuse pneumonia with neutrophil infiltration. The liver showed extensive centrilobular hepatocyte necrosis. Immunohistochemistry for influenza A nucleoprotein revealed positivity in the ciliated columnar epithelium of the bronchi and negativity in the trachea, lungs, and liver. Hypoxic hepatitis is characterized by an abrupt and massive increase in aminotransferase levels (＞ 20 times upper normal limit) due to anoxic centrilobular hepatocyte necrosis. The occurrence of hypoxic hepatitis requires a pre-existing, chronic condition, such as anemia, causing reduced oxygen supply to the liver, followed by an acute decrease in hepatic oxygen supply, such as septic shock. Therefore, this report suggests that hypoxic hepatitis can be an important causative factor for acute liver failure associated with influenza virus infection.

An Unusual Invasive Ectopic Thymoma in the Thyroid and Anterior Mediastinum.

An 81-year-old woman with a 2-year history of dysphagia detected a cervical mass. Computed tomography showed a thyroid tumor extending through the superior and anterior mediastinum. Analysis of an incisional biopsy specimen revealed a thymoma. Total resection of the thyroid and mediastinal tumor was performed. The thymoma invaded the anterior tracheal wall and left brachiocephalic vein. Pathologic examination revealed thymoma type B1 concomitant with B2 and B3 (World Health Organization classification), Masaoka IVb, and T3 N2 M0-IVb, with cervical lymph node metastasis. Clinicians must be cautious during radical operations for invasive ectopic thymomas.

Clinicopathological characteristics of distant metastases of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma: An autopsy study of older Japanese patients.

AIM: We aimed to clarify the characteristics of malignancies in older adults focusing on distant metastasis in the whole body. METHODS: We retrospectively evaluated 7710 cases of autopsies (4011 men, 3699 women, median age of 80 years), and analyzed the characteristics of metastasis of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma in each organ. RESULTS: The total number of cases with adenocarcinoma, squamous cell carcinoma or urothelial carcinoma was 2856, and most of them were adenocarcinomas. Among them, 1604 had metastatic lesions, and patients with metastasis were younger than those without metastasis. The major primary organs of adenocarcinoma were the stomach, colon, lung, prostate, gallbladder and pancreas, whereas those for squamous cell carcinoma were the lung, esophagus and uterus. Urothelial carcinoma cases were found in the urinary bladder, kidney and ureter. Metastatic adenocarcinomas mainly originated from the stomach, colon, lung, pancreas and gallbladder. Metastatic squamous cell carcinomas were from the lung, esophagus and uterus, whereas the kidney, bladder and ureter were the primary origins of metastatic urothelial carcinomas. Squamous cell carcinoma showed the highest incidence of metastasis, suggestive of it being of an aggressive phenotype. Furthermore, metastatic ability and the preferred metastatic sites varied among primary organs. CONCLUSIONS: We revealed an accurate incidence and the characteristics of metastatic cancer in a large-scale autopsy study of older Japanese patients from one institution. Identifying these features might prompt screening for malignancies, and consequently improve quality of life for older adults. Geriatr Gerontol Int 2018; 18: 211-215.

Carbohydrate Antigen 19-9-Positive Gastric Adenocarcinoma: Autopsy Findings and Review of the Literature.

Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for pancreatobiliary cancer, and several studies have shown that an elevated serum CA19-9 level is associated with more aggressive biological behavior in gastric cancer (GC). However, the clinicopathological characteristics of CA19-9-positive GC remain unclear. We herein report an autopsy case of CA19-9-positive GC in an 84-year-old man who was admitted to our hospital because of paralysis and anemia. Autopsy revealed an ulcerative-invasive tumor measuring 72 × 60 mm in the anterior wall of the gastric body. The tumor had invaded beyond the muscularis propria, and metastasized to the lung, liver, and regional lymph nodes. Histologically, the tumor cell had oval nuclei with abundant clear cytoplasm, and tubular and/or papillary features with prominent lymphovascular permeation and perineural invasion, mimicking pancreatobiliary carcinoma. Immunohistochemically, the tumor cells showed diffuse immunopositivity for CA19-9 and carcinoembryonic antigen. According to a review of cases reported in the literature, CA19-9-positive GCs show clinicopathological characteristics such as antral location, ulcerative-infiltrating gross feature, differentiated histology, prominent lymphatic and venous invasion, higher proportion of metastasis, and higher clinical stage. These results suggest that CA19-9-positive GC is pathologically a distinctive type of tumor with aggressive biological behavior.