Textbook outcome in colon carcinoma: implications for overall survival and disease-free survival.

BACKGROUND: Textbook outcome (TO) is a multidimensional quality management tool that uses a set of traditional surgical measures to reflect an "ideal" surgical result for a particular pathology. The aim of the present study is to record the rate of TO in patients undergoing elective surgery for colon cancer (CC). MATERIAL AND METHODS: Retrospective study of all patients undergoing scheduled CC surgery at a Spanish university hospital from September 2012 to August 2016. Patients with rectal cancer were excluded. The variables included in the definition of TO were: R0 resection, number of isolated nodes ≥ 12, no Clavien-Dindo ≥ IIIa complications, no prolonged stay, no readmissions, and no mortality in the first 30 days. The main objective of this study is to analyse the achievement of TO in these patients and to assess the relationship between TO and overall and disease-free survival. RESULTS: Five hundred and sixty-four patients were included in the study. TO was achieved in 49.8%. The sample had a mean age of 69 ± 11 years, and 60% were male. Female sex (OR 1.61; 95% CI 2.30-1.13), T3 and T4 classification (OR 2.50, 95% CI 4.59-1.36, and OR 2.55, 95% CI 5.21-1.24 respectively) and laparoscopic approach (OR 1.53, 95% CI 2.33-1.00) were independent factors that were significantly associated with achieving a TO. Patients who achieved TO had higher overall survival (p = 0.008) than those who did not. However, with regard to disease-free survival, no statistically significant differences were found (p = 0.303). CONCLUSION: TO is a useful, easy-to-interpret management tool for measuring oncological results and for predicting patient survival.

Is brachioplasty acceptable as an outpatient procedure? A prospective study comparing ambulatory and traditional hospitalization procedures.

BACKGROUND: Ambulatory or outpatient surgery is defined as surgery that does not require an overnight hospital stay. It offers patients both convenience and reduced costs. With the increased use of bariatric surgery, Extended L-shaped Lipo-brachioplasty is now frequently requested as a follow-up procedure. Although numerous studies have focused on its technique and outcomes, none have evaluated its acceptability as an outpatient procedure. This was the aim of this prospective study. PATIENTS AND METHODS: This study was performed between January 2016 and September 2019. All patients undergoing extended L-shaped Lipo-brachioplasty during that period were included and divided into two groups, according to the type of hospitalization. For both groups, we recorded the demographics, medical and surgical data, as well as any postoperative complications. In the outpatient group, we also recorded discharge failures at day 0. RESULTS: 75 patients were included in the study (40 outpatients, 35 hospitalizations). There were no significant differences between the two groups in terms of demographics, surgical data, or the incidence of complications. In the outpatient group, three patients could not be discharged the evening of the procedure and had to stay overnight. No readmissions or major complications were reported in this group. CONCLUSION: Our prospective study shows that outpatient Extended L-shaped Lipo-brachioplasty safely provides the same outcomes as those performed during traditional hospitalization. We believe that for eligible patients, it should routinely be performed as an outpatient procedure.

The impact of tumour histology and recursive partitioning analysis classification on the prognosis of patients treated with whole-brain hypofractionated radiotherapy for brain metastases: analysis of 382 patients.

PURPOSE: Recursive partitioning analysis (RPA) is a prognostic index capable of predicting survival in patients with brain metastases. Histology of the primary tumour has only recently been introduced among the factors that could potentially affect the prognosis of these patients. The main purpose of this study was to analyse the impact of RPA in correlation with histology of the primary tumour in patients with brain metastases treated with hypofractionated radiotherapy. MATERIALS AND METHODS: A total of 382 patients were treated at the Department of Radiotherapy of Brescia University, and RPA classes were retrospectively assigned to all patients. Univariate and multivariate analyses were then performed to verify the role of the single prognostic variables, for the entire group and for each prognostic class, as well as in correlation with histology of the primary tumour. RESULTS: Most patients were classified as RPA prognostic class 2 (48%). The majority of patients was treated with a total dose of 30 Gy delivered in ten fractions, whereas the dose of 20 Gy in four or five fractions was primarily used in patients classified as RPA class 3. At univariate analysis, the main variable correlating with overall survival (OS) was RPA class (p=0.000). Uni- and multivariate analysis performed on RPA class 1 patients only confirmed the role of general performance status, number of metastases and total radiotherapy dose for predicting OS. In the group with the worst prognosis (RPA class 3), none of the variables had a statistically significant role in improving OS. Tumour histology and radiotherapy dose influence OS, even in RPA class 1 and 2 patients. CONCLUSIONS: This analysis confirms that RPA prognostic class is the factor that most predicts survival. Primary tumour histology helps determine prognosis, especially in RPA prognostic classes 1 and 2. As regards RPA class 3, no factor influences survival prognosis.

Low thyroglobulin concentrations after thyroidectomy increase the prognostic value of undetectable thyroglobulin levels on levo-thyroxine suppressive treatment in low-risk differentiated thyroid cancer.

DESIGN: Recombinant human TSH-stimulated thyroglobulin (Tg) levels (rhTSH-Tg) are sufficient for early follow-up of low-risk differentiated thyroid cancer (DTC) patients after thyroidectomy and radioiodine (131I) remnant ablation (RAI). Serum Tg levels at the time of remnant ablation (ablation-Tg) is thought to be related with rhTSH-Tg and may be predictive of recurrent disease. During long-term follow-up, Tg levels on levo-T4 (L-T4) suppressive treatment (suppressive-Tg) is sufficiently sensitive to avoid further evaluations in patients with undetectable rhTSH-Tg. The aim of our study was to verify whether, in a subgroup of low-risk DTC patients, the association of low ablation-Tg levels (<10 microg/l) with undetectable suppressive-Tg concentrations has a sufficient negative predictive value (NPV) for recurrence of disease, leading to avoid rhTSH testing. METHODS: We enrolled 169 low-risk DTC patients treated by thyroidectomy + RAI and undetectable suppressive-Tg at 12-month followup. In all patients, we retrospectively evaluated ablation-Tg and rhTSH-Tg. For all patients, 2-yr follow-up was available. RESULTS: Based on rhTSH-Tg>2 microg/l, relapsing disease was histologically proven in 2 patients. rhTSH-Tg levels between 0.6-2.0 microg/l, with no evidence of disease, was observed in 10 patients (6%). One hundred and fifty-seven patients showed undetectable rhTSH-Tg. The NPV of undetectable suppressive- Tg was 92.8%. The ablation-Tg level was <10 microg/l in 140 patients. In this group, the NPV of undetectable suppressive- Tg was 100%. CONCLUSION: Our data indicate that undetectable suppressive-Tg value, combined with ablation- Tg levels <10 microg/l, may avoid a significant number of high-cost rhTSH-Tg test.

Salvage Low Dose Rate Brachytherapy For Recurrent Prostate Cancer After External Beam Radiotherapy: Results From A Single Institution With Focus On Toxicity And Functional Outcomes.

BACKGROUND/AIM: Low dose rate brachytherapy has been used as salvage therapy for locally recurrent prostate cancer (PC) after primary external beam radiation therapy (EBRT), along with surgery and cryotherapy. All these techniques, in particular, when applied to the whole gland, involve a relatively high risk of toxicity and may worsen the patient's quality of life. Our aim is to evaluate the results of whole-gland salvage brachytherapy (SBT) after primary EBRT in terms of toxicity, functional outcomes, and efficacy. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 19 patients consecutively treated with SBT at our institution between June 2012 and November 2015. Local recurrences were identified with 11C-choline positron emission tomography/computed tomography and pelvic magnetic resonance imaging after biochemical recurrence according to Phoenix criteria (prostate-specific antigen nadir + 2). Low dose rate brachytherapy was performed by 125I permanent seeds implantation to the whole prostate gland, with a prescription dose of 130 Gy. At the time of SBT, only 2 patients were receiving androgen deprivation therapy. Acute and late toxicities were recorded using the CTCAE 4.0 scoring system. Quality of life was assessed using IPSS (International Prostate Symptoms Score) and IIEF (International Index of Erectile Function) questionnaires at baseline and 6, 12, and 24 months after SBT, and the respective mean values were compared using Student t test. Biochemical relapse-free survival (BRFS) was also calculated. RESULTS: Median follow-up after SBT was 24 months. Of 19 patients, 2 patients experienced a G3 cystitis (10.2%) and 1 patient experienced a G4 proctitis (5.3%), respectively. Mean pre-SBT IPSS scores and 6, 12, and 24 months after SBT were 5.84, 10.22, 15.72, and 8.10, respectively. Mean pre-SBT IIEF scores and 6, 12, and 24 months after SBT were 8.42, 3.55, 7.89, and 6.40, respectively. At the time of analysis, only 2 patients showed a biochemical relapse (3-year BRFS 85.2%). The Student t test demonstrated a worsening of functional outcome 6 months and 1 year after treatment but a subsequent improvement 2 years after SBT. CONCLUSIONS: Salvage brachytherapy for recurrent PC after primary EBRT seems to be a feasible treatment for selected patients. Our series revealed a severe toxicity peak 6 months and 1 year after local re-treatment and then they decrease. Early BRFS rates are good. However, these are very preliminary results so further patient accrual, long-term follow-up, and prospective trials are needed in the future.

Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. PATIENTS AND METHODS: A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. RESULTS: During these mutational screening procedures one case presented three mutations classified in the Breast Cancer Information Core Database as unknown variants. These were 655A/G found in exon 8 of BRCA1, 1575T/C and 1767A/C found in exon 11 of the same gene. The identification of the three unknown variants in the proband (16SIRIO) and in her mother and sister indicates that such alterations exist in cis. CONCLUSIONS: Our results suggest that the charge and stechiometry variations determined by the changes in the amino acids Y179C, F486L and N550H might produce an effect on the conformation of the protein and, consequently, on its function.

Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics--a phase II multicenter study.

PURPOSE: A Phase II multicenter trial testing an accelerated regimen of radiotherapy in locally advanced and inoperable cancers of the head and neck, in patients selected on the basis of 5-bromo-2-deoxyuridine/DNA flow cytometry-derived tumor potential doubling time (Tpot). METHODS AND MATERIALS: From September 1992 to September 1993, 23 patients consecutively diagnosed to have locally advanced, inoperable carcinomas of the oral cavity and the oropharynx, with Tpot of < or = 5 days, received an accelerated radiotherapy regimen (AF) based on a modification of the concomitant boost technique: 2 Gy/fraction once a day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fraction twice a day, with a 6-h interval, one of the two fractions being delivered as a concomitant boost to reduced fields, up to 66 Gy total dose (off-cord reduction at 46 Gy), shortening the overall treatment time to 4.5 weeks. A contemporary control group of 46 patients with Tpot of >5 days or unknown was treated with conventional fractionation (CF): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5 weeks, with fields shrinkage after 46 Gy. RESULTS: All patients completed the accelerated regimen according to protocol and in the prescribed overall treatment time. Immediate tolerance was fairly good: 65% of the patients in the AF group experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms related to mucosal reactions seemed to persist longer in AF than in CF patients. The crude proportion of mild (Grades 1 and 2) late effects on skin (p < 0.01) and salivary glands (p < 0.05) was higher in AF than in CF patients, although these reactions did not exceed the limits of tolerance. Three patients in the AF and 1 in the CF arm experienced a late Grade 4 bone complication. Actuarial estimates of severe (Grades 3 and 4) late complications showed a 2-year hazard of 33.3% in the AF arm and 49.7% in CF (p = NS). The actuarial 2-year local control rate of the AF patients was 49.4%, while actuarial 2-year overall survival for the same patients was 43.5%. CONCLUSION: The results suggested that this accelerated regimen is worth testing in a controlled randomized trial to compare different accelerated schedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA flow cytometry technique as a suitable method of evaluating tumor cell kinetics in multicenter clinical studies, on condition that all measurements are carried out by one most experienced laboratory.

Disubstituted indazoles as potent antagonists of the integrin alpha(v)beta(3).

A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC(50) 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

Prothrombin activation in rabbits.

The suitability of rabbit prothrombin activation fragment F 1.2 as a marker for the activation of the coagulation system was tested. Monoclonal antibodies to rabbit F 1.2 were raised, and a competitive F 1.2 ELISA was developed. Within the detection limit of the ELISA, no increase in rabbit F 1.2 was detected upon recalcification of plasma, whereas human F 1.2 increased 1500-fold. The apparent lack of F 1.2 formation in rabbit serum was confirmed by immunoblotting analysis of endogenous and biotin-labeled prothrombin. Meizothrombin and the B-chain of thrombin were the only prothrombin fragments detectable. In contrast, labeled human prothrombin formed, in addition, prethrombin 2 and F 1.2 in both human and rabbit serum. In contrast, rabbit F 1.2 formation could be demonstrated using purified rabbit prothrombin and factor Xa. These observations raise the possibility that rabbit prothrombin is less susceptible than the human counterpart to factor Xa cleavage at the 271/272 peptide bond. Thus, the primary structure of rabbit prothrombin was deduced by cDNA sequencing. While the 320/321 Xa cleavage site giving rise to meizothrombin was identical in rabbit and human prothrombin, the flanking region of the 271/272 Xa sensitive site contained a six amino acid deletion in the rabbit sequence. Taken together, these observations suggest that the observed differences between human and rabbit prothrombin activation may be due to different susceptibilities of the two Xa cleavage sites rather than plasma or serum cofactor(s).

A rapid, high capacity assay for basic fibroblast growth factor binding.

A rapid, high capacity assay for the binding of basic fibroblast growth factor has been developed. Rat lung tissue was selected as the optimum source of membranes and 2M sodium chloride used to remove endogenous growth factor. The assay has been adapted to the Millipore Multi-Screen system so that it can be run in 96-well format with a volume of 300 microliters. The assay has been validated through the demonstration of inhibition by standard inhibitors such as suramin and protamine sulfate. The assay has proven useful for the screening of random compounds as well as the more detailed examination of suspected inhibitors. By running compounds in the presence and absence of a mid-range concentration of unlabeled bFGF, an estimate of the proportion of the inhibition due to high affinity binding can be obtained. Suramin and protamine sulfate show no selectivity and inhibit high affinity binding and overall binding with similar potencies. Another inhibitor, dimercaptothiadiazole, is more potent against high affinity binding.

A novel angiotensin II binding site in murine tissues.

A novel binding site for angiotensin II has been identified in certain murine tissues. This site, denoted ATm, is distinct from both the AT1 and AT2 sites, as well as the various atypical sites that have been described. The site has a low affinity for angiotensin II (100 nM) and is not blocked by losartan, PD123177 or saralasin. The site shows structural specificity for angiotensin II since both angiotensin III and angiotensin II (1-7) failed to inhibit the binding. Numerous standard drugs, including various receptor blockers, enzyme inhibitors and therapeutic agents, showed no affinity for the site. In murine tissues the site is associated with active tissue generation, as found in spleen, placenta and growing tumors, but its occurrence appears to be rare outside of the mouse.

Synthesis of carboxyalkylthio-triazoles and bicyclic derivatives with antiinflammatory and analgesic activity.

3-Carboxyalkylthio derivatives of 5-alkoxyphenyl-1,2,4-triazole were prepared, performing some substitutions both on carboxyalkyl chain, by lengthening it or introducing substituents with increasing molecular weight in alpha- at the carboxy group, and on N-4 atom in the triazole ring, by introducing an amino or methyl group, so that to vary steric conformation along with the lipophilicity of molecules. The corresponding bicyclic thiazolo-triazolone and triazolo-thiazinone derivatives, which represent the rigid models of carboxymethylthio- and carboxyethylthio- open structures, were also obtained. All the compounds show "in vivo" antiinflammatory activity, while only carboxyalkylthio derivatives of 4-amino- and 4-methyltriazole display an appreciable analgesic one. From the relief of some data on substituent present in the synthesized compounds, a structure-activity relationship is also suggested.

[Biliary surgery and cholescintigraphy with iminodiacetic acid (IDA) analogs. An evaluation of the results and the complications]. / Chirurgia biliare e colescintigrafia con analoghi dell'acido iminodiacetico (IDA). Valutazione dei risultati e complicanze.

Hepatobiliary scintigraphy with analogs of iminodiacetic acid (IDA) has become one of the primary tools in the diagnosis of biliary tract diseases, especially in the evaluation of surgical results and detection of complications that may arise from biliary operative procedures. We have performed cholescintigraphy in 19 patients. Of them, 9 underwent choledochojejunostomy with Roux-en-Y reconstruction for recurrent choledocholithiasis, 1 underwent right hepatic resection for metastasis extirpation, 8 were post cholecystectomy patients effected with upper abdominal pain located either in the epigastric region or right upper quadrant referable to post cholecystectomy syndrome and the last exhibited chronic pancreatitis ans suspicious sphincter of Oddi stenosis. The scintigraphy data were compared with the information yielded by sonography, intravenous cholangiogram (IVC) and, when possible, by endoscopic retrograde cholangiopancreatography (ERCP). Scans were considered pathologic when one or more of the following criteria were present: a) delayed biliary to bowel transit (greater than 1 hr), b) abnormal time-activity dynamic, c) no intestinal activity (obstruction), d) apparent ductal dilatation. In the group of biliary-enteric anastomosed patients, cholescintigraphic findings have shown 3 normal cases, 3 cases of biliary-intestinal obstruction confirmed by surgery, and 3 with abnormal activity retention in the jejunum loop due, in 2 patients, to hypokinesia since the quick emptying following the administration of 10 mg i.v. of metoclopramide, while in the other one, the surgery reexploration exhibited the presence of adhesions producing intestinal stricture. in the last patient of this group, the cholescintigraphy was performed to detect possible biliary leaks. In the post cholecystectomy patients, the cholescintigraphy exhibited in 3 cases dilated common duct with functional patency since the normal biliary-bowel transit time (less than 1 hr); this was confirmed by sonogram and IVC.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiotherapy and spinal brace: still first-choice treatment for vertebral metastases from breast cancer.

In metastatic breast cancer the goal to reach must be the best possible palliation with minimum discomfort for the patient. We reviewed our experience with radiotherapy (20 or 30 Gy), systemic therapy and brace. Among 2200 breast cancer patients, we extracted 28 potential candidates for resection. All of them developed new metastases outside the treated field within one year. Local control was achieved in 68%, and 80% of them had stable or better performance status at 3 months. From our analysis, even patients with a so called "solitary lesion" do not seem to have a better prognosis than others. We conclude that radiotherapy (with systemic therapy and a brace) is still first-choice treatment for vertebral metastases; CT-guided percutaneous biopsy can avoid worthless major operations. The role of surgery should be limited to neurological compression, severe mechanical instability and to salvage the failures of conservative treatment.

[Conservative surgery in the environment of a screening program for breast carcinoma: evaluation of the results in terms of local recurrence]. / Chirurgia conservativa nell'ambito di un programma di screening per il carcinoma della mammella: valutazione dei risultati in termini di recidiva locale.

This report evaluates the results of conservative surgery plus radiotherapy (QUART) in a group of 123 patients from the screening programme of the District Health Board USSL 41 in Brescia, Italy (over 250 tumours diagnosed in two screening rounds, between 1987 and 1993). To date no recurrence of neoplasms in the operated breast have been diagnosed in either of the two QUART groups (64 patients from the first round, average follow-up 28 months, median 66 months; 59 patients from the second round, average follow-up 28 months, median 30 months). A new carcinoma in the contralateral breast occurred in 3 patients (2 from the first and 1 from the second round), while in 3 cases there was a recurrence in another site (2 from the first and 1 from the second round). These results confirm both the proven effectiveness of conservative treatment in the local control of breast tumours, and the importance of the correct choice of conservative treatment in optimising aesthetic and therapeutic results.

In vivo multiclonal transfer of bla(KPC-3) from Klebsiella pneumoniae to Escherichia coli in surgery patients.

During active surveillance at the Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT, Palermo, Italy) with the CARBA screening medium, five pairs of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae and Escherichia coli strains were isolated in each of five colonized patients. In each patient, lateral gene transfer was demonstrated by comparing K. pneumoniae and E. coli strains, both possessing KPC-3, Tn4401a and pKpQIL-IT elements. The isolates were found to be multiclonal by multilocus sequence typing (sequence type (ST) 512 related to ST258, and ST307 belonging to a clonal complex different from the habitual sequence clone ST258 isolated in Italy) and pulsed-field gel electrophoresis. The results of our study highlight the easy transfer of KPC among Enterobacteriaceae colonizing the human intestine, and the active and careful surveillance required to identify and prevent the spread of these multidrug-resistant microorganisms.

Could [18]F-fluorodeoxyglucose PET/CT change the therapeutic management of stage IV thyroid cancer with positive (131)I whole body scan?

AIM: Stage-IV differentiated thyroid cancer (DTC) patients may present elevated serum thyroglobulin (Tg) levels associated with positive [(131)I] whole-body-scan (WBS). Nevertheless some patients in whom WBS does not reveal new sites of disease show increased Tg levels. This finding prompts thorough restaging in order to exclude the presence of metastases unable to concentrate iodine. The aim of our study was to evaluate the impact of [(18)F]FDG-PET/CT in both the assessment of overall extent of the disease and the therapeutic management in a group of stage-IV DTC patients. METHODS: On suspicious of non-iodine concentrating additional metastases, 20 stage-IV DTC patients with increasing Tg levels and stable positive post-therapy WBS were enrolled. Conventional imaging (CI) procedures, including neck ultrasonography, bone-scintigraphy and computed tomography (CT) were performed before [(18)F]FDG-PET/CT. RESULTS: [(18)F]FDG-PET/CT was positive in 16 out of 20 patients (80%). In 9 patients (45%) [(18)F]FDG PET/CT detected a larger number of tumour recurrences/metastatic sites than WBS+CI. [(18)F]FDG PET/CT findings prompted modification of the management of 11 patients (55%), in whom surgery or external radiotherapy were eventually considered more appropriate than radioactive iodine therapy. These further therapies improved the quality of life in several patients but did not change their survival rate. CONCLUSION: Our results showed that [18F]FDG-PET/CT can detect new radioiodine-negative metastases in advanced DTC patients with unchanged positive WBS and increasing Tg levels. [(18)F]FDG-PET/CT may constitute a useful tool in the choice of the best therapeutic strategy in such difficult cases.