Synchronous double cancers of the remnant stomach and pancreas: Report of a case

We present here in the case of a 75-year-old man who developed synchronous double cancers of the remnant stomach and pancreas 12 years after undergoing distal gastrectomy for gastric carcinoma. The patient was referred to our hospital in March, 1993, with a provisional diagnosis of carcinoma of the remnant stomach. Laboratory data on admission showed an abnormal level of CA19-9 (116.1 U/ml) and positive occult blood in the stools. An upper gastrointestinal series and gastroendoscopy demonstrated an ulcerative polypoid tumor in the gastric stump proximal to the gastroduodenostomy anastomosis, and a biopsy confirmed the findings of mucinous adenocarcinoma. Abdominal computed tomography (CT) scan revealed a low-density nodule anterior to the abdominal aorta, suggestive of a nodal metastasis. A laparotomy was performed which also disclosed a low-density mass located within the head of the pancreas. The patient was subsequently diagnosed as having double carcinomas of the remnant stomach and pancreas, and total gastrectomy and pancreatoduodenectomy were carried out. The histologic sections from the remnant stomach showed mucinous adenocarcinoma, whereas those from the pancreas showed tubular adenocarcinoma. Double carcinomas in this association are extremely rare and this case may in fact be the first observation of synchronous double cancers of the remnant stomach and pancreas.     

Effect of heparin addition on expansion of cord blood hematopoietic progenitor cells in three-dimensional coculture with stromal cells in nonwoven fabrics

Primary human cord blood mononuclear cells (CB MNCs) were inoculated into layers of primary human bone marrow stromal cells prepared in a nonwoven fabric porous carrier [three dimensional (3-D)] or on a dish [two dimensional (2-D)] using a cytokine-free medium and were cultured for 7 days with or without the addition of heparin. The number of progenitor cells increased threefold during the 3-D coculture, whereas it decreased in the 2-D culture. Heparin addition to the 3-D coculture further increased the number of progenitors twofold, whereas the addition of desulfated heparin had no effect. The heparin effect was also observed in a 3-D culture of CB MNCs without stromal cells when conditioned medium was employed. The coating of the carrier with N-(O--(6-O-sulfogalactopyranosyl)-6-oxyhexyl)-3,5-bis (dodecyloxy)-benzamide instead of heparin addition also increased the number of progenitor cells in the 3-D culture of CB MNCs without stromal cells when the conditioned medium was employed. The 3-D coculture constructed with nonwoven fabrics and stromal cells was clearly superior to the 2-D culture because of the expansion of CB hematopoietic progenitor cells without cytokine addition. Heparin addition to the 3-D coculture further increased the number of progenitor cells, which may result from a synergistic effect of soluble cytokines produced by stromal cells with the sulfur group of heparin.     

Evidence of immunostimulating lipoprotein existing in the natural lipoteichoic acid fraction

Lipoteichoic acid (LTA) is a cell surface glycoconjugate of gram-positive bacteria and is reported to activate the innate immune system. We previously reported that purified LTA obtained from Enterococcus hirae has no immunostimulating activity, but a subfraction (Eh-AF) in an LTA fraction possesses activity. In this study, we established a mouse monoclonal antibody neutralizing the activity of Eh-AF and investigated its inhibitory effects. Monoclonal antibody (MAbEh1) was established by the immunization of BALB/c mice with Eh-AF, followed by hybridoma screening based on its inhibitory effect for the production of interleukin-6 (IL-6) induced by Eh-AF. MAbEh1 neutralized the production of IL-6 by LTA fraction from not only E. hirae but also Staphylococcus aureus, while it failed to block that of lipopolysaccharide, suggesting that the antibody recognized a common active structure(s) in LTA fractions. Synthetic glycolipids in these LTAs did not induce cytokine production, at least in our system. Interestingly, the antibody was found to inhibit the activity of immunostimulating synthetic lipopeptides, Pam(3)CSK(4) and FSL-1. These results suggest that MAbEh1 neutralizes the activity of lipoprotein-like compounds which is responsible for the activity of the LTA fraction of E. hirae and S. aureus.     

Outbreak of Mucormycosis in Coronavirus Disease Patients,Pune, India

We provide an overview of the epidemiology and clinical course of mucormycosis in the coronavirus disease (COVID-19) pandemic era. We conducted a retrospective chart review of 178 patients with clinical or diagnostic, endoscopically or histopathologically confirmed rhino-sino-orbital or cerebral mucormycosis after COVID-19 treatment during the second wave of COVID-19 in Pune, India. Median time to symptom onset from COVID-19 detection was 28 days. Moderate or severe COVID-19 was seen in 73% of patients and diabetes in 74.2%. A total of 52.8% received steroids. Eschar over or inside the nose was seen in 75%, but baseline clinical and laboratory parameters were mostly unremarkable. Bone penetration was present in ≈90% of cases, 30% had soft-tissue swelling of the pterygopalatine fossa and 7% had cavernous sinus thrombosis, and 60% had multifocal mucormycosis. Of the 178 study cases, 151 (85%) underwent surgical debridement. Twenty-six (15%) died, and 16 (62%) of those had multifocal mucormycosis.     

Common bile duct exploration—Primary closure of the duct with retrograde transhepatic biliary drainage—

A new method of retrograde transhepatic biliary drainage (RTBD) using and RTBD tube with primary closure of the common duct was investigated with special reference to the usefulness and feasibility of this procedure. At operation, an atraumatic vinyl chloride tube was inserted from a choledochotomy incision and in most cases advancedvia the left hepatic duct to the liver surface, which was then penetrated. After the choledochotomy incision had been primarily sutured, the RTBD tube was fixed to the abdominal wall. This drainage method was applied to 71 patients as an alternative to the conventional T-tube drainage and its effect on bile drainage was prominent. The insertion of an RTBD tube did not influence liver function tests and an RTBD tube cholangiography revealed no severe deformity at the primary closure site of the bile duct. The most common complication was movement of the optimal site for stenting of the bile duct, however, no serious complications were encountered. On average, the RTBD tube was removed on the 16th postoperative day, the mean postoperative stay in hospital being 22 days. These findings suggest the need for a prospective randomized clinical trial to prove the usefulness and feasibility of primary bile duct closure using our drainage method.     

Absence of associations between influenza-associated encephalopathy and human herpesvirus 6 or human herpesvirus 7

BACKGROUND: Influenza-associated encephalopathy is a severe complication of influenza virus infection, but its pathogenesis is unknown. It was recently suggested that the neurologic complications of influenza, including encephalopathy, are associated with human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7).AIM To confirm or refute the association between influenza-associated encephalopathy and HHV-6 or HHV-7. METHODS: Cerebrospinal fluid and serum from 25 patients with central nervous system complications of influenza (18 patients with encephalopathy and 7 patients with febrile convulsions) were investigated. The specimens were examined by real time polymerase chain reaction (PCR) and nested PCR for HHV-6 and HHV-7 DNA. RESULTS: In the cerebrospinal fluid samples neither HHV-6 DNA nor HHV-7 DNA was detected by real time PCR or nested PCR. HHV-6 DNA was detected in a single serum sample from a patient with febrile convulsions. CONCLUSION: In our study there was no association with HHV-6 or HHV-7 in most patients with central nervous system complications of influenza.     

Sitagliptin added to voglibose monotherapy improves glycemic control in patients with type 2 diabetes

Aims/Introduction

Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control. The present multicenter, randomized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy (0.2–0.3 mg three times daily) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control (glycated hemoglobin ≥6.9% and <10.5%).

Materials and Methods

The present study had an initial 12‐week, double‐blind treatment period in which patients were randomized (1:1) to sitagliptin 50 mg/day (n = 70) or placebo (n = 63), followed by a 40‐week, open‐label treatment period during which all patients received sitagliptin 50 mg/day, that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria.

Results

After 12 weeks, treatment with sitagliptin resulted in placebo‐subtracted mean changes from baseline in glycated hemoglobin (the primary end‐point), fasting plasma glucose and 2‐h postmeal glucose of –0.9%, –22.5 mg/dL and –51.3 mg/dL, respectively (all, P < 0.001). During the double‐blind period, adverse experiences were reported with similar frequency in both treatment groups, and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low. In the open‐label period, sustained improvements in glycemic parameters were observed with sitagliptin treatment, and sitagliptin was generally well tolerated.

Conclusions

Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control. This trial was registered with ClinicalTrails.gov (no. NCT00837577).     

Formulation development of inhalation powders for FK888 using the E-haler to improve the inhalation performance at a high dose, and its absorption in healthy volunteers.

FK888 is a candidate selective NK1 receptor antagonist, and it exhibits poor absorption from the gastrointestinal tract in healthy volunteers. In a previous study, the optimized dry powder inhaler (DPI) formulation with carrier lactose using the Spinhaler was developed, although the maximum dose per capsule was only 5mg because the fine particle fraction (FPF) was reduced at doses over 5mg. The objective of this study was to develop an optimized DPI formulation for higher doses, such as 40 mg, with proportional systemic absorption. The Spinhaler and E-haler were used as the inhalation devices, and the in vitro deposition was evaluated using a multistage cascade impactor at different flow rates (28.3 and 60 l/min). When hydroxypropyl methylcellulose (HPMC) capsules were used as the container, and spherical soft agglomerates of fine FK888 particles (soft pellets) and the E-haler were used, the fraction of particles emitted from the inhalation system (Em) was significantly improved, to over 80% of the nominal dose, and no significant difference was found between the airflow rates (84.3+/-2.3% for 28.3 l/min, 88.1+/-3.6% for 60 l/min). It was also found that the E-haler was an extremely suitable device for obtaining the higher respirable particle percentage of emitted particles (RP) in the 40 mg formulation with the soft pellets contained in HPMC capsules (35.0+/-1.8% for 28.3 l/min and 42.5+/-3.5% for 60 l/min), compared with the Spinhaler (13.8+/-3.0% for 28.3 l/min and 28.9+/-1.0% for 60 l/min). Using the formulations with the E-haler, proportional systemic absorption was achieved up to 40 mg FK888 in healthy volunteers (62.91+/-27.58, 103.70+/-40.19 and 254.79+/-85.01 ngh/ml as AUCs for 10, 20 and 40 mg FK888, respectively; R(2)=0.9641). It is also expected that the E-haler will act as an efficient device when a higher dose, such as 40 mg, is required in clinical situations.