Secretory Carcinoma with ETV6-NTRK3 Gene Fusion and Lymph Node Metastasis in Maxillary Gingiva: A Case Report with Pathological and Molecular Correlative Studies.

Secretory carcinoma (SC), also known as mammary analogue secretory carcinoma (MASC), is a rare salivary gland neoplasm with distinctive morphology that harbors a diagnostic ETV6 gene rearrangement. MASC was first described as a type of salivary gland neoplasm in 2010 and resembles breast secretory carcinoma. It is often mistaken for other neoplasms. It usually acts as an indolent tumor but can occasionally behave in an aggressive manner. We present a rare case of a patient with an aggressive SC/MASC of maxillary gingivobuccal sulcus with microcystic, solid and papillary patterns that showed ETV6 gene rearrangement by fluorescence in situ hybridization. Next-generation sequencing revealed t(12;15)(p13;q25) ETV6-NTRK3 translocation. Because SC/MASCs harbor the ETV6-NTRK3 translocation, molecular studies and immunostains are crucial to confirm the diagnosis and direct therapy.

Cardiac sarcoidosis preceded by sick sinus syndrome presenting as biventricular involvement and intracardiac giant thrombus: a case report.

Background: Sarcoidosis is a granulomatous disorder characterized by the formation of non-necrotizing granulomas in various organs. Cardiac sarcoidosis presents with various clinical, anatomical, and electrophysiological manifestations. As cardiac involvement is related to adverse outcomes, the early diagnosis of cardiac sarcoidosis is crucial and sometimes challenging. Case summary: A 65-year-old woman was initially treated for sick sinus syndrome (SSS) with normal cardiac function. Cardiac conduction defects and biventricular dysfunction continued to progress over a short clinical course, and the patient was eventually referred to our hospital for further investigation and treatment of cardiogenic shock due to pacemaker pacing failure. An echocardiography revealed a large thrombus formation in the right ventricle and atrium. An urgent thrombectomy was performed, and myocardial biopsy confirmed the diagnosis of cardiac sarcoidosis. Steroid pulse therapy was initiated and was effective in treating the cardiogenic shock. One year after discharge, the patient manifested with sustained ventricular tachycardia and ultimately died of severe cardiac pump failure. On autopsy, diffuse fibrotic tissues were noted in both ventricles and atria. Discussion: While conduction abnormalities, such as right bundle brunch block and atrioventricular block, are common clinical manifestations, SSS is rarely reported as a primary manifestation of cardiac sarcoidosis. Thus, clinicians should ensure that sufficient investigations are carried out when diagnosing idiopathic SSS.

Pulmonary tumor thrombotic microangiopathy caused by metastatic ovarian high-grade serous carcinoma: a case report and literature review.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare entity with poor prognosis, and often diagnosed postmortem. PTTM is resulting from tumor emboli induced activation of coagulation cascade, fibrin clot formation and fibrocellular intimal proliferation in pulmonary microvasculature. CASE: The patient was a 65-year-old female, with past medical history of ovarian high-grade serous carcinoma, presented with chest pain and shortness of breath. The chest computed tomography (CT) revealed innumerable new lung nodules as well as small hazy and patchy opacities compared to the chest CT 2 months before current presentation. She developed progressive respiratory failure and expired. A lung-restricted autopsy showed diffuse subcentimetric nodules in bilateral lungs grossly. Microscopic examination revealed the lung parenchyma demonstrated numerous tumor emboli consisting of pleomorphic tumor cells with varying degrees of fibrin deposition and fibrocellular intimal proliferation in the pulmonary arterioles, small arteries, and capillaries in the alveolar septa. Immunohistochemistry confirmed the ovarian origin of the tumor cells. The findings were consistent with PTTM secondary to metastasis of ovarian high-grade serous carcinoma. Literature review of PTTM caused by ovarian cancer was conducted. CONCLUSION: PTTM is a fatal entity with rare association with primary ovarian malignancy. This case study demonstrates the clinicopathological features of PTTM associated with high-grade serous carcinoma, and it will be the second case of PTTM with this association in the literature.

Nuclear Ceramide Is Associated with Ataxia Telangiectasia Mutated Activation in the Neocarzinostatin-Induced Apoptosis of Lymphoblastoid Cells.

Ceramide is a bioactive sphingolipid that mediates ionizing radiation- and chemotherapy-induced apoptosis. Neocarzinostatin (NCS) is a genotoxic anti-cancer drug that induces apoptosis in response to DNA double-strand breaks (DSBs) through ataxia telangiectasia mutated (ATM) activation. However, the involvement of ceramide in NCS-evoked nuclear events such as DSB-activated ATM has not been clarified. Here, we found that nuclear ceramide increased by NCS-mediated apoptosis through the enhanced assembly of ATM and the meiotic recombination 11/double-strand break repair/Nijmengen breakage syndrome 1 (MRN) complex proteins in human lymphoblastoid L-39 cells. NCS induced an increase of ceramide production through activation of neutral sphingomyelinase (nSMase) and suppression of sphingomyelin synthase (SMS) upstream of DSB-mediated ATM activation. In ATM-deficient lymphoblastoid AT-59 cells compared with L-39 cells, NCS treatment showed a decrease of apoptosis even though ceramide increase and DSBs were observed. Expression of wild-type ATM, but not the kinase-dead mutant ATM, in AT-59 cells increased NCS-induced apoptosis despite similar ceramide accumulation. Interestingly, NCS increased ceramide content in the nucleus through nSMase activation and SMS suppression and promoted colocalization of ceramide with phosphorylated ATM and foci of MRN complex. Inhibition of ceramide generation by the overexpression of SMS suppressed NCS-induced apoptosis through the inhibition of ATM activation and assembly of the MRN complex. In addition, inhibition of ceramide increased by the nSMase inhibitor GW4869 prevented NCS-mediated activation of the ATM. Therefore, our findings suggest the involvement of the nuclear ceramide with ATM activation in NCS-mediated apoptosis. SIGNIFICANCE STATEMENT: This study demonstrates that regulation of ceramide with neutral sphingomyelinase and sphingomyelin synthase in the nucleus in double-strand break-mimetic agent neocarzinostatin (NCS)-induced apoptosis. This study also showed that ceramide increase in the nucleus plays a role in NCS-induced apoptosis through activation of the ataxia telangiectasia mutated/meiotic recombination 11/double-strand break repair/Nijmengen breakage syndrome 1 complex in human lymphoblastoid cells.

Early gastric mixed neuroendocrine-non-neuroendocrine neoplasm with early poor prognosis after endoscopic submucosal dissection: A case report.

Early gastric mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare diseases, with no data on their incidence and prognosis. We report the case of intramucosal gastric MiNENs for endoscopic submucosal dissection (ESD) treatment. An 80-year-old male underwent esophagogastroduodenoscopy for screening and was suspected of early gastric cancer type 0-IIa+IIc on the lesser curvature of the antrum, for which ESD treatment was performed. Histopathologically, the diagnosis was MiNENs. Synaptophysin-positive adenoductal structures were observed in the adenocarcinoma component, suggesting that adenocarcinoma had dedifferentiated into neuroendocrine carcinoma. The tumor was located within the mucosal layer, with lympho-vascular invasion. The patient was kept under observation; however, 6 months after the ESD, computed tomography scan revealed prominent ascites, enlarged lymph nodes, and liver metastases, and MiNENs were suspected to have poor prognosis. If MiNENs diagnosis is made preoperatively or postoperatively, surgical resection may be considered as treatment regardless of the tumor depth or lympho-vascular invasion.

Rate of Return to Work After Periacetabular Osteotomy and Its Influencing Factors.

BACKGROUND: Periacetabular osteotomy (PAO) has been reported as a treatment for patients with symptomatic developmental dysplasia of the hip (DDH). Several studies have investigated the rate of return to sports activities after PAO, but few studies have evaluated the rate of return to work. In the present study, we aimed to identify the rate of return to work at 1 year after PAO and its affecting factors. METHODS: We retrospectively evaluated 83 patients (85 hips) with symptomatic DDH who had undergone PAO between December 2015 and June 2020. Patients who had returned to work at 1 year after PAO were classified into the returnee group, and those who had not were classified into the non-returnee group. The returnee group included patients who could return to their original job (original) or to a different job (non-original). The non-returnee group included patients who could not return to work because of hip symptoms (hip) and those who did not return for reasons other than hip symptoms (non-hip). We analyzed clinical parameters, including the Harris hip score, Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire, 36-Item Short Form Survey, and radiographic parameters, as well as the type of work. RESULTS: Sixty-eight patients (70 hips; 82.4%) returned to work at 1 year after PAO (returnee group), and 15 patients (15 hips; 17.6%) were in the non-returnee group. Among the 15 patients in the non-returnee group, 7 were classified into the non-hip subgroup and 8 were classified into the hip subgroup. No significant differences were observed between the returnee group and the hip subgroup in terms of clinical parameters or type of work. CONCLUSIONS: One year after PAO, 8 patients (8 hips; 9.4%) could not return to work because of hip symptoms; both clinical parameters and the type of work showed no direct relationship with postoperative working status. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

One step fabrication of aligned carbon nanotubes using gas rectifier.

We report the one-step fabrication of aligned and high-quality carbon nanotubes (CNTs) using floating-catalyst chemical vapor deposition (FCCVD) with controlled fluidic properties assisted by a gas rectifier. The gas rectifier consists of one-dimensional straight channels for regulating the Reynolds number of the reaction gas. Our computational fluid dynamics simulation reveals that the narrow channels of the gas rectifier provide steady and accelerated laminar flow of the reaction gas. In addition, strong shear stress is induced near the side wall of the channels, resulting in the spontaneous formation of macroscopic CNT bundles aligned along the direction of the gas flow. After a wet-process using chlorosulfonic acid, the inter-tube voids inherently observed in as-grown CNT bundles are reduced from 16 to 0.3%. The resulting CNT fiber exhibits a tensile strength of 2.1 ± 0.1 N tex-1 with a Young's modulus of 39 ± 4 N tex-1 and an elongation of 6.3 ± 0.6%. FCCVD coupled with the strong shear stress of the reaction gas is an important pre-processing route for the fabrication of high-performance CNT fibers.

Laparoscopic intraperitoneal mesh repair of a large incisional hernia in a kidney transplantation patient: A case report.

A 73-year-old woman presented to our hospital because of painful bulging in the right lower abdomen, and developed a 17 × 12 cm incisional hernia after kidney transplantation using right oblique incision. Laparoscopic intraperitoneal onlay mesh (IPOM) repair was performed. Since a transplanted kidney is close to the abdominal wall defect, the space between the transplanted kidney and the abdominal wall was peeled off to secure enough space for the mesh to be place. After that the fascial defect was detected precisely, and the polypropylene-polyglycolic acid composite mesh was fixed with 3 cm overlapping of the hernia ring by non-absorbable tacks. The patient was discharged 9 days after surgery. In general, abdominal incisional hernias after kidney transplantation are relatively large with boundary defect of abdominal wall ensuing between the abdominal and allograft. However, laparoscopic IPOM repair of incisional hernia after kidney transplantation can be performed safely and effectively.

Relationship between fatty liver change and nutritional status after total gastrectomy in gastric cancer patients: a retrospective study.

BACKGROUND: The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG. METHODS: We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups. RESULTS: Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006). CONCLUSIONS: We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG.

A Method for Cardiac Differentiation, Purification, and Cardiac Spheroid Production of Human Induced Pluripotent Stem Cells.

Human induced pluripotent stem cells (hiPSCs) are one of the most promising cell sources for regenerative medicine. To realize the promise of hiPSCs for cardiac regenerative therapy, three major obstacles must be overcome: the first is the achievement of large-scale production of cardiomyocytes, the second is the successful elimination of non-cardiac cells containing residual pluripotent stem cells (PSCs) to prevent tumor formation, and the third is the achievement of high engraftment efficiency of transplanted cardiomyocytes. In this chapter, we introduce our protocols for cardiac differentiation, purification, and preparation of cardiac spheroids for safe and effective regenerative medicine.

Advanced gastric cancer with abdominal wall invasion treated with curative resection after chemotherapy: a case report.

INTRODUCTION: In patients with gastric cancer, 6-27% of patients are diagnosed with T4b disease that invades adjacent organs, and curative resection can improve the prognosis of these patients. CASE PRESENTATION: A 70-year-old Japanese man presented with an abdominal tumor and was diagnosed with advanced gastric cancer (L-Circ type 3 T4b N2 M0 H0 stage IVA, based on the 15th edition of the Japanese Classification of Gastric Carcinoma) with extensive abdominal wall invasion. We performed open gastrojejunal bypass for gastric obstruction and initiated a chemotherapeutic regimen comprising S-1 (120 mg/day) and oxaliplatin (100 mg/m2). Upper gastrointestinal endoscopy performed after the administration of six courses of the S-1 and oxaliplatin regimen revealed a persistent primary lower gastric wall lesion; however, the diameter of the abdominal wall invasion and metastatic lymph nodes was significantly reduced, in addition to decreased serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Subsequently, the patient underwent distal gastrectomy with D2 lymphadenectomy combined with transverse colon and abdominal wall resection. We performed radical en bloc resection and achieved a tumor-free resection margin. Simple abdominal wall closure was performed without mesh or musculocutaneous flap placement. Histopathological examination of the resected tumor specimen showed direct invasion of the mesocolon and rectus abdominis muscle. The patient was postoperatively diagnosed with L Gre-Ant type5 T4b (SI: rectus abdominis muscle) N2 PM0 DM0 Stage IIIA R0 Grade 2a gastric cancer based on histopathological findings and received S-1 as adjuvant chemotherapy, 2 months postoperatively. No recurrence was detected 6 months postoperatively. CONCLUSIONS: We report a case of advanced gastric cancer with extensive abdominal wall invasion that was successfully treated with gastrectomy combined with resection of adjacent organs showing tumor invasion after effective systemic chemotherapy. A therapeutic approach comprising curative surgery combined with perioperative chemotherapy is useful in patients with T4b gastric cancer.

Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals.

The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

[Role of Surgical Resection after Chemoradiotherapy in Locally Advanced Pancreatic Cancer].

We investigated 34 cases of preoperative chemoradiotherapy(CRT)for locally advanced pancreatic cancer including resectable pancreatic cancer in our department during the past 11 years. For resectable(R)or borderline resectable(BR)pancreatic cancer, survival curves were generally higher in the CRT plus S-1 group treated after CRT than in the CRT group treated with post-CRT chemotherapy, but there was no statistically significant difference. In non-resected cases, local exacerbation was observed, which was one of the causes of a decline in terminal QOL. From the above, at present, it is desirable to remove R or BR pancreatic cancer after CRT, but the significance of surgery may change in the future due to the improvement of multidisciplinary treatment.

Development of Cardiac Regenerative Medicine Using Human iPS Cell-derived Cardiomyocytes.

Heart failure is a life-threatening disease prevalent worldwide. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages represent a critical issue. Cardiac regenerative therapy is beneficial, but it is currently unsuitable as a substitute for cardiac transplantation. Human induced pluripotent stem cells (hiPSCs) are excellent sources for the generation of terminally differentiated cells. The preparation of a large number of pure cardiomyocytes (CMs) is the major premise for translational studies. To control the quality of the generated CMs, an efficient differentiation method, purification strategy, and mass-scale culture must be developed. Metabolic purification and large-scale culture systems have been established, and pure hiPSC-derived CMs of clinical grade are now available for translational research. The most critical challenge in cell therapy is the engraftment of transplanted cells. To overcome the low engraftment ratio of single CMs, aggregations of CMs are developed as cardiac spheroids. A cardiac transplantation device with domed tips and lateral holes has been developed for the transplantation of cardiac spheroids. Large animal models are necessary as the next step in the process toward clinical application. The transplant device has successfully been used to inject cardiac spheroids uniformly into myocardial layers in swine, and this approach is progressing toward clinical use. Remaining issues include immunological rejection and arrhythmia, which will require further investigation to establish safe and effective transplantation. This review summarizes the present status and future challenges of cardiac regenerative therapies.

Predictive factors for developing acute cholangitis and/or cholecystitis in patients undergoing delayed cholecystectomy: A retrospective study.

BACKGROUND: /Objective: We evaluated the risk of acute cholangitis and/or cholecystitis while waiting for cholecystectomy for gallstones. METHODS: We retrospectively enrolled 168 patients who underwent cholecystectomy for gallstones after conservative therapy. We compared clinical data of 20 patients who developed acute cholangitis and/or cholecystitis while waiting for cholecystectomy (group A) with 148 patients who did not develop (group B). We investigated surgical outcomes and risk factors for developing acute cholangitis and/or cholecystitis. RESULTS: Preoperatively, significant numbers of patients with previous history of acute grade II or III cholecystitis (55.0% vs 10.8%; p < 0.001) and biliary drainage (20.0% vs 2.0%; p = 0.004) were observed between groups A and B. White blood cell counts (13500/µL vs 8155/µL; p < 0.001) and C-reactive protein levels (12.6 vs 5.1 mg/dL; p < 0.001) were significantly higher in group A than in group B; albumin levels (3.2 vs 4.0 g/dL; p < 0.001) were significantly lower in group A. Gallbladder wall thickening (≥5 mm) (45.0% vs 18.9%; p = 0.018), incarcerated gallbladder neck stones (55.0% vs 22.3%; p = 0.005), and peri-gallbladder abscess (20.0% vs 1.4%; p = 0.002) were significantly more frequent in group A than in group B. A higher conversion rate to open surgery (20.0% vs 2.0%; p = 0.004), longer operation time (137 vs 102 min; p < 0.001), and higher incidence of intraoperative complications (10.0% vs 0%; p = 0.014) were observed in group A, compared with group B. CONCLUSION: A history of severe cholecystitis may be a risk factor for acute cholangitis and/or cholecystitis in patients waiting for surgery; it may also contribute to increased surgical difficulty.

Chronological Changes in Neutrophil/lymphocyte Ratio in Advanced Gastric Cancer Patients Treated with Nivolumab: a Report of Nine Cases.

BACKGROUND: Nivolumab has been approved for use in advanced gastric cancer (GC) after third-line chemotherapy in Japan. However, it remains difficult to predict favorable nivolumab response before treatment. METHODS: We evaluated the clinical course with a focus on the chronological changes in neutrophil/lymphocyte ratio (NLR) throughout the chemotherapy and assessed the relationship between nivolumab response and chronological changes in NLR before nivolumab administration. RESULTS: We experienced nine cases who received nivolumab monotherapy for unresectable advanced or postoperative recurrent GC. Nivolumab was used as third-line chemotherapy in all patients, and partial response (PR) and stable disease (SD) were observed in two patients each. Nivolumab treatment resulted in progressive disease (PD) in five patients. In patients with PR or SD, changes in the NLR tended to correspond to the response of target metastatic lymph nodes to first- and second-line chemotherapy. In the four cases with PR or SD following nivolumab, ∆NLRresponses that was the difference in the degree of decline during the most effective pretreatment chemotherapy were 1.39, 0.73, 1.62, and 1.22. However, the patients with PD showed lower ∆NLRresponses, at 0.66, 0.66, 0.25, 0.13, and -0.05 in the five cases. Mean ∆NLRresponses in the patients with PR or SD and patients with PD were 1.17 and 0.33, respectively (P = 0.0008). CONCLUSIONS: We experienced nine GC cases treated with nivolumab and assessed the association between chronological NLR changes throughout chemotherapy and tumor response to nivolumab. Changes in NLR during pretreatment chemotherapy might predict tumor response to nivolumab monotherapy in patients with advanced GC.
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Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells.

The role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.

[A Case of Effective Disease Control of Advanced Gastric Cancer with Distant Lymph Node Metastases Following Nivolumab Treatment].

A 66-year-old man was diagnosed with advanced gastric cancer(L, Less, Type 2, T4a[SE], N2, M1[LYM], H0, P0, cStage Ⅳ)and received treatment with S-1/cisplatin as first-line chemotherapy. This treatment resulted in partial response(PR) after 3 months, with reduction in the sizes of metastatic lymph nodes surrounding the pancreatic head and paraaortic lesion. However, the sizes of metastatic lymph nodes increased after 7 months of chemotherapy. Ramucirumab/nab-paclitaxel was then administered as second-line chemotherapy, and the diameter of the metastatic lymph nodes subsequently decreased after 4 months of the regimen. However, progressive disease was observed at 7 months, and blood transfusion was required because of bleeding from the primary gastric tumor. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the first treatment. After nivolumab administration, a 28% reduction in metastatic lymph nodes was achieved within 3 months, together with the regression of the primary gastric tumor and improvement in anemia within 6 months. PR was achieved after 12 months of nivolumab administration, and effective disease control was maintained for 16 months without any adverse reaction to nivolumab.

A Case of Advanced Gastroesophageal Junction Cancer with Bulky Lymph Node Metastases Treated with Nivolumab.

A 71-year-old woman was diagnosed with advanced gastroesophageal junction cancer with bulky lymph nodes along the cardiac region and the lower mediastinum (GE-Circ type 3 T3 N3 M0 H0 stage III) and received treatment with S-1 and oxaliplatin (SOX) as first-line chemotherapy. After 3 cycles of SOX, severe anorexia and diarrhea were observed. We converted from this regimen of systemic chemotherapy to ramucirumab (RAM) monotherapy as second-line chemotherapy. This treatment resulted in a reduction in size of the metastatic lymph nodes along the cardiac region and the lower mediastinum. However, progression of lymph node metastasis and the primary tumor was observed following 7 months of RAM monotherapy. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the initial treatment. After 3 months of nivolumab administration, a 47% reduction in metastatic lymph nodes was achieved and a regression of the primary gastric tumor as seen on an enhanced computed tomography scan. After 7 months of nivolumab monotherapy, the diameter of the target lymph nodes had reduced by 81% from baseline, and there was no evidence of malignancy upon pathological assessment of the primary tumor site biopsy. The patient survived with nivolumab monotherapy for approximately 2 years after her first visit, without any adverse reaction to nivolumab.

Pancreatic neuroendocrine tumor featuring growth into the main pancreatic duct and tumor thrombus within the splenic vein: a case report.

A 48-year-old woman was admitted to our hospital because of upper abdominal pain. Computer tomography showed an enhancing mass in the pancreatic body, dilation of the main pancreatic duct (MPD) and a filling defect within the splenic vein. On the basis of the preoperative diagnosis of pancreatic body cancer, distal pancreatectomy was scheduled. The pancreas was divided along the left edge of the gastroduodenal artery; however, frozen pathological examination of the pancreatic stump was tumor positive, and therefore a total pancreatectomy was performed. The lesion was a white expansive nodular mass that had spread into the MPD and protruded into the splenic vein. A pathological diagnosis of non-functioning neuroendocrine tumor (NET) was made. In general, imaging findings of disruption of the MPD and tumor vein thrombus are characteristics of pancreatic ductal adenocarcinoma, but are uncommon in NET. However, NET should be included in the differential diagnosis for such patients.