Repeated Resection for Recurrent Metastatic Solid Pseudopapillary Neoplasm of the Pancreas.

BACKGROUND Solid pseudopapillary neoplasm (SPN) accounts for 1.0% to 2.0% of all pancreatic neoplasms. SPN generally has good prognosis after surgery; however, 10% to 15% of patients have local recurrence or distant metastasis. There have been a few reports of successful surgical resection of isolated recurrent tumors after radical resection and sporadic reports of multiple metastasectomies. Herein, we present a case of recurrent SPN treated by repeated surgeries. CASE REPORT A 49-year-old woman was referred to our hospital with jaundice and right upper abdominal pain. Computed tomography (CT) scanning revealed a 73×43-mm heterogeneous mass in the pancreatic head. We performed a pancreatoduodenectomy and diagnosed SPN. The patient was discharged without any complications and was followed up by CT once every 6 to 12 months. Six years later, a 15×15-mm tumor was detected in Couinaud segment VI of the liver. A liver biopsy showed a pathological match to the pancreatic tumor. We performed a partial hepatectomy, and the pathology report confirmed metastatic SPN. At 8 and 10 years after the initial surgery, the patient underwent further partial hepatectomies for confirmed solitary liver metastases of SPN. The Ki-67 index increased for each metastasis identified (initial tumor, 1.88%; 6 years, 7.38%; 8 years, 5.53%; 10 years, 11.22%). No further masses were detected, and the patient survived more than 10 years following surgery. CONCLUSIONS Despite histological transformation to high-grade malignant disease, repeated aggressive surgical resection led to long-term survival in our patient with SPN.

Comparing catch-up vaccination programs based on analysis of 2012-13 rubella outbreak in Kawasaki City, Japan.

During the 2012-13 rubella outbreak in Japan, local governments implemented subsidy programs for catch-up vaccination to mitigate the rubella outbreak and prevent congenital rubella syndrome (CRS). In most local governments, to prevent CRS, eligible persons of the subsidy program were women who were planning to have a child and men who were partners of pregnant women. On the other hand, in Kawasaki City, unimmunized men aged 23-39 years were additionally included in the eligible persons, because they were included in an unimmunized men group resulting from the historical transition of the national routine vaccination in Japan. The number of rubella cases in the city decreased earlier than that in the whole Japan. First, in order to estimate the effect of the catch-up vaccination campaign in Kawasaki City on the epidemic outcome, we performed numerical simulations with a Susceptible-Vaccinated-Exposed-Infectious-Recovered (SVEIR) model incorporating real data. The result indicated that the catch-up vaccination campaign showed a beneficial impact on the early decay of the rubella cases. Second, we numerically compared several different implementation strategies of catch-up vaccinations under a fixed amount of total vaccinations. As a result, we found that early and intensive vaccinations are vital for significant reduction in the number of rubella cases and CRS occurrences. Our study suggests that mathematical models with epidemiological and social data can contribute to identifying the most effective vaccination strategy.

A case of Williams syndrome with suspected coexisting ectopic aldosterone-producing tumor in the liver.

SUMMARY: A 31-year-old man with Williams syndrome (WS) was referred to our hospital because of a 9-year history of hypertension, hypokalemia, and high plasma aldosterone concentration to renin activity ratio. A diagnosis of primary aldosteronism (PA) was clinically confirmed but an abdominal CT scan showed no abnormal findings in his adrenal glands. However, a 13-mm hypervascular tumor in the posterosuperior segment of the right hepatic lobe was detected. Adrenal venous sampling (AVS) subsequently revealed the presence of an extended tributary of the right adrenal vein to the liver surrounding the tumor. Segmental AVS further demonstrated a high plasma aldosterone concentration (PAC) in the right superior tributary vein draining the tumor. Laparoscopic partial hepatectomy was performed. The resected tumor histologically separated from the liver was composed of clear cells, immunohistochemically positive for aldesterone synthase (CYP11B2), and subsequently diagnosed as aldosterone-producing adrenal adenoma. After surgery, his blood pressure, serum potassium level, plasma renin activity and PAC were normalized. To the best of our knowledge, this is the first report of WS associated with PA. WS harbors a high prevalence of hypertension and therefore PA should be considered when managing the patients with WS and hypertension. In this case, the CT findings alone could not differentiate the adrenal rest tumor. Our case, therefore, highlights the usefulness of segmental AVS to distinguish adrenal tumors from hepatic adrenal rest tumors. LEARNING POINTS: Williams syndrome (WS) is a rare genetic disorder, characterized by a constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. WS is a disease with a high frequency of hypertension but the renin-aldosterone system in WS cases has not been studied at all. If a patient with WS had hypertension and severe hypokalemia, low PRA and high ARR, the coexistence of primary aldosteronism (PA) should be considered. Adrenal rest tumors are thought to arise from aberrant adrenal tissues and are a rare cause of PA. Hepatic adrenal rest tumor (HART) should be considered in the differential diagnosis when detecting a mass in the right hepatic lobe. Segmental adrenal venous sampling could contribute to distinguish adrenal tumors from HART.

Profiling physicochemical and planktonic features from discretely/continuously sampled surface water.

There is an increasing need for assessing aquatic ecosystems that are globally endangered. Since aquatic ecosystems are complex, integrated consideration of multiple factors utilizing omics technologies can help us better understand aquatic ecosystems. An integrated strategy linking three analytical (machine learning, factor mapping, and forecast-error-variance decomposition) approaches for extracting the features of surface water from datasets comprising ions, metabolites, and microorganisms is proposed herein. The three developed approaches can be employed for diverse datasets of sample sizes and experimentally analyzed factors. The three approaches are applied to explore the features of bay water surrounding Odaiba, Tokyo, Japan, as a case study. Firstly, the machine learning approach separated 681 surface water samples within Japan into three clusters, categorizing Odaiba water into seawater with relatively low inorganic ions, including Mg, Ba, and B. Secondly, the factor mapping approach illustrated Odaiba water samples from the summer as rich in multiple amino acids and some other metabolites and poor in inorganic ions relative to other seasons based on their seasonal dynamics. Finally, forecast-error-variance decomposition using vector autoregressive models indicated that a type of microalgae (Raphidophyceae) grows in close correlation with alanine, succinic acid, and valine on filters and with isobutyric acid and 4-hydroxybenzoic acid in filtrate, Ba, and average wind speed. Our integrated strategy can be used to examine many biological, chemical, and environmental physical factors to analyze surface water.

Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats.

Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFα and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. © 2016 Wiley Periodicals, Inc.

Midline extraperitoneal approach for bilateral widespread retroperitoneal abscess originating from anorectal infection.

INTRODUCTION: Anorectal abscess is one of the most common anorectal conditions encountered in practice. However, such abscesses may rarely extend upward and cause life-threatening medical conditions. PRESENTATION OF CASE: A 53-year-old woman presented with symptoms of anorectal abscess and evidence of severe inflammatory response and acute kidney injury. Computed tomography revealed a widespread abscess extending to the bilateral retroperitoneal spaces. Surgical drainage was performed via a totally extraperitoneal approach through a lower midline abdominal incision, and the patient had a rapid and uncomplicated recovery. DISCUSSION: Although retroperitoneal abscesses originating from the anorectal region are rare, they are life-threating events that require immediate treatment. Percutaneous abscess drainage has been recently evolved; however, surgical drainage is required sometimes that may be challenging, particularly in the case of widespread abscesses, as in our case. CONCLUSION: The midline extraperitoneal approach reported here might be an effective surgical option for patients with bilateral widespread retroperitoneal abscesses.

Synthesis and biological activity of the C'D'E'F' ring system of maitotoxin.

Stereoselective synthesis of the C'D'E'F' ring system of maitotoxin was achieved starting from the E' ring through successive formation of the D' and C' rings based on SmI2-mediated reductive cyclization. Construction of the F' ring was accomplished via Suzuki-Miyaura cross-coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C'D'E'F' ring system inhibited maitotoxin-induced Ca(2+) influx in rat glioma C6 cells with an IC50 value of 59 µM.

Swainsonine reduces 5-fluorouracil tolerance in the multistage resistance of colorectal cancer cell lines.

BACKGROUND: Drug resistance is a major problem in cancer chemotherapy. Acquisition of chemo-resistance not only reduces the effectiveness of drugs, but also promotes side effects and markedly reduces the patient's quality of life. However, a number of resistance mechanisms have been reported and are thought to be the reason for the difficulties in solving drug-resistance problems. RESULT: To investigate the mechanisms of drug resistance, a set of cell lines with different levels of sensitivity and possessing different mechanisms of resistance to 5-fluorouracil (5-FU) was established from a colorectal cancer cell line. The expression of thymidylate synthase, orotic acid phosphoribosyltransferase and dihydropyrimidine dehydrogenase, which are well known to be related to drug resistance, differed among these cell lines, indicating that these cell lines acquired different resistance mechanisms. However, swainsonine, an inhibitor of N-glycan biosynthesis, reduced 5-FU-tolerance in all resistant cells, whereas the sensitivity of the parental cells was unchanged. Further analysis of the N-glycan profiles of all cell lines showed partial inhibition of biosynthesis and no cytotoxicity at the swainsonine dosage tested. CONCLUSION: These observations suggest that N-linked oligosaccharides affect 5-FU resistance more widely than do drug-resistance related enzymes in colorectal cancer cells, and that the N-glycan could be a universal target for chemotherapy. Further, swainsonine may enhance the performance of chemotherapy by reducing tolerance.

Interferon-beta inhibits liver metastases from murine colon 26 carcinoma and its highly metastatic variant.

PURPOSE: The antitumor effects of Interferon-beta (IFN-beta) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5). METHODS: We examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo. RESULTS: The proliferation of CT 26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5 (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the mice inoculated with L5 administered IFN-beta every other day, or every day was higher than in the control group (P<0.05). A dorsal air sac assay demonstrated that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor. CONCLUSION: These results showed that IFN-beta directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-beta might effectively inhibit liver metastases.

[A phase I study of postoperative combination therapy with TS-1 and low dose cisplatin against stage IV gastric carcinoma].

A dose-escalation study was conducted for postoperative patients with stage IV gastric cancer to determine the recommended dose of daily intravenous cisplatin combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for 2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25 to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed. Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the grade of toxicity. Three patients enrolled in each level. Dose escalation was performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the recommended dose (RD) in this protocol for postoperative stage IV gastric carcinoma.