Prevalence of Hepatocellular Carcinoma and Its Characteristics in 10 Years of Transplantation in a University Hospital in Brazil.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for up to 90% of all primary liver neoplasms. HCC treatment options depend on tumor burden, the degree of liver dysfunction, and performance status. Orthotopic liver transplant offers the best chance for cure. The selection criteria adopted for transplant are based on the Milan Criteria (MC), which depend on tumor size and number (1 lesion ≤5 cm or up to 3 lesions of ≤3 cm, without vascular invasion or extrahepatic spread). In Brazil, an expanded version of the original MC, named the Brazilian Criteria (BC), takes into consideration only tumors larger or equal to 2 cm. This retrospective cohort aims to describe the prevalence of primary liver tumors and analyze the macro and microscopic characteristics of HCC on explant pathology in a university hospital over 10 years. Of 485 transplants, 243 (50.1%) had HCC. Most patients were men (77.4%) with a mean age of 58.4 years, and the most common primary etiology of liver disease was hepatitis C infection (64.2%). The total number of tumors was 628, generally multicentric (55.6%); segment VIII was the most affected, and alpha-fetoprotein was altered in 70.7% of the cases. Most patients had tumors meeting MC at pretransplant and on explant evaluation, along with higher overall survival when compared to those exceeding MC and BC, and especially with those outside both criteria. In addition, tumors outside MC represent an independent risk factor associated with death.

Fumarate hydratase-deficient renal cell carcinoma: A tumor with diverse morphology including cannibalism, lymphocytic emperipolesis, and defective autophagy.

We report the clinicopathological findings of the first series of 3 patients from Brazil with fumarate hydratase-deficient renal cell carcinoma. The clinicopathological findings disclosed a very aggressive tumor. All 3 patients had solitary tumor at the left side, metastasis and advanced stage at the time of diagnosis; were females with a median age of 40 years; had a history of uterine leiomyomas; and, at follow-up two patients are deceased and one patient alive. The microscopic findings of these 3 patients are in accordance with the literature disclosing a variety of morphologic features being papillary arrangement, eosinophilic cytoplasm, and prominent nucleoli surrounded by clear halo the constant and most frequent findings. Previously not reported in this tumor, we describe presence of cannibalism, lymphocytic emperipolesis, and cytoplasmic vacuoles with eosinophilic inclusions associated with overexpression of p62 in immunohistochemistry which is considered to be evidence of defective autophagy. Lymphocytic emperipolesis was a more frequent finding than cannibalism and immunohistochemistry for p62 was overexpressed only in the 2 patients disclosing cytoplasmic vacuoles with eosinophilic inclusions. The presence, frequency and significance of these novel findings should be checked in large series of this rare and aggressive tumor aiming to associate with clinical behavior and eventually influence the strategy of treatment.

Prognostic significance of architectural subtypes of Gleason grade 4 prostate cancer in radical prostatectomy: A semiquantitative method of evaluation.

Studies have shown that Gleason grade 4 extent as well as architectural subtypes provide prognostic information. We aimed to evaluate the influence on biochemical recurrence following radical prostatectomy of patients with organ-confined tumor, Gleason score 7, and negative surgical margins. Total tumor extent, Gleason grade 4 total extent and the extent of each architectural subtype (fused glands, poorly defined glands, cribriform glands, and glomeruloid glands) were evaluated by a semiquantitative point-count method using different colors to identify each subtype. Microscopic morphology of glomeruloid glands was considered regardless of morphology: size (small or large), attachment (narrow or extensive), and cribriform or solid intraluminal protrusion. Gleason grade 4 total extent significantly predicted shorter time to biochemical recurrence in univariate and multivariate analysis. Stratifying extent, Gleason grade 4 with >30% of the total grade 4 extent was significantly predictive for time of recurrence. Considering architectural subtypes, cribriform and glomeruloid glands but not fused and poorly formed glands extent, significantly predicted shorter time to recurrence in univariate analysis. An important issue related to the studies on prognostic significance of Gleason grade 4 subtypes is the lack of uniformity in the definition of microscopic morphology of the subtypes particularly of the glomeruloid architecture.

Subacute toxicity assessment of biobased ionic liquids in rats.

Ionic liquids (ILs) derived from compounds obtained from natural sources, such as fatty acids (FAs) have attracted the interest of the scientific and industrial communities because of their sustainable appeal and possible low toxic effects or nontoxicity. These aspects open new perspective of applications in other fields, which demands a better comprehension of their toxicity. This work evaluated the subacute toxicity of bis(2-hydroxyethyl)ammonium carboxylates in Wistar rats, considering the alkyl chain length of FAs (capric and oleic acids), and the concentration (0.16%, 1.6% or 3.2%, wIL/wOil) of ILs added in diets. The blood serum of the rats was evaluated in relation to total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and γ-glutamyl transferase. Lipid peroxidation was determined in plasma, liver and kidney tissues by determining the level of thiobarbituric acid reactive substances. Histological analyses of the liver and kidney tissues were performed in order to evaluate morphological changes. No signal of toxicity was observed according to lipid peroxidation. Triglycerides increased with the increasing of the concentration and alkyl chain length of the IL, but no difference in serum level of lipid peroxidation was observed. This behavior may be attributed to the amphiphilic nature of FAs based ILs, which might facilitate lipid digestion. However, more studies are necessary in order to understand such behavior. Therefore, the synthesis of ILs from FAs, has been evaluated as a strategy to produce compounds with low or without toxicity for the agro-food, pharmaceutical or cosmetic industries.

Lower Urinary Tract Symptoms Due to Xanthoma of the Prostate After Kidney Transplantation: A Case Report.

BACKGROUND: Prostatic xanthoma is a lesion of unknown cause that is often an incidental finding in patients undergoing needle biopsy or transurethral resection. To the best of our knowledge, we report on a unique case of a pure xanthoma without benign prostatic hyperplasia of the prostate in a patient with lower urinary tract symptoms manifested after kidney transplantation. METHODS: A 62-year-old man was submitted for a kidney transplant in April 2018. He had no urinary complaints previous to the transplant. Since July 2019, he had complained of lower urinary tract symptoms. In October 2019, he had acute urinary retention being submitted to a transurethral resection of an estimated 47 g prostate. All measures of cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) were within the normal range-except triglycerides, which were mildly elevated in 2 measures. RESULTS: The pathologic examination of the resected prostate showed pure xanthoma without benign prostatic hyperplasia. A similar lesion with a xanthomatous cell component is verruciform xanthoma. It is a rare benign lesion of unknown etiology not associated with underlying disorders of lipid metabolism that has been reported in patients with bone marrow, kidney, and liver transplant. CONCLUSIONS: We report a unique case of prostate enlargement caused by pure xanthoma in a patient with renal transplant. In absence of any apparent infection, normal cholesterol measures, and appearance of symptoms after the transplant and considering the morphologic similarity with verruciform xanthoma, a lesion also reported in transplanted patients, we speculate that the pathogenesis of the lesion in this particular patient may be related to immunosuppression.

Vanishing bile duct syndrome related to DILI and Hodgkin lymphoma overlap: A rare and severe case.

Vanishing bile duct syndrome is a rare acquired condition, characterized by progressive loss of intrahepatic bile ducts leading to ductopenia and cholestasis. It can be associated with infections, ischemia, drug adverse reactions, neoplasms, autoimmune disease, and allograft rejection. Prognosis is variable and depends on the etiology of bile duct injury. We report the case of a 25-year-old female with cholestatic hepatitis and concomitant intakes of hepatotoxic substances, such as garcinia, field horsetail, and ketoprofen. On suspicion of a drug-induced liver injury, the drugs were promptly withdrawn and ursodeoxycholic acid was started with initial clinical and laboratory improvement, and the patient was discharged from the hospital. One month later, she had a new increase in bilirubin levels and canalicular enzymes, requiring a liver biopsy that showed significant loss of intrahepatic bile ducts, which was compatible with vanishing bile duct syndrome. This was confirmed by using cytokeratin 19 on immunohistochemistry. There was subsequent lymph node enlargement in several chains, and relevant weight loss. Histological analysis of a cervical lymph node revealed nodular sclerosis-subtype classic Hodgkin lymphoma. In this setting, vanishing bile duct syndrome was related to Hodgkin lymphoma and a drug-induced liver injury overlap, leading to progressive cholestasis with a worse prognosis. The patient's response to chemotherapy was poor, requiring biological therapy with brentuximab vedotin. It is crucial for physicians to create a broad differential diagnosis in suspected vanishing bile duct syndrome patients, especially to rule out malignancies.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer

ABSTRACT Purpose: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. Materials and Methods: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. Results: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. Conclusions: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer.

PURPOSE: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. MATERIALS AND METHODS: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. RESULTS: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. CONCLUSIONS: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

Does index tumor predominant location influence prognostic factors in radical prostatectomies?

ABSTRACT Purpose To find any influence on prognostic factors of index tumor according to predominant location. Materials and Methods Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model. Results Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis. Conclusions The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.

Does index tumor predominant location influence prognostic factors in radical prostatectomies?

PURPOSE: To find any influence on prognostic factors of index tumor according to predominant location. MATERIALS AND METHODS: Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model. RESULTS: Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis. CONCLUSIONS: The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.

Predictive criteria of insignificant prostate cancer: what is the correspondence of linear extent to percentage of cancer in a single core?

OBJECTIVE: The aim of active surveillance of early prostate cancer is to individualize therapy by selecting for curative treatment only patients with significant cancer. Epstein's criteria for prediction of clinically insignificant cancer in surgical specimens are widely used. Epstein's criterion "no single core with >50% cancer has no correspondence in linear extent. The aim of this study is to find a possible correspondence. MATERIALS AND METHODS: From a total of 401 consecutive patients submitted to radical prostatectomy, 17 (4.2%) met criteria for insignificant cancer in the surgical specimen. The clinicopathologic findings in the correspondent biopsies were compared with Epstein's criteria for insignificant cancer. Cancer in a single core was evaluated in percentage as well as linear extent in mm. RESULTS: Comparing the clinicopathologic findings with Epstein's criteria predictive of insignificant cancer, there was 100% concordance for clinical stage T1c, no Gleason pattern 4 or 5, ≤ 2 cores with cancer, and no single core with >50% cancer. However, only 25% had density ≤ 0.15. The mean, median and range of the maximum length of cancer in a single core in mm were 1.19, 1, and 0.5-2.5, respectively. Additionally, the mean, median, and range of length of cancer in all cores in mm were 1.47, 1.5, and 0.5-3, respectively. CONCLUSION: To pathologists that use Epstein's criteria predictive of insignificant cancer and measure linear extent in mm, our study favors that "no single core with >50% cancer" may correspond to >2.5 mm in linear extent.

Predictive criteria of insignificant prostate cancer: what is the correspondence of linear extent to percentage of cancer in a single core?

Objective The aim of active surveillance of early prostate cancer is to individualize therapy by selecting for curative treatment only patients with significant cancer. Epstein’s criteria for prediction of clinically insignificant cancer in surgical specimens are widely used. Epstein’s criterion “no single core with >50% cancer” has no correspondence in linear extent. The aim of this study is to find a possible correspondence. Materials and Methods From a total of 401 consecutive patients submitted to radical prostatectomy, 17 (4.2%) met criteria for insignificant cancer in the surgical specimen. The clinicopathologic findings in the correspondent biopsies were compared with Epstein’s criteria for insignificant cancer. Cancer in a single core was evaluated in percentage as well as linear extent in mm. Results Comparing the clinicopathologic findings with Epstein’s criteria predictive of insignificant cancer, there was 100% concordance for clinical stage T1c, no Gleason pattern 4 or 5, ≤2 cores with cancer, and no single core with >50% cancer. However, only 25% had density ≤0.15. The mean, median and range of the maximum length of cancer in a single core in mm were 1.19, 1, and 0.5-2.5, respectively. Additionally, the mean, median, and range of length of cancer in all cores in mm were 1.47, 1.5, and 0.5-3, respectively. Conclusion To pathologists that use Epstein’s criteria predictive of insignificant cancer and measure linear extent in mm, our study favors that “no single core with >50% cancer” may correspond to >2.5 mm in linear extent. .

The value of the 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system as a predictor of biochemical recurrence after radical prostatectomy.

PURPOSE: To compare time and risk to biochemical recurrence (BR) after radical prostatectomy of two chronologically different groups of patients using the standard and the modified Gleason system (MGS). METHODS: Cohort 1 comprised biopsies of 197 patients graded according to the standard Gleason system (SGS) in the period 1997/2004, and cohort 2, 176 biopsies graded according to the modified system in the period 2005/2011. Time to BR was analyzed with the Kaplan-Meier product-limit analysis and prediction of shorter time to recurrence using univariate and multivariate Cox proportional hazards model. RESULTS: Patients in cohort 2 reflected time-related changes: striking increase in clinical stage T1c, systematic use of extended biopsies, and lower percentage of total length of cancer in millimeter in all cores. The MGS used in cohort 2 showed fewer biopsies with Gleason score ≤ 6 and more biopsies of the intermediate Gleason score 7. Time to BR using the Kaplan-Meier curves showed statistical significance using the MGS in cohort 2, but not the SGS in cohort 1. Only the MGS predicted shorter time to BR on univariate analysis and on multivariate analysis was an independent predictor. CONCLUSIONS: The results favor that the 2005 International Society of Urological Pathology modified system is a refinement of the Gleason grading and valuable for contemporary clinical practice.

Hepatic inflammatory pseudotumor: A case series.

INTRODUCTION: Inflammatory pseudotumor (IPT) is a rare lesion consisted of inflammatory and myofibroblastic cells. These lesions may be found in different organs. There are less than 300 described cases. PRESENTATION OF CASE: Case 1. 64-year-old cirrhotic male with a palpable epigastric mass. CT showed a lesion in liver segments 2 and 3 and left hepatic artery aneurism. Percutaneous embolization and wide spectrum antibiotics were tried, however the lesion grew. Left lateral hepatectomy was performed, and HIPT diagnosed. The patient died due to multiple organ dysfunction. Case 2. 30-year-old male with abdominal pain and fever. CT showed a hepatic hilar lesion. Surgical resection was performed after an ineffectual antibiotic trial, and HIPT was confirmed. The patient is doing well. Case 3. 73-year-old female with abdominal pain and fever. CT showed a 7cm lesion in the left liver lobe. Unrewarding cancerous screening was performed, and unsuccessful antibiotic course was tried. Resection was performed, and HIPT diagnosed. The patient is doing well. Case 4. 50-year-old cirrhotic male with abdominal pain. CT showed a segment 6 lesion and portal vein thrombosis. Considering cancer as the first hypothesis and the MELD score of 9, segmentectomy was performed. HIPT was the final diagnosis. The patient died due to abdominal sepsis. DISCUSSION: HIPT is a lesion with a vast list of differential diagnosis. Antibiotics are the first line of therapy, although surgery is often necessary. Overall prognosis is good, although comorbidities may worsen it. CONCLUSION: HIPT is a rare and misleading entity.