Intestinal perforation after nivolumab immunotherapy for a malignant melanoma: a case report.

BACKGROUND: Nivolumab is a monoclonal antibody against programmed death 1 and has become a standard treatment of advanced melanoma because of its durable response and survival benefits. In this report, we present a case of severe intestinal perforation after nivolumab immunotherapy for malignant melanoma. CASE PRESENTATION: A 73-year-old man with stage IV malignant melanoma underwent nivolumab therapy. The patient presented to our hospital because of a progressing abdominal pain. Radiological evaluation revealed evidence of free intraperitoneal air. Therefore, we diagnosed the patient as having an intestinal perforation, which was successfully resolved after surgical treatment. CONCLUSION: Although intestinal perforation after nivolumab immunotherapy is rare, it can be severe and requires early diagnosis and emergency surgery to ensure a favorable prognosis.

Perforation of jejunal diverticulum with ectopic pancreas.

Perforation of jejunal diverticulum is a rare complication. Here, we report a case of jejunal diverticulum penetration with surrounding ectopic pancreas. An 83-year-old female patient was admitted to our department with acute onset of severe abdominal pain lasting for half a day. Abdominal computed tomography showed outpouching of the small intestine that contained air/fluid, with multiple surrounding air bubbles in the mesentery of the small intestine. She was diagnosed with penetration of the small intestine, and an emergency laparotomy was indicated. The penetrated jejunal diverticulum was identified ~20-cm distal to the ligament of Treitz. Partial resection of the jejunum was performed, and her postoperative course was uneventful. The pathological findings confirmed diverticulum penetration into the mesentery and severe inflammation at the site, with surrounding ectopic pancreas. Furthermore, the pancreatic ducts were opened through the penetrated diverticulum. This rare case shows that the ectopic pancreas might have caused penetration of jejunal diverticulum owing to the pancreatic duct opening through the diverticulum.

Implantation of a Left Ventricular Assist Device for Danon Cardiomyopathy.

This is the first report of Danon cardiomyopathy managed with a left ventricular assist device (LVAD). Danon disease is an X-linked dominant inheritance disorder. Heart failure with Danon cardiomyopathy results in a poor prognosis, and heart transplantation is the treatment of choice. We present two cases of successful implantation of an LVAD for Danon cardiomyopathy. Patient 1 was in the dilatated phase of hypertrophic cardiomyopathy (HCM) with Danon cardiomyopathy, and she underwent LVAD implantation. She is waiting for transplantation. Patient 2 had dilatated cardiomyopathy with Danon cardiomyopathy and received transplantation 990 days after LVAD implantation without myopathy or intellectual disability.

Umbilical Cord Blood Transplantation-associated Nephrotic Syndrome Successfully Treated by Low-density Lipoprotein Apheresis.

The development of nephrotic syndrome (NS) after umbilical cord transplantation (UBT) has been reported in only four cases to date. We herein report the case of a 50-year-old woman who developed NS 94 days after UBT. She fell into oliguria and required dialysis. A kidney biopsy revealed focal and segmental glomerulosclerosis. Although glucocorticoid monotherapy did not improve her condition, the addition of low-density lipoprotein (LDL) apheresis resulted in remission of NS, a drastic improvement in her renal function, and withdrawal from dialysis. To the best of our knowledge, this is the first report of UBT-associated NS treated with LDL apheresis.

Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis.

An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of Hunner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder.

Comparison of volume and attenuation of the spleen between postmortem and antemortem computed tomography.

OBJECTIVES: The purpose of this study is to compare the postmortem changes in computed tomography (CT) findings between normal spleen, splenic infarct, and splenic tumor infiltration. METHODS: The institutional review board approved this study, and informed consent was obtained from the next of kin. We studied 63 consecutive subjects who underwent antemortem CT, postmortem CT, and autopsy between February 2012 and December 2013. Postmortem CT was performed within 1678 min after death and was followed by pathological studies. The subjects were divided into three groups based on the pathological findings: normal, splenic infarct, and splenic tumor infiltration. The volume and attenuation of the spleen were compared between antemortem and postmortem CT using paired t tests. Gender, age, time elapsed since death, and the causes of death were examined as potential confounding factors of the postmortem changes in volume and attenuation. RESULTS: In all groups, the spleen decreased in volume and attenuation increased on postmortem CT compared with antemortem CT. The postmortem changes in spleen volume and attenuation were not significantly associated with sex, age, time elapsed since death, or causes of death. CONCLUSIONS: Spleen volume decreased and attenuation increased on postmortem CT compared with antemortem CT in subjects with a normal spleen, splenic infarct, or splenic tumor infiltration. These results should caution us against underestimating the significance of splenomegaly on postmortem CT, misinterpreting reduced splenic volume as the presence of hypovolemic or distributive shock in the subject while alive, and confusing postmortem splenic hyperattenuation with diseases characterized by this finding.

The reduced expression of proximal tubular transporters in acquired Fanconi syndrome with κ light chain deposition.

In a case of acquired Fanconi syndrome associated with smoldering myeloma, we confirmed the deposition of protease-resistant κ light chain proteins in a proximal tubular injury and found the decreased expression of apical tubular transporters including sodium glucose co-transporter, sodium phosphate co-transporter, uric acid transporter 1, and a decrease of Na(+)/K(+)-ATPase in the basolateral membrane. The protease-resistant kappa light chain has a pathological role in the expression of tubular transporters in the proximal tubule and causes Fanconi syndrome associated with smoldering myeloma.

Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy (18)F-FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease.

IgG4-related pericardial involvement has rarely been reported and its clinical features remain unknown. We herein report a case of a 50-year-old woman with pericarditis who presented with a fever, elevated C-reactive protein levels, elevated serum IgG4 concentrations, and thickened pericardium with a patchy (18)F-fluorodeoxyglucose (FDG) uptake. A biopsy specimen of (18)F-FDG accumulated in the mediastinal lymph nodes revealed an abundant infiltration of IgG4-bearing plasma cells without fibrosis. Moderate-dose glucocorticoids promptly resolved the physical, serological, and imaging abnormalities, thus indicating a relatively acute and reversible nature of IgG4-related pericardial involvement.

Phospholipase A2 receptor positive membranous nephropathy long after living donor kidney transplantation between identical twins.

Although membranous nephropathy (MN) is a commonly observed cause of post-transplant glomerulonephritis, distinguishing de novo from recurrent MN in kidney allograft is often difficult. Phospholipase A2 receptor (PLA2R) staining is useful for diagnosing recurrent MN in allografts similarly to idiopathic MN in native kidney. No specific treatment strategy has been established for MN, especially when accompanied with HCV infection in kidney transplant recipients. This report describes a 66-year-old man who was diagnosed as having PLA2R positive membranous nephropathy accompanied with already-known IgA nephropathy and HCV infection 26 years after kidney transplantation conducted between identical twins. PLA2R was detected along capillary loops, implying that this patient is affected by the same pathogenic mechanism as idiopathic MN, not secondary MN associated with other disorders such as HCV infection. The patient successfully achieved clinical remission after steroid therapy.

Early postmortem volume reduction of adrenal gland: initial longitudinal computed tomographic study.

We aimed to confirm whether postmortem adrenal volumetric changes occur by measuring adrenal volumes on computed tomography (CT). Fifty-five adrenal glands from 28 subjects who died were included. All subjects underwent antemortem CT (AMCT) and postmortem CT (PMCT) within 94-1,191 min after death, followed by conventional autopsy. CT volumetry was performed using freely-available software. Differences between AMCT and PMCT adrenal volumes were evaluated statistically along with differences in the degree of volume change, elapsed time to PMCT, and presence of underlying malignant disease. The mean volume of the right adrenal gland decreased from 3.8 cm(3) on AMCT to 2.6 cm(3) on PMCT (P < 0.001); the left adrenal gland decreased from 4.2 cm(3) on AMCT to 3.1 cm(3) on PMCT (P < 0.001). Conventional autopsy revealed decreased intracellular lipid components in portions of the adrenal glands. No correlation between the adrenal gland reduction rate and the elapsed time from AMCT to death or from death to PMCT was observed (P = 0.99 and 0.79; P = 0.28 and 0.59 for the right and left adrenal glands, respectively). Significant differences in both the bilateral adrenal gland reduction rates and underlying malignant disease were found for the left adrenal gland (P = 0.015), but not for the right (P = 0.74). Adrenal volume reduction was observed on PMCT compared to AMCT. This highlights the need to further elucidate the mechanism of adrenal shrinkage during the agonal stage and after death. This may be explained by pathological findings of intracellular lipid depletion.

Survival advantage of EBV-associated gastric carcinoma: survivin up-regulation by viral latent membrane protein 2A.

EBV-associated gastric carcinoma is a distinct subset of gastric carcinoma infected with EBV, which shows latency I type expression of EBV latent genes (EBNA1, EBER, BARF0, and LMP2A). To clarify the role of EBV in this type of gastric carcinoma, the cell biological characteristics (growth, apoptosis, and migration) were evaluated in gastric carcinoma cell lines (MKN-1, TMK1, MKN-74 and MKN-7) with and without infection of recombinant EBV harboring the neomycin resistance gene. The infection reiterated the latency I type infection, and the only difference observed in EBV-infected gastric carcinoma cell lines was the resistance to serum deprivation-induced apoptosis. Comparative analyses of transcripts of apoptosis-associated genes in MKN-1 and EBV-MKN-1 and subsequent quantitative reverse transcription-PCR analysis showed up-regulation of the cellular survivin gene in EBV-infected gastric carcinoma cell lines. Small interfering RNA-mediated knockdown of survivin increased apoptosis in EBV-MKN-1 to the level of the original MKN-1 cells. Transfection of EBV-latent genes into MKN-1 showed that LMP2A, but not EBNA1, EBER, or BARF0, up-regulated survivin gene expression. LMP2A-mediated survivin up-regulation in gastric carcinoma cells was inhibited with a nuclear factor-kappaB (NF-kappaB) inhibitor, Bay 11-7082. In parallel with these findings in vitro, survivin expression was frequent in carcinoma tissues of gastric carcinoma by immunohistochemistry, and significantly more in EBV-associated gastric carcinoma (12 of 13) than in EBV-negative gastric carcinoma in the advanced stage (P = 0.0307). Thus, EBV uses its latent protein, LMP2A, to activate the NF-kappaB-survivin pathway to rescue EBV-infected epithelial cells from serum deprivation, and up-regulation of survivin may play a role in the progression of this specific type of gastric carcinoma infected with EBV.