Conservative surgical treatment in rectal cancer after complete pathological response to neoadjuvant treatment. Prospective observational study.

In 2012 we started a prospective observational study at San Giovanni Addolorata Hospital in Rome for patients with rectal cancer with complete response to neoadjuvant therapy (nCRT). In our, IRB approved protocol, patients are evaluated at time 0 by physical, endoscopic, pathological and radiological examinations. 6 weeks after completion of nCRT they are re-evaluated. In case of persistence or progression of disease patients undergo surgery with Total Mesorectal Excision. In case of complete or major clinical response they are re-evaluated at 12 weeks and subjected to transanal surgical excision to confirm complete pathological response (pCR). If tumor is found in the transanal excision specimen the patient is operated upon whereas patients with pCR are followed up at 3 months interval.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes.

Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Mitotane increases the radiotherapy inhibitory effect and induces G2-arrest in combined treatment on both H295R and SW13 adrenocortical cell lines.

Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD) is an agent with adrenotoxic effect, which is able to block cortisol synthesis. This drug and radiotherapy are used also in adrenal cancer treatment even if their biological action in this neoplasia remains unknown. We investigated the effects of o,p'-DDD and ionizing radiations (IR) on cell growth inhibition and cell cycle perturbation in H295R and SW13 adrenocortical cancer cells. Both cell lines were irradiated at a 6 Gy dose and were treated with o,p'-DDD 10(-5) M separately and with IR/o,p'-DDD in combination. This combination treatment induced an irreversible inhibition of cell growth in both adrenocortical cancer cells. Cell cycle analysis showed that IR alone and IR/o,p'-DDD in combination induced the cell accumulation in the G2 phase. At 120 h after IR, the cells were able to recover the IR-induced G2 block while cells treated with IR/o,p'-DDD were still arrested in G2 phase. In order to study the molecular mechanism involved in the G2 irreversible arrest, we have considered the H295R cell line showing the highest inhibition of cell proliferation associated with a noteworthy G2 arrest. In these cells, cyclin B1 and Cdk2 proteins were examined by western blot and Cdk2 kinase activity measured by assay kit. The H295R cells treated with IR/o,p'-DDD shared an increase in cyclin B1 amount as the coimmunoprecipitation of Cdc2-cyclin B1 complex. The kinase activity also shows an increase in the treated cells with combination therapy. Moreover, in these cells, sequence analysis of p53 revealed a large deletion of exons 8 and 9. The same irreversible block on G2 phase, induced by IR/o,p'-DDD treatment, happened in H295R cells with restored wild-type p53 suggesting that this mechanism is not mediated by p53 pathway.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients.

OBJECTIVES: The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. PATIENTS AND METHODS: 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) > or = 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m(2) per day followed by six cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. RESULTS: The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3-4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. CONCLUSIONS: Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.

Choroid plexus carcinoma in the adult: is there a role for chemotherapy?

Choroid plexus carcinoma is a rare primary brain neoplasm arising from epithelial differentiated tissue, originating from the choroids plexus of the ventricles and, in 90% of the cases, in the lateral and fourth ventricles. This neoplasm is seen mainly in children and reported infrequently in adults. The treatment of choroid plexus carcinoma is based on scarce evidence in literature. We report a rare case of an adult woman affected by a choroid plexus tumour and a discussion on the therapeutic management of this uncommon adult malignancy.

Electron arc therapy treatment planning verification with alanine/EPR dosimetry.

Alanine/EPR dosimetry was applied to measure dose distributions during electron arc therapy treatments generated by electron beams moving isocentrically over a stated arc. Alanine-polyethylene pellets, prepared at ISS according to the NIST recipe, inserted in a homogeneous cylindrical and anthropomorphic phantoms, were used. Preliminary, alanine response to static electron beams in the (6-20) MeV nominal energy range was studied. Then alanine dosimetry was applied to determine the dose versus the gantry angle at a reference point in a cylindrical homogeneous phantom. Finally, arc therapy treatment planning verification was performed in anthropomorphic phantom.

Adjuvant chemotherapy in clinical stage M0 sarcoma of soft tissue.

The clinical course of 117 patients who were treated for Stages IIB-IIIC sarcoma of soft tissues by the combined approach of radiation and surgery at MGH during the period 1971-1984 have been analyzed for an effect of adjuvant chemotherapy to improve clinical results. Thirty-two patients received adjuvant chemotherapy and 85 were treated by local methods alone. The chemotherapy protocols featured doxorubicin (25 patients) or VAC (seven patients). The no chemotherapy patients were controls matched for tumor grade and size and were treated over approximately the same period. The two groups were not well matched for age: median age of 38.5 and 54 years for the treated and control groups, respectively. There was no significant difference in survival. However, the time to first metastasis was longer in the treated group, P = 0.04. Furthermore, the local failure rate appeared to be lower in the treated group, P = 0.06.

Protracted effect of converting-enzyme inhibition on the rat's response to intraarterial bradykinin.

Intravenous infusion of the converting-enzyme (CE) inhibitor, MK422 (1 mg X kg-1 X hr-1 for 30 minutes) in normotensive controls and two-kidney, one clip (2K1C) rats in the acute phase of renovascular hypertension had a significant hypotensive effect that persisted after 24 hours. In contrast to that prolonged effect, inhibition of the pressor responses to intraarterial or intravenous angiotensin I, and the potentiation of the depressor responses to intravenous bradykinin (BK), were evident during the hour following the infusion of MK422, but not 24 hours later. Potentiation of intraarterially administered BK, however, persisted for 24 hours after infusion of the CE inhibitor. It is concluded that at least the prolonged (24-hour) effect of the treatment with MK422 was due to inhibition of the CE activity in tissues other than the lung, and that increased levels of endogenous BK may be responsible for the inhibitor's hypotensive effect.