Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Radiological assessment of peritoneal carcinomatosis: a primer for resident.

The imaging has critical responsibility in the assessment of peritoneal lesions along with estimating the overall extent. Valuing disease burden is crucial for selection of combining cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC) treatment. An approach that combines the strength of several imaging tools and increases diagnostic accuracy, should be chosen, even if the preferred imaging tool in patients with suspected Peritoneal Carcinomatosis (PC) is CT. The outcomes of PC are mainly correlated to tumor spread, localization, and lesion size. Accurate assessment of these features is critical for prognosis and treatment planning. These data can be evaluated by Peritoneal Cancer Index (PCI), a quantitative index suggested by Harman and Sugarbaker. Additionally, precise predictive biomarkers should be established to predict PC in patients at risk. The radiomics analysis could predict PC throughout the evaluation of cancers heterogeneity.

Multicentre randomized clinical trial of colonic J pouch or straight stapled colorectal reconstruction after low anterior resection for rectal cancer.

BACKGROUND: Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer. METHODS: This multicentre RCT included patients with rectal carcinoma who underwent low anterior resection followed by colorectal anastomosis. Patients were assigned randomly to receive a colonic J pouch or straight colorectal anastomosis. The main outcome measure was the occurrence of major anastomotic leakage. The incidence of global (major plus minor) anastomotic leakage and general complications were secondary outcomes. Risk factors for anastomotic leakage were identified by regression analysis. RESULTS: Of 457 patients enrolled, 379 were evaluable (colonic J pouch arm 190, straight colorectal arm 189). The incidence of major and global anastomotic leakage, and general complications was 14·2, 19·5 and 34·2 per cent respectively in the colonic J pouch group, and 12·2, 19·0 and 27·0 per cent in the straight colorectal anastomosis group. No statistically significant differences were observed between the two arms. In multivariable logistic regression analysis, male sex (odds ratio 1·79, 95 per cent c.i. 1·02 to 3·15; P = 0·042) and high ASA fitness grade (odds ratio 2·06, 1·15 to 3·71; P = 0·015) were independently associated with the occurrence of anastomotic leakage. CONCLUSION: Colonic J pouch reconstruction does not reduce the incidence of anastomotic leakage and postoperative complications compared with conventional straight colorectal anastomosis. Registration number NCT01110798 (http://www.clinicaltrials.gov).

T1 colon cancer in the era of screening: risk factors and treatment.

BACKGROUND: The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit. METHODS: The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases. RESULTS: Out of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN. CONCLUSIONS: Some factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.

Estrogen Receptors and Chronic Venous Disease.

OBJECTIVE/BACKGROUND: Chronic venous disease (CVD) is a common and relevant problem affecting Western people. The role of estrogens and their receptors in the venous wall seems to support the major prevalence of CVD in women. The effects of the estrogens are mediated by three estrogen receptors (ERs): ERα, ERß, and G protein-coupled ER (GPER). The expression of ERs in the vessel walls of varicose veins is evaluated. METHODS: In this prospective study, patients of both sexes, with CVD and varicose veins undergoing open venous surgery procedures, were enrolled in order to obtain vein samples. To obtain control samples of healthy veins, patients of both sexes without CVD undergoing coronary artery bypass grafting with autologous saphenous vein were recruited (control group). Samples were processed in order to evaluate gene expression. RESULTS: Forty patients with CVD (10 men [25%], 30 women [75%], mean age 54.3 years [median 52 years, range 33-74 years]) were enrolled. Five patients without CVD (three men, two women [aged 61-73 years]) were enrolled as the control group. A significant increase of tissue expression of ERα, ERß and GPER in patients with CVD was recorded (p < .01), which was also related to the severity of venous disease. CONCLUSION: ERs seem to play a role in CVD; in this study, the expression of ERs correlated with the severity of the disease, and their expression was correlated with the clinical stage.

Air contamination in the sclerosing foam for the treatment of varicose veins.

BACKGROUND: Fluids and drugs formulated for intravenous infusion may potentially promote the growth of microorganisms that can cause infections. The aim of this study is to test the sterility of sclerosing foam. METHODS: Polidocanol was used for the production of the foam. The Tessari method was used in order to generate the foam. The preparation was carried out both in the operating theater and in an outpatient room. A validation test with microorganisms was also performed. RESULTS: The measurements showed no evident growth of microorganisms and in the validation tests the foam appeared to even display bacteriostatic and/or bactericide properties. CONCLUSIONS: Sclerosing foam seems to be safe from a microbiological point of view.

Practice parameters for early colon cancer management: Italian Society of Colorectal Surgery (Società Italiana di Chirurgia Colo-Rettale; SICCR) guidelines.

Early colon cancer (ECC) has been defined as a carcinoma with invasion limited to the submucosa regardless of lymph node status and according to the Royal College of Pathologists as TNM stage T1 NX M0. As the potential risk of lymph node metastasis ranges from 6 to 17% and the preoperative assessment of lymph node metastasis is not reliable, the management of ECC is still controversial, varying from endoscopic to radical resection. A meeting on recent advances on the management of colorectal polyps endorsed by the Italian Society of Colorectal Surgery (SICCR) took place in April 2014, in Genoa (Italy). Based on this material the SICCR decided to issue guidelines updating the evidence and to write a position statement paper in order to define the diagnostic and therapeutic strategy for ECC treatment in context of the Italian healthcare system.

Practice parameters for early rectal cancer management: Italian Society of Colorectal Surgery (Società Italiana di Chirurgia Colo-Rettale; SICCR) guidelines.

The introduction of new technologies for diagnosis and screening programs led to an increasing rate of early detection of colorectal cancer. This, associated with the evolution of endoscopic techniques of local excision, led to the assessment of new strategies to reduce morbidity related to treatment, especially for early rectal cancer (ERC). Nevertheless, the definition of ERC and its staging and treatment algorithm are still under debate. The Italian Society of Colorectal Surgery developed practice guidelines to provide recommendations on the diagnosis, staging and treatment of ERC. A systematic review on the topic was performed by a multidisciplinary group of experts selected based on their clinical and scientific expertise in endoscopy, endoscopic ultrasound, magnetic resonance and surgery, with the aid of an external international audit.

From mininvasive to maxinvasive surgery in colorectal cancer: modem evolution of oncologic specialized units.

In the last years a wide range of new technique offers the possibility to have R0 resection in colorectal cancer. We report our experience about Single Port Laparoscopic Surgery (SPL) for not advanced right colon cancer and about pelvectomy with cilindric Abdominal Perineal Resection (APR) for advanced rectal cancer. SPL offer mainly cosmetic advantages but also quicker recovery. No touch technique with adequate surgical margin and lymphectomy were respected. Operative time of SPL was 85-115 minutes, the incision was 5 cm long. There were no complications. Length of hospital stay was 4-6 days. With advanced pelvic cancer, pelvic exenteration with en-bloc resection is indicated. Then we propose a case of a 55 years old woman with a pelvic recurrence from a metastatic rectal cancer involving the right obturator fossa, the vaginal stump, the right ureter. Modern surgical technique give us the chance to offer the most appropriate oncologic surgical treatment.

Unstable dynamics, nonequilibrium phases, and criticality in networked excitable media.

Excitable systems are of great theoretical and practical interest in mathematics, physics, chemistry, and biology. Here, we numerically study models of excitable media, namely, networks whose nodes may occasionally be dormant and the connection weights are allowed to vary with the system activity on a short-time scale, which is a convenient and realistic representation. The resulting global activity is quite sensitive to stimuli and eventually becomes unstable also in the absence of any stimuli. Outstanding consequences of such unstable dynamics are the spontaneous occurrence of various nonequilibrium phases--including associative-memory phases and one in which the global activity wanders irregularly, e.g., chaotically among all or part of the dynamic attractors--and 1/f noise as the system is driven into the phase region corresponding to the most irregular behavior. A net result is resilience which results in an efficient search in the model attractor space that can explain the origin of some observed behavior in neural, genetic, and ill-condensed matter systems. By extensive computer simulation we also address a previously conjectured relation between observed power-law distributions and the possible occurrence of a "critical state" during functionality of, e.g., cortical networks, and describe the precise nature of such criticality in the model which may serve to guide future experiments.

A nonlinear lumped parameters model to analyze the dynamics of venous reflux.

The aim of this work is to formulate a lumped parameters model of the venous tree of the lower limbs in order to study the effects and the possible clinical treatments for Chronic Venous Insufficiency (CVI). CVI is a pathology characterized by an important socio-economic impact due to its relevant prevalence, the costs for its diagnosis and treatment being more frequently widespread among the working population. The planning of haemodynamic surgical operations is critical to treat a pathological pattern of venous blood flow; such planning, in turn, depends on the right analysis of the possible consequences of flow modification. To this regard, the blood flow correction allows to solve the most important venous pathologies, in order to guarantee the restoration of normal blood flow by means of proper modifications of the venous tree. The developed model preserves the geometry of the venous network and considers some non linear resistive and capacitive effects. In fact, the study of the variability of some parameters (i.e. vessel radius) is very important to allow a correct diagnosis of vascular diseases. This variability causes a non linear behaviour of resistance and compliance effects. With the aid of the developed model we evaluate the time profile of blood velocity, flow and pressure in the entire venous network, both in physiological and pathological cases. The obtained results are discussed in comparison with available experimental data.

A haemodynamic model of the venous network of the lower limbs.

The pathologies of the venous system are characterized by a relevant socioeconomic impact in western countries. To this regard, the blood flow correction allows to solve the most important venous pathologies. In these cases, in order to guarantee the restoration of normal blood flow by means of proper modifications of the venous network, the correct planning of haemodynamics surgical operations is needed; such planning in turn depends on the right analysis of the possible consequences of flow modification. To this end, a mathematical model, that allows to precisely study the physiological and pathological behaviour of the venous network of the lower limbs, has been developed. The final goal is to use this model as an instrument helpful to plan surgical operations and give guidelines for the design and the test of new artificial devices. As for the modelling processing, a lumped parameters model has been derived with a resolution which allows to take into account the anatomic characteristics of the venous system.

[Our experience with treatment of varicocele in a day-surgery protocol]. / Nostra esperienza nel trattamento del varicocele in regime di day-surgery.

In the last few years the increasing interest for non-invasive operating techniques has allowed to reevaluate the sublinguinal varicocelectomy surgical technique for idiopathic varicocele surgical treatment. During the years 1998-2001, 29 patients have been operated on sub-inguinal varicocelectomy (14 patients were suffering from idiopathic varicocele of third grade, 11 of second grade, 3 of first grade, and 1 subclinical). Out of the 29 patients, only 10 were unable to procreate. All patients were operated under local anesthesia and discharged the same day (day-surgery). Owing to Authors' experience, the sublinguinal varicocelectomy by optical magnifying devices represents the "gold standard" in the idiopathic varicocele treatment because it allows to minimize relapsing rates, to limit post-operation complications, to improve the reproductive faculty of seminal fluid both qualitatively and quantitatively, to cut patient's operating costs significantly, to keep the operation time within acceptable limits, and to be easily learned and carried out.

[Video-assisted surgery of the thyroid: outlines of the technique and analysis of the results]. / La chirurgia video-assistita della tiroide: note di tecnica e analisi dei risultati.

INTRODUCTION: The authors described the technique of the video-assisted approach to thyroid surgery (MIVAT: minimally invasive video-assisted thyroidectomy), selection criteria of the patients and evaluated the technical feasibility of this method. MATERIALS AND METHODS: Patients selection is based on many parameters. Exclusion criteria are: nodules greater than 35 mm, presence of thyroiditis, thyroid volume greater than 20 mL, previous neck surgery and irradiation. The surgical procedures are conducted through a minimal substernal skin incision (1-3 cm); the procedure performed using external retractors and needlescopic instruments. RESULTS: MIVAT was accomplished in 20 patients (15 female and 5 men). One cervicotomy was required to perform total thyroidectomy (positive frozen section). Mean operative time was 70 min. Two patients have reported transient hypoparathyroidism; one patient has reported transient recurrent nerve palsy. DISCUSSION: MIVAT has not yet met the favor of most endocrine surgeons; nevertheless we think that this technique is safe and feasible for benign thyroid diseases in selected cases, with the advantage of satisfactory cosmetic results Conversion to conventional surgery is required generally for local bleeding and to perform total thyroidectomy for positive frozen section. CONCLUSIONS: MIVAT is feasible and may improve cosmetic outcome. The indications are limited at present, but the results are encouraging for the future.