Paraneoplastic REG1α Cast Nephropathy Associated With Mixed Acinar-Neuroendocrine Carcinoma.
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ABSTRACT:
SUBMITTER: Nasr SH
PROVIDER: S-EPMC8071637 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient's renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.
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Project description: Not available
| S-EPMC8767029 | biostudies-literature
Project description:Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of Bence Jones proteins. Myeloma-like cast nephropathy (MLCN) has been reported in the literature to occur in various primary renal and nonrenal diseases. We present a series of three rare cases of cast nephropathy, two of which are HIV patients, and the third patient is receiving cisplatin-based chemotherapy. However, in all three patients plasma cell dyscrasia has been ruled out. A 30-year-old male was admitted to the hospital with facial cellulitis. The second patient is a 31-year-old male who presented with Pneumocystis jiroveci pneumonia. The third patient was treated with cisplatin-based chemotherapy for carcinoma. First two cases revealed foci of diffuse tubular dilatation containing hyaline casts and interstitial inflammatory infiltrate, in addition to globally sclerotic glomeruli with ultrastructural foot process fusion and mesangium expansion. The third case showed acute tubular injury and cast formation of irregular casts composed of amorphous or granular material of low density admixed with scattered high electron-dense globules. Myeloma-like cast nephropathy and true myeloma cast nephropathy pose similar destructive effects on renal parenchyma. This new pattern of HIV-related nephropathy should be considered in HIV patients with MLCN, once monoclonal gammopathy is ruled out.
| S-EPMC5523540 | biostudies-other
Project description:Simple Summary Mixed acinar neuroendocrine carcinoma of the pancreas (MANEC-P) is one of the rarest pancreatic carcinomas. Although MANEC-P is rare, it is associated with a bad prognosis. The distribution of this fatal cancer is unknown worldwide. Our contribution is expected to be a detailed understanding of the epidemiology of this cancer in the United States. Expected results from the proposed research include an estimation of the incidence, prevalence, and cancer-specific survival of patients diagnosed with MANEC-P from a population-based cancer registry. This study will be followed by multiple epidemiological studies on the distribution of this fatal cancer worldwide. These epidemiological benchmarks will be used to initiate a consortium to generate real-world evidence with a natural history study for risk identification and treatment optimization for MANEC-P. The long-term goal is to develop an up-to-date epidemiologic and multi-omics knowledge library to enhance the diagnostics and therapeutics options and improve survival among patients diagnosed with MANEC-P. Abstract Mixed acinar neuroendocrine carcinoma of the pancreas (MANEC-P) is an extremely rare malignancy with a poor prognosis. However, epidemiological estimates of MANEC-P remain unknown. This study aimed to estimate and compare the incidence, prevalence, and cancer-specific survival (CSS) of MANEC-P in the United States (US). Patients with MANEC-P were identified through the Surveillance, Epidemiology, and End Results (SEER) and National Program of Cancer Registries databases between 2000–2017. The primary outcomes included age-adjusted incidence rate, limited-duration prevalence, and CSS. A total of 630 patients were identified for the incidence analysis and 149 for the prevalence and CSS analyses. The MANEC-P incidence rate was 0.011 per 100,000 individuals, which was the lowest among pancreatic cancer histologic subtypes. The incidence rate was significantly higher in men and Black races and peaked at 75–79 years of age. The incidence rate was the lowest in the midwestern region (0.009) and the highest in the northeastern US (0.013). The 17-year prevalence was 0.00005%, indicating that 189 patients were alive in the United States at the beginning of 2018. The median CSS of MANEC-P was estimated to be 41 (23, 69) months. In conclusion, MANEC-P is very rare, and its incidence rate has been steady in the US over the last two decades. MANEC-P has a poor prognosis and is the 5th leading cause of pancreatic cancer-related death in the US.
| S-EPMC9913846 | biostudies-literature
Project description:Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study.
2024-08-11 | GSE240700 | GEO
Project description:ObjectiveOur aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.DesignThis is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria.MethodsTwenty-one patients with EPNS were detected: 16 with ectopic Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (?-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis.ResultsThe prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P?=?0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P?=?0.001 and P?<?0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P?=?0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P?=?0.12).ConclusionEPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.
| S-EPMC6531606 | biostudies-literature
Project description:Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic syndromes (PNS). NEPC is becoming more frequent. It can initially manifest as PNS, complicating diagnosis. Therefore, we reviewed the literature on the different PNS associated with NEPC. We systematically reviewed English-language articles from January 2017 to September 2023, identifying 17 studies meeting PRISMA guidelines for NEPC and associated PNS. A total of 17 articles were included in the review. Among these, Cushing's Syndrome (CS) due to ectopic Adrenocorticotropic hormone (ACTH) secretion was the most commonly reported PNS. Other PNS included syndrome of inappropriate Anti-Diuretic Hormone secretion (SIADH), Anti-Hu-mediated chronic intestinal pseudo-obstruction (CIPO), limbic encephalitis, Evans Syndrome, hypercalcemia, dermatomyositis, and polycythemia. Many patients had a history of prostate adenocarcinoma treated with androgen deprivation therapy (ADT) before neuroendocrine features developed. The mean age was 65.5 years, with a maximum survival of 9 months post-diagnosis. NEPC is becoming an increasingly more common subtype of PCa that can result in various PNS. This makes the diagnosis and treatment of NEPC challenging. Further research is crucial to understanding these syndromes and developing standardized, targeted treatments to improve patient survival.
| S-EPMC10969281 | biostudies-literature
Project description:BackgroundParaneoplastic cerebellar degeneration (PCD) is a classical tumor-associated, immune-mediated disease typically associated with gynecological malignancies, small-cell lung-cancer or lymphoma.Case presentationHere we present the case of a 38-year old male with an over 12 months rapidly progressive cerebellar syndrome. Extensive diagnostic workup revealed selective hypermetabolism of the right tonsil in whole-body PET. Histological examination after tonsillectomy demonstrated a lymphoepithelial carcinoma of the tonsil and the tongue base strongly suggesting a paraneoplastic cause of the cerebellar syndrome. To the best of our knowledge this is the first case of an association of a lymphoepithelial carcinoma, a rare pharyngeal tumor, with PCD.ConclusionsIn cases of classical paraneoplastic syndromes an extensive search for neoplasms should be performed including whole-body PET to detect tumors early in the course of the disease.
| S-EPMC4016266 | biostudies-literature
Project description: Not available
| S-EPMC4999323 | biostudies-literature
Project description:Mixed acinar-endocrine carcinoma (MAEC) of the pancreas is a rare entity. We present a 65-year-old Chinese female who was admitted with jaundice and nagging epigastric pain with intermittent diarrhea for 1 month. She eventually underwent abdominal magnetic resonance imaging, which showed an 8×6 cm mass in the head of the pancreas and showed two abnormal lesions in the liver simultaneously. MAEC of the pancreas with synchronous hepatic metastasis was confirmed with immunohistochemistry after Whipple operation and hepatic partial resection of the lesions. Postoperative recovery of this patient was uneventful, and no evidence of recurrence or metastasis was observed after 12 months of follow-up. MAEC of pancreas is thought to be extremely rare and lack of typical clinical symptoms. The prognosis is poor overall, but early detection with complete resection may be beneficial to patients.
| S-EPMC4498721 | biostudies-literature