Vincenzo Petrozza

Rotator cuff re-tear or non-healing: histopathological aspects and predictive factors

PurposeThe aim of the study was to evaluate the histopathological changes that occur in the tendon and subacromial bursal tissue in patients with rotator cuff tear trying to correlate these changes to their healing capability.MethodsEighty-four patients were clinically evaluated with the Constant Scale. Radiographs and MRI were performed preoperatively and ultrasound were performed postoperatively. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed, and the specimens were histopathologically analyzed.ResultsTendons histopathological features consisted of loss of structural organization, poor or absent neoangiogenesis, chondral metaplasia, and fibrosis. Bursal features consisted of neoangiogenesis, absence of chondral metaplasia, hyperplasia/hypertrophy, and absence of necrosis. Direct correlation was seen between tendon and bursal hyperplasia and time of the onset of symptoms; between tendon chondral metaplasia, fibrosis, bursal neoangiogenesis, inflammation, and patient age; between tendon neoangiogenesis, hyperplasia, necrosis, fibrosis, bursal necrosis, inflammation, and lesion size; on the contrary, tendon fibrosis, necrosis, and bursal tissue inflammation decrease as time passes from the onset of symptoms. Tendon fibers disarray, neoangiogenesis, and inflammation decreases as the patient’s age increases. Bursal tissue fibrosis decreases as lesion size increases.ConclusionsSimple histopathological techniques should be employed routinely to assess the tissue quality, with the aim to predict future clinical evolution (repair or non-repair). Comparing the histopathological data with the demographical information and the descriptive statistics, it is possible to define the RCT repair at risk and identify which RCT will be able to heal.Level of evidence II.

Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell

The survival of osteosarcoma patients is connected to metastasis. The ezrin expression is associated with the development of metastasis and poor outcome in osteosarcoma. Ezrin is present in the cytoplasm and after phosphorylation assumes an active form and links F-actin to the cell membrane. This study evaluated ezrin and phosphorylated ezrin at site Tyr354 and Thr567 expression and its subcellular localization in osteosarcoma. We studied 50 osteosarcoma patients (mean follow-up 9.8 years). Ezrin expression was assessed using immunohistochemical and immunofluorescence analysis on tissue microarray and cultured cells of human osteosarcoma 143B. The western blot analysis was carried out on cultured cells. The majority of osteosarcomas, showing cytoplasmic positivity for ezrin, phosphorylated and unphosphorylated, were associated with membranous and nuclear positivity for phosphorylated ezrin Thr567 and phosphorylated ezrin Tyr354, respectively. Ezrin expression was associated with high-grade osteosarcoma (P=0.04), with metastasis (P=0.04) and with tumors that developed metastasis (P=0.04); phosphorylated ezrin Thr567 expression was present mostly in tumors with metastasis (P=0.01) and in osteosarcomas that did not develop metastasis (P=0.002). The osteosarcoma patients with ezrin expression have a short survival. The cytoplasmic ezrin expression in osteosarcoma matches its role of membrane-cytoskeleton linker protein. The subcellular trafficking of ezrin is not blocked and it is linked to ezrin phosphorylation, also in cancer. The phosphorylated ezrin Tyr354 nuclear localization suggests its possible role as a nuclear factor in osteosarcoma. The phosphorylated ezrin Thr567 phosphorylation may not be necessary in osteosarcoma metastatic progression but it was modulated. The ezrin expression is associated with more aggressive osteosarcomas and with metastasis.

A multistep approach to manage Fournier’s gangrene in a patient with unknown type II diabetes: surgery, hyperbaric oxygen, and vacuum-assisted closure therapy: a case report

IntroductionFournier’s gangrene is an infectious necrotizing fasciitis of the perineum and genital regions and has a high mortality rate. It is a synergistic infection caused by a mixture of aerobic and anaerobic organisms and predisposing factors, including diabetes mellitus, alcoholism, malnutrition, and low socioeconomic status. We report a case of Fournier’s gangrene in a patient with unknown type II diabetes submitted to 24-hour catheterization 15 days before gangrene onset.Case presentationThe patient, a 60-year-old Caucasian man, presented with a swollen, edematous, emphysematous scrotum with a crepitant skin and a small circle of necrosis. A lack of resistance along the dartos fascia of the scrotum and Scarpa’s lower abdominal wall fascia combined with the presence of gas and pus during the first surgical debridement also supported the diagnosis of Fournier’s gangrene. On the basis of the microbiological culture, the patient was given multiple antibiotic therapy, combined hypoglycemic treatment, hyperbaric oxygen therapy, and several surgical debridements. After five days the infection was not completely controlled and a vacuum-assisted closure device therapy was started.ConclusionsThis report describes the successful multistep approach of an immediate surgical debridement combined with hyperbaric oxygen and negative pressure wound therapy. The vacuum-assisted closure is a well-known method used to treat complex wounds. In this case study, vacuum-assisted closure treatment was effective and the patient did not require reconstructive surgery. Our report shows that bladder catheterization, a minimally invasive maneuver, may also cause severe infective consequences in high-risk patients, such as patients with diabetes.

BRAF and NRAS Mutations are Heterogeneous and Not Mutually Exclusive in Nodular Melanoma

Inhibitors of RAF inhibit the MAPK pathway that plays an important role in the development and progression of those melanoma carrying the V600E BRAF mutation, but there’s a subset of such patients who do not respond to the therapy. Various mechanisms of drug resistance have been proposed which include the clonal heterogeneity of the tumor. We have studied a population of nodular melanoma to investigate the intratumor and intertumor heterogeneity by Laser Capture Microdissection (LCM) analysis. Our results showed that BRAF and NRAS mutations were detected in 47% and 33% of nodular melanoma, respectively, and that there is a discrepancy in mutational pattern of tumoral sample because in the 36% of patients a different mutation, in at least 1 area of the tumor, was found by LCM analysis, giving evidence of the presence of different clonal cells populations. Moreover, we found that mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens and we observed that when the 2 different mutations were present one is a high-frequency mutation and the other is a low-frequency mutation. This was more evident in lymphonodal metastasis that resulted from wild type to mutational analysis, but showed different mutations following LCM analysis. Therefore, we believed that, when primary tumoral sample results negative to mutational analysis, if it is possible, metastases should be investigated to verify the presence of mutations. Generally, it should be searched for other mutations, in addition to BRAF V600E, so as to better understand the mechanism of drug resistance.

Transurethral resection of prostate and the role of pharmacological treatment with dutasteride in decreasing surgical blood loss.

PURPOSE Transurethral resection of prostate (TURP) still represents the gold standard in the surgical treatment of symptomatic benign prostatic hyperplasia (BPH). The most frequent complication is represented by intra- and perioperative bleeding. Preoperative use of 5-alpha-reductase inhibitors (finasteride or dutasteride) to reduce surgical bleeding is still a topic of debate in literature. Previous studies provided favorable data on blood loss reduction by preoperative administration of finasteride or dutasteride. The aim of this study was to evaluate whether pretreatment with dutasteride for six weeks before surgery can reduce surgical blood loss. METHODS A total of 142 patients with BPH-who were to undergo TURP-were enrolled and randomized into two groups. The dutasteride group comprising of 71 patients, was treated with dutasteride (0.5 mg/day) for 6 weeks before surgery and the control group, comprising of other 71 patients, did not receive dutasteride. Blood loss was evaluated in terms of a reduction in the serum hemoglobin level (ΔHb and ΔHCT), and was estimated by measuring the Hb and hematocrit levels before and 24 hours after surgery. RESULTS None of the patients treated with dutasteride reported any side effects. A significantly lower mean blood loss was observed in the dutasteride group compared to the control group (ΔHb=-1.29 ± 0.81 v -1.83 ± 1.25, respectively, p<0.0027; ΔHCT=-5.67 ± 2.58 v -6.50 ± 2.40, respectively, p<0.0491). CONCLUSIONS Our results showed that pretreatment with dutasteride for 6 weeks before TURP reduces the surgical bleeding considerably. This treatment schedule can be used routinely to decrease TURP surgical bleeding.

Cardiomyopathies due to homoplasmic mitochondrial tRNA mutations: morphologic and molecular features☆

Isolated hypertrophic cardiomyopathy may represent the sole clinical feature of a mitochondrial disorder in adult patients. The clinical outcome is characterized by a rapid progression to dilation and failure. A mitochondrial etiology in these cases is not obvious at clinical investigation and may represent an unexpected finding at autopsy or after cardiac transplant. We describe the morphologic, biochemical, and molecular features of hearts from 3 transplanted patients with isolated mitochondrial cardiomyopathy caused by homoplasmic mutations in the MTTI gene, coding for mitochondrial isoleucine tRNA (mt-tRNA(Ile)). On gross examination, the 3 hearts showed a symmetric pattern of hypertrophy. At histology, cardiomyocytes were hypertrophic and showed sarcoplasmic vacuoles filled with granules that stain with antimitochondrial antibodies. On frozen sections, the combined cytochrome c oxidase (COX)/succinate dehydrogenase stain showed a large prevalence of COX-deficient cardiomyocytes. Mitochondrially encoded COX subunit I was almost absent on immunohistochemistry, whereas the nuclear-encoded COX subunit IV was normally expressed. Ultrastructural analysis confirmed the marked mitochondrial proliferation. Biochemical studies of cardiac homogenates revealed a combined respiratory chain defect. Quantitative restriction fragment length polymorphism analysis of DNA from cardiac homogenate confirmed that the mt-tRNA mutations were also detected in the patients blood. High-resolution Northern blot analysis showed a marked decrease in the steady-state level of mt-tRNA(Ile), confirming pathogenicity. In conclusion, pathologists play a major role in unraveling the mitochondrial etiology of isolated hypertrophic cardiomyopathies, provided that a detailed diagnostic flowchart is followed. Once the mitochondrial etiology is clearly defined, molecular analyses on the heart are an invaluable tool to assign mutation pathogenicity.

Overactive bladder in diabetes mellitus patients: a questionnaire based observational investigation

PurposeBladder dysfunction, secondary to diabetes, is mainly characterized by poor bladder emptying and overflow incontinence. However, there is evidence in literature that storage symptoms, as those suggestive for overactive bladder (OAB), may also affect people with diabetes. The aim of this study was to evaluate the prevalence of overactive bladder, the complaint of urinary urgency with/without urge incontinence, usually with frequency and nocturia, in people with diabetes compared to healthy subjects (control group).MethodsSymptoms were assessed through the overactive bladder questionnaire (OAB-q), an investigative tool, specifically developed for OAB diagnosis.ResultsOAB-q scores resulted higher in diabetic people than those of the control group. Age and disease duration resulted in measurements that showed a statistical correlation with the OAB-q scores.ConclusionsOAB symptoms are more prevalent in diabetic people than in non-diabetic people. This prompts further research to determine whether the onset of OAB symptoms can be considered as an indicator of diabetic neuropathy.

Perfusion MDCT of prostate cancer: correlation of perfusion CT parameters and immunohistochemical markers of angiogenesis.

OBJECTIVE The aim of our study was to correlate perfusion MDCT parameters and immunohistochemical markers of angiogenesis in prostate cancer. SUBJECTS AND METHODS Twenty-two patients scheduled for radical surgical prostatectomy because of biopsy-proven prostate cancer underwent perfusion CT on a 64-MDCT scanner. Eight contiguous 5-mm sections were acquired at 1-second intervals for 45 seconds followed by three additional scans every 10 seconds after the administration of 80 mL of iodinated contrast medium (350 mg I/mL). Blood volume, blood flow, mean transit time, and permeability surface-area product were calculated, dividing each slice into nine square regions. Values obtained were correlated with the mean microvessel density (MVD) and mean vascular area of corresponding areas on histologic macrosections. RESULTS The mean values of the perfusion parameters detected on all square fields of patients with prostate cancer, benign hyperplasia, chronic prostatitis, and healthy tissue were, respectively, 18.36 ± 6.30, 19.49 ± 8.46, 19.67 ± 11.44, and 20.32 ± 4.53 mL/min/100 g for blood flow; 8.45 ± 2.75, 6.21 ± 4.32, 4.94 ± 2.31, and 5.44 ± 2.67 mL/100 mg for blood volume; 19.19 ± 4.45, 18.74 ± 4.91, 16.24 ± 4.12, and 16.37 ± 4.83 seconds for mean transit time; and 26.34 ± 11.88, 18.67 ± 9.15, 18.08 ± 7.72, and 19.93 ± 7.22 mL/min/100 g for permeability surface-area product. Both blood volume and the permeability surface-area product of cancerous squares showed the highest correlation with mean MVD and mean vascular area (0.618 [p < 0.01] and 0.614 [p < 0.01], respectively) and the highest area under the curve (0.769 and 0.708). CONCLUSION Our results show that blood volume and permeability surface-area product measurements obtained with perfusion CT have the highest correlation with immunohistochemical markers of angiogenesis in prostate cancer.

Incidentally Detected Giant Oncocytoma Arising in Retroperitoneal Heterotopic Adrenal Tissue

A nonfunctional retroperitoneal oncocytoma incidentally discovered in a 40-year-old woman is described. The tumor, which was 17 cm in largest dimension, was completely separated from the kidneys and adrenal glands and consisted of nests of polygonal cells with large, granular, eosinophilic cytoplasm. Significant nuclear atypia, necrosis, and mitosis were absent. Ultrastructural analysis confirmed the oncocytic nature of the neoplastic cells. Since neoplastic cells were not immunoreactive for chromogranin and did not contain dense-core secretory granules, the diagnosis of oncocytic paraganglioma was excluded. Cells immunoreactive for 3beta-hydroxysteroid dehydrogenase, the enzyme catalyzing the conversions of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione, were identified in the tumor, thus strongly indicating adrenocortical tissue origin. Multiple nests of 3beta-hydroxysteroid dehydrogenase-positive cells were detected in the loose retroperitoneal connective tissue. These findings strongly support the origin of the tumor from heterotopic retroperitoneal rests of the adrenal gland. To our knowledge, only 1 similar case has been described in the literature to date.

Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure

Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown. We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium.