Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity

BackgroundDealing with chemotherapy-related cardiac dysfunction (CTRCD) remains a significant problem complicated by the difficulty in early detection of cardiotoxicity. Electrocardiogram (ECG) is expected to be the most realistic methodology due to lower cost-performance and non-invasiveness. We investigated the long-term visual fluctuations in the ECG waveforms in patients with chronic doxorubicin (DOX)-induced cardiotoxicity to identify ECG indices for the early detection of cardiotoxicity.MethodsWe conducted a retrospective case series study by reviewing the medical records of 470 consecutive patients with malignant lymphoma who were treated with DOX at our institute between January 2010 and December 2017. Of them, 23 (4.9%) patients developed left ventricular dysfunction and were diagnosed with CTRCD using echocardiography. We assessed the ECG indices on 12-lead ECG recordings before and after treatment in 15 patients; eight patients were excluded due to conduction disturbances or atrial fibrillation.ResultsCTRCD was detected at a median of 475 (interquartile range, IQR: 341–1333) days after initiating chemotherapy. The evaluation of ECG indices preceding CTRCD development was performed 93 (IQR: 52–232) days before the detection of CTRCD. In the stage of CTRCD, the most significant ECG change was T-wave flattening in leads V3–V6 (12 patients, 80%). Additionally, QTa prolongation was observed in leads I and aVL (n = 10, 66%), leads II, III, and aVF (n = 9, 60%), and leads V3–V6 (n = 10, 73%). These ECG changes were not observed before the treatment but were detected mildly in the pre-CTRCD stage, which subsequently worsened in the CTRCD stage.ConclusionsThis study indicated that T-wave changes and QTa prolongation may be useful as an early indicator before the onset of CTRCD in patients with DOX-induced cardiotoxicity.     

Complete Resolution of a Case of TAFRO Syndrome Accompanied by Mediastinal Panniculitis,Adrenal Lesion,and Liver Damage with Hyperbilirubinemia

TAFRO syndrome is a systemic inflammatory, lymphoproliferative disorder, but the pathophysiology of the disease is unknown. It is typically characterized by thrombocytopenia, anasarca, a fever, reticulin fibrosis, renal dysfunction, and organomegaly. However, other manifestations have been also reported. We encountered a 43-year-old man with TAFRO syndrome who showed mediastinal panniculitis, liver damage, and adrenal lesions in addition to the core signs. He achieved complete remission with combination therapy of corticosteroids, tocilizumab, and cyclosporin, and remission was maintained even after drug discontinuation at 15 months. Atypical manifestations and complete remission of TAFRO syndrome were remarkable features of our case.     

Ratio of submucosal thickness to total bowel wall thickness as a new sonographic parameter to estimate endoscopic remission of ulcerative colitis

Journal of Gastroenterology - The development of feasible, reliable parameters and criteria for intestinal ultrasound (IUS) to estimate endoscopic remission of ulcerative colitis (UC) is a crucial...     

A Superinfection of Salmonella typhi and Hepatitis E Virus Causes Biphasic Acute Hepatitis

A 47-year-old Japanese man was referred to our hospital because of a sustained high fever with diarrhea 12 days after a flight from India. Liver enzymes were elevated with rose spots, hepatosplenomegaly, relative bradycardia, and acute cholecystitis. A liver biopsy depicted the dense infiltration of lymphocytes and Kupffer cells in sinusoids and the granulomatous formation in the parenchyma. The liver damage was initially resolved with the administration of ceftriaxone for 16 days but flared up 1 week later. Laboratory tests yielded positive reactions for Salmonella typhi and hepatitis E virus RNA. The pathophysiological presentations of concurrent typhoid and type E hepatitis are discussed.     

The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy

Background

Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood.

Methods

This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients.

Results

FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy.

Conclusions

This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.

     

Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma

Journal of Gastroenterology - Liquid biopsies, particularly those involving circulating tumor DNA (ctDNA), are rapidly emerging as a non-invasive alternative to tumor biopsies. However, clinical...     

Increased DNA-incorporated thiopurine metabolite as a possible mechanism for leukocytopenia through cell apoptosis in inflammatory bowel disease patients with NUDT15 mutation

Journal of Gastroenterology - Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory...     

Somatostatin-like immunoreactivity in mammalian thyroid glands: contents and partial characterization

Somatostatin (SRIF)-like immunoreactivity (SLI) in the thyroid glands of human and several animal species were compared, and the SLI peptides were characterized chromatographically and immunologically. All specimens were extracted with 2 M acetic acid, and the SLI content determined by RIA. The SLI concentrations in guinea pigs [34.3 +/- (SE) 4.8 ng/mg protein] and rabbits (9.4 +/- 0.8 ng/mg protein) were much greater than those in other mammals: dogs, rats, mice, and humans. On gel filtration of extracts of the guinea pig, rabbit and dog thyroids, the major peak of SLI (1.6 K SLI) coeluted with synthetic SRIF-14 (S-14). Two other forms of SLI ("big" SLI and 3 K SLI) were also detected, although their relative proportions to total SLI were small (2.3 to 8.2%). The 3 K SLI and 1.6 K SLI from guinea pig and rabbit thyroids contained peptides coeluting with synthetic SRIF-28 (S-28) and S-14, respectively, on reverse-phase high performance liquid chromatography. The dilution curves of the two molecular forms of SLI, i.e. 3 K SLI and 1.6 K SLI, were parallel to the displacement curves of S-28 and S-14 in the SRIF RIA. It is concluded 1) that the thyroid contents of SLI varied greatly from species to species, with the highest content being found in guinea pig thyroids; 2) that in guinea pigs, rabbits, and dogs, the predominant form of thyroid SLI is 1.6 K SLI; and 3) that the 3 K SLI and 1.6 K SLI peptides from guinea pig and rabbit thyroids are immunologically and chromatographically indistinguishable from S-28 and S-14, respectively.