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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.
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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.
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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.
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Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Hipertermia Induzida/efeitos adversos , Neoplasias Peritoneais/secundário , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Peritônio/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
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.
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Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Hipertermia Induzida , Segunda Neoplasia Primária/secundário , Neoplasias Peritoneais/secundário , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Hipertermia Induzida/métodos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/educação , Procedimentos Cirúrgicos do Sistema Digestório/educação , Hipertermia Induzida , Curva de Aprendizado , Mentores , Neoplasia Residual/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Quimioterapia do Câncer por Perfusão Regional/métodos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Bolsas de Estudo , Feminino , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Peritoneais/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados UnidosRESUMO
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.
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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.
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Biomarcadores Tumorais/genética , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/genética , Prognóstico , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
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.
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Antineoplásicos/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário , Terapia Combinada , Feminino , Humanos , Injeções Intraperitoneais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundárioRESUMO
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.
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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.
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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.
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The treatment of patients at high risk of developing colorectal peritoneal carcinomatosis is still debated since the absence of peritoneal disease synchronous with the primitive cancer makes the application of aggressive treatments less obvious. In this subset of patients hyperthermic intraperitoneal chemotherapy (HIPEC), after the resection of the primitive cancer, may improve long-term survival. Over the period from December 2003 to June 2008 142 patients affected by different kinds of cancers underwent HIPEC in the surgical division of Bentivoglio Hospital, A.U.S.L. Bologna. In 13 patients HIPEC was combined only with the resection of the primitive cancer and no major cytoreductive surgery was performed. Nine of these 13 patients were affected by colorectal cancer and at high risk of developing carcinomatosis. The average surgical time was 420 min (range: 300-510). No intraoperative complications occurred, but 3 cases of postoperative morbidity were reported; only 1 of these was a major complication At an average follow-up of 22 months 1 patient with a liver metastasis died of complications unrelated to progression of the disease, 1 patient had a lymph node relapse and is currently on systemic chemotherapy, while the remaining 7 patients are alive and free from peritoneal disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/terapia , Neoplasias Colorretais/terapia , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Colectomia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
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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.
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Antineoplásicos/efeitos adversos , Carcinoma/terapia , Cisplatino/efeitos adversos , Nefropatias/induzido quimicamente , Túbulos Renais/efeitos dos fármacos , Neoplasias Peritoneais/tratamento farmacológico , Peritônio/cirurgia , Albuminúria/diagnóstico , Albuminúria/urina , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Creatina/urina , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hipertermia Induzida , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Túbulos Renais/metabolismo , Túbulos Renais/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
We report a case of primary endodermal sinus tumor of the omentum in a 46-year-old woman. The patient had been referred to our hospital for pain in the right abdomen. CT scan revealed a right-sided abdominal mass. At laparotomy, a large omental tumor extending to the bowel, uterus, ovaries and peritoneum was found, and it was totally resected. The tumor displayed the typical histological patterns observed in endodermal sinus tumor, and the immunohistochemical findings confirmed the diagnosis. Serum AFP level was 21.550 ng/ml prior to laparotomy, and decreased to 13.845 ng/mL after surgery, whereas the level of serum beta human chorionic gonadotropin was normal. Post-surgery, the patient received combination chemotherapy consisting of cisplatin, etoposide and bleomycin every 3 weeks for a total of 6 cycles. At the end of the treatment, all the findings, including AFP level, were normal.
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Tumor do Seio Endodérmico , Omento , Neoplasias Peritoneais , Biomarcadores Tumorais/análise , Tumor do Seio Endodérmico/química , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Omento/patologia , Omento/cirurgia , Neoplasias Peritoneais/química , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgiaRESUMO
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Hipertermia Induzida , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Quimioterapia Adjuvante , Quimioterapia do Câncer por Perfusão Regional/métodos , Cisplatino/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Projetos Piloto , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
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.
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Carcinoma/secundário , Carcinoma/terapia , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Carcinoma/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias dos Genitais Femininos/mortalidade , Humanos , Masculino , Neoplasias Peritoneais/mortalidade , Resultado do TratamentoRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/genética , Tomada de Decisões , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/secundário , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
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.