PAX5 alterations in an infant case of KMT2A‐rearranged leukemia with lineage switch

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A‐rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A‐MLLT3‐rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A‐MLLT3‐rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre‐post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.     

Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1α/GLUT-1 expression

Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18). Results The overall positive ratios were as follows: HIF-1α, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1α, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas. Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.     

Current national practice patterns for inpatient management of ventral abdominal wall hernia in the United States

Background

The health-care burden related to ventral hernia management is substantial, with more than 3 billion dollars in expenditures annually in the US. Previous studies have suggested that the utilization of laparoscopic repair remains relatively low although national volume estimates have not been reported. We sought to estimate the inpatient national volume of elective ventral hernia surgery and characterize the proportion of laparoscopic versus open operations.

Methods

We analyzed data from the Nationwide Inpatient Sample to identify adults with a diagnosis of an umbilical, incisional, or ventral hernia who underwent an elective inpatient repair between 2009 and 2010. Cases that involved other major abdominal or pelvic operations were excluded. Covariates included patient demographics, surgical approach, and use of mesh. National surgical volume estimates were generated and length of stay and total hospital charges were compared for laparoscopic versus open repairs.

Results

A total of 112,070 ventral hernia repairs were included in the analysis: 72.1 % (n = 80,793) were incisional hernia repairs, while umbilical hernia repairs comprised only 6.9 % (n = 7,788). Laparoscopy was utilized in 26.6 % (n = 29,870) of cases. Mesh was placed in 85.8 % (n = 96,265) of cases, including 49.3 % (n = 3,841) of umbilical hernia repairs and 90.1 % (n = 72,973) of incisional hernia repairs. Length of stay and total hospital charges were significantly lower for laparoscopic umbilical, incisional, and “other” ventral hernia repairs (p values all <0.001). Total hospital charges during this 2-year period approached 4 billion dollars ($746 million for laparoscopic repair; $3 billion for open repair).

Conclusions

Utilization of laparoscopy for elective abdominal wall hernia repair remains relatively low in the US despite its excellent outcomes. Given the substantial financial burden associated with these hernias, future research focused on preventing the development and optimizing the surgical treatment of ventral abdominal wall hernias is warranted.     

Transarterial Chemoembolization With Cisplatin as Second-Line Treatment for Hepatocellular Carcinoma Unresponsive to Chemoembolization With Epirubicin-Lipiodol Emulsion

Purpose  

The purpose of this retrospective study was to investigate the efficacy of transarterial chemoembolization (TACE) using cisplatin as a second-line treatment for advanced hepatocellular carcinoma (HCC) unresponsive to TACE using epirubicin–Lipiodol emulsion at our institution.     

Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy

Background: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty‐three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single‐blind, parallel‐group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre‐ and postoperative interleukin (IL)–6, C‐reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL‐6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre‐ and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). Conclusions: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.     

Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow up

Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management.     

Newborn screening for congenital adrenal hyperplasia in Sapporo City: sixteen years experience

A screening program for congenital adrenal hyperplasia (CAH) in Sapporo began in 1982, 7 years prior to the introduction of the national program. Since its inception, testing has involved the detection of 17-hydroxyprogesterone (17-OHP) in dried blood samples, using ELISA. Up to the end of March 1998, of 298,731 newborn screened, second samples were requested in 1,723 cases (0.6%). This number included 789 newborns who weighed less than 2,000 gm at birth. A total of 14 cases were diagnosed with 21-hydroxylase deficiency (21-OHD). "Salt-wasting type (SW)" outnumbered "simple virilizing type (SV)" by 11:3. The ratio of male to female was a converse. but unrelated, 3:11. Our study from 1982-1997 revealed that the incidence of 21-OHD in Sapporo City was 1:21.338, markedly similar to the worldwide incidence of 1:15,000. In order to improve the program, other type of analysis are also currently in use and under evaluation. These include highly sensitive HPLC analysis for 17-OHP and molecular analysis to identify some mutations associated with the 21-OHD gene (CYP21). These methodologies are very useful for the confirmation of information acquired from dried blood specimens.     

Common antigenicities between Angiostrongylus cantonensis and various species of snails

Studies on common antigenicities were carried out by using rabbit sera immunized with Angiostrongylus cantonensis adult worms or the third stage larvae and antigens of various species of snails and vice versa by the immunoblotting technique. The results obtained are summarized as follows: (1) Common antigenicities between A. cantonensis adult worms and snails susceptible to A. cantonensis were observed in a range of molecular weights of 14.3 to 200 kDa. In Puerto Rican pigmented Biomphalaria glabrata and Achatina fulca, which had high infection rates with A. cantonensis, we recognized 15 to 16 bands against the adult worm, especially the band with a molecular weight of 29 kDa, which had a more intense reaction. (2) Common antigenicities between A. cantonensis third stage larvae and snails susceptible to A. cantonensis, were observed in a range of molecular weights of 14.3 to 97.4 kDa, especially A. fulica and B. glabrata, where we detected many bands in molecular weight range of 18.4 to 43 kDa. Based on the common antigenicities between A. cantonensis and snails susceptible to A. cantonensis, it is possible that the common antigenicities are one of the factors defining the different susceptibilities of various species of snails to A. cantonensis, and more bands are seen with increasing infection rates with A. cantonensis. Of those bands, the protein with the molecular weight of 29 kDa may be the main common antigen between the A. cantonensis adult worm, the third stage larvae and the snails susceptible to A. cantonensis.     

Infection of sabA-positive H. pylori does not induce anti-Lewis X antibody in host

BACKGROUND/AIMS: H. pylori uses the sialic acid-binding adhesin (SabA) to recognize Lewis X (LeX) antigen of gastric epithelial cells. SabA is associated with nonopsonic activation of human neutrophils. The aims of this study were to examine the association of bacterial sabA status to the presence of anti-LeX antibody in host and the grade of gastritis. METHODOLOGY: 44 H. pylori strains cultured from gastric biopsies were examined by PCR for presence of 23SrRNA, cagA, and sabA. Serum samples were obtained from all the patients to measure the level of anti-LeX antibody. Histological grade of gastritis was graded according to the updated Sydney System. RESULTS: 23SrRNA gene and the cagA gene were seen in all the samples while 21 strains were sabA positive. The mean titer of anti-LeX antibody was 0.09 and 0.18 in patients infected with sabA-positive and -negative strain, respectively (NS). The grade of inflammatory infiltration was not significantly different between groups in both the corpus and the antral mucosa. CONCLUSIONS: Possession of the sabA gene by infected H. pylori strain might not associate with the presence of anti-LeX antibody in the host. Possession of sabA gene by infected H. pylori might not associate with severity of gastric mucosal inflammation.