Protruding isolated rectal and anal neoplastic polyps removed by local transanal excision: our experience with 16 cases

Local transanal excision as primary treatment of rectal and anal canal adenomas in selected patients is supported by the recent literature. Sixteen patients with low rectal or anal canal neoplastic polyps underwent transanal resection. Postoperatively, 5 patients (31.25%) had complications, consisting in 2 cases of bleeding (12.5%) and 3 of urine retention (18.75%). Histologically, 2 were tubular adenomas without atypia (12.5%), 3 were tubulo-villous adenomas with moderate atypia (18.75%), 8 were tubulo-villous adenomas (50%) with severe atypia, 2 were tubulo-villous adenomas with locally invasive foci of adenocarcinoma (12.5%), and 1 case was a pT1 cloacogenic carcinoma (6.25%). The mean follow-up was 21.7 months (range: 12-36 months). One patient had a double recurrence at 8 months and after a further 6 months. After the third surgical operation the patient had no further recurrence. The outcomes were similar to those reported in the recent literature, showing that the procedure, when correctly performed, is simple and effective, with a good risk/benefit ratio.     

Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice

Primary myelofibrosis (PMF) is the most serious myeloproliferative disorder, characterized by clonal myeloproliferation associated with cytokine-mediated bone marrow stromal reaction including fibrosis and osteosclerosis. Current drug therapy remains mainly palliative. Because the NF-kappaB pathway is implicated in the abnormal release of cytokines in PMF, the proteasome inhibitor bortezomib might be a potential therapy. To test its effect, we used the lethal murine model of myelofibrosis induced by thrombopoietin (TPO) overexpression. In this TPO(high) model, the development of the disease is related to a deregulated MPL signaling, as recently described in PMF patients. We first demonstrated that bortezomib was able to inhibit TPO-induced NF-kappaB activation in vitro in murine megakaryocytes. It also inhibited NF-kappaB activation in vivo in TPO(high) mice leading to decreased IL-1alpha plasma levels. After 4 weeks of treatment, bortezomib decreased TGF-beta1 levels in marrow fluids and impaired marrow and spleen fibrosis development. After 12 weeks of treatment, bortezomib also impaired osteosclerosis development through osteoprotegerin inhibition. Moreover, this drug reduced myeloproliferation induced by high TPO level. Finally, bortezomib dramatically improved TPO(high) mouse survival (89% vs 8% at week 52). We conclude that bortezomib appears as a promising therapy for future treatment of PMF patients.     

Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease

This study defined the clinical features and assessed the prognosis of 47 patients (17 males, 30 females, median age 63 years) with primary nodal marginal zone B-cell lymphoma. Forty-five per cent had stage IV disease. Hepatitis C virus serology was positive in 24%. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 33% were classified as low-risk, 34% as intermediate-risk, and 33% as high-risk. The 5-year overall survival (OS) was 69%. In univariate analysis worse OS was associated with: FLIPI (P = 0.02), age > 60 years (P = 0.05) and raised lactate dehydrogenase (P = 0.05). In multivariate analysis, only FLIPI predicted a worse OS (P = 0.02).     

Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

Background  

Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study.     

Radiotherapy in gastric cancer: a systematic review of literature and new perspectives

Gastric cancer is still a major problem for oncologists. Surgery is the main therapeutic approach; a complete surgical resection is usually necessary to offer potentially curative therapy to patients with adenocarcinoma of the stomach. However, many patients with more locally advanced tumors will experience local and distal recurrences. When a recurrence occurs, only palliative therapy is possible. In operable gastric cancer, both the extent of surgery and the value of adjuvant treatment remain subject to considerable international controversies. To improve local control, surgeons address the role of standardized surgery and of more extended surgery. Radiotherapy appears to improve local control and survival in the adjuvant arms, but perspective randomized trials are scarce and reported over many years. Retrospective experience demonstrated a low local recurrence rate, but was affected by large heterogeneity. However, evidence published in the last few years, improved radiotherapy technologies, better knowledge of the at-risk areas (enabling smaller radiotherapy volumes) and growing interest in neoadjuvant approaches support the role of radiotherapy in gastric cancer.     

Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: a phase I clinical trial

AIM: This is a phase I study investigating the toxicity and the potential efficacy of thalidomide and oral cyclophosphamide in patients with hormone refractory prostate cancer (HRPC), previously treated with docetaxel-based regimens. METHODS: Two dose levels of thalidomide (100 and 200 mg every day) were studied. Patients were accrued to each dose level in cohorts of 3 starting from dose 1 level (100 mg). Thalidomide was started on day 1 at the assigned dose and continued for four consecutive weeks; oral cyclophosphamide (50 mg for day) was given for four consecutive weeks (1 cycle) starting on the same day initiating thalidomide. Toxicity was evaluated every two weeks; changes in prostate-specific antigen (PSA) levels were evaluated every cycle. Treatment was planned for four cycles. RESULTS: Sixteen men were treated. Ten patients in cohort 1, and 6 in cohort 2 were enrolled respectively. Grade 1-2 constipation, peripheral neuropathy and fatigue were the most common side effects, noted in 6 (37.5%), 5 (31.25%) and 3 (19%) patients, respectively. Three patients stopped the treatment at level 2, during the first cycle, for toxicity. Those three patients were evaluable only for toxicity. The MTD was 100 mg thalidomide. Thirteen patients completed two cycles. Two patients (15%) had a >50% decrease in PSA, while in one patient (8%) the PSA decrease was less of 50%. Overall PSA decrease was of 23%. CONCLUSIONS: The oral combination of thalidomide and cyclophosphamide is well tolerated and appears to be associated with biochemical response in this population. Future phase II trials, in pre-treated and untreated patients, are needed to evaluate clinical efficacy of this regimen in HRPC.     

ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival

ObjectivesWe tested and compared the improvement in prognostic ability related to the consideration of either ECOG performance status (ECOGPS) and/or symptom classification (S-CLASS) in renal cell carcinoma specific mortality (RCC-SM) predictions.MethodsUnivariate and multivariate Cox regression analyses targeted RCC-SM in 2570 RCC patients treated with either partial or radical nephrectomy. The increment in predictive accuracy related to the addition of either ECOGPS, S-CLASS or both was quantified using Harrell’s concordance index.ResultsFollow-up ranged from 0.1 to 23 years (median 3.2) and 610 patients (23.7%) died of RCC. In multivariable analyses, ECOGPS and S-CLASS represented independent predictors of RCC-SM. The addition of ECOGPS to established RCC-SM predictors increased the predictive accuracy by 0.3% (p = 0.8) versus 0.6% (p = 0.5) for S-CLASS versus 0.6% (p = 0.5) for both.ConclusionsNeither ECOGPS nor S-CLASS improves the ability to predict RCC-SM. Therefore, these variables may be safely omitted when RCC-SM risk is quantified.     

Sentinel lymph node biopsy and non-sentinel node involvement in special type breast carcinomas with a good prognosis

This study aimed at identifying factors related to sentinel lymph node (SLN) involvement in patients with tubular, cribriform, mucinous or papillary breast carcinoma and those related to non-SLN metastases if an SLN was positive. Multivariate analyses involved logistic and stepwise regressions. The SLNs harboured metastases in 85 of 572 cases, 78 of whom underwent axillary dissection; 19 presented non-SLN positive disease. Lack of lymphovascular invasion, a tumour size < or = 10 mm and a single SLN removed were the factors predicting an SLN metastasis rate <10%, and patients with these features could be candidates for no surgical axillary staging. A positive SLN proportion of < or = 50% and no lymphovascular invasion were associated with a <10% rate of non-SLN invasion; patients with a positive SLN and these features could be candidates for the omission of completion axillary dissection. The opposite presentation of these factors would mandate SLN biopsy and axillary dissection, respectively.