Feasibility and efficacy of a multidisciplinary palliative approach in patients with advanced interstitial lung disease. A pilot randomised controlled trial.

INTRODUCTION AND OBJECTIVES: Interstitial lung diseases (ILDs) encompass a heterogeneous group of parenchymal lung disorders which have a significant burden on quality of life and exercise. The primary purpose of this randomised pilot trial performed in advanced ILD was to determine the feasibility and efficacy of a multidisciplinary palliative care approach (including physiotherapist, psychologist, pulmonologists, and palliative care doctors) to relieve patients' symptoms of dyspnoea, depression measured with the Center for Epidemiological Studies-Depression (CES-D) scale and quality-of-life (QoL) at 6 and 12 months. MATHERIALS AND METHODS: Fifty patients with confirmed interstitial lung disease at computed tomography (CT) scan and advanced disease were enrolled at our clinic. Patients were randomised to usual care group vs intervention group; in the intervention group, patients were scheduled to meet a physiotherapist, a psychologist, a palliative care doctor, and a pulmonologist specialized in ILD care. Data on dyspnoea, cough, quality of life and depression were recorded; patients in the intervention group were also tested to assess lower body flexibility and strength. RESULTS: Both groups showed a worsening in dyspnoea during the time course of the trial, but the Borg scale was less in the intervention group at 6 and 12 months. A similar trend was observed also for the CES-D scale. No differences were observed for the other scales. CONCLUSIONS: A multi-disciplinary palliative care intervention in patients with advanced fibrosing interstitial lung disease is feasible and effective. TRIAL REGISTRATION: NCT02929966 on ClinGovTrial.

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.

Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy.

The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy.

Factors influencing survival after hepatectomy for metastases from gastric cancer.

PURPOSE: To investigate clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. METHODS: Retrospective multi-center chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. RESULTS: One hundred and five patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting of the disease. In 89 cases a R0 resection was achieved, while in 16 a R+ hepatic resection was performed. Adjuvant chemotherapy was administered to 29 patients. Surgical mortality was 1% and morbidity 13.3%. Median disease-free survival was 10 months, median overall survival was 14.6 months. Overall 1, 3, and 5-year survival rates were 58.2%, 20.3%, and 13.1%, respectively. Survival was influenced independently by the factor T of the gastric primary (p < 0.001), by the curativity of surgical procedure (p = 0.001), by the timing of hepatic involvement (p < 0.001) and by adjuvant chemotherapy (p < 0.001). T4 gastric cancer, R+ resection, synchronous metastases, and abstention from adjuvant chemotherapy were associated with a worse prognosis; T4 gastric cancer and R+ resections displayed a cumulative effect (p < 0.001). CONCLUSIONS: Our data show that R0 resection must be pursued whenever possible. Furthermore, in the synchronous setting, the coexistence of T4 gastric primaries and R+ resections suggests prudence and probably abstention from hepatectomy. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results.

Challenge in differential diagnosis of a liver mass histologically defined as a metastatic lesion from an occult primary intestinal tumour. The importance of clinical findings and the limitations of histology and molecular profiles. A case report.

Differential diagnosis of liver lesion in the absence of proven primary tumor is still a challenge. We experienced a case of an asymptomatic 14 cm lesion of right hemiliver in a 67 year-old man submitted to right hepatectomy in December 2010. One year before the patient underwent to endoscopic removal of a tubular adenoma of the right colon. Preoperative diagnosis was supported by ultrasound, CT scan, PET and liver biopsy. The patient received 6 cycles of preoperative chemotherapy (FOLFOX) with down-staging of the lesion diameter. Immunohistochemistry on the surgical specimen showed positivity for cytokeratins 19 and 20, CEA, MUC-2, negativity for cytokeratin 7 and a-fetoprotein. Moreover, the neoplastic cells showed a focal positivity with lower intensity for MUC-1 and MUC-5AC. The immunohistochemical profile suggested the possibility of a metastatic tumour from the large bowel, without excluding a primitive mucinous cholangiocarcinoma with intestinal phenotype. At 6 months after intervention, the patient was submitted to chemotherapy (FOLFOX). At present he is in good condition, without radiological signs of recurrence. Oncologists must evaluate the possible benefits of further adjuvant treatments based on the differential diagnosis between a primitive or metastatic liver tumour. In conclusion, correct diagnosis of liver masses is mandatory and remains a challenge that can differentiate either follow-up or surgical and adjuvant treatment. Histology and immunohistochemistry must be related to clinical findings as they may not always be sufficient to reach a correct final diagnosis, and can even be confusing. At present, molecular biology cannot be considered a helpful for diagnosis in these cases.

Simultaneous occurrence of primary diffuse large B-cell lymphoma and extranodal marginal zone (MALT) B-cell lymphoma in the gallbladder: a case report.

Primary lymphoma of the gallbladder is extremely rare. We present an asymptomatic case of primary combined DLBCL--MALT lymphoma of the gallbladder in a 78-year-old man in whom definitive diagnosis was made with laparotomic cholecystectomy. Preoperative diagnosis was supported by NMR, CT and PET scans. The pathological report identified a polypoid lesion measuring 3.5 cm in diameter. A non-Hodgkin lymphoma with two different coexisting patterns was identified histologically: large diffuse B-cell lymphoma (DLBCL) associated with focal areas of extranodal marginal zone B-cell lymphoma (MALT-type) of the gallbladder. The postoperative course was uneventful and the patient is currently without clinical or radiological signs of disease. Chemotherapy was not indicated due to cardiopathy. In conclusion, a primary gallbladder lymphoma is a rare entity. Radiological findings may be helpful, but cholecistectomy may be necessary for definitive diagnosis. In this report, we describe the possible association between MALT and DLBCL of the gallbladder.

[The results of the experimental prospective study on the effectiveness and efficiency of the implementation of clinical pathways]. / I risultati dello studio sperimentale prospettico di efficacia ed efficienza dell'implementazione dei percorsi assistenziali.

Our study was undertaken to determine how the use of care pathways in hospital affected the quality of the care of the patients. We performed a cluster-randomized trial. The use of diagnostic procedures and of medical treatments was more appropriate in the care pathways group, as well as the discharge process. As a consequence the outcomes indicators adopted in our study showed better performances in the care pathways group when compared to the usual care group. Our study added evidences on the value of clinical pathways that can be effectively used to improve the quality of hospital care. The use of CP helped to create a constant dialogue within the clinicians, ensured that important areas of treatment were not overlooked and unnecessary delays were prevented by timely interventions. We think that our results are reliable because we adopted a cluster-randomized controlled trial design that is widely accepted as the most reliable method of determining effectiveness of complex interventions in healthcare.

[Benign solitary fibrous tumor of the pancreas: a rare location of extra-pleural fibrous tumor. Single case report and review of the literature]. / Tumore fibroso benigno solitario del pancreas: una rara localizzazione di tumore fibroso extrapleurico. Caso clinico e revisione della letteratura.

BACKGROUND/AIMS: Extra pleural solitary fibrous are very rare, but occasionally they appear in extraserosal soft tissues or parenchymatous organs, where their diagnosis is often a challenge. In this report we describe the case of a patient with a single primary solitary fibrous tumor of the pancreatic head with a review of the literature. METHODS/RESULTS: A 62 years old woman underwent a Traverso-Longmire procedure in November 2004. Sixteen months after resection there is no evidence of recurrence. The tumour showed immunoreactivity for CD34, CD99, bcl-2, vimentin and smooth muscle actin. MIB-1 proliferating activity was < 5%. CONCLUSIONS: Extra pleural solitary fibrous tumor are often benign lesions. In the pancreas only 2 cases have been described so far. Other mesenchymal tumours that may occur in the pancreas include leiomyosarcoma, tumours of the peripheral nerve sheath, fibrous histiocytic tumours and rare vascular tumours. The differential diagnosis is mainly based on immunohistochemistry. The surgical approach is fundamental for the treatment of solitary fibrous tumour.

Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. PATIENTS AND METHODS: We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. RESULTS: Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). CONCLUSIONS: Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.

Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre.

BACKGROUND: Differences in risk factors for survival and recurrence after liver resection for hepatocellular carcinoma (HCC) in patients with or without cirrhosis are not fully clarified. AIM: To review a single-centre experience of curative liver resections for HCC in order to evaluate clinicopathologic features and the long-term outcome of cirrhotic and noncirrhotic patients. METHODS: From 1981 to 2002, 308 curative liver resections for HCC on cirrhosis (Group 1) and 135 for HCC without cirrhosis (Group 2) were performed. The main demographic, clinicopathologic and operative parameters, as well as early results were analysed and compared. Overall and disease-free survival were evaluated. Prognostic factors for survival and for tumour recurrence were studied by univariate and multivariate analysis. RESULTS: Group 1 had worse preoperative liver function and higher frequency of hepatitis C virus infection. In Group 2, HCC showed larger mean tumour diameter (P < 0.001), poorer differentiation (P < 0.05) and more frequent macrovascular invasion (P < 0.05). Although more extended resections were performed in Group 2 (P < 0.001), there were no differences in blood transfusions, while post-operative complication rate was higher in Group 1 (P < 0.005). After 1992, in-hospital mortality was 2.9% in Group 1 and 1.1% in Group 2 (P = N.S.). The 3- and 5-year overall survival was 63.7% and 42.2% in Group 1, and 67.9% and 51% in Group 2 (P < 0.05). The 3- and 5-year disease-free survival was 49.3% and 27.8% in Group 1, and 58% and 45.6% in Group 2 (P < 0.005). Serum bilirubin level > 1.2 mg/dL, multiple nodules, micro and macrovascular invasion, diaphragm infiltration and blood transfusions independently affected survival in Group 1. Blood replacement was the only negative prognostic factor in Group 2. Independent risk factors for tumour recurrence were satellite nodules and resection performed before 1992 in Group 1, and age < 60 in Group 2. CONCLUSIONS: Despite a more aggressive behaviour, HCC without cirrhosis led to better overall and disease-free survival compared to HCC with cirrhosis after curative liver resection. Age and intra-operative blood transfusions are the only predictors of outcome in patients without cirrhosis. The impact of the latter on long-term survival in both our groups outlines the importance of surgical technique on the results of hepatectomies.

Mechanisms and immediate outcome of in-hospital cardiac arrest in patients with advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

To differentiate patients with congestive heart failure who are more prone to develop malignant ventricular tachyarrhythmias or severe bradyarrhythmias as the terminal event, we retrospectively evaluated a group of 48 patients with advanced heart failure who experienced a monitored cardiac arrest during hospital stay. We found no significant differences with respect to several variables, apart from clinical status, which was worse in patients whose cardiac arrest was precipitated by severe bradycardia or electromechanical dissociation.

Highly aggressive policy of hepatic resections for neuroendocrine liver metastases.

BACKGROUND/AIMS: Neuroendocrine tumors are usually slow growing and carry a prolonged prognosis. The presence of liver metastases significantly impairs long-term survival. The clinical experience with 28 patients admitted since 1981 for liver metastases from neuroendocrine tumors was retrospectively reviewed to analyze the clinical and surgical management and to evaluate their outcome. METHODOLOGY: Surgery was indicated in 25 (89.2%) patients. Three had metachronous metastases. A correct diagnosis of these liver metastases was achieved before laparotomy in 15 (68.1%) of the remaining 22. The primary tumor site, unknown in 14/22 patients, was located during surgery only in 8 (57.1%). RESULTS: Due to tumoral spread, surgery was limited to exploration in 3 cases. Liver resections were performed in 19/22 patients (3 for palliation): 11/19 (57.9%) were major hepatectomies and in 8/19 (42.1%) cases they were accomplished by procedures for removing the primary tumor. Overall, curative procedures were carried out in 16/28 (57.1%). Resections were performed in 6 cases without the knowledge of the primary site. There was no operative mortality. Overall recurrence rate was 50.0%. Four-year actuarial survival was 92.6% after resection and 18.5% for patients that did not receive surgery (P < 0.001). CONCLUSIONS: Our experience confirms that the small number of patients makes the management of liver metastases from neuroendocrine tumors difficult to plan. In consideration of the satisfactory results achieved with an aggressive policy of resection, we advise referral of these patients to specialized liver units where major hepatic procedures, even if extended, can be safely performed.

Clinical feasibility of low energy internal atrial cardioversion with a three-electrode configuration in patients with unsuccessful conventional configurations.

Low energy internal cardioversion is a safe and highly effective method for atrial fibrillation termination. We will describe 6 patients in whom the conventional 2-electrode systems with the defibrillation leads positioned in the right atrium and in the coronary sinus or left pulmonary artery failed to terminate the arrhythmia despite the use of maximal available energies. A 3-electrode configuration including right atrium, coronary sinus and left pulmonary artery was used in order to encompass as much atrial mass as possible between the cathode and the anode. The atrial fibrillation was successfully interrupted in 4 out of 6 patients. The creation of a 3-electrode configuration may be a further technical expedient in order to increase the success rate of internal cardioversion when usual manoeuvres like lead repositioning, reversion of polarity, or addition of antiarrhythmic drugs are ineffective.