Long-term follow up of patients affected by pulmonary carcinoid at the Istituto Nazionale Tumori of Milan: a retrospective analysis

Neuroendocrine tumors of the lung involve an heterogeneous group of tumors representing a wide range of histological variants, from well-differentiated typical carcinoid (TC) tumors to poorly differentiated small cell carcinomas. The epidemiology, clinical outcome, and management of these neoplasms differ significantly from other lung malignancies. The main aim of this report consists in describing the single Center experience of the Istituto Nazionale Tumori of Milan on neuroendocrine lung tumors, with an emphasis on bronchopulmonary carcinoid subtypes. From 1986 to 2009, 91 cases of carcinoid tumors were diagnosed; these were divided in two series, according to typical (66 patients) or atypical [25] histotypes. These two groups were compared in relation to various features, including pathologic classification, clinical behavior, treatment modalities and long-term survival. At the moment of diagnosis 11 patients had locally advanced/metastatic disease, while 80 patients showed non metastatic disease. The comparative analysis between typical and atypical series disclosed significant differences in terms of long-term survival; in fact, 5-year and 10-year survival rates were 98 % and 94 % for the first carcinoid series versus 76 % and 18 % for the atypical series, respectively (p<0.001). The median overall survival (OS) was 76 months (range 3-182) for atypical carcinoids and has not yet been reached for TCs patients.     

Pancreas and kidney transplantation: the San Raffaele Hospital (Milan, Italy) experience

Results of 33 simultaneous pancreas and kidney transplantations performed at the San Raffaele Hospital, Milan, Italy are presented. In 26 cases segmental neoprene duct-injected grafts were transplanted and in seven cases, duodenopancreatic bladder-drained grafts. Five-year patient, kidney and pancreas survival were respectively, 89%,72% and 58%. Five-year survival in patients with technically successful pancreas transplants was 73%. Thrombosis occured in 20% of cases. Mortality was 6% and overall morbidity 76%. Surgical complications were present in 51% of cases.     

Liver transplantation for hepatocellular carcinoma exceeding the Milan criteria: a single-center experience

Purpose

To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT).

Methods

A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence.

Results

Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I—risk index equal to 0, grade II—risk index from 0 to 2, grade III—risk index from 2 to 6 and grade IV—risk index >6. RFS rates of patients with grade I–IV (n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients (n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148).

Conclusions

The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria.     

Colorectal carcinoma: A decade of experience at the Lahey Clinic

Summary Carcinoma of the colon and rectum is the commonest visceral malignancy in this country today. Uncorrected fiver-year survival rates (1967–1971) for Dukes' A, B, and C lesions were 81 per cent, 62 per cent, and 33 per cent respectively, and are essentially the same as those observed in the previous five-year period (1962–1966). The actuarially corrected five-year survival rates for Dukes' A, B, and C lesions for the ten-year period (1962–1971) were 95 per cent 90 per cent, and 55 per cent. Further improvement in these statistics depends on bringing the patient to operation with less advanced disease and possibly on supplementing resection with other modalities of therapy.     

Infliximab in treatment of Crohn''s disease: the Milan experience

BACKGROUND: Efficacy of infliximab in treatment of patients with moderate-to-severe refractory and fistulizing Crohn's disease has been shown in controlled clinical trials. Moreover, audit data from North America and North Europe have confirmed efficacy in clinical practice comparable to that in clinical trials. AIM: To report clinical experience using infliximab in treatment of Crohn's disease in Italy, comparing efficacy and safety with those reported in clinical trials and other published series. PATIENTS AND METHODS: The study population comprised 63 patients (31 males and 32 females, median age 33 years) treated with infliximab for refractory/inflammatory (31 patients) and/or fistulizing Crohn's disease (32 patients). All patients received an infusion of infliximab at a dose of 5 mg/kg at weeks 0, 2 and 6. After the first infusion, clinical and laboratory assessments were repeated at weeks 2, 6 and 10. For refractory inflammatory Crohn's disease, clinical remission was defined as a Crohn's Disease Activity Index of < or = 150 at each scheduled visit, clinical response as a reduction in the Crohn's Disease Activity Index score of > or = 70 points in comparison to baseline. For fistulizing Crohn's disease, a complete response was defined as closure of any draining fistulae at week 10. A fistula was defined as closed when it no longer drained despite gentle finger pressure. A partial response was defined as reduction in number, size or drainage of fistulae, at the same visit. RESULTS: According to an intention-to-treat evaluation on the 31 patients with refractory/inflammatory Crohn's disease, at week 2, 42.5% (14 patients) had a clinical response and 31.3% of patients (10 patients) were in clinical remission. At week 10 (4 weeks after the end of third infusion), 80.6% (25 patients) had a clinical response and 71% (22 patients) were in clinical remission and 14/19 (74%) had discontinued steroid treatment. Of the 32 patients with fistulizing Crohn's Disease, 15 (46.9%) had a complete response, 8 (25%) a partial response, and 9 (28.1%) no response at week 10 check-up. The incidence of side-effects was low (16%) and not influenced by concurrent immunomodulatory therapy. CONCLUSION: The present experience with infliximab in clinical practice confirms its efficacy, in particular in inflammatory/refractory Crohn's disease and its safety, at least, in short-term follow-up.     

A retrospective evaluation of microbiology of acute otitis media complicated by spontaneous otorrhea in children living in Milan, Italy

Purpose

To evaluate the microbiology of acute otitis media (AOM) with otorrhea due to spontaneous tympanic membrane perforation (STMP) in children living in Milan, Italy.

Methods

We evaluated middle ear fluid (MEF) specimens taken from children affected by AOM associated with STMP and otorrhea between January 2001 and December 2011. The fluid was collected by means of direct swab sampling, sent for culture, and processed within 4 h.

Results

A total of 705 specimens were obtained from 458 children (233 boys; mean age ± SD 28.3 ± 19.9 months), and were positive for bacteria in 487 cases (69.1 %). The most frequently cultured infectious agent in single-pathogen cultures was Haemophilus. influenzae (51.0 %), followed by Streptococcus pneumoniae (19.4 %), Streptococcus pyogenes (17.4 %), and Staphylococcus aureus (10.7 %). After adjusting for the sub-period of data collection, age, gender, and previous full heptavalent pneumococcal conjugate vaccine (PCV-7) schedule, it was found that the prevalence of H. influenzae slightly increased in 2008–2010, and the prevalence of S. pneumoniae significantly decreased over time (p = 0.02).

Conclusions

AOM with STMP is a particular form of AOM in which S. pyogenes plays a significant causative role although, as in uncomplicated cases, H. influenzae and S. pneumoniae retain their etiological importance. The frequency of the detection of S. aureus in MEF deserves further study because this pathogen can give rise to severe clinical problems. Finally, although the use of PCV-7 was relatively efficacious, the benefit of pneumococcal vaccination would be increased by vaccines including a larger number of serotypes.     

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan,Italy

BackgroundTocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19.MethodsIn this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days.ResultsForty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%).ConclusionTocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.     

Colorectal cancer: Lahey clinic experience, 1972–1976

The records of 344 consecutive patients with colorectal cancer treated operatively at the Lahey Clinic from 1972 through 1976 were reviewed, and the effects of 41 clinical and pathologic variables on survival were analyzed. The variables associated with poorer five-year survival rates were advanced Dukes' stage, four or more positive nodes, blood vessel invasion, lymphatic invasion, circumferential involvement, and obstruction at initial presentation. As a group, patients with right colon cancers (cecum and ascending colon) had the best survival rates. When fistula formation or localized perforation had occurred,en bloc resection of locally involved adjacent viscera improved survival rates. These prognostic indicators aid in the selection of patients for wider colonic and mesenteric resections.     

Proximalisation of Colorectal Carcinoma: A 10-year Study in Italy

Introduction Proximalisation of colon carcinoma has been reported over the course of the last 60 years. Changes in site distribution are receiving increasing attention on account of their implications for screening programmes. Objective A retrospective observational study to determine whether the site distribution of colorectal carcinoma in Italy has varied in the last years and whether changes have been influenced by age and sex. Methods Findings of colonscopies conducted at Turin University from 1992 to 2001 were examined. Inclusion criteria were: outpatients, screening, presence of anaemia or gastrointestinal bleeding, weight loss, constipation or changes in evacuation frequency. Exclusion criteria were: uncompleted, surgical endoscopies or conducted for positive flexible sigmoidoscopy, with doubtful findings. Carcinomas and benign polyps were diagnosed histologically. Age, sex, date of examination, nature and location of lesions were recorded. Lesions were classed as carcinoma, and polyps <1 and ≥1 cm. Data were grouped into different year periods and compared with the chi square test. We compared 1992–1993 vs. 2000–2001 and 1992–1996 vs. 1997–2001. Results Of the 8,132 colonoscopies performed, 7,342 were included in the study. Proximal carcinomas moved from 12.2% in 1992–1993 to 14.9% in 2000–2001 (P = 0.57), proximal polyps rose from 16.6% to 22.1% (P < 0.0001). Furthermore proximal carcinomas moved from 16.5% in 1992–1996 to 14.4% in 1997–2001 (P = 0.48); proximal polyps rose from 18.4% to 27.8% (P < 0.005). In the period 1996–2001 there was higher female prevalence (P = 0.0011) and older age (P = 0.0191). Discussion We can suppose that proximalisation of carcinoma has not yet appeared in Italy.     

Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions

Milan criteria are currently the benchmark related to liver transplantation(LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria(yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of "Metroticket" and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.     

Nocardia brasiliensis in Italy: a nine-year experience

In the past, no case reports concerning N. brasiliensis infections were published from Italy. We now report 4 cases observed during 1998-2006 in 4 Italian patients, 1 immunosuppressed and 3 immunocompetent.