Hepatic Injury Induced by a Single Dose of Nivolumab - a Case Report and Literature Review.

BACKGROUND: The use of nivolumab in the treatment of metastatic melanoma has become well established during past years. Despite its undeniable efficacy, immune-related side effects may occur, including acute liver injury. Liver toxicity caused by nivolumab is usually observed as liver enzyme elevation with mild or no symptoms; further, there is limited information regarding any histopathological findings. CASE: We report a case of a 38-year-old woman with metastatic melanoma who developed unusual nivolumab-induced hepatic injury after a single dose of nivolumab. A liver biopsy was performed to assess the aetiology of hepatic lesions as no other analysis concerning biochemistry, virology, autoantibodies, nor imaging studies revealed any pathology. The histopathological analysis showed an oedema in the portal fields and mixed inflammation consisting of eosinophilic and neutrophilic granulocytes. The major finding was a prominent, predominantly intracellular, cholestasis. CONCLUSION: To our knowledge, no such histopathological pattern of liver injury has been described in relation to nivolumab therapy elsewhere. This type of liver injury shows higher resistance to corticosteroids, which may warrant upfront high-dose corticotherapy combined with other immunosuppressive agents, including mycophenolate mofetil. This case highlights a necessary awareness regarding immunotherapy-related adverse events, which could be severe and potentially life-threatening.

Lichen planus as a possible rare cause of an ocular disease.

Lichen planus is a relatively common mucocutaneous papulosquamous disorder of unknown etiology that is thought to be immunologically mediated. Ocular involvement of lichen planus (LP) is a rare event, which can lead to irreversible damage to the ocular surface and loss of vision from cicatrizing blepharoconjunctivitis and corneal scarring. Steroids are the first treatment choice. Treatment with topical ciclosporin A is also a possible treatment. We report a case of 79-year-old woman who was treated for long lasting severe inflammatory disease of a ocular surface. It led to blindness of one eye and low vision of the second eye. The diagnosis was made thanks to correlation of biopsy results from oral and ocular surface. The patient was also diagnosed with middle-stage dementia. Negative impact of steroid therapy on mental condition of this patient was considered. On the other hand, dementia could cause worse compliance with recommended treatment regime. Chronic inflammatory disease of ocular surface requires long lasting treatment very often and it is sometimes not as effective as expected. Discovering etiological causes of the disease is a priority for the right treatment. We emphasize also the key role of physical and mental condition in management of ocular surface disease.

The effect of humic acids on the reverse osmosis treatment of hazardous landfill leachate.

This study deals with the treatment of hazardous waste landfill leachate with the help of reverse osmosis. The landfill is located in an abandoned brown coal pit in northern Bohemia. The leachate contained 7.2 g/L of dissolved inorganic salts. Among other contaminants were heavy metals, arsenic, ammonia nitrogen and associated organic pollutants, especially chlorinated compounds. A mobile membrane unit (LAB M30) equipped with a spiral wound element (FILMTEC SW30-4040), with a membrane area equaling 7.4 m2 was used for the pilot plant experiments. All experiments were carried out in batch mode. 94% conversion of the input stream into the permeate was achieved by use of a two-stage arrangement. Removal efficiencies of the monitored contaminants in the feed ranged from 94% for ammonia nitrogen to 99% for the two-valent ions. Removal efficiency for total dissolved solids was 99.3% on average. Due to varying levels of humic acids in the leachate throughout the year, fouling experiments were performed to investigate the separation process under different conditions than those used in the pilot plant. Leachates containing different concentrations of added humic acids were separated using a thin film composite on a propylene membrane. The added humic acids were obtained from samples of contaminated oxihumolite.

Papillary adenoma of the extrahepatic biliary tract--a rare cause of obstructive jaundice.

The authors present a case of papillary adenoma of the extrahepatic biliary tract presenting as obstructive jaundice. The diagnosis was based on the endoscopic retrograde cholangiopancreatography (ERCP), and above all cholangioscopy findings. The patient was treated by bile duct resection with Roux-en-Y hepaticojejunostomy. Adenoma of the bile duct is a rare entity. Only a few cases have been described in the world literature so far.

Renal biopsy in children with steroid-dependent nephrotic syndrome.

BACKGROUND: There is lack of consensus on the necessity of renal biopsy in children with steroid-dependent nephrotic syndrome (SDNS) prior to cytotoxic therapy. OBJECTIVES: To retrospectively evaluate: (a) the benefit of renal biopsy (RB) prior to cyclophosphamide therapy; (b) relationship between histopathologic results of RB samples and clinical course in children with SDNS. PATIENTS, MATERIALS AND METHODS: RB was performed in 18 SDNS patients (11 boys and 7 girls). The mean age of the children at the time of nephrotic syndrome (NS) diagnosis was 6.4 +/- 3.9 years and 9.7 +/- 4.3 years at the time of RB. Following the RB, all children received prednisone and cyclophosphamide treatment for 12 weeks. Duration of remission and relapse rate was recorded. RESULTS: The histologic evaluation revealed minimal change disease (MCD; n = 14) and IgM nephropathy (n = 4). These results didn't affect the ongoing therapy. MCD patients had longer remission compared to IgM nephropathy (3.2 +/- 1.5 vs 1.7 +/- 0.8 years; p = 0.05). Relapse rate did not differ significantly between MCD and IgM nephropathy (p = 0.22). The duration of remission was inversely correlated to relapse rate after the treatment (r = -0.66, p = 0.01). CONCLUSION: We suggest that RB prior to cyclophosphamide therapy is not necessary in patients with SDNS (Tab. 2, Ref. 14). Full Text (Free, PDF) www.bmj.sk.

[Retroperitoneal hemangioma--a case report]. / Hemangiom retroperitonea--kazuistika.

Localization of hemangioma in retroperineum causes late diagnosis of the disease. The tumour is usually detected only when the clinical symptoms caused by the pressure of the surrounding tissues occur. This article presents the case of retroperitoneal hemangioma preoperatively diagnosed as suspect feochromocytoma.

[Combined radiologic and microscopic examination of nonpalpable breast lesions with microcalcification]. / Kombinované rentgenologické a mikroskopické vysetrení nehmatných lézí prsu s mikrokalcifikacemi.

Radiograms of nonpalpable breast lesions containing calcifications represent one of the most important fields of using x-ray in breast pathology. An analysis of a group of 52 nonpalpable lesions of breast with calcifications revealed a discrepancy between the presence of calcifications in radiograms and in histological sections. An absence of calcifications was observed in 47 of 301 (15.7%) paraffin blocks. Calcifications were lost by cutting them off from the blocks, by leaving them deeper in blocks so that they were absent in sections, or by losing them by various other ways during processing of the blocks. An algorithm for examination of nonpalpable calcified lesions of breast has been developed. During the procedure, tissue slices and paraffin block were x-rayed, thus increasing the detection of calcifications in blocks from 76% to 84.3%.

[Solid and papillary epithelial tumor of the pancreas: cytologic and histologic features]. / Solidní a papilární epiteliální tumor pankreatu: cytologický a histologický obraz.

Cytologic and histologic features in a case of solid and papillary epithelial neoplasm (SPEN) of the pancreas in a 34-year-old female are presented. In the fine-needle aspiration material, there was a predominance of pseudopapillary fragments with delicate fibrovascular core lined with one or more layers of uniform tumor cells with clear cytoplasm. There were also acinar-like or rosette-like structures and dispersed tumor cells. Tumor cells had small, round to oval nuclei, with finely granular chromatin and inconspicuous nucleolus. Rarely, nuclear grooves were present. Mitoses were not seen. Histologically, the encapsulated tumor was predominantly solid, with focal pseudocystic and pseudopapillary areas; foreign body granulomas were focally present. Tumor cells were small and uniform with clear cytoplasm. Mitoses were extremely rare. Immunohistochemically, the tumor cells revealed diffuse positivity of vimentin, and focal positivity for alpha 1-antitrypsin and CD68. No immunoreactivity for chromogranin, synaptophysin, cytokeratin, HMB 45, estrogen and progesterone receptors was found. In differential diagnosis, it is important to distinguish SPEN mainly from mucinous tumors of the pancreas, microcystic adenoma and pseudocysts, but also from endocrine tumors of the pancreas, acinic cell carcinoma, renal cell carcinoma, adrenal cortical adenoma and primary extrapulmonary sugar tumor.

Familial and sporadic renal oncocytomas--a comparative molecular-genetic analysis.

OBJECTIVES: Genetic causes of sporadic and familial renal oncocytomas are not known. We analyzed these tumors genetically in order to detect tumor-specific chromosome alterations. METHODS: DNA from 26 sporadic and 31 familial renal oncocytomas were screened by comparative genomic hybridization according to standard protocols including degenerate oligonucleotide-primed PCR. RESULTS: Chromosome alterations were detected in 19/26 sporadic (73%) and in 4/31 familial renal oncocytomas (13%). Partial or complete losses of chromosome 1 were most frequently found in both sporadic (15/26) and familial tumors (2/4). Less frequently, loss of chromosome 14 (3/26) was detected in sporadic renal oncocytomas as well as losses of 2p, 2q, 4q, 10 and 18 and gains of 1q and 17q in individual sporadic tumors. Inter-tumor variation of chromosome aberrations was prominent in 1 patient, where 1 tumor showed gains of chromosomes 5, 6q, 7, 10p, 12 and 13q, whereas the second tumor exhibited gains of chromosomes 5 and 7 and loss of 10q. In contrast to sporadic renal oncocytomas, most familial tumors (87%) were devoid of chromosome instabilities. CONCLUSION: Our results demonstrate that partial or complete loss of chromosome 1 is the most common alteration in renal oncocytomas, sporadic and familial. However, chromosome changes are much rarer in familial than in sporadic renal oncocytomas.

[Aspergillosis--a rare complicating disease in patients after renal transplantation]. / Aspergilóza--vzácné komplikující onemocnení u nemocných po renální transplantaci.

The authors submit a detailed analysis of the death of a 42-year-old man after a second renal transplantation. The patient died with symptoms of cardiac failure in a septic condition of obscure etiology where even detailed examination did not provide a timely answer as regards the lethal pathogen. Aspergillus fumigatus is a rare lethal pathogen. Despite this it is, as all opportune infections, for patients with immunosuppressive therapy a serious life threatening infection [1, 2]. In a group of 650 transplantations performed since 1961 in Hradec Králové it is the first death caused by generalized Aspergillus infection.

[Oncocytoma of the kidney--morphologic variation in 102 cases]. / Onkocytom ledviny--morfologická variabilita 102 prípadu.

From the collection of 2500 cases of renal epithelial tumors in our files, 102 renal oncocytomas were analyzed for size, multifocality and a morphologic spectrum of the growth pattern. The size of the tumors ranged from 1.5 to 13 cm in diameter, with a mean of 6.3 cm. Three cases were multifocal, four cases were combined with another primary renal tumor (1x angiomyolipoma, 1x conventional renal carcinoma, 2x papillary renal cell carcinoma). A central fibrosis or a scar was noted in 13 cases, and there was a gross area of hemorrhage in 11 cases. In 4 cases extensive necroses were recognized. Histologically, an alveolar pattern was noted in 70 cases. A tubular pattern was revealed in 31 cases and an unusual tubopapillar ("glomeruloid") pattern was noted in one case. Foci of atypical nuclei were identified in 58 cases. In 4 oncocytomas broad areas of clearance of the oncocytes were found. Psammoma bodies were recognized in 9 tumors and foci of ossification were present in 4 cases. Intracellular and extracellular hyaline globules were noted in two cases. Renal oncocytoma has a variable morphologic spectrum, and its diagnosis should be based on an analysis of structural and cytologic features. Differential diagnosis of renal oncocytomas with various tumors of the kidney which contain granular cytoplasm is discussed. These tumors with granular cytoplasm include conventional renal cell carcinomas, chromophobe cell carcinomas, and rare examples of papillary renal carcinomas.

Genetic alterations in metastatic renal cell carcinoma detected by comparative genomic hybridization: correlation with clinical and histological data.

In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disease. We analyzed 46 renal tumors along with their metastases, and 15 non-metastatic renal tumors. Tumors were classified pathologically according to the Heidelberg classification of RCC, and staged according to the TNM-system. Standard CGH was performed using microdissected archival tissues and DOP-PCR. The average numbers of chromosomal aberrations per tumor were 3.0, 2.1 and 3.9 in patients without metastasis, in patients who developed metastases after a two-year latency period (late onset of metastatic disease) and in patients who developed metastases within two years after therapy of the primary tumor (early onset of metastatic disease). CGH revealed chromosomal aberrations in 91% of primary metastatic tumors. Deletions or losses of chromosomes 9 (26% vs 6%), 10 (21% vs 6%) and 18 (23% vs 0) and 17 (28% vs 7%) occurred more often in metastatic tumors than in non-metastatic tumors. Furthermore, these aberrations were more common in patients with early metastases. CGH analysis of 40 pairs of primary RCCs and their corresponding metastasis revealed similar aberrations in 70% of cases. In 30%, however, metastases showed additional chromosomal aberrations not detected in the corresponding primary tumors. In conclusion, we identified genetic alterations associated with metastatic disease in RCC which could be useful for predicting prognosis. Genetic changes leading to metastases occurred early in tumorigenesis of metastatic tumors.

[A localized form of metastatic pulmonary calcification in a patient after renal transplantation]. / Lokalizovaná forma metastatického plicního zvápenení u pacienta po renální transplantaci.

A 51-year-old woman with a 20-year history of renal transplantation during the end-stage of chronic renal failure caused by tubulointerstitial nephritis. She died of chronic graft rejection. An interstitial calcification limited to 1. and 2. left segments was encountered as an incidental autoptic finding. There were two unusual microscopic findings, i.e., no involvement of arterioles and larger vessel inclusive veins, and a foreign-body response to some of the calcified tissue.

[Malignant lymphoma of the small intestine as an uncommon cause of obstructive ileus]. / Maligní lymfom tenkého streva jako méne obvyklá prícina obstrukcního ileu.

The authors draw attention to an uncommon cause of obstructive ileus in children, i.e. malignant lymphoma of the small intestine in a 10-year-old boy.

[Chronic mesenteric ischemia]. / Chronická mezenteriální ischemie.

Chronic mesenteric ischemia often called intestinal angina too, is the clinical syndrome that originates as a result of chronic obstruction of the splanchnic arteries. Intestinal angina is defined by the clinical triad of postprandial abdominal pain, sitophobia (fear of eating) and chronic weight loss. Postprandial abdominal pain is analogous to angina pectoris and calf claudication, two more common manifestations of episodic tissue hypoxia. The authors present the case-history of a 50-year-old woman with intestinal angina due to obliteration of the all three main splanchnic arteries. The authors describe the course of the disease and point out new diagnostic approaches in the diagnosis of chronic mesenteric ischemia (Doppler ultrasound of the splanchnic arteries, helical CT angiography of the splanchnic vasculature). In the discussion they point out the possible atypical clinical manifestation of chronic mesenteric ischemia and existence of gastric ulceration and chronic ischemic gastritis caused by chronic mesenteric ischemia.

[Increased incidence of renal cell carcinoma in central Europe. Does diagnostic increase reflect a true increase in incidence?]. / Inzidenzzunahme beim Nierenzellkarzinom in Mitteleuropa. Entspricht die diagnostische einer echten Inzidenzzunahme?

In the last years the incidence of renal cell carcinoma diagnosis increased about 15-20%. The main aim of this study was to analyse the reason of the increase of incidence. In the present autopsy series comprising 23,801 autopsies the percentage of patients who died of renal cell carcinoma is 1.77% in Jena and 1.55% in Königgrätz (200,000 inhabitants each). Over this time the incidence of renal cell carcinoma in autopsies has increased. In spite of the increased amount of incidentally found renal cell carcinomas since beginning widespread use of ultrasonography the percentage of clinically recognized renal cell carcinomas on the total of all found renal cell carcinomas in autopsies is nearly constant about the 12-year period in Jena and 10-year period in Königgrätz. Thus, the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography. The increasing trend of the incidence of renal cell carcinoma seems to be real.

Increase of renal cell carcinoma incidence in central Europe.

OBJECTIVE: In recent years the incidence of renal cell carcinoma (RCC) diagnosis has increased about 15-20%. It remains to be established whether this increase of incidence is reality or not. The main aim of this study was to analyze the reason for the increase of incidence. METHODS: In the present study, 23, 247 autopsies performed in the years 1985-1995 in the area of Jena (Germany) (14,793 autopsies) and Hradec Králové (Czech Republic) (8,454 autopsies) were analyzed. RESULTS: In this autopsy series comprising 23,247 autopsies, the percentage of patients who died of RCC is 1.76% in Jena and 1.55% in Hradec Králové (200,000 inhabitants each). Over this time the incidence of RCC in autopsies has increased. CONCLUSION: In spite of the increased amount of incidentally found RCCs since beginning widespread use of ultrasonography, the percentage of clinically recognized RCCs in the total of all found RCCs in autopsies is nearly constant over the 11-year period in Jena and 10-year period in Hradec Králové. Thus, the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography. The increasing trend of the incidence of RCC seems to be real.

[Rapidly progressing streptococcal sepsis in a patient after transplantation of a cadaver kidney]. / Rychle progredující streptokoková sepse u nemocného po transplantaci kadaverózní ledviny.

The authors submit the case-history of an adverse rapidly progressing phlegmon and septicaemia in a patient after transplantation of a cadaverous kidney with a functional graft. The patient was admitted repeatedly to the Transplantation Centre of the Urological Clinic, Faculty Hospital Hradec Králové with acute cellular rejection for corticosteroid treatment.