Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects.

BACKGROUND AND AIM: Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD). METHODS: Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years). RESULTS: Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these. CONCLUSIONS: The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.

The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis.

BACKGROUND: MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. OBJECTIVE: To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. METHODS: Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), < 2. OUTCOMES: (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. RESULTS: Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. CONCLUSIONS: The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.

[An unusual location of urethral leiomyoma, the most common pelvic tumour in the female]. / Leiomioma de la uretra, localización inusual del tumor pélvico femenino más frecuente.

Urethral leiomyoma is a rare benign mesenchymal tumour arising from the smooth muscle of the urethra. It most often appears in females of reproductive age. Approximately 100 cases have been reported to date. The most usual presentation is urinary infection, hematuria or a mass. We report a case of a 42 year old woman who presented with sporadic hematuria, dysuria and dyspareunia. Histopathological studies confirmed urethral leiomyoma.

BCL-2, TP53 and BAX protein expression in superficial urothelial bladder carcinoma.

Whether TP53, BCL-2 and BAX expressions add independent prognostic information in patients with Ta/T1 bladder urothelial carcinoma remains unclear. TP53 overexpression correlated with high tumor grade (p=0.004), WHO grading categories (0.045), BAX expression (p=0.043) and pathologic stage (p=0.05). BCL-2 immunostaining was inverse associated with tumor grade (p=0.008). Lack of BAX expression was related to reduced patient's survival (p=0.028). Mortality was higher in patients with BCL-2+/TP53+ (p=0.023) or TP53+/BAX- (p=0.027) phenotype. BAX and pathologic stage were independent predictors of progression-free and overall survival, respectively. Therefore, BAX expression might be relevant in patient's prognosis.

Chromosome-12 copy number alterations and MDM2, CDK4 and TP53 expression in soft tissue liposarcoma.

BACKGROUND: Liposarcoma is a heterogeneous group of soft tissue sarcomas in which definitive prognostic parameters need to be identified. MATERIALS AND METHODS: The series included 33 consecutive soft tissue (well-differentiated, WDLPS, n=19; and dedifferentiated, DDLPS, n=14) liposarcoma. Clinicopathological variables included age, gender, body location, degree of dedifferentiation and mitotic count. The rrolecular analysis included MDM2, CDK4 and TP53 expressions and chromosome-12 copy number alterations. RESULTS: Centrally located (retroperitoneal, abdominal cavity or groin region) WDLPS had more dedifferentiation (p=0.001). Patients with DDLPS and a high mitotic rate died (p=0.070) or experienced recurrencies (p=0.029) more frequently. Co-expression of MDM2/CDK4 (p=0.001) and TP53 accumulation (p=0.017) related to dedifferentiation but not to recurrence or death, both in WDLPS and DDLPS. DDLPS had higher centromeric chromosome-12 copy number than WDLPS (p=0.013), but this was unrelated to recurrence or death. CONCLUSION: Central location is a risk factor in WDLP. Co-expression of MDM2/CDK4/TP53 and chromosome-12 alterations characterize DDLPS suggesting a link with dedifferentiation.

[Triple synchronous primary gynaecological tumours. A case report]. / Tumores triple sincrónicos ginecológicos. Reporte de un caso.

BACKGROUND: Synchronous multiple primary malignancies in the female genital tract are infrequent. From 50 to 70% of them corresponds to synchronous cancers of the endometrium and ovary. To our knowledge, this is only the third case report in the international literature of three concurrent gynaecological cancers of epithelial origin. A case is presented, as well as a literature review due to the infrequency of its diagnosis and the lack of information on the subject. CLINICAL CASE: A 49-year-old woman, with previous gynaecological history of ovarian endometriosis. She underwent a hysterectomy and bilateral oophorectomy, as she had been diagnosed with endometrial hyperplasia with atypia. The final histopathology reported synchronous ovarian, Fallopian tube, and endometrial cancer. An extension study and complete surgical staging was performed, both being negative. She received adjuvant treatment of chemotherapy and radiotherapy. She is currently free of disease. CONCLUSIONS: The aetiology is uncertain. There is controversy relating to increased susceptibility of synchronous neoplasms to pelvic endometriosis and inherited genetic syndromes. Its diagnosis needs to differentiate them from metastatic disease. Additionally, they are problematical from a clinical, diagnostic, therapeutic, and prognostic point of view. The presentation of more cases of triple synchronous cancers is necessary for a complete adjuvant and surgical treatment.

TP53, BCL-2, p21Waf1/Cip1 and metallothionein as markers of differentiation, response to treatment and prognosis in neuroblastic tumors.

OBJECTIVE: To identify markers of response to therapy in neuroblastic tumors. STUDY DESIGN: A total of 58 patients with neuroblastic tumor (38 neuroblastomas, 13 ganglioneuroblastomas and 7 ganglioneuromas) were included in the study. TP53, BCL-2, p21Waf1/Cip1 and metallothionein were included as a biologic approach to tumor differentiation, response to therapy and prognosis. RESULTS: Patients who died of disease had the following immunophenotype: BCL-2 (9 of 10), nuclear TP53 (7 of 10) and metallothionein (7 of 10). TP-53 expression was related to clinical stage (p = 0.062) and disease outcome (p = 0.0218). All patients in whom treatment failed expressed metallothionein (3 of 3). CONCLUSION: TP53, BCL-2, p21Waf1/Cip1 and metallothionein had limited value reflecting tumor maturation (differentiation) or predicting response to therapy. Only nuclear TP53 accumulation may be relevant in patient's prognosis.

[Giant adrenal myelolipoma]. / Mielolipoma adrenal gigante.

OBJECTIVE: We report a case of a giant myelolipoma of the adrenal gland METHODS/RESULTS: A case of a giant myelolipoma of the adrenal gland, an uncommon non-functioning tumour of the adrenal cortex comprised of haematopoietic and adipose tissue, that had been detected incidentally during evaluation with CT because of its characteristic fatty composition. The clinical features, diagnosis and treatment are discussed.