Encapsulated fat necrosis mimicking abdominal liposarcoma: A case report and literature review.

We report a case of an encapsulated fat necrosis without significant medical history. To differentiate from liposarcoma, it should be recognized that a half of abdominal encapsulated fat necrosis cases have a history of inflammation and surgery.

Total Syntheses of Marrubiin and Related Labdane Diterpene Lactones.

Total syntheses of the labdane diterpene lactones marrubiin, marrulibacetal, desertine, marrulibacetal A, marrubasch F, cyllenine C, marrulanic acid, and marrulactone are described. The trans-decalin moiety of these molecules was constructed in a stereoselective manner by a Pauson-Khand reaction, and the resultant cyclopentenone was oxidatively cleaved for formation of the lactone ring. Elongation of the side chain at C9 was achieved by an epoxide-opening reaction with a variety of nucleophiles, and the functional group manipulations completed the syntheses of these natural products. Stereochemistries of desertine could be established by the transformations.

Investigation of the Utility and Safety of Dynamic Computed Tomography with Vasodilators.

BACKGROUND: Dynamic computed tomography (CT) angiography is useful for evaluating of hepatic vascularity. Although vasodilators increase hepatic blood flow, the utility of dynamic CT with vasodilators is unclear. Here we investigated the utility and safety of dynamic CT with vasodilators. METHODS: A prospective case-control radiographic evaluation using abdominal dynamic CT with and without vasodilator was performed at a single center between October 2015 and September 2016. We compared the CT values in Hounsfield units of the aorta; celiac artery; and common, right, and left hepatic arteries in the arterial phase and the main trunk; right and left branches of the portal vein; and right, middle, and left hepatic veins in the portal phase with and without vasodilators. The region of interest was set in each element of the liver vasculature. Four radiological technologists independently and visually compared the scores of the portal vein (P-score) and hepatic vein (V-score) on a 5-point scale with and without vasodilators. RESULTS: The CT values of arteries and veins using vasodilators were significantly higher than those without vasodilators. With and without vasodilators, the P-scores were 3.1 ± 1.2 and 4.0 ± 1.1 (P < 0.05) and the V-scores were 3.3 ± 1.4 and 4.3 ± 1.0 (P < 0.05). Only one patient with vasodilator use had transient hypotension and recovered immediately without medication. CONCLUSION: Dynamic CT with vasodilators can provides better visualization of vascular structures.

Thyroid nodule prevalence among women in areas of high natural background radiation, Karunagappally, Kerala, India.

PURPOSE: Radiation exposure has been reported to cause thyroid nodules. The study area was Karunagapally, which has several areas with high natural radiation levels derived from thorium and its decay products. Since thyroid abnormalities are more common in women, the focus was only on women. METHODS: The examinations included interview, ultrasonography of the thyroid and serum assays of free thyroxine (FT4), thyrotropin (TSH), and anti-thyroglobulin levels. Cumulative dose during the childhood and lifetime cumulative dose (lagged by 5 years) were estimated. RESULTS: We examined 524 female residents aged 17-73 years and found 75 cases of solitary solid thyroid nodules. The prevalence of thyroid nodules were 14.1 % (n = 42) in high dose panchayats and 14.5% (n = 33) in low-dose panchayats. In the logistic regression analysis adjusted for age, the prevalence of solitary thyroid nodule was not linearly related to childhood cumulative dose (P for trend = 0.159) and lifetime cumulative dose (P for trend = 0.333). The prevalence of thyroiditis and hypothyroidism was not related to natural radiation exposure. Serum levels of FT4 or TSH were not related to natural radiation exposure. CONCLUSIONS: The results obtained from the present study do not support the increase of solitary thyroid nodule, thyroiditis or hypothyroidism in relation to high-natural-background-radiation exposure.

Clinical importance of preoperative and postoperative prognostic nutritional index in patients with pancreatic ductal adenocarcinoma.

BACKGROUNDS/AIMS: The prognostic nutritional index (PNI) is based on the albumin concentration and absolute lymphocyte count and is designed to assess the nutritional and immunological status of patients. In this study, we evaluated the prognostic importance of the preoperative and postoperative PNI in patients who underwent curative resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2006 to 2017, 50 patients with PDAC underwent curative resection at our hospital. We performed distal pancreatectomy (DP) with splenectomy in 15 patients, pancreaticoduodenectomy (PD) in 27 patients, PD combined with portal vein partial resection in 6 patients, and total pancreatectomy with splenectomy in 2 patients. We compared the preoperative PNI and postoperative PNI (1 and 2 months postoperatively) and analyzed the prognostic importance for these patients. RESULTS: The mean PNI significantly decreased from 45.5 preoperatively to 39.8 at 1 month postoperatively (p<0.001), but recovered to 42.7 at 2 months postoperatively. In 23 patients, the PNI at 2 months postoperatively recovered to the preoperative level (recovered group), but in the remaining 27 patients, the PNI at 2 months postoperatively did not reach the preoperative level (non-recovered group). The overall median survival time in the recovered group (29 months) was significantly longer than that in the non-recovered group (12 months, p=0.003). The multivariate overall analysis demonstrated that good recovery of the postoperative PNI was strongly correlated with a better prognosis. CONCLUSIONS: Effective postoperative nutrition may have a prognostic benefit for patients with operable PDAC.

Median arcuate ligament syndrome and aneurysm in the pancreaticoduodenal artery detected by retroperitoneal hemorrhage: A case report.

Here, we report a case with successful treatment of inferior pancreaticoduodenal artery aneurysm rupture due to celiac artery trunk compression caused by the median arcuate ligament. When clinicians see visceral aneurysms, the possibility of arcuate midline ligament compression syndrome (MALS) and ligamentectomy for MALS should be considered.

A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder. Despite its severity, there are no effective treatments because of the complexity of its pathogenesis. As one of the underlying mechanisms of Cu, Zn superoxide dismutase (SOD1) gene mutation-induced ALS, SOD1 mutants (SOD1mut) commonly interact with an endoplasmic reticulum-resident membrane protein Derlin-1, triggering motoneuron death. However, the importance of SOD1-Derlin-1 interaction in in vitro human model and in vivo mouse model remains to be elucidated. Here, we identify small-molecular-weight compounds that inhibit the SOD1-Derlin-1 interaction by screening approximately 160,000 compounds. The inhibitor prevents 122 types of SOD1mut from interacting with Derlin-1, and significantly ameliorates the ALS pathology both in motoneurons derived from patient induced pluripotent stem cells and in model mice. Our data suggest that the SOD1-Derlin-1 interaction contributes to the pathogenesis of ALS and is a promising drug target for ALS treatment.

C-Reactive Protein/Albumin Ratio and Prognostic Nutritional Index Are Strong Prognostic Indicators of Survival in Resected Pancreatic Ductal Adenocarcinoma.

Purpose: We evaluated the clinical importance, such as the occurrence of postoperative pancreatic fistula (POPF) or prognosis, of preoperative serum markers of chronic inflammation, nutrition, and immunity, as well as that of serum tumor markers after curative resection of pancreatic ductal adenocarcinomas (PDACs). Methods: Between 2006 and 2015, 43 patients with PDACs underwent curative resection at Tottori Prefectural Central Hospital. We analyzed which preoperative indicators (i.e., C-reactive protein/albumin ratio [CAR], neutrophil/lymphocyte ratio [NLR], prognostic nutritional index [PNI], carcinoembryonic antigen [CEA], and carbohydrate antigen 19-9 [CA 19-9]) were the most relevant risk factors for occurrence of POPF and poor patient survival. Results: POPF was detected in 8/43 (18.6%) patients. One patient died of pancreatic fistula at 2 months postoperatively. Among nine candidate factors (operative procedure, operation time, tumor stage, preoperative serum amylase, preoperative CAR, NLR, PNI, CEA, and CA 19-9), we did not identify any significant risk factor for the occurrence of POPF. The 5-year overall survival (OS) rate of the 43 patients was 22.4%, and the overall median survival time was 21 months. The multivariate OS analysis demonstrated that high CAR and low PNI were strong preoperative markers of poor prognosis independently of tumor stage. Conclusions: Preoperative CAR and PNI are useful prognostic markers for patients with operable PDACs.

Isolated port-site metastasis of hepatocellular carcinoma after laparoscopic liver resection.

Port-site metastasis of hepatocellular carcinoma (HCC) is extremely rare, and only one case has been reported in the English-language literature. Contamination with malignant cells along the needle tract during percutaneous biopsy or radiofrequency ablation is a well-recognized cause of HCC recurrence. Here, we describe a case of port-site metastasis after laparoscopic liver resection of HCC. The patient, who had undergone laparoscopic partial resection of the left lateral segment of the liver 18 months earlier, was diagnosed with HCC. CT showed a nodule in the abdominal wall where the laparoscopic port had been inserted during resection. Local excision was performed, and histological examination revealed HCC consistent with recurrence after laparoscopic resection. The experience described in this report highlights the risk of port-site metastasis of HCC. Imaging for oncologic surveillance after laparoscopic resection must include all port sites.

Total Syntheses of (+)-Marrubiin and (-)-Marrulibacetal.

A stereoselective total synthesis of (+)-marrubiin has been accomplished starting from a chiral building block via the CyNH2-promoted Pauson-Khand reaction (PKR) followed by oxidative cleavage of the resultant cyclopentenone ring. Two successive oxidations and internal transacetalization culminated in the total synthesis of the antispasmodic labdane diterpenoid (-)-marrulibacetal.

Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas.

The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated. In this retrospective study, 84 enrolled patients diagnosed with resectable clinical stage I-III thoracic esophageal squamous cell carcinomas (ESCCs) underwent thoracic esophageal resection and three-field lymph node dissection at Tottori University Hospital between January 2007 and December 2013. The correlations among preoperative patient markers (GPS, NLR, PNI, SCC-Ag and CYFRA 21-1) and the occurrence of postoperative complications and patient survival were analyzed. The operative mortality was 2.4%, and morbidity was 42.9%. Strong correlations between occurrence of postoperative complications and open thoracotomy (P=0.083) and high-serum CYFRA 21-1 (P=0.007) were observed. In 15 patients with high-serum CYFRA 21-1, postoperative complications were detected in 11 of them (73.3%); on the other hand, complications occurred in 25 of 69 (36.2%) with low-serum CYFRA 21-1. The 5-year disease-free survival rate and 5-year overall survival rate of all the patients were 52.2 and 50.8%, respectively. Among the prognostic parameters, preoperative high NLR was determined to be a poor prognostic factor, independent of the tumor stage in the multivariate analysis. These results may indicate that, in patients with preoperative high-serum CYFRA 21-1, more attention should be paid to the occurrence of postoperative complications. Therefore, in such cases, anastomosis between blood vessels of the substitute esophagus and cervical vessels would be recommended. Furthermore, in patients with high preoperative NLR, effective adjuvant chemoradiotherapy should be considered to prolong the patients' survival, even of stage I or II patients.

Comparison of single-stapling and hemi-double-stapling methods for intracorporeal esophagojejunostomy using a circular stapler after totally laparoscopic total gastrectomy.

BACKGROUND: Laparoscopic total gastrectomy is not widely performed because of the difficulty of esophagojejunal reconstruction. This study analyzed complication rates of two different methods for reconstruction by a circular stapler after totally laparoscopic total gastrectomy (TLTG). METHODS: Between 2010 and 2014, clinical data of 19 patients who underwent TLTG for gastric adenocarcinoma were collected retrospectively. There were two methods to fix the anvil of a circular stapler into the distal esophagus: In the single-stapling technique (SST) group, Endo-PSI(II) was used for purse-suturing on the distal esophagus for reconstruction, and in the hemi-double-stapling technique (hemi-DST) group, the esophagus was cut by linear stapler with the entry hole of the anvil shaft opened after inserting the anvil tail. In both groups, surgical procedures were the same, except for the reconstruction. RESULTS: All TLTGs were performed securely without mortality. Intracorporeal laparoscopic esophagojejunal anastomosis was performed successfully for all the patients. In the hemi-DST group, four patients experienced anastomotic stenosis, three of whom required endoscopic balloon dilation. In contrast, no stenosis was seen in the SST group (p = 0.033). CONCLUSIONS: Anastomosis with SST is preferred to that with hemi-DST to minimize postoperative complications.

Construction of Bridged Polycyclic Systems by Polyene Cyclization.

A stereoselective construction of bridged tri- and tetracyclic systems embedded in some 3,5-dimethylorsellinic acid (DMOA)-derived meroterpenoids was achieved by exploiting a polyene cyclization of suitably functionalized epoxyallylsilanes. Both the olefinic substituent on the epoxide and allylic trimethylsilyl (TMS) group were found to play pivotal roles in the success of the present reaction. The fact that the cyclization of monocyclized byproducts did not proceed strongly suggests that the reaction could be a concerted transformation.

Glycosylation with 2-Acetamido-2-deoxyglycosyl Donors at a Low Temperature: Scope of the Non-Oxazoline Method.

A direct construction of 1,2-trans-ß-linked 2-acetamido-2-deoxyglycosides was investigated. The 3,4,6-tri-O-benzyl- and 3,4,6-tri-O-acetyl-protected glycosyl diethyl phosphites and 4,6-O-benzylidene-protected galactosyl diethyl phosphite each reacted with a variety of acceptor alcohols in the presence of a stoichiometric amount of Tf2NH in CH2Cl2 at -78 °C to afford the corresponding ß-glycosides in good to high yields with complete stereoselectivity. Some experiments provided strong evidence that the corresponding oxazolinium ions are not responsible for the reaction. We demonstrated that glycosylations with the corresponding glycosyl imidate and thioglycoside also proceeded at a low temperature, indicating the possibility of these donors being attractive alternatives to the phosphite. A plausible reaction mechanism, which features glycosyl triflimide and contact ion pair as reactive intermediates, is proposed on the basis of the results obtained with 2-acetamido-2-deoxymannosyl donors.

Synthesis of the Tetrasaccharide Repeating Unit from Acinetobacter baumannii Serogroup O18 Capitalizing on Phosphorus-Containing Leaving Groups.

The first convergent synthesis of the tetrasaccharide repeating unit of the polymeric O antigen isolated from Acinetobacter baumannii serogroup O18 has been achieved. The ManNAcß1→4Gal and GalNAcß1→3Gal units were successfully obtained through ß-selective glycosylation with 2-azido-4,6-O-benzylidene-2-deoxymannosyl diphenyl phosphate and Tf2NH-promoted glycosylation with 2-acetamido-2-deoxygalactosyl diethyl phosphite, respectively. The disaccharide units could be coupled with the aid of TMSClO4 as an activator of the diphenyl phosphate leaving group, and global deprotection completed the synthesis of the tetrasaccharide.

Stereoselective synthesis of the CDE ring system of antitumor saponin scillascilloside E-1.

A stereoselective synthesis of the CDE ring portion of the antitumor saponin scillascilloside E-1 has been achieved, utilizing an Ireland-Claisen rearrangement to construct the contiguous tetrasubstituted stereocenters at C13 and C17 simultaneously and intramolecular nitrile oxide cycloaddition to form the five-membered ring as key steps.

Synthesis of chiral building blocks for oxygenated terpenoids through a simultaneous and stereocontrolled construction of contiguous quaternary stereocenters by an Ireland-Claisen rearrangement.

Methods for highly stereocontrolled syntheses of chiral building blocks with a triad of contiguous stereocenters, including two quaternary ones, have been developed. Ireland-Claisen rearrangement of the (Z)-silyl ketene acetal generated stereoselectively from the (R)-3-methylcyclohex-2-enyl ester derived from an acyclic carboxylic acid proceeded through a chairlike transition state to give the rearranged product with an S configuration at the position α to the carboxyl group. Introduction of a cyclic conformational constraint in the acid component completely switched the transition state of the rearrangement to a boatlike one, leading to the predominant formation of a product with an R configuration, from which pseudodiastereomeric α-hydroxy esters were obtained in a four-step sequence. The enyne obtained through a base-mediated double eliminative ring-opening reaction was successfully converted into advanced intermediates for the synthesis of 9-oxygenated labdane diterpenoids through a Heck reaction and a regioselective transformation of the resultant diene.

Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer. METHODS: Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints. RESULTS: Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B. CONCLUSIONS: Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

Total syntheses of (+)-polygalolide†a and (+)-polygalolide†b: elucidation of the absolute stereochemistry and biogenetic implications.

The total syntheses of (+)-polygalolide A and (+)-polygalolide B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh(2) (OAc)(4)]-catalyzed carbonyl ylide formation/intramolecular 1,3-dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol-type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero-Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3 % overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose-derived oxypyrylium zwitterion with an isoprene derivative.

Cancer and non-cancer mortality among Inhabitants in the high background radiation area of Yangjiang, China (1979-1998).

The present study aimed to evaluate the effects of high background radiation (HBR) on mortality. A cohort of 31,604 men and women aged 30-74 y living in the study area in Guangdong Province, China, was followed during the period 1979-1998. The information on deaths and migrations of cohort members was collected by visiting study areas every 3-4 y. Cumulative external radiation dose, lagged by 2 y for leukemia and 10 y for cancer excluding leukemia, was estimated for each individual based on hamlet-specific indoor and outdoor doses, and gender- and age-specific house occupancy factors. The follow-up study accumulated 736,942 person-years at risk and ascertained 6,005 deaths, including 956 cancer deaths and 4,525 non-cancer disease deaths. Mean cumulative radiation doses from natural radiation in the HBR and control area residents were 84.8 mGy and 21.6 mGy, respectively. Mortality due to leukemia (15 deaths) or cancer excluding leukemia (941 deaths) was not related to cumulative radiation dose. The excess relative risk (ERR) Gy of cancer excluding leukemia was estimated to be -1.01 (95% CI: -2.53, 0.95). In site-specific analysis, liver-cancer mortality was inversely related to the cumulative dose (p=0.002). Note, however, that liver cancer is well known for its difficulty in accurate diagnosis. The ERR Gy of cancer excluding leukemia and liver cancer was 0.19 (95% CI: -1.87, 3.04). Non-cancer disease mortality was not related to cumulative radiation dose either. The cumulative HBR dose was not related to the mortality due to cancer or all non-cancer diseases among residents in Yangjiang HBR areas.