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Aims: Brugada syndrome (BrS) is an inherited arrhythmic disease characterized by a coved ST-segment elevation in the right precordial electrocardiogram leads (type 1 ECG pattern) and is associated with a risk of malignant ventricular arrhythmias and sudden cardiac death. In order to assess the predictive value of the Shanghai Score System for the presence of a SCN5A mutation in clinical practice, we studied a cohort of 125 patients with spontaneous or fever/drug-induced BrS type 1 ECG pattern, variably associated with symptoms and a positive family history., Methods: The Shanghai Score System items were collected for each patient and PR and QRS complex intervals were measured. Patients were genotyped through a next-generation sequencing (NGS) custom panel for the presence of SCN5A mutations and the common SCN5A polymorphism (H558R)., Results: The total Shanghai Score was higher in SCN5A+ patients than in SCN5A- patients. The 81% of SCN5A+ patients and the 100% of patients with a SCN5A truncating variant exhibit a spontaneous type 1 ECG pattern. A significant increase in PR (P = 0.006) and QRS (P = 0.02) was detected in the SCN5A+ group. The presence of the common H558R polymorphism did not significantly correlate with any of the items of the Shanghai Score, nor with the total score of the system., Conclusion: Data from our study suggest the usefulness of Shanghai Score collection in clinical practice in order to maximize genetic test appropriateness. Our data further highlight SCN5A mutations as a cause of conduction impairment in BrS patients., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Although ultrasound-guided axillary vein access (USGAVA) has proven to be a highly effective and safe method for cardiac electronic implantable device (CIED) lead placement, the collapsibility of the axillary vein (AV) during tidal breathing can lead to narrowing or complete collapse, posing a challenge for successful vein puncture and cannulation. We investigated the potential of the Valsalva maneuver (Vm) as a facilitating technique for USGAVA in this context. Out of 148 patients undergoing CIED implantation via USGAVA, 41 were asked to perform the Vm, because they were considered unsuitable for venipuncture due to a narrower AV diameter, as assessed by ultrasound (2.7 ± 1.7 mm vs. 9.1 ± 3.3 mm, p < 0.0001). Among them, 37 patients were able to perform the Vm correctly. Overall, the Vm resulted in an average increase in the AV diameter of 4.9 ± 3.4 mm ( p < 0.001). USGAVA performed during the Vm was successful in 30 patients (81%), and no Vm-related complications were observed during the 30-day follow-up. In patients with unsuccessful USGAVA, the Vm resulted in a notably smaller increase in AV diameter (0.5 ± 0.3 mm vs. 6.0 ± 2.8 mm, p < 0.0001) compared to patients who achieved successful USGAVA, while performing the Vm. Therefore, the Vm is a feasible maneuver to enhance AV diameter and the success rate of USGAVA in most patients undergoing CIED implantation while maintaining safety.

Background: Although ultrasound guidance for axillary vein (AV) access (USGAVA) has been described as a reliable technique for cardiac implantable electronic device (CIED) implantation, no data is available on the use of handheld ultrasound devices (HUD) in such a setting., Objective: We investigated the feasibility of using a HUD for USGAVA in patients referred to our Institution for CIED implantation., Methods: The procedure details of 80 consecutive patients undergoing USGAVA (Group-1) from June 2020 to June 2021 were prospectively collected and compared to those of an age and sex-matched cohort of 91 patients (Group-2) who had undergone AV access with the traditional venipuncture guided by fluoroscopic landmarks., Results: The two groups were comparable for the success rate of venous access (92.5% versus 93.4%, p = 0.82), complication rate (1.3% versus 0.9%, p = 1.0), and procedure time (71 ± 32 min versus 70 ± 29 min, p = 0.9). However, Group-2 had a longer X-ray exposure time (7.6 ± 8.4 min versus 5.7 ± 7.3 min, p = 0.03). In Group-1, the univariate logistic regression analysis demonstrated that the AV diameter was associated with successful USGAVA (odds ratio = 3.34, 95% confidence interval 1.47-7.59, p < 0.01), with a 3-fold increase of probability of success per each 1 mm increase in the AV diameter., Conclusions: USGAVA using a HUD for CIED implantation is a feasible, effective, and safe technique; moreover, it saves X-ray exposure time without lengthening the implant procedure time., Competing Interests: The authors declare no conflict of interest. Daniele Muser was serving as Guest Editor of this journal. We declare that Daniele Muser had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jerome L. Fleg., (Copyright: © 2022 The Author(s). Published by IMR Press.)

We experimentally demonstrate, for the first time, noise diagnostics by repeated quantum measurements, establishing the ability of a single photon subjected to random polarization noise to diagnose non-Markovian temporal correlations of such a noise process. Both the noise spectrum and temporal correlations are diagnosed by probing the photon with frequent (partially) selective polarization measurements. We show that noise with positive temporal correlations corresponds to our single photon undergoing a dynamical regime enabled by the quantum Zeno effect (QZE), whereas noise characterized by negative (anti) correlations corresponds to regimes associated with the anti-Zeno effect (AZE). This is the first step toward a novel noise spectroscopy based on QZE and AZE in single-photon state probing able to extract information on the noise while protecting the probe state, a conceptual paradigm shift with respect to traditional interferometric measurements.

Quantum mechanics allows distribution of intrinsically secure encryption keys by optical means. Twin-field quantum key distribution is one of the most promising techniques for its implementation on long-distance fiber networks, but requires stabilizing the optical length of the communication channels between parties. In proof-of-principle experiments based on spooled fibers, this was achieved by interleaving the quantum communication with periodical stabilization frames. In this approach, longer duty cycles for the key streaming come at the cost of a looser control of channel length, and a successful key-transfer using this technique in real world remains a significant challenge. Using interferometry techniques derived from frequency metrology, we develop a solution for the simultaneous key streaming and channel length control, and demonstrate it on a 206 km field-deployed fiber with 65 dB loss. Our technique reduces the quantum-bit-error-rate contributed by channel length variations to <1%, representing an effective solution for real-world quantum communications., (© 2022. The Author(s).)

We show that, by using temporal quantum correlations as expressed by pseudo-density operators (PDOs), it is possible to recover formally the standard quantum dynamical evolution as a sequence of teleportations in time. We demonstrate that any completely positive evolution can be formally reconstructed by teleportation with different temporally correlated states. This provides a different interpretation of maximally correlated PDOs, as resources to induce quantum time evolution. Furthermore, we note that the possibility of this protocol stems from the strict formal correspondence between spatial and temporal entanglement in quantum theory. We proceed to demonstrate experimentally this correspondence, by showing a multipartite violation of generalized temporal and spatial Bell inequalities and verifying agreement with theoretical predictions to a high degree of accuracy, in high-quality photon qubits.

Background: In Italy, a nationwide full lockdown was declared between March and May 2020 to hinder the novel coronavirus disease 2019 (COVID-19) pandemic. The potential individual health effects of long-term isolation are largely unknown. The current study investigated the arrhythmic consequences of the COVID-19 lockdown in patients with defibrillators (ICDs) living in the province of Ferrara, Italy., Methods: Both the arrhythmias and the delivered ICD therapies as notified by the devices were prospectively collected during the lockdown period (P1) and compared to those occurred during the 10 weeks before the lockdown began (P2) and during the same period in 2019 (P3). Changes in outcome over the three study periods were evaluated for significance using McNemar's test., Results: A total of 413 patients were included in the analysis. No differences were found concerning either arrhythmias or shocks or anti-tachycardia pacing. Only the number of patients experiencing non-sustained ventricular tachycardias (NSVTs) during P1 significantly decreased as compared to P2 (p = 0.026) and P3 (p = 0.009). The subgroup analysis showed a significant decrease in NSVTs during P1 for men (vs. P2, p = 0.014; vs. P3, p = 0.040) and younger patients (vs. P2, p = 0.002; vs. P3, p = 0.040) and for ischemic etiology (vs. P2, p = 0.003). No arrhythmic deaths occurred during P1., Conclusions: The complete nationwide lockdown, as declared by the Italian government during the first COVID-19 pandemic peak, did not impact on the incidence of arrhythmias in an urban cohort of patients with ICDs., (© 2021 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

The current narrative review provides an update of available knowledge on venous access techniques for cardiac implantable electronic device implantation, with a focus on axillary vein puncture. Lower procedure-related and lead-related complications have been reported with extrathoracic vein puncture techniques compared with intrathoracic accesses. In particular, extrathoracic lead access through the axillary vein seems to be associated with lower complication incidence than subclavian vein puncture and higher success rate than cephalic vein cutdown. In literature, many techniques have been described for axillary vein access. The use of contrast venography-guided puncture has facilitated the diffusion of the axillary vein approach for device implantation. Venography may be particularly useful in specific demographic and clinical device implantation contexts. Ultrasound-guided or microwire-guided vascular access for lead positioning can be considered a valid alternative to venography, although current applications for axillary vein puncture need further evaluations., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Pseudo-density matrices are a generalisation of quantum states and do not obey monogamy of quantum correlations. Could this be the solution to the paradox of information loss during the evaporation of a black hole? In this paper we discuss this possibility, providing a theoretical proposal to extend quantum theory with these pseudo-states to describe the statistics arising in black-hole evaporation. We also provide an experimental demonstration of this theoretical proposal, using a simulation in optical regime, that tomographically reproduces the correlations of the pseudo-density matrix describing this physical phenomenon.

Background: Premature ventricular complexes (PVCs) are the most common form of ventricular arrhythmia in the general population. While in most cases PVCs represent a primitive phenomenon with benign behavior, in a non-negligible proportion of subjects frequent PVCs may be epiphenomenon of underlying occult heart diseases, requiring special medical attention since they have been resulted linked to increased total and cardiac mortality. Nevertheless, PVCs themselves, when incessantly frequent, may be responsible for left ventricular dysfunction in otherwise normal heart. Aim of this narrative review is to update current knowledge on the general approach to patients with frequent PVCs on the basis of available data, with a special focus on the value of imaging., Hypothesis: Routine diagnostic work-up not infrequently miss subtle concealed arrhythmic substrate, leading to erroneously refer to such arrhythmias as to "idiopathic"., Methods: Literature search of PVCs articles was conducted in PubMed and Scopus electronic database., Results: Conflicting data arise from literature about the true clinical significance of idiopathic PVCs. There is growing body of data providing evidence that more advanced non-invasive imaging modalities, such as cardiac magnetic resonance, have an incremental diagnostic and prognostic value. On the other hand, in some cases the prognostic significance of isolated subtle myocardial structural abnormalities in patients with PVCs, still remains area of uncertainty., Conclusion: In selected subjects with PVCs and high-risk features for concealed arrhythmic substrate, traditional assessment to rule out the presence of heart disease, including surface ECG and transthoracic echocardiography, should be implemented with more advanced cardiovascular imaging modalities., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Recently, the fast development of quantum technologies led to the need for tools allowing the characterization of quantum resources. In particular, the ability to estimate non-classical aspects, e.g. entanglement and quantum discord, in two-qubit systems, is relevant to optimise the performance of quantum information processes. Here we present an experiment in which the amount of entanglement and discord are measured exploiting different estimators. Among them, some will prove to be optimal, i.e., able to reach the ultimate precision bound allowed by quantum mechanics. These estimation techniques have been tested with a specific family of states ranging from nearly pure Bell states to completely mixed states. This work represents a significant step towards the development of reliable metrological tools for quantum technologies.

Closed timelike curves are striking predictions of general relativity allowing for time-travel. They are afflicted by notorious causality issues (e.g. grandfather's paradox). Quantum models where a qubit travels back in time solve these problems, at the cost of violating quantum theory's linearity-leading e.g. to universal quantum cloning. Interestingly, linearity is violated even by open timelike curves (OTCs), where the qubit does not interact with its past copy, but is initially entangled with another qubit. Non-linear dynamics is needed to avoid violating entanglement monogamy. Here we propose an alternative approach to OTCs, allowing for monogamy violations. Specifically, we describe the qubit in the OTC via a pseudo-density operator-a unified descriptor of both temporal and spatial correlations. We also simulate the monogamy violation with polarization-entangled photons, providing a pseudo-density operator quantum tomography. Remarkably, our proposal applies to any space-time correlations violating entanglement monogamy, such as those arising in black holes.

Background: Survival improvements have been reported in selected patients affected by colorectal peritoneal metastases who were undergoing cytoreductive surgery with intraperitoneal hyperthermic chemotherapy. Treatment of peritoneal metastases associated with extraperitoneal disease is still controversial., Objective: We assessed the prognostic impact of a history of extraperitoneal disease that was curatively treated either at the same time as or before the onset of peritoneal metastases., Design: We reviewed 2 prospective databases. Peritoneal involvement was scored by Peritoneal Cancer Index., Settings: Our study was conducted in 2 high-volume peritoneal malignancy management institutions., Patients: A total of 148 patients with peritoneal metastases were included. In 27 patients, extraperitoneal disease involving the liver (n = 23), lung (n = 1), both lung and liver (n = 2), or inguinal lymph nodes and liver (n = 1) was curatively treated either simultaneously with peritoneal metastases (n = 22) or before their onset (n = 5)., Interventions: All of the macroscopic tumors were removed by means of peritonectomy procedures and visceral resections. Microscopic residual disease was treated by mitomycin C/cisplatin-based hyperthermic intraperitoneal chemotherapy., Main Outcome Measures: Overall survival was the primary outcome measure., Results: After a median follow-up of 34.6 months (95% CI, 22.6-65.7 mo), 5-year survival of patients treated for both peritoneal and extraperitoneal disease versus peritoneal metastases alone was 16.5% versus 52.0% (p = 0.019). After multivariate analysis, reduced survival correlated with extraperitoneal disease (p = 0.001), Peritoneal Cancer Index >19 (p = 0.004), and peritoneal residual disease >2.5 mm (p = 0.018). Three prognostic groups were defined, and median survival was not reached for group 1 (Peritoneal Cancer Index ≤19 and no extraperitoneal disease), reached in 27.0 months for group 2 (Peritoneal Cancer Index ≤9 and extraperitoneal disease), and reached in 11.6 months for group 3 (Peritoneal Cancer Index >19 and no extraperitoneal disease or Peritoneal Cancer Index >9 and extraperitoneal disease)., Limitations: The main study limitation is its observational nature., Conclusions: A history of extraperitoneal disease is associated with poorer prognosis. However, survival benefit may be obtained in selected patients with limited peritoneal involvement. See Video Abstract at http://links.lww.com/DCR/A655.

Objective: We investigated the correlation between ploidy or S-phase fraction (SPF) and the clinical pathological characteristics of patients with peritoneal carcinomatosis from ovarian cancer. We also assessed their relation with the in vivo and in vitro response to several chemotherapeutic agents., Patients and Methods: Fifty-three patients with peritoneal carcinomatosis from ovarian cancer were enrolled. Frozen tumor tissue was dissociated by a detergent-trypsin method, and the resulting cell suspension was stained with RNase A and propidium iodide. Samples were then analyzed for ploidy and SPF by flow cytometry. Fresh tumor tissue was dissociated by enzymatic digestion, and cells were exposed to different concentrations of cisplatin, adriamycin, carboplatin, gemcitabine and taxol for 72 hours. In vitro drug sensitivity was then measured using the sulforhodamine B assay., Results: No significant correlation was found between ploidy or SPF and patient characteristics, even though primary carcinomas were mainly hyperdiploid and more proliferative than recurrent tumors. SPF differed significantly among ploidy categories ( P =0.01), and high SPF was associated with short-term survival ( P =0.48). Patients with multiploid tumors were the most resistant to platinum-based chemotherapy, whereas those with hyperdiploid tumors were the most responsive. In vitro multiploid tumors were the least sensitive, while hypodiploid samples showed the highest sensitivity to the tested drugs. Sensitivity to adriamycin was significantly correlated with ploidy ( P =0.03), whereas sensitivity to taxol was correlated with SPF ( P =0.04)., Conclusion: Our results indicate that ploidy and SPF could facilitate the choice of therapy for patients with peritoneal carcinomatosis., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are maximally effective in early-stage colorectal cancer peritoneal metastases (CRC-PM); however, the use of HIPEC to treat subclinical-stage PM remains controversial. This prospective two-center study assessed adjuvant HIPEC in CRC patients at high risk for metachronous PM ( www.clinicaltrials.gov NCT02575859)., Methods: During 2006-2012, a total of 22 patients without systemic metastases were prospectively enrolled to receive HIPEC simultaneously with curative surgery, plus adjuvant systemic chemotherapy (oxaliplatin/irinotecan-containing ± biologics), based on primary tumor-associated criteria: resected synchronous ovarian (n = 2) or minimal peritoneal (n = 6) metastases, primaries directly invading other organs (n = 4) or penetrating the visceral peritoneum (n = 10). A control group retrospectively included 44 matched (1:2) patients undergoing standard treatments and no HIPEC during the same period. The cumulative PM incidence was calculated in a competing-risks framework., Results: Patient characteristics were comparable for all groups. Median follow-up was 65.2 months [95 % confidence interval (CI) 50.9-79.5] in the HIPEC group and 34.5 months (95 % CI 21.1-47.9) in the control group. The 5-year cumulative PM incidence was 9.3 % in the HIPEC group and 42.5 % in the control group (p = 0.004). Kaplan-Meier estimated 5-year overall survival (OS) was 81.3 % in the HIPEC group versus 70.0 % in the control group (p = 0.047). No operative death occurred. Grade 3-4 [National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4] morbidity rates were 18.2 % in the HIPEC group and 25 % in controls (p = 0.75). At multivariate analysis, HIPEC correlated to lower PM cumulative incidence [hazard ratio (HR) 0.04, 95 % CI 0.01-0.31; p = 0.002], and better OS (HR 0.25, 95 % CI 0.07-0.89; p = 0.039) and progression-free survival (HR 0.31, 95 % CI 0.11-0.85; p = 0.028)., Conclusion: Adjuvant HIPEC may benefit CRC patients at high-risk for peritoneal failure. These results warrant confirmation in phase III trials.

Aims: Inflammation-based scores such as neutrophil-lymphocyte ratio (NLR) and Onodera nutritional index (ONI) have been identified as new prognosticators in several tumors. We conducted a prognostic analysis of these markers and performed a risk stratification of PMP patients submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: 226 patients from two peritoneal surface malignancies centers participated in this study. Cox proportional modeling was used to select predictors of overall survival (OS) among baseline inflammation-based scores, serum tumor markers, clinical and surgical variables. Risk stratification was done using conditional inference tree model., Results: One hundred eighty-two cases had diffuse peritoneal adenomucinosis subtype. Fifty-four cases had received previous systemic chemotherapy. The means of ONI and NLR were 51.4 (SD = 9.8) and 3.2 (SD = 2.3), respectively. Two hundred ten cases were optimally cytoreduced. Cox analysis identified completeness of cytoreduction, histological subtype, previous systemic chemotherapy, NLR, and CA 19-9 as independent prognosticators. Conditional inference tree method identified two poor prognostic subsets: NLR ≤2.7 and CA 19-9>336 (5yr-OS = 15%) and NLR >2.7 and ONI ≤42 (5yr-OS = 30%)., Conclusions: NLR, ONI, and CA 19-9 are new prognosticators that contributed to improve prediction of OS in PMP patients treated by CRS and HIPEC. These markers allowed a risk stratification that could optimize therapeutic management of PMP patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an effective but potentially morbid treatment for colorectal cancer peritoneal metastases. The impact of treatment-related morbidity on long-term survival has been reported in various malignancies, but it has never been assessed in this clinical setting., Objective: The aim of this study was to assess the impact of major postoperative complications on oncological outcomes after cytoreduction and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases., Design: Two prospective databases were reviewed. Major complications were defined as grade 3 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The extent of peritoneal involvement was scored by the use of the Peritoneal Cancer Index., Settings: This study was conducted in 2 high-volume peritoneal malignancy management centers., Patients: One hundred one consecutive patients with peritoneal metastases potentially amenable to macroscopically complete cytoreduction were selected., Interventions: Peritonectomy procedures and multivisceral resections were used to remove all macroscopic tumor, and mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy was used to control microscopic residual disease., Main Outcome Measures: The primary outcomes measured were overall and disease-specific survival., Results: Mortality and major morbidity were 3.0%, and 23.8%. Median follow-up was 44.9 months (95% CI, 24.1-65.7). Five-year disease-specific survival was 14.3% for patients who experienced major complications and 52.3% for those who did not (p = 0.001). Five-year overall survival was 11.7% for patients who experienced major complications, and 58.8% for those who did not (p = 0.003). At multivariate analysis, major morbidity correlated to both worse overall and disease-specific survival, along with a Peritoneal Cancer Index >19, and suboptimal cytoreduction. Poor performance status correlated only to worse disease-specific survival, and liver metastases correlated to worse overall survival. Longer operative time (OR, 4.1; 95% CI, 1.3-12.6; p = 0.01) and Peritoneal Cancer Index >19 (OR, 2.6; 95% CI, 1.1-6.0; p = 0.02) were independent risk factors for major morbidity., Limitations: This study is limited by its observational design., Conclusions: The prevention of major complications, by refining surgical technique and patient selection, is crucial because it affects oncologic outcome.

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.

Aims and Background: The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases., Methods: Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed., Results: Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%., Conclusions: Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

Unlabelled: Peritoneal carcinomatosis (PC) is observed in approximately 10% of patients with colorectal cancer at the time of primary cancer resection. Most of these patients receive 5-fluorouracil (5-FU)- or oxaliplatin-containing chemotherapy regimens as first-, second-, or third-line treatment. In the present study, sensitivity and resistance to drugs used to treat PC were better defined by a conventional chemosensitivity test than by biomarker expression., Background: 5-Fluorouracil- or oxaliplatin-based regimens are the treatments of choice in patients with PC from colon cancer. There are currently no useful preclinical evaluations to guide the decision-making process for tailored therapy. The aim of the present study was to compare the advantages and limits of a conventional in vitro chemosensitivity test with those of a panel of biomolecular markers in predicting clinical response to different drugs used to treat colon cancer-derived PC., Patients and Methods: Fresh surgical biopsy specimens were obtained from 28 patients with peritoneal carcinomatosis from colon cancer. TS, TP, DPD, MDR1, MRP-1, MGMT, BRCA1, ERCC1, GSTP1, and XPD gene expression levels were determined by real-time reverse transcription polymerase chain reaction. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient., Results: Expression levels of the genes analyzed were generally poorly related to each other. TS and ERCC1 expression was inversely related to response to 5-FU-and/or oxaliplatin-containing regimens. Significant predictivity in terms of sensitivity but poor predictivity of resistance (56.2%) (P=.037) were observed for ERCC1 expression (90%), and high predictivity of resistance (100%) but very low predictivity of sensitivity (40%) (P=.014) were registered for TS. The best overall and significant predictivity was observed for chemosensitivity test results (62.5% sensitivity and 89% resistance; P=.005)., Conclusions: Sensitivity and resistance to drugs used in vivo was better defined by the chemosensitivity test than by biomarker expression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process., Methods: Six hundred and forty-one cases submitted to CRS using peritonectomy procedures and HIPEC were considered. After having overcome its own LC, the NCI of Milan has provided technical assistance to Bentivoglio's centre for the development of a new PSM program since 2003. The risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of the two centers. Outcomes were incomplete cytoreduction, G3-5 morbidity (NCI-CTCAE.v3) and procedure-related mortality (PRM)., Results: Rates of incomplete cytoreduction, G3-5 morbidity, and PRM were 8.4%, 30.1%, and 3.9%, respectively, in the entire series. The breaking points of the LC concerning incomplete cytoreduction, G3-5 morbidity, and PRM were achieved at 141, 158, and 144 cases, in the Milan's experience, and at 126, 134, and 60 cases in the Bentivoglio's experience., Conclusions: Surgical tutoring could substantially shorten the steep LC associated with CRS and HIPEC. Our data should be confirmed by further studies on LC focusing oncological outcomes. Other factors that could influence the length of learning process should be identified., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims and Background: Pseudomyxoma peritonei (PMP) is a rare clinical entity characterized by diffuse intraabdominal gelatinous collections with mucinous implants on the peritoneal surfaces and omentum. This condition should be considered a borderline malignancy with disease progression over time. Encouraging treatment results have been recently reported with the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: . From December 2003 to December 2010, 18 patients with PMP were referred to our institution. All patients underwent peritonectomy and CRS combined with HIPEC in accordance with Sugarbaker's procedure., Results: The mean Peritoneal Cancer Index score was 27.6 (range, 5-39). Twelve (67%) patients had disseminated peritoneal adenomucinosis and 6 (33%) peritoneal mucinous carcinomatosis. Optimal cytoreduction with no visible residual disease or residual disease ≤2.5 mm in diameter was achieved in all patients. The mean duration of the surgical procedure including HIPEC was 9 hours and 30 minutes (range, 5-13 hours); major morbidity occurred in 30% of patients and the mortality was 11%. The mean follow-up was 27 months (range, 1-72) and the 5-year overall survival 66%., Conclusions: In line with the existing literature, our experience suggests that patients with PMP could benefit from CRS + HIPEC in terms of survival and locoregional disease control.

Objective: To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC)., Design: A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM., Population: Patients with recurrent EOC., Methods: Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C., Main Outcome Measures: Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates., Results: The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease ≤2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction., Conclusions: Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Background: Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy., Case Report: A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors., Conclusions: To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.

Neuroendocrine gastroenteropancreatic tumors constitute a heterogeneous group of neoplasms, with the primary tumors being located in the gastric mucosa, pancreas, and small and large intestine. The development of a second primary malignancy in patients with these tumors is a well-described phenomenon, and the reported incidence ranges from 12% to 46%. The most common site of associated noncarcinoid malignancies is the gastrointestinal tract, which involves from 30% to 60% of the tumors. We report a case of concurrent colon carcinoma and two neuroendocrine tumors of the duodenum.

Situs viscerum inversus totalis is a rare defect with a genetic predisposition, which can present difficulties in the management of abdominal pathology, especially in laparoscopic surgery (mirror-image anatomy). We report the case of a 52-year-old female with situs viscerum inversus totalis, known from pediatric age, with a medical history of colic pain in the epigastrium radiating to the right abdominal quadrant. Laparoscopic cholecistectomy was safely performed with a three trocar technique. To the best of our knowledge this is the first time that laparoscopic cholecistectomy by three trocars was performed in a patient with situs viscerum inversus. We also review the relevant literature concerning this issue.

Disorders of an organ not usually found in the right iliac fossa, such as the sigmoid colon, are an uncommon cause of right iliac fossa pain. We present a case of right iliac fossa pain caused by a sigmoid perforation due to involuntary ingestion of a rabbit bone, and describe the main features of this condition.

Objective: The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC)., Methods: Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m(2)) for 6 cycles., Results: Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2% (median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS., Conclusions: In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer., Methods: Fresh surgical biopsy specimens were obtained from 30 patients with primary or recurrent peritoneal carcinomatosis from ovarian cancer. ERCC1, GSTP1, MGMT, XPD, and BRCA1 gene expression levels were determined by Real-Time RT-PCR. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient., Results: MGMT and XPD expression was directly and significantly related to resistance to platinum-containing treatment (p = 0.036 and p = 0.043, respectively). Significant predictivity in terms of sensitivity and resistance was observed for MGMT expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity of resistance (90.9%) but very low predictivity of sensitivity (37.5%) (p = 0.06) were observed for XPD. The best overall and significant predictivity was observed for chemosensitivity test results (85.7% sensitivity and 91.3% resistance; p = 0.0003)., Conclusions: The in vitro assay showed a consistency with results observed in vivo in 27 out of the 30 patients analyzed. Sensitivity and resistance profiles of different drugs used in vivo would therefore seem to be better defined by the in vitro chemosensitivity test than by expression levels of markers.

Aim: The present study was specifically designed to assess the major clinical and pathological variables of patients with colorectal peritoneal carcinomatosis in order to investigate whether currently used criteria appropriately select candidates for peritonectomy procedures (cytoreductive surgery) combined with hyperthermic intraperitoneal chemotherapy (HIPEC)., Patients and Methods: Preoperative, operative and follow-up data on 146 consecutive patients presenting with peritoneal carcinomatosis of colorectal origin and treated by surgical cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers were prospectively entered in a common database. Univariate and multivariate analyses were used to assess the prognostic value of clinical and pathologic factors., Results: Over a minimum 24-month follow-up, the overall morbidity rate was 27.4% (mortality rate: 2.7%) and was directly related to the extent of surgery. Peritoneal cancer index (PCI), unfavorable peritoneal sites, synchronous or previously resected liver metastasis and the completeness of cytoreduction, all emerged as independent prognostic factors correlated with survival., Conclusions: Until research provides more effective criteria for selecting patients based upon the biomolecular features of carcinomatosis, patients should be selected according to the existing independent prognostic variables., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Hepatobiliary cystoadenoma is a rare cystic tumor of the liver that can undergo malignant change and become lethal. Accurate diagnosis of such lesions, even though not always possible, is of importance as the management is totally different from that of other nonneoplastic cysts. We report a case of a 60-year-old woman with aspecific symptoms, which was diagnosed using ultrasound scan and CT scan and treated with hepatic resection, and review the main features of this tumor.

We describe a case of a 76-year-old man with a giant ileal gastrointestinal stromal tumour (GIST) causing an intestinal subocclusion and a subsequent haemoperitoneum. During his hospital stay for a sudden hypovolemic shock, the patient underwent an urgent laparotomy and a 20 cm × 15 cm ruptured ileal GIST causing haemoperitoneum was found. Only 13 cases of ileal GIST causing peritoneal bleeding have been described since 2000, the one we presented is the largest. Although rare this pathological entity should be kept in mind in case of sudden abdominal pain and hypovolemic shock in patients with a large intraabdominal mass.

Peritoneal carcinomatosis has always been regarded as a contraindication in traditional cancer surgery treatment; however, good results have been reported by using new combined medical-surgical loco-regional techniques. Peritonectomy and chemohyperthermic perfusion with cisplatinum (CIIP) seem to play a central role in obtaining a better survival rate than with the traditional procedures, even though there is a cisplatinum nephrotoxic effect. The aim of this study was to investigate entity and type of renal injury after CIIP. Forty-two patients (12 males and 30 females) with recurrent or primary peritoneal carcinomatosis who underwent peritonectomy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy with cisplatin were enrolled. A significant worsening in renal function was observed on the third post-operative day and this condition then persisted for three months. A reduction in estimated-Glomerular Filtration Rate (e-GFR) and an alteration in the albumin:creatinine ratio proved tubular injury. On the third post-operative day after cisplatinum administration, a high toxicity peak was found following platinum free fraction excretion. Proximal tubular injury was confirmed even at the three month analysis. A significant correlation between the total protein reduction rate and the decrease in renal function was established. In relation to that, the platinum free fraction could increase because of a binding protein shortage and the nephrotoxic effect could be enhanced due to platinum accumulation within the post-operative period. This finding suggests that the higher the protein reduction is, the lower the e-GFR determination is at three months.