Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments.

Ribavirin suppresses erythroid differentiation and proliferation in chronic hepatitis C patients.

Combination therapy with pegylated interferon (pegIFN) plus ribavirin (RBV) is the standard of care for chronic hepatitis C. One of the major treatment-related side effects is anaemia, attributed to RBV-induced haemolysis. However, haemolysis biomarkers are not present in all patients supporting the existence of other pathogenetic mechanisms. We studied the role of RBV in inducing haemolysis and its effects on erythropoiesis. In 18 hepatitis C virus (HCV) genotype 2 patients treated with pegIFN-alpha-2a (180 mcg/week) plus RBV (800 mg/day) for 24 weeks and in 10 hepatitis B virus (HBV) patients treated with pegIFN-alpha-2a (180 mcg/week) for 48 weeks, haemolysis was assessed by serum LDH, haptoglobin and reticulocyte count. Erythropoiesis was evaluated both ex vivo, analysing the clonogenic activity of patients' erythroid progenitors, as well as in vitro adding pegIFN and RBV to liquid cultures obtained from CD34+ cells of healthy volunteers. The majority of patients developed anaemia; the week 4 mean haemoglobin decrease was greater in HCV than in HBV patients (1.7 vs 0.47 g/dL, P = 0.01). Only three HCV patients (17%) and no HBV patients showed signs of haemolysis. The 15 nonhaemolytic HCV patients and all HBV patients showed a delay in erythroid differentiation, with a reduction in colony number and a relative increase in undifferentiated colony percentage. Haemolytic HCV patients had an increase in colony number at week 4 of therapy. In vitro, erythroid cell proliferation and differentiation were inhibited by both pegIFN and RBV. Both pegIFN and RBV have an inhibitory effect on erythroid proliferation and differentiation.

[Multiple granular cell tumor: case report and review of the literature]. / Tumore a cellule granulose multiplo. Descrizione di un caso e revisione della letteratura.

We describe a case of multiple granular cell tumour (GCT) in 41 years old man. It manifested as subcutaneous synchronous multiple lesions. GCT is, usually, a benign lesion that is histologically diagnosed after biopsy or surgical excision. It raises doubts about his benignity in relation to multiple and distant localizations as in the present case.

Renal cell carcinoma: histological findings in peritumoral tissue after organ-preserving surgery.

OBJECTIVE AND METHOD: This study assessed the involvement of peritumoral renal cell carcinoma tissue and evaluated the efficacy of partial resection versus enucleation by an anatomopathological investigation into the resection margins in 28 cases of partial nephrectomy. RESULTS: Histological findings showed no peritumoral infiltration in 91.6% of elective partial resections (24 patients) and resection margin involvement in 75% of necessary partial resections (4 patients). CONCLUSION: Although the debate between organ-preserving and radical surgery remains open, the conservative approach can undoubtedly be recommended in selected patients.

Bleomycin, ifosfamide and cis-platin chemotherapy in recurrent and persistent cervical cancer, a prospective study.

Thirty patients with histologically proven recurrent or persistent squamous cell cervical carcinoma were treated with chemotherapy, consisting of a combination of bleomycin, ifosfamide and cis-platin (BIP). All patients were evaluable for response. An objective response was seen in nine of the 30 patients (30%): complete in two (6.7%) and partial in the other seven (23.3%). A total of 39 tumor sites was treated: five responses were observed in 26 irradiated areas (19%), whereas seven responses were observed in 13 nonirradiated areas (53.8%). Side-effects were mainly nausea, vomiting, alopecia, myelosupression, fever and impaired renal function. Encephalopathy was recorded in four patients (severe in one). No patient died from the toxic effects of chemotherapy. The results indicate that BIP is an active combination in recurrent and advanced cervical carcinoma, with acceptable toxicity; however, this combination failed to prove any superiority over other single or multi-drug treatments proposed in the last decade.

Giant cell reparative granuloma of the maxillary bone: case report and review of diagnostic criteria.

This paper reports a case of giant cell reparative granuloma of the right maxillary bone of a 13-year-old caucasian girl. It may be very difficult to distinguish this entity from other lesions of mandible, maxilla and skull bones which contain multinucleated giant cells. The differential diagnosis, especially from giant cell tumors of the bone, is discussed. Accurate diagnosis lies on correct integration of clinical, radiographical and histopathological data.

Fine-needle aspiration cytodiagnosis of the "cold" thyroid nodule.

The results of 1886 fine-needle cytoaspirations of solid, palpable thyroid nodules, "cold" on scintiscanning, performed between 1 January 1978 and 31 December 1986, were analyzed. In total 36 diagnoses of malignancy were made (1.9%). The results of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and discordance in 16 consisting of 13 false negatives (11.4%) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, positive predictive value 93.8%, negative predictive value 80% and test efficiency 86%. These values are in the range of those reported in the literature and confirm the validity of fine-needle aspiration cytology in the preoperative diagnosis of thyroid neoplasms.

Cytodiagnosis of gastric cancer by brushing: 1978-1983.

A total of 1652 endoscopic cytologic brushings from 1131 patients, 823 males aged 15 to 87 years and 358 females aged 21 to 88 years, were examined. From these we diagnosed 96 carcinomas, 69 in males and 27 in females. In 1621 samplings from 1151 patients it was possible to compare the cytologic and histologic diagnoses. To evaluate the diagnostic accuracy of both methods, brushing and biopsy, used separately or in association, we analyzed 81 cases where gastric cancer was confirmed by histologic examination of the removed stomach. The sensitivity rate of the cytodiagnosis was 88.3% and that of histology was 93.4%. Combining the two methods gave a sensitivity yield of 96.2%. These values are among the highest reported in the literature and confirm the utility of combining both methods for diagnosing gastric carcinoma.