Masahiko Tanigawa

Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study.

PurposeThe prospective pilot study was designed to evaluate the preventive effects of amino-acid-rich elemental diet (ED), Elental®, on chemotherapy-induced oral mucositis in patients with colorectal cancer. The factors influencing its efficacy are also investigated.MethodsA total of 22 eligible patients with colorectal cancer experiencing grade 1–3 oral mucositis during treatment with fluorouracil-based chemotherapy entered the current study. Their average age was 67xa0years. There were 10 male and 12 female. The PS was 0 in the majority of patients. Patients received two courses of the same chemotherapy regimen and Elental® concurrently after recovery to grade 0 or 1 oral mucositis.ResultsFOLFOX6xa0+xa0bevacizumab in 8 patients, FOLFIRIxa0+xa0bevacizumab in 8 patients, FOLFIRIxa0+xa0panitumumab in 1 patient, FOLFIRI in 1 patient, XELOXxa0+xa0bevacizumab in 2 patients, and S-1xa0+xa0cetuximab in 2 patients were used as first-line (16 cases) or as second-line (6 cases) chemotherapy. Dose reduction of 5-fluorouracil (5-FU) or oral fluoropyrimidine was performed in the 2 patients achieving grade 3 oral mucositis and in the 3 patients achieving grade 2 oral mucositis. The maximum grade of oral mucositis decreased in 18 of the 22 patients during the first treatment course with Elental® (pxa0=xa00.0002) and in 20 of the 22 patients in the second course (pxa0<xa00.0001). Multivariate analyses found that the dose reduction in 5-FU or oral fluoropyrimidine, ED intake, and the prior administration of ED were each a significant factor for the preventive efficacy on oral mucositis.ConclusionThe amino-acid-rich elemental diet Elental® may be useful as a countermeasure for 5-FU-based chemotherapy-induced oral mucositis in patients with colorectal cancer.

Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor

Insulinoma-associated protein 1 (INSM1) is an important biomarker of Achaete-scute homolog-like 1-driven pathways. For diagnosis of pancreatic neuroendocrine tumors (PanNET), chromogranin A (CGA), synaptophysin (SYP), and neural cell adhesion molecule (NCAM) were also considered as potential biomarkers. However, it is often difficult to diagnose it immunohistochemically. Hence, we examined the expression pattern of INSM1 in pancreatic solid tumors. We detected INSM1, CGA, SYP, and NCAM immunohistochemically, in 27 cases of NET [pure type: 25 cases, mixed adenoneuroendocrine carcinoma (MANEC): 2 cases]. We included 5 cases of solid-pseudopapillary neoplasm (SPN), 7 cases of acinar cell carcinoma (ACC), and 15 cases of pancreatic ductal adenocarcinoma (PDAC) as the control group. Nuclear expression of INSM1 was found in all PanNET pure type cases. However, expression of INSM1 was negative in PDAC, ACC, and SPN in all cases, whereas faint expression was seen in the cytoplasm from SPN. MANEC comprises of two components: neuroendocrine carcinoma and adenocarcinoma components. The NET component was positive for INSM1 expression, whereas the PDAC component does not express INSM1, which aids in distinguishing these components. Our results suggest that INSM1 is a useful immunohistochemical marker for diagnosing pancreatic neuroendocrine tumor.

Granulocyte colony-stimulating factor-producing pancreatic anaplastic carcinoma in ascitic fluid at initial diagnosis: A case report: G-CSF EXPRESSION IN PAC

Granulocyte colony‐stimulating factor (G‐CSF)‐producing pancreatic tumors are extremely rare. These tumors have an aggressive clinical course and no established treatment. Here, we report an autopsy case of G‐CSF‐production in pancreatic anaplastic carcinoma (PAC). A 72‐year‐old woman presented with a large pancreatic head mass and multiple liver metastases. Laboratory data showed leukocytosis (leukocyte count 113.3 × 103/µL) and high serum G‐CSF levels (441 pg/mL; normal range: <39.0 pg/mL). The ascitic fluid was submitted to our pathology laboratory at initial diagnosis. Cytopathology showed that smears from the ascitic fluid were highly cellular and contained numerous malignant cells, mainly in loose groupings. Occasional pseudoglandular formations and giant cells were also present. The malignant cells were round, and no spindle‐shaped cells were visible. The nuclei were round to ovoid with coarsely granular chromatin and large prominent nucleoli. Upon immunocytochemistry, tumor cells were positive for G‐CSF and vimentin; there was no E‐cadherin expression. Histopathological examination of the tumor showed a mixed composition of adenocarcinomatous and sarcomatous regions. Upon immunohistochemistry, both components were positive for G‐CSF. Few CD34‐positive myeloblasts were observed in the bone marrow. Thus, we diagnosed this as a case of G‐CSF production in PAC with leukocytosis. To the best of our knowledge, this is the first report on G‐CSF expression immunocytochemically confirmed in PAC. Diagn. Cytopathol. 2017;45:463–467.

PD-L1 expression in pancreatic adenosquamous carcinoma: PD-L1 expression is limited to the squamous component

AIMnWe examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).nnnMETHODSnFifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compareu3000the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1u2009≤u2009TPS ≤ 49% and high expression; ≥ 50%).nnnRESULTSnPD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%).nnnDISCUSSIONnAlthough assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.

Pathological findings that contribute to tissue stiffness in the spleen of liver cirrhosis patients: Pathology of the spleen in cirrhosis

Spleen stiffness is increased in liver cirrhosis (LC). We attempted to characterize the pathological features of spleen in LC.

Cytopathological and immunocytochemical findings of pancreatic anaplastic carcinoma with ZEB1 expression by means of touch imprint cytology

Pancreatic anaplastic carcinoma (PAC) is rare and has an aggressive clinical course. We report an autopsy case of PAC focusing on the cytopathological characteristics of the tumor and immunocytochemical staining for vimentin, E‐cadherin, and zinc finger E‐box binding homeobox 1 (ZEB1), which markers are associated with epithelial markers of epithelial‐mesenchymal transition (EMT). A 50‐year‐old woman presented to our hospital with a chief complaint of jaundice. A pancreatic head tumor and multiple liver nodules were detected on abdominal computed tomography. Biliary cytology under endoscopic retrograde cholangiopancreatography suggested ductal adenocarcinoma. Three months after admission, she died of multiorgan failure. At autopsy, touch imprint cytology using squash preparation of the pancreatic tumor identified two different cell types; numerous isolated malignant cells with large and pleomorphic nuclei and a few clusters showing irregularly overlapped nuclei and irregular contours within the necrotic background. Immunocytochemically, isolated cells were positive for vimentin and ZEB1, and negative for E‐cadherin. Conversely, clusters were negative for vimentin and ZEB1, and positive for E‐cadherin. Histologically, the tumor was composed of sarcomatous cells with small foci of adenocarcinoma, which were consistent with a diagnosis of PAC. Immunohistochemical staining of the adenocarcinoma and sarcomatous cells corresponded to those of the clusters and isolated malignant cells, respectively. Immunostaining of these EMT markers is useful to distinguish sarcomatous cells from adenocarcinoma and can contribute to the accurate diagnosis of pancreatic tumors with EMT.

SurePath® LBC improves the diagnostic accuracy of intrahepatic and hilar cholangiocarcinoma

The current study aimed to compare cytology using SurePath® (SP)‐LBC and biliary tissue histology (BTH) for the diagnosis of biliary disease.

INSM1 expression in pancreatic neuroendocrine tumors in endoscopic ultrasound-guided fine needle aspiration cytology: an analysis of 14 patients

Insulinoma‐associated protein 1 (INSM1) has been reported to be a useful marker for diagnosing pancreatic neuroendocrine tumours (PNETs). However, INSM1 expression in endoscopic ultrasound‐guided fine needle aspiration cytology has not been examined. We evaluated INSM1 expression in the cytology of cases diagnosed with PNETs.

Granulocyte-colony stimulating factor producing mucinous cystic neoplasm with an associated invasive carcinoma of the pancreas

The present case study documents an autopsy case of granulocyte-colony stimulating factor (G-CSF)-producing mucinous cystic neoplasm (MCN), with an associated invasive carcinoma of the pancreas. A 65-year-old woman presented to Omuta City Hospital (Omuta Japan) with a primary complaint of abdominal pain. Multiple liver nodules and a pancreatic cyst were detected upon abdominal computed tomography. Initially, liver abscess was suspected as the patient exhibited leukocytosis and elevated C-reactive protein level. However, the serum concentration of G-CSF was 98.8 pg/ml (normal, <39.0 pg/ml). At 6 weeks after admission, the patient succumbed to liver failure. At autopsy, a cystic lesion was identified in the pancreatic tail that contained bloody necrotic fluid. Microscopically, the cystic lesion was composed of columnar and mucin-producing epithelium associated with ovarian-type subepithelial stroma. The stroma exhibited positive immunostaining for vimentin, estrogen receptor and progesterone receptor. Calcification on the cystic wall was observed. The tumor invaded the pancreatic parenchyma and metastasized to the liver and lungs. The lesion was diagnosed as invasive adenocarcinoma arising in MCN. By contrast, liver nodules predominantly consisted of pleomorphic cancer cells with small foci of adenocarcinoma. Pancreatic and hepatic cancer cells were confirmed to be positive for G-CSF staining. The present case report indicates that G-CSF-producing MCNs may be associated with an aggressive clinical course, particularly when anaplastic changes are observed.

Interstitial pneumonia in a patient treated with TAS-102 for metastatic colorectal cancer: a case report

BackgroundTAS-102, a new treatment option for patients with metastatic colorectal cancer that is refractory or intolerant to standard therapies, has been improving survival with acceptable tolerability and adverse events. Adverse hematological events associated with TAS-102 treatment were extensively profiled in the RECOURSE trial, but pulmonary toxicities associated with TAS-102 therapy are distinctly uncommon. In a recent early post-marketing phase vigilance on TAS-102 in Japan, seven cases of pulmonary disease were reported, but patient follow-up in this study was incomplete. Here, we present the first case of interstitial lung disease occurring in association with TAS-102 treatment.Case presentationA 57-year-old Japanese man who had previously received two standard treatments was admitted in 2014, at which time we administered TAS-102 (110 mg/day) as a third-line chemotherapy. He was safely treated with TAS-102 for the first planned cycle; however, approximately 4 days after receiving the second cycle of TAS-102, he complained of high fever and subsequent dyspnea with severe hypoxemia and went to the emergency room. A chest X-ray revealed diffuse coarse reticular shadows with ground-glass opacity on both lungs. Furthermore, a chest computed tomography scan showed thickening of the bronchovascular bundles with extensive ground-glass opacification and pleural effusions in both lung fields.In addition, a peripheral blood lymphocyte stimulation test with TAS-102 showed higher values compared with control samples. Consequently, we suspected drug-induced interstitial pneumonia, and discontinued treatment. Our patient was given an initial administration of high-dose methylprednisolone (1000 mg/day) for 3 days and oxygen. Our patient was discharged with oral prednisolone (20 mg/day) and improved symptomatically and radiologically.ConclusionsThese findings suggest that interstitial pneumonia is a rare complication of TAS-102 chemotherapy, but the possibility of interstitial pneumonia should always be considered when a patient presents with a respiratory disorder while undergoing TAS-102 systemic chemotherapy.Prompt discontinuation of TAS-102 and treatment with high-dosage corticosteroids is needed to avoid exacerbating respiratory symptoms.