Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial.

BACKGROUND: As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored. PATIENTS AND METHODS: Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS-HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm. RESULTS: Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively. CONCLUSIONS: In patients with resectable CPM randomized to perioperative systemic therapy or CRS-HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial's previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.

Effectiveness of a Tailored Work-Related Support Intervention for Patients Diagnosed with Gastrointestinal Cancer: A Multicenter Randomized Controlled Trial.

Purpose The aim of this research was to study the effectiveness on return to work (RTW) of an early tailored work-related support intervention in patients diagnosed with curative gastrointestinal cancer. Methods A multicenter randomized controlled trial was undertaken, in which patients were assigned randomly to the intervention or the control group (usual care). The intervention encompassed three psychosocial work-related support meetings, starting before treatment. Five self-reported questionnaires were sent over twelve months of follow-up. Primary outcome was days until RTW (fulltime or partial) and secondary outcomes included work status, quality of life, work ability, and work limitations. Descriptive analysis, Kaplan-Meier analysis, relative risk ratio and linear mixed models were applied. Results Participants (N = 88) had a mean age of 55 years; 67% were male and the most common cancer type was colon cancer (66%). Of the participants, 42 were randomized to the intervention group. The median time from sick leave until RTW was 233 days (range 187-279 days) for the control group, versus 190 days (range 139-240 days) for the intervention group (log-rank p = 0.37). The RTW rate at twelve months after baseline was 83.3% for the intervention group and 73.5% for the control group. Work limitations did statistically differ between the groups over time (p = 0.01), but quality of life and work ability did not. Conclusion Patients in the intervention group seem to take fewer days to RTW, albeit not to a statistically significant extent.Trial registration Trial NL4920 (NTR5022) (Dutch Trial Register https://www.trialregister.nl ).

A low incidence of perineal hernia when using a biological mesh after extralevator abdominoperineal excision with or without pelvic exenteration or distal sacral resection in locally advanced rectal cancer patients.

BACKGROUND: Extralevator abdominoperineal excision (ELAPE), abdominoperineal excision (APE) or pelvic exenteration (PE) with or without sacral resection (SR) for locally advanced rectal cancer leaves a significant defect in the pelvic floor. At first, this defect was closed primarily. To prevent perineal hernias, the use of a biological mesh to restore the pelvic floor has been increasing. The aim of this study, was to evaluate the outcome of the use of a biological mesh after ELAPE, APE or PE with/without SR. METHODS: A retrospective study was conducted on patients who had ELAPE, APE or PE with/without SR with a biological mesh (Permacol™) for pelvic reconstruction in rectal cancer in our center between January 2012 and April 2015. The endpoints were the incidence of perineal herniation and wound healing complications. RESULTS: Data of 35 consecutive patients [22 men, 13 women; mean age 62 years (range 31-77 years)] were reviewed. Median follow-up was 24 months (range 0.4-64 months). Perineal hernia was reported in 3 patients (8.6%), and was asymptomatic in 2 of them. The perineal wound healed within 3 months in 37.1% (n = 13), within 6 months in 51.4% (n = 18) and within 1 year in 62.9% (n = 22). In 17.1% (n = 6), the wound healed after 1 year. It was not possible to confirm perineal wound healing in the remaining 7 patients (20.0%) due to death or loss to follow-up. Wound dehiscence was reported in 18 patients (51.4%), 9 of whom needed vacuum-assisted closure therapy, surgical closure or a flap reconstruction. CONCLUSIONS: Closure of the perineal wound after (EL)APE with a biological mesh is associated with a low incidence of perineal hernia. Wound healing complications in this high-risk group of patients are comparable to those reported in the literature.

Neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: a feasibility and safety study.

BACKGROUND: Standard treatment for colorectal peritoneal carcinomatosis typically involves cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and if possible, postoperative adjuvant chemotherapy. However, a substantial percentage of patients never receive adjuvant chemotherapy because of postoperative complications. Neoadjuvant chemotherapy could be beneficial in this setting, so we assessed its feasibility and safety when used before cytoreductive surgery and HIPEC. METHODS: In this non-randomized, single-center, observational feasibility study, patients were scheduled to receive six cycles of capecitabine and oxaliplatin before cytoreductive surgery and HIPEC. Computed tomography was performed after the third and sixth chemotherapy cycles to evaluate tumor response, and patients underwent cytoreductive surgery and HIPEC if there were no pulmonary and/or hepatic metastases. Postoperative complications, graded according to the Clavien-Dindo classification, were compared with those of a historic control group that received postoperative adjuvant chemotherapy. RESULTS: Of the 14 patients included in the study, 4 and 3 had to terminate neoadjuvant chemotherapy early because of toxicity and tumor progression, respectively. Cytoreductive surgery and HIPEC were performed in eight patients, and the timing and severity of complications were comparable to those of patients in the historic control group treated without neoadjuvant chemotherapy. CONCLUSION: Patients with peritoneal metastases due to colorectal carcinoma can be treated safely with neoadjuvant chemotherapy before definitive therapy with cytoreductive surgery and HIPEC. TRIAL REGISTRATION NUMBER: NTR 3905, registered on 20th march, 2013, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3905.

Multicentre study evaluating the surgical learning curve for posterior retroperitoneoscopic adrenalectomy.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy has gained international popularity in the past decade. Despite major advantages, including shorter duration of operation, minimal blood loss and decreased postoperative pain, many surgeons still prefer laparoscopic transperitoneal adrenalectomy. It is likely that the unfamiliar anatomical environment, smaller working space and long learning curve impede implementation. The present study assessed the number of procedures required to fulfil the surgical learning curve for posterior retroperitoneoscopic adrenalectomy. METHODS: The first consecutive posterior retroperitoneoscopic adrenalectomies performed by four surgical teams from university centres in three different countries were analysed. The primary outcome measure was duration of operation. Secondary outcomes were conversion to an open or laparoscopic transperitoneal approach, complications and recovery time. The learning curve cumulative sum (LC-CUSUM) was used to assess the learning curves for each surgical team. RESULTS: A total of 181 surgical procedures performed by four surgical teams were analysed. The median age of the patients was 57 (range 15-84) years and 61·3 per cent were female. Median tumour size was 25 (range 4-85) mm. There were no significant differences in patient characteristics and tumour size between the teams. The median duration of operation was 89 (range 29-265) min. There were 35 perioperative and postoperative complications among the 181 patients (18·8 per cent); 17 of 27 postoperative complications were grade 1. A total of nine conversions to open procedures (5·0 per cent) were observed. The LC-CUSUM analysis showed that competency was achieved after a range of 24-42 procedures. CONCLUSION: In specialized endocrine surgical centres between 24 and 42 procedures are required to fulfil the entire surgical learning curve for the posterior retroperitoneoscopic adrenalectomy.

Laparoscopic anterior versus endoscopic posterior approach for adrenalectomy: a shift to a new golden standard?

PURPOSE: There has been an increased utilization of the posterior retroperitoneal approach (PRA) for adrenalectomy alongside the "classic" laparoscopic transabdominal technique (LTA). The aim of this study was to compare both procedures based on outcome variables at various ranges of tumor size. METHODS: A retrospective analysis was performed on 204 laparoscopic transabdominal (UMC Groningen) and 57 retroperitoneal (UMC Utrecht) adrenalectomies between 1998 and 2013. We applied a univariate and multivariate regression analysis. Mann-Whitney and chi-squared tests were used to compare outcome variables between both approaches. RESULTS: Both mean operation time and median blood loss were significantly lower in the PRA group with 102.1 (SD 33.5) vs. 173.3 (SD 59.1) minutes (p < 0.001) and 0 (0-200) vs. 50 (0-1000) milliliters (p < 0.001), respectively. The shorter operation time in PRA was independent of tumor size. Complication rates were higher in the LTA (19.1%) compared to PRA (8.8%). There was no significant difference in recovery time between both approaches. CONCLUSIONS: Application of the PRA decreases operation time, blood loss, and complication rates compared to LTA. This might encourage institutions that use the LTA to start using PRA in patients with adrenal tumors, independent of tumor size.

High-resolution magnetic field imaging with a nitrogen-vacancy diamond sensor integrated with a photonic-crystal fiber.

We demonstrate high-resolution magnetic field imaging with a scanning fiber-optic probe which couples nitrogen-vacancy (NV) centers in diamond to a high-numerical-aperture photonic-crystal fiber integrated with a two-wire microwave transmission line. Magnetic resonance excitation of NV centers driven by the microwave field is read out through optical interrogation through the photonic-crystal fiber to enable high-speed, high-sensitivity magnetic field imaging with sub 30 µm spatial resolution.

Stimulated fluorescence quenching in nitrogen-vacancy centers of diamond: temperature effects.

Laser-induced fluorescence quenching in nitrogen-vacancy (NV) centers in diamond is studied simultaneously with in situ measurements of the heating-induced shift of the electron spin resonance of NV centers in the presence of a microwave field. These experiments reveal a strong correlation between fluorescence suppression in NV centers and the rise of the local temperature inside the diamond crystal. This finding sheds light on quantum pathways behind stimulated fluorescence quenching in NV centers of diamond and may imply significant limitations on the applications of this effect as a method of superresolving imaging in biological systems.

Fiber-optic electron-spin-resonance thermometry of single laser-activated neurons.

Optically detected electron spin resonance in fiber-coupled nitrogen-vacancy (NV) centers of diamond is used to demonstrate a fiber-optic quantum thermometry of individual thermogenetically activated neurons. Laser-induced temperature variations read out from single neurons with the NV-diamond fiber sensor are shown to strongly correlate with the fluorescence of calcium-ion sensors, serving as online indicators of the inward Ca2+ current across the cell membrane of neurons expressing transient receptor potential (TRP) cation channels. Local laser heating above the TRP-channel activation threshold is shown to reproducibly evoke robust action potentials, visualized by calcium-ion-sensor-aided fluorescence imaging and detected as prominent characteristic waveforms in the time-resolved response of fluorescence Ca2+ sensors.

Quantum entanglement between an optical photon and a solid-state spin qubit.

Quantum entanglement is among the most fascinating aspects of quantum theory. Entangled optical photons are now widely used for fundamental tests of quantum mechanics and applications such as quantum cryptography. Several recent experiments demonstrated entanglement of optical photons with trapped ions, atoms and atomic ensembles, which are then used to connect remote long-term memory nodes in distributed quantum networks. Here we realize quantum entanglement between the polarization of a single optical photon and a solid-state qubit associated with the single electronic spin of a nitrogen vacancy centre in diamond. Our experimental entanglement verification uses the quantum eraser technique, and demonstrates that a high degree of control over interactions between a solid-state qubit and the quantum light field can be achieved. The reported entanglement source can be used in studies of fundamental quantum phenomena and provides a key building block for the solid-state realization of quantum optical networks.

Fiber-optic magnetometry with randomly oriented spins.

We demonstrate fiber-optic magnetometry using a random ensemble of nitrogen-vacancy (NV) centers in nanodiamond coupled to a tapered optical fiber, which provides a waveguide delivery of optical fields for the initialization, polarization, and readout of the electron spin in NV centers.

Generation of single optical plasmons in metallic nanowires coupled to quantum dots.

Control over the interaction between single photons and individual optical emitters is an outstanding problem in quantum science and engineering. It is of interest for ultimate control over light quanta, as well as for potential applications such as efficient photon collection, single-photon switching and transistors, and long-range optical coupling of quantum bits. Recently, substantial advances have been made towards these goals, based on modifying photon fields around an emitter using high-finesse optical cavities. Here we demonstrate a cavity-free, broadband approach for engineering photon-emitter interactions via subwavelength confinement of optical fields near metallic nanostructures. When a single CdSe quantum dot is optically excited in close proximity to a silver nanowire, emission from the quantum dot couples directly to guided surface plasmons in the nanowire, causing the wire's ends to light up. Non-classical photon correlations between the emission from the quantum dot and the ends of the nanowire demonstrate that the latter stems from the generation of single, quantized plasmons. Results from a large number of devices show that efficient coupling is accompanied by more than 2.5-fold enhancement of the quantum dot spontaneous emission, in good agreement with theoretical predictions.

Results of surgery for perforated gastroduodenal ulcers in a Dutch population.

OBJECTIVE: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment. PATIENTS AND METHODS: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality. RESULTS: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class. CONCLUSIONS: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment.

AMEE 2009 spotlight on educational research.

The AMEE meeting is unique among the medical education conferences in that it is truly international. Educational research presented at the 2009 AMEE Meeting was both diverse and robust. In this article, we will present an overview of educational research from the meeting. We will begin with outlining our methods for the selection and categorization of themes, discuss some highpoints from some of the respective themes, and finally from the conference overall.

Impact of extent of disease on 1-year healthcare costs in patients who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: retrospective observational cohort study.

BACKGROUND: The goal of this retrospective observational study was to determine the impact of the extent of peritoneal disease on 1-year healthcare costs in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). The extent of peritoneal disease, expressed by the Peritoneal Cancer Index (PCI), directly affects the complexity of CRS + HIPEC and ultimately survival outcomes. The impact of the PCI on treatment-related healthcare costs remains unknown. METHODS: Data from patients with colorectal PM who underwent CRS + HIPEC between January 2012 and November 2017 were extracted retrospectively from an institutional database. Patients were divided into four subgroups with PCI scores ranging from 0 to 20. Treatment-related costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the χ2 test and Kruskal-Wallis H test. RESULTS: Seventy-three patients were included (PCI 0-5, 22 patients; PCI 6-10, 19 patients; PCI 11-15, 17 patients; PCI 16-20, 15 patients). Median (i.q.r.) costs were significantly increased for the PCI 11-15 and PCI 16-20 groups (€51 029 (42 500-58 575) and €46 548 (35 194-60 533) respectively) compared with those for the PCI 0-5 and PCI 6-10 groups (€33 856 (25 293-42 235) and €39 013 (30 519-51 334) respectively) (P = 0·009). CONCLUSION: Treatment-related healthcare costs are significantly increased among patients with extensive tumour burden (PCI score 10 or above) who undergo CRS + HIPEC for the treatment of colorectal PM.

ANTECEDENTES: El objetivo de este estudio observacional retrospectivo fue determinar el impacto de la extensión de la enfermedad peritoneal sobre los costes de atención médica al año en pacientes con metástasis peritoneales (peritoneal metastases, PM) de origen colorrectal que se someten a cirugía citorreductora con quimioterapia intraperitoneal hipertérmica (cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, CRS + HIPEC). La extensión de la enfermedad peritoneal, expresada por el índice de carcinomatosis peritoneal (peritoneal cancer index, PCI), afecta directamente a la complejidad de la CRS + HIPEC y, en última instancia, a los resultados de supervivencia. El impacto de la PCI en los costes de la atención médica relacionados con el tratamiento sigue siendo desconocido. MÉTODOS: Los datos de pacientes con PM de origen colorrectal que se sometieron a CRS + HIPEC entre enero de 2012 y noviembre de 2017 se extrajeron retrospectivamente de una base de datos institucional. Los pacientes se dividieron en cuatro subgrupos con PCI que variaron de 0 a 20. Los costes relacionados con el tratamiento hasta un año después de la CRS + HIPEC se obtuvieron del departamento financiero. Las diferencias en los costes y los resultados de supervivencia se compararon mediante los tests χ2 y de Kruskal-Wallis H. RESULTADOS: Se incluyeron 73 pacientes (PCI 0-5, 22 pacientes; PCI 6-10, 19 pacientes; PCI 11-15, 17 pacientes y PCI 16-20, 15 pacientes). Los costes medios aumentaron significativamente para los grupos PCI 11−15 y PCI 16−20 (51.029€ (rango intercuartílico, RIQ) 42.500€−58575€)) y 46.548€ (RIQ 35.194€-60.533€), respectivamente)) en comparación con los de los grupos PCI 0−5 y PCI 6-10 (33.856€ (RIQ 25.293€−42.23€) y 39.013€ (RIQ 30.519€-51.334€), respectivamente, P = 0,009). CONCLUSIÓN: Los costes de la atención médica relacionados con el tratamiento aumentan significativamente entre los pacientes con una carga tumoral extensa (es decir, PCI ≥ 10) que se someten a CRS + HIPEC para el tratamiento de PM de origen colorrectal.

Long-term survival after hyperthermic intraperitoneal chemotherapy using mitomycin C or oxaliplatin in colorectal cancer patients with synchronous peritoneal metastases: A nationwide comparative study.

OBJECTIVES: In the Netherlands, limited variability exists in performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among centers treating colorectal peritoneal metastases (PM), except for the intraperitoneal drug administration. This offers a unique opportunity to investigate any disparities in survival between the two most frequently used HIPEC regimens worldwide: mitomycin C (MMC) and oxaliplatin. METHODS: This was a comparative, population-based cohort study of all Dutch patients diagnosed with synchronous colorectal PM who underwent CRS-HIPEC between 2014 and 2017. They were retrieved from the Netherlands Cancer Registry. Main outcome was overall survival (OS). The effect of the intraperitoneal drug on OS was investigated using multivariable Cox regression analysis. RESULTS: In total, 297 patients treated between 2014 and 2017 were included. Among them, 177 (59.6%) received MMC and 120 (40.4%) received oxaliplatin. Only primary tumor location was different between the two groups: more left-sided colon in the Oxaliplatin group (47.5% vs. 33.3%, respectively, p=0.048). The 1-, 2- and 3-year OS were 84.6% vs. 85.8%, 61.6% vs. 63.9% and 44.7% vs. 53.5% in patients treated with MMC and oxaliplatin, respectively. Median OS was 30.7 months in the MMC group vs. 46.6 months in the oxaliplatin group (p=0.181). In multivariable analysis, no influence of intraperitoneal drug on survival was observed (adjusted HR 0.77 [0.53-1.13]). CONCLUSIONS: Long-term survival between patients treated with either MMC or oxaliplatin during CRS-HIPEC was not significantly different.

Effect of intraperitoneal chemotherapy concentration on morbidity and survival.

BACKGROUND: Selected patients with colorectal peritoneal metastases are treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The concentration of intraperitoneal chemotherapy reflects the administered dose and perfusate volume. The aim of this study was to calculate intraperitoneal chemotherapy concentration during HIPEC and see whether this was related to clinical outcomes. METHODS: An observational multicentre study included consecutive patients with colorectal peritoneal metastases who were treated with CRS-HIPEC between 2010 and 2018 at three Dutch centres. Data were retrieved from prospectively developed databases. Chemotherapy dose and total circulating volumes of carrier solution were used to calculate chemotherapy concentrations. Postoperative complications, disease-free and overall survival were correlated with intraoperative chemotherapy concentrations. Univariable and multivariable logistic regression, Cox regression and survival analyses were performed. RESULTS: Of 320 patients, 220 received intraperitoneal mitomycin C (MMC) and 100 received oxaliplatin. Median perfusate volume for HIPEC was 5·0 (range 0·7-10·0) litres. Median intraperitoneal chemotherapy concentration was 13·3 (range 7·0-76·0) mg/l for MMC and 156·0 (91·9-377·6) mg/l in patients treated with oxaliplatin. Grade III or higher complications occurred in 75 patients (23·4 per cent). Median overall survival was 36·9 (i.q.r. 19·5-62·9) months. Intraperitoneal chemotherapy concentrations were not associated with postoperative complications or survival. CONCLUSION: CRS-HIPEC was performed with a wide variation in intraperitoneal chemotherapy concentrations that were not associated with complications or survival.

ANTECEDENTES: Ciertos pacientes seleccionados con metástasis peritoneales de cáncer colorrectal (peritoneal metastases, PM) se tratan con cirugía citorreductora (cytoreductive surgery, CRS) y quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC). La concentración de quimioterapia intraperitoneal refleja la dosis administrada y el volumen perfundido. El objetivo de este estudio fue calcular la concentración de quimioterapia intraperitoneal durante HIPEC y evaluar si ello se relacionaba con los resultados clínicos. MÉTODOS: Estudio observacional multicéntrico en el que se incluyeron pacientes consecutivos con PM de cáncer colorrectal que fueron tratados con CRS-HIPEC entre 2010 y 2018 en tres centros holandeses. Se obtuvieron los datos a partir de bases de datos mantenidas de forma prospectiva. La dosis de quimioterapia y los volúmenes circulantes totales de solución de perfusión se usaron para calcular las concentraciones de quimioterapia. Las complicaciones postoperatorias y las supervivencias libre de enfermedad y global se correlacionaron con las concentraciones de quimioterapia intraoperatoria. Se realizaron regresiones logísticas univariable y multivariable, regresión de Cox y análisis de supervivencia. RESULTADOS: De 320 pacientes, 220 recibieron mitomicina C intraperitoneal (MMC) y 100 oxaliplatino (OXA). El volumen medio de perfusión para HIPEC fue 5,0 L (rango 0,7-10,0). La mediana de concentración intraperitoneal del agente quimioterápico fue de 13,3 mg/L (rango 7,0-76,0) para MMC y 156,0 mg/L (rango 91,9 - 377,6) en pacientes tratados con OXA. Las complicaciones de grado 3 o mayores ocurrieron en 23,4% (n = 75). La mediana de supervivencia global fue de 36,9 meses (rango intercuartílico 19,5-62,9). Las concentraciones de quimioterapia intraperitoneal no se asociaron con las complicaciones postoperatorias ni con la supervivencia. CONCLUSIÓN: La CRS-HIPEC se realizó con una amplia variación en las concentraciones de quimioterapia intraperitoneal que no se asociaron con las complicaciones ni con la supervivencia.

Role of diagnostic laparoscopy in patients with suspicion of colorectal peritoneal metastases to evaluate suitability for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Background: The aim of the present study was to determine the feasibility and safety of performing diagnostic laparoscopy (DLS) routinely in patients with suspicion of colorectal peritoneal metastases (PM) to evaluate suitability for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Methods: Data for consecutive patients who underwent DLS between 2012 and 2018 were extracted retrospectively from an institutional database. The primary outcome was the degree of visibility of the abdominal cavity during DLS. Good laparoscopic evaluation of the abdominal cavity was defined as visibility of at least the regions of the diaphragm, pelvis and small bowel. Secondary outcomes were reasons for perioperative exclusion for CRS + HIPEC, major postoperative complications (Clavien-Dindo grade III or above) and difference in overall survival (OS) between patients deemed suitable or unsuitable for CRS + HIPEC. Kaplan-Meier analyses were performed. Results: Some 184 patients were analysed. Good laparoscopic evaluation was possible in 138 patients (75·0 per cent), and 24 (13·0 per cent) had conversion to an open procedure. Ninety-three patients (50·5 per cent) were excluded for CRS + HIPEC, most commonly because of absence of colorectal PM (34 patients, 37 per cent) or extensive disease (Peritoneal Cancer Index 20 or above) (33 patients, 35 per cent). Major complications occurred in five patients (2·7 per cent), with no postoperative deaths. Median OS was significantly decreased in patients who were excluded due to extensive disease (14 (95 per cent c.i. 10 to 18) months) compared with patients suitable for CRS + HIPEC (36 (27 to 45) months) (P < 0·001). Conclusion: Routinely performing DLS in patients with suspicion of colorectal PM to evaluate suitability for CRS + HIPEC is feasible and safe, avoiding the morbidity of an unnecessary laparotomy in patients with extensive disease.

Antecedentes: El objetivo del presente estudio fue determinar la viabilidad y seguridad de realizar una laparoscopia diagnóstica (diagnostic laparoscopy, DLS) de rutina en pacientes con sospecha de metástasis peritoneal (peritoneal metastasis, PM) de origen colorrectal para evaluar la idoneidad para la cirugía citorreductora con quimioterapia intraperitoneal hipertérmica (cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, CRS+HIPEC). Métodos: Los datos de los pacientes consecutivos que fueron sometidos a DLS entre 2012 y 2018 se obtuvieron retrospectivamente de una base de datos institucional. La visualización de al menos las regiones de los diafragmas, pelvis e intestino delgado se definió como una correcta evaluación laparoscópica de la cavidad abdominal. Los resultados secundarios fueron las complicaciones postoperatorias mayores (Clavien­Dindo grado ≥ III), razones para la exclusión perioperatoria para CRS+HIPEC y diferencia en supervivencia global (overall survival, OS) entre pacientes que se consideraron apropiados y no apropiados para CRS+HIPEC. Se realizaron análisis de Kaplan­Meier y análisis de riesgos proporcionales. Resultados: Se analizaron 181 pacientes. En 138 pacientes (75,0%) fue posible una adecuada evaluación laparoscópica, mientras que 24 casos (13%) fueron convertidos a un procedimiento abierto. Se excluyeron 93 (50,5%) pacientes para CRS+HIPEC, más comúnmente por la ausencia de PM colorrectales (36,6%) o enfermedad extensa (37,6%). En cinco pacientes aparecieron complicaciones mayores (2,7%), sin mortalidad postoperatoria. La mediana de la OS disminuyó de forma significativa en pacientes que fueron excluidos debido a enfermedad extensa (14 meses, i.c. del 95% 10­18) en comparación con pacientes idóneos para CRS+HIPEC (35 meses, i.c. del 95% 30­40, P < 0,0001). Conclusión: La realización rutinaria de DLS en pacientes con sospecha de PM de origen colorrectal para evaluar la idoneidad de la CRS+HIPEC es viable y segura. La morbilidad de una laparotomía innecesaria puede prevenirse en pacientes con enfermedad extensa o ausencia de PM colorrectales.

Fast-light in a photorefractive crystal for gravitational wave detection.

We demonstrate superluminal light propagation using two frequency multiplexed pump beams to produce a gain doublet in a photorefractive crystal of Ce:BaTiO(3). The two gain lines are obtained by two-wave mixing between a probe field and two individual pump fields. The angular frequencies of the pumps are symmetrically tuned from the frequency of the probe. The frequency difference between the pumps corresponds to the separation of the two gain lines; as it increases, the crystal gradually converts from normal dispersion without detuning to an anomalously dispersive medium. The time advance is measured as 0.28 sec for a pulse propagating through a medium with a 2 Hz gain separation, compared to the same pulse propagating through empty space. We also demonstrate directly anomalous dispersion profile using a modified experimental configuration. Finally, we discuss how anomalous dispersion produced this way in a faster photorefractive crystal (such as SPS: Sn(2)P(2)S(6)) could be employed to enhance the sensitivity-bandwidth product of a LIGO type gravitational wave detector augmented by a White Light Cavity.