Quantum Zeno and Anti-Zeno Probes of Noise Correlations in Photon Polarization.

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.

Coherent phase transfer for real-world twin-field quantum key distribution.

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.

Temporal teleportation with pseudo-density operators: How dynamics emerges from temporal entanglement.

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.

Non-Monogamy of Spatio-Temporal Correlations and the Black Hole Information Loss Paradox.

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.

Optimal estimation of entanglement and discord in two-qubit states.

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.

Theoretical description and experimental simulation of quantum entanglement near open time-like curves via pseudo-density operators.

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.

Should a History of Extraperitoneal Disease Be a Contraindication to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Metastases?

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.

DNA ploidy and S-phase fraction analysis in peritoneal carcinomatosis from ovarian cancer: correlation with clinical pathological factors and response to chemotherapy.

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.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the Time of Primary Curative Surgery in Patients with Colorectal Cancer at High Risk for Metachronous Peritoneal Metastases.

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.

Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases.

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.

Peritoneal carcinomatosis.

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.

Role of conventional chemosensitivity test and tissue biomarker expression in predicting response to treatment of peritoneal carcinomatosis from colon cancer.

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.

Learning curve for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal surface malignancies: analysis of two centres.

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.

Pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic chemotherapy: a 7-year single-center experience.

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.

Synchronous association of two neuroendocrine gastroenteropancreatic tumors, an adenocarcinoma of the cecum, and a Meckel's diverticulum: a case report.

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.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial.

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.

Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy.

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.

Hepatobiliary cystoadenoma: a wolf in sheep's clothing.

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.

Giant ileal gastrointestinal stromal tumour presenting as an intestinal subocclusion and subsequent haemoperitoneum: a case report and a review of the literature.

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.