Improving the design and conduct of aquatic toxicity studies with oils based on 20 years of CROSERF experience.

Laboratory toxicity testing is a key tool used in oil spill science, spill effects assessment, and mitigation strategy decisions to minimize environmental impacts. A major consideration in oil toxicity testing is how to replicate real-world spill conditions, oil types, weathering states, receptor organisms, and modifying environmental factors under laboratory conditions. Oils and petroleum-derived products are comprised of thousands of compounds with different physicochemical and toxicological properties, and this leads to challenges in conducting and interpreting oil toxicity studies. Experimental methods used to mix oils with aqueous test media have been shown to influence the aqueous-phase hydrocarbon composition and concentrations, hydrocarbon phase distribution (i.e., dissolved phase versus in oil droplets), and the stability of oil:water solutions which, in turn, influence the bioavailability and toxicity of the oil containing media. Studies have shown that differences in experimental methods can lead to divergent test results. Therefore, it is imperative to standardize the methods used to prepare oil:water solutions in order to improve the realism and comparability of laboratory tests. The CROSERF methodology, originally published in 2005, was developed as a standardized method to prepare oil:water solutions for testing and evaluating dispersants and dispersed oil. However, it was found equally applicable for use in testing oil-derived petroleum substances. The goals of the current effort were to: (1) build upon two decades of experience to update existing CROSERF guidance for conducting aquatic toxicity tests and (2) to improve the design of laboratory toxicity studies for use in hazard evaluation and development of quantitative effects models that can then be applied in spill assessment. Key experimental design considerations discussed include species selection (standard vs field collected), test substance (single compound vs whole oil), exposure regime (static vs flow-through) and duration, exposure metrics, toxicity endpoints, and quality assurance and control.

The Challenges of Characterizing the Zooplankton Community Response Following Simulated Spills of Diluted Bitumen into Boreal Lake Limnocorrals.

We attempted to characterize zooplankton community response following spills of the unconventional crude oil, diluted bitumen (dilbit), into 10-m diameter, ~ 100 m3, ~ 1.5-m deep boreal lake limnocorrals, including two controls and seven dilbit treatments ranging from 1.5 to 180 L (1:100,000 to 1:1,000 v/v, dilbit:water). Community composition and abundances were monitored weekly to bi-weekly over three months. Total zooplankton biomass and abundance seemingly collapsed in all limnocorrals, regardless of treatment, though some rotifer species persisted. As a result, it was not possible to determine the impacts of dilbit. We theorize several potential non-oil-related reasons for the sudden community collapse - including elevated zinc levels, fish grazing pressures, and sampling biases - and provide guidance for future work using in-lake enclosures.

Rat age-related benign prostate hyperplasia is concomitant with an increase in the secretion of low ramified α-glycosydic polysaccharides.

This work analysed the expression of prostate polysaccharides in rats with age-related benign prostatic hyperplasia (BPH) for a better understanding of the possible relationship between prostate polysaccharides secretion and BPH onset. For this, prostatic glands from 1 month-old, 3 months-old, 6 months-old and 12 months-old Sprague-Dawley rats were processed in order to identify their overall polysaccharide content. Additionally, serum testosterone was also determined. One-month old rats showed significantly (P < 0.05) lower testosterone levels (0.77 ng/mL±0.12 ng/mL) compared with the other groups, which showed no significant difference among them. PAS staining showed positive polysaccharides markings in both the prostatic lumen and inside of luminal prostatic cells in all groups. Semiquantitative analysis of intraluminal PAS showed that one month-old rats had significantly (P < 0.005) lower PAS intensity when compared with all other groups (100.0 ± 0.5, arbitrary units vs. 107.3 ± 0.6, arbitrary units in 3 months-old ones), whereas 12 months-old ones showed significantly (P < 0.005) higher values when compared with all other groups (133.6 ± 3.5, arbitrary units in 12 months-old rats vs. 108.6 ± 1.4, arbitrary units in 6 months-old ones). The PAS + content practically disappeared when tissues were pre-incubated with either α-amylase or amyloglucosidase, regardless of a previous incubation with proteinase K. Incubation of prostate extracts from 12 months-old rats for 2 h with α-amylase yielded a significantly higher amount of free glucose (1.47 nmol/mg protein±0.23 nmol/mg protein vs. 0.32 nmol/mg protein±0.01 nmol/mg protein in untreated extracts). Similar results were obtained when extracts were pre-incubated with amyloglucosidase. Contrarily, pre-incubation with N-glycosidase induced a significantly (P < 0.05), much lower increase of free glucose. Pre-treatment with proteinase K did not significantly modify these results, which indicate that BPH is related to an increase in the secretion of low ramified ductal α-glycosydic polysaccharides that were not protected against lysis by any type of protein protective core. These changes seem to not be related with concomitant variations in serum testosterone levels.

Simulating diluted bitumen spills in boreal lake limnocorrals - part 2: Factors affecting the physical characteristics and submergence of diluted bitumen.

We examined the fate and behaviour of diluted bitumen (dilbit) as it weathered for 70 days in freshwater limnocorrals (10 m diameter × 1.5 m depth) installed in a boreal lake to simulate dilbit spills in a natural aquatic environment. We added seven different dilbit spill volumes, ranging from 1.5 to 180 L, resulting in oil-to-water ratios between 1:71,000 (v/v, %) and 1:500 (v/v, %). Volatile hydrocarbons in the dilbit slick decreased rapidly after the dilbit was spilled on the water's surface, and dilbit density and viscosity significantly increased (>1 g mL-1 and >5,000,000 mPa s, respectively). Dilbit sank to the bottom sediments in all treatments, and the time to sinking was positively correlated with spill volume. The lowest dilbit treatment began to sink on day 12, whereas the highest dilbit treatment sank on day 31. Dilbit submerged when its density surpassed the density of freshwater (>0.999 g mL-1), with wind, rain, and other factors contributing to dilbit sinking by promoting the break-up of the surface slick. This experiment improves our ability to predict dilbit's aquatic fate and behaviour, and its tendency to sink in a boreal lake. Our findings should be considered in future pipeline risk assessments to ensure the protection of these important aquatic systems.

Oncological impact of hypothyroidism and levothyroxine supplementation following hemithyroidectomy in patients with papillary thyroid carcinoma.

BACKGROUND: We aimed to evaluate the oncological impact of hypothyroidism and levothyroxine (LT) supplementation after hemithyroidectomy in patients with papillary thyroid carcinoma (PTC). METHODS: We retrospectively examined 401 patients who underwent hemithyroidectomy for classic PTC and who were postoperatively followed-up with ≥3 thyroid function measurements for ≥24 months. RESULTS: During 77.4 months of follow-up, 268/401 patients (66.8%) developed hypothyroidism and 19/401 patients (4.7%) showed recurrence. Recurrence rates did not differ between the euthyroidism and hypothyroidism development groups. Recurrence rates were significantly lower in the LT group than in the no-LT group, although mean postoperative thyroid-stimulating hormone (TSH) levels were not different between the two groups. Univariate and multivariate analysis showed that tumors sized >1 cm and lack of LT supplementation were significantly associated with recurrence. CONCLUSIONS: Postoperative hypothyroidism development was not a risk factor for PTC recurrence after hemithyroidectomy. Nevertheless, LT supplementation reduced recurrence risk without suppressing TSH.

Identifying the incidence of respiratory complications following diaphragmatic cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy.

INTRODUCTION: In patients with peritoneal carcinomatosis (PC), the incidence of respiratory complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is not well established. We aimed to describe the center-specific incidence and patient characteristics associated with respiratory complications following CRS and HIPEC in patients receiving treatment for PC. MATERIALS AND METHODS: We used the University Hospital of Arrixaca study database to identify patients who underwent CRS and HIPEC for PC. Patients who experienced a post-operative respiratory complication were categorized according to the National Cancer Institute-Common Terminology Criteria for Adverse Events. Multivariable regression methods were used to identify independent risk factors for developing a respiratory complication following CRS and HIPEC. RESULTS: Between 2008 and 2017, we identified 247 patients who underwent CRS and HIPEC for PC. A total of eight patients (3.2%) were categorized as having a post-operative respiratory complication. A diaphragmatic peritonectomy and a PC index of > 14 were identified as independent risk factors for developing a respiratory complication. Radiographic evidence of a pleural effusion was identified in 72 patients who had CRS of the diaphragmatic peritoneum; however, only 6 (8.3%) of these patients required pleural drainage. CONCLUSIONS: Only 3.2% of patients developed a symptomatic respiratory complication following CRS and HIPEC. A pleural effusion was identified in almost all patients requiring a diaphragmatic peritonectomy as part of their CRS; however, less than one in ten of these patients required pleural drainage. Prophylactic insertion of a pleural drainage tube is, therefore, not indicated following CRS and HIPEC.

Survival outcomes in patients aged 75 years and over with peritoneal colorectal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): multicenter study of the Spanish Group of Peritoneal Cancer Surgery (GECOP).

BACKGROUND: The attitude toward cytoreductive surgery with HIPEC in peritoneal carcinomatosis from colorectal cancer is unclear. The aim of this study is to report the perioperative outcomes after cytoreductive surgery with HIPEC in patients ≥ 75 years. METHODS: This retrospective multicenter study collected the data the Spanish Group of Peritoneal Cancer Surgery. Thirty-six patients with peritoneal carcinomatosis from colorectal cancer met the selection criteria for the study. Morbidity, mortality, disease-free and overall survival were analyzed. RESULTS: Morbidity (grade III-IV) was 17% and 2 patients died of complications related to the procedure (5.4%). Median disease-free survival (DFS) was 16 months. DFS at 1 and 3 years was 81% and 42%, respectively. Overall survival at 1 and 3 years was 96% and 75%. In the univariate analysis, preoperative comorbidities (p = 0.01), liver metastases (p = 0.02), blood transfusion (p = 0.001) and postoperative complications (p = 0.001); and in the multivariate analysis, perioperative blood transfusion (OR 2.56, 95% CI 1.95-6.24, p = 0.03) and postoperative complications (OR 3.25, 95% CI 2.35-7.56, p = 0.02) were associated with a lower overall survival. CONCLUSIONS: Age is not an absolute contraindication to perform cytoreduction surgery with HIPEC in highly selected elderly patients with colorectal peritoneal carcinomatosis.

Effectiveness of craniosacral therapy in the treatment of infantile colic. A randomized controlled trial.

OBJECTIVES: To determine the effectiveness of Craniosacral Therapy (CST) for the treatment of infantile colic. MATERIAL AND METHODS: This randomized controlled trial was conducted on 58 infants, aged 0-84 days, diagnosed with infantile colic. The babies received a 30-40 minute CST session once a week (experimental group) or no treatment (control group). Babies in the CST group received either 1, 2 or 3 CST sessions over a 14-day period. Data were collected at 4 different times over the 24-day period, day 0 (baseline), day 7, day 14 and day 24. Crying (primary outcome) and sleep (secondary outcome) were evaluated using a crying and sleep diary, and colic severity was measured using the Infant Colic Severity Questionnaire (secondary outcome). RESULTS: There was a statistically significant difference between groups (CST and control) in crying hours (F = 188.47; p < 0.0005; η2 = 0.78), sleep hours (F = 61.20; p < 0.0005, η2 = 0.54) and colic severity (F = 143.74; p < 0.0005, η2 = 0.73) across all the time points. In comparison with the control group, CST babies reported significant and clinically relevant effects in crying hours on day 7 (-2.47 h (95%CI, -2.95 to -1.99); p < 0.0005; d = 1.73), on day 14 (-3.29 h (95%CI, -3.7 to -2.8); p < 0.0005; d = 2.87) and on day 24 (-3.20 h (95%CI, -3.7 to -2.6); p < 0.0005; d = 2.54); in sleep hours on day 7 (-2.47 h (95%CI, -2.95 to -1.99); p < 0.0005; d = 1.73) on day 14 (-3.29 h (95%CI, -3.7 to -2.8); p < 0.0005; d = 2.87) and on day 24 (-3.20 h (95%CI, -3.7 to -2.6); p < 0.0005; d = 2.54). CONCLUSIONS: Craniosacral therapy appears to be effective and safe for infantile colic by reducing the number of crying hours, the colic severity and increasing the total hours of sleep.

Intense pulsed light therapy: A promising complementary treatment for dry eye disease. / Terapia de luz pulsada intensa regulada: un tratamiento complementario prometedor para la enfermedad de ojo seco.

OBJECTIVE: To propose the Intense Pulsed Light (IPL) therapy as a helpful supplementary treatment in patients with dry eye disease. MATERIAL AND METHODS: Retrospective cross sectional design. Medical records of patients in whom dry eye disease symptoms were not satisfactorily controlled with medical therapy alone and who underwent additional IPL with at least three sessions completed. Data were analyzed before therapy and 3weeks after its completion to asses improvement. Determination of symptoms, through a visual analog scale; tear film stability, through tear Break Up Time (tBUT); measurement of tear secretion, through Schirmer Test; and ocular surface staining with Van Bijsterveld score were evaluated. SPSS software and nonparametric analysis of repeated measures were used. The study was approved by the ethics committee. RESULTS: 50 eyes from 25 subjects were reviewed. There were 9 males (36%) and 16 females (64%), with a median age of 59years (IQR 52-64). The median of the symptoms scale was 8 (IQR 8-9) and 3 (IQR 2-4) before and after the therapy respectively (P<.05). The median of BUT was 4 (IQR 3-5) and 10 (IQR 8-11), Schirmer test was 13 (IQR 12-15) and 15 (IQR 13-20), and Van Bijsterveld score was 3 (RIC 3-4) and 2 (IQR 2-3) before and after the therapy respectively (P<.05, for all measurements). CONCLUSION: IPL treatment has excellent results regarding both: dry eye disease symptoms improvement and in office objective tests such as tBUT, Schirmer test and Van Bijsterveld score; IPL could be considered as an effective adjunct for dry eye disease.

Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model.

BACKGROUND: Paclitaxel has been used frequently for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC are associated with high rates of morbidity being anastomotic dehiscence one of the most frequent. The objective of this study is to quantify the effect of Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model. METHODS: After left colon resection and anastomosis, animals were randomized into four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four, animals' peritoneal cavities were examined macroscopically, colon anastomosis burst pressures measured and specimens analyzed histologically. RESULTS: Thirty-nine animals were randomized and 36 were included in the analysis. H group presented the highest burst pressure 105.11 ± 22.9 mmHg, which was 27% higher than C (77.89 ± 27.6 mmHg). On the other hand, HP presented the lowest burst pressure 64 ± 26 mmHg, 16% lower than C group and 39% lower than H, being this latter difference statistically significant (p = 0.004). There were no significant differences regarding weight loss, adhesion scores, perianastomotic abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis, and collagen among groups). CONCLUSION: Strength of colonic anastomosis was improved by isolated hyperthermia and negatively affected by Paclitaxel-based HIPEC.

Short term protein supplementation during a long interval prostaglandin-based protocol for timed AI in sheep.

The aim of this study was to evaluate the reproductive impact of a short-term protein supplementation on a long interval prostaglandin-based protocol (two PG injections 15 d apart; PG15) for timed artificial insemination in sheep. During the breeding season, 437 multiparous Merino ewes grazing native pastures (forage allowance of 6 kg of dry matter/100 kg of live weight; crude protein: 10.8%, metabolic energy: 2.1 Mcal/kg of dry matter) were selected. Ewes were allocated, according to body condition score (3.2 ± 0.2) and body weight (40.6 ± 4.9 kg, mean ± SD), to a 2 × 2 factorial design: type of estrus -spontaneous estrus (SE) or induced with PG15 (PG15)-, and supplementation (yes or no) before insemination (+FF; soybean meal at Days -10 to -3; crude protein: 51.9%, metabolic energy: 2.8 Mcal/kg of dry matter; average consumption 0.9% live weight/ewe/day of dry matter). All ewes were cervically artificial inseminated (Day -2 to -3 in SE ewes at estrus detection; Day 0 = timed artificial insemination in PG15 ewes). Ovulation rate on Day 7, non-return to service on Day 23, conception, fertility, prolificacy and fecundity on Day 60 were evaluated. Ovulation rate (1.17 ± 0.40 vs. 1.06 ± 0.25), non-return to service at Day 23 (81.7 vs. 64.2%), conception (78.8 vs. 61.5%), fertility (75.2 vs. 61.5%) and fecundity (0.77 vs. 0.62) were higher in ewes from SE than PG15 group (P < 0.05). However, no differences were observed in prolificacy (1.02 ± 0.16 vs. 1.01 ± 0,12) between groups (P > 0.05). Protein supplementation increased ovulation rate (1.30 ± 0.45 vs. 1.17 ± 0.40), prolificacy (1.18 ± 0.39 vs. 1.02 ± 0.16) and fecundity (0.94 vs. 0.77%; P < 0.05), but not non-return to service on Day 23 (83.8 vs. 81.7%), conception (82.9 vs. 78.8%) or fertility (79.1 vs. 75.2%; P > 0.05) in SE group. The supplement feed to PG15 ewes increased ovulation rate (1.35 ± 0.45 vs. 1.06 ± 0.25), prolificacy (1.25 ± 0.43 vs. 1.01 ± 0.12) and fecundity (0.79 vs. 0.62%; P < 0.05) to levels comparable to SE + FF ewes (P > 0.05). The magnitude of the increase in ovulation rate in PG15 was greater than in the SE group (27 vs. 11%; P < 0.05). However, non-return to service on Day 23 (65.1 vs. 64.2%), conception (63.3 vs 61.5%), and fertility rate (63.3 vs. 61.5%; P < 0.05) remained similar in PG15 supplemented or not supplemented ewes. In conclusion, a short-term protein supplementation before cervical time artificial insemination improved the reproductive performance of ewes synchronized with the PG15 protocol to levels comparable to the SE group.

Prevención y diagnóstico precoz de osteoporosis infantil: ¿estamos haciendo lo correcto? / Prevention and early diagnosis of childhood osteoporosis: are we doing the right thing?

Objetivos: Evaluar la prevención, el diagnóstico precoz y la formación recibida de la osteoporosis en la Pediatría de nuestro medio. Material y métodos: Encuesta dirigida a facultativos de Pediatría de Atención Primaria (AP) y Atención Especializada (AE) que valora su actividad en prevención, detección y formación recibida en osteoporosis, y que fue difundida a través de las sociedades científicas pertinentes. Resultados: Participaron 420 pediatras (324 de AP y 96 de AE). El 93,5% de los pediatras de AP y el 89,6% de los de AE valoraban la actividad física de los pacientes; el 85,19% y 35,4% de ellos, respectivamente, la ingesta de lácteos. El 45,68% de AP y el 70,2% de AE suplementaban con calcio y vitamina D ante aporte nutricional bajo, realizándoles seguimiento el 39,2% de AP y el 47,2% de AE. El 39,6% de pediatras de AE solicitaba densitometría ósea ante enfermedad o tratamiento de riesgo, y el 47,9% medía los niveles de 25-OH-vitamina D. El 25,93% de AP y el 45,3% de AE preguntaban por la existencia de fracturas, el 90,4% y 96,8% valoraban el mecanismo etiopatogénico. El 40% de AP y el 86,2% de AE solicitaban una densitometría ósea o derivaban al especialista ante fracturas por traumatismos de baja energía, con criterios específicos en el 13,7% y 5,86%, respectivamente. El 92% de AP y el 82,3% de AE no habían recibido formación reciente en osteoporosis infantil. Conclusión: La detección, los circuitos de derivación y la formación de los pediatras respecto a la salud ósea en nuestro país es mejorable. Optimizar estos aspectos es fundamental para favorecer el pico de masa ósea en nuestra población

Objectives: To assess prevention, early diagnosis and training received regarding osteoporosis among the pediatrics professionals in our area. Material and methods: Survey directed to physicians of pediatricians of Primary Care (PC) and Specialized Care (SC) in order to evaluate their activity in prevention, detection and training received in osteoporosis. The survey was disseminated through the relevant scientific societies. Results: 420 pediatricians participated (324 from PC and 96 from SC). 93.5% of PC pediatricians and 89.6% of SC pediatricians valued the physical activity of the patients; 85.19% and 35.4% of them, respectively, the intake of dairy products. 45.68% of PC and 70.2% of SC recommended calcium and vitamin D supplements in the case of low nutritional intake, whereas 39.2% of PC and 47.2% of SC favored follow-up. 39.6% of SC pediatricians requested bone densitometry for this disease or risk treatment, and 47.9% measured the levels of 25-OH-vitamin D. 25.93% of PC and 45.3% of SC asked about the existence of fractures, 90.4% and 96.8% requested etiopathogenic mechanism. 40% of PC and 86.2% of SC requested a bone densitometry or referred to the specialist for fractures due to low trauma energy, with specific criteria in 13.7% and 5.86%, respectively. 92% of PC and 82.3% of SC had not received recent training in childhood osteoporosis. Conclusion: Detection, derivation circuits and the training of pediatricians regarding bone health in our country can be improved. Optimizing these aspects is essential to favor the peak of bone mass in our population

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. METHODS: This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. RESULTS: Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). CONCLUSION: Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. TRIAL REGISTRATION: researchregistry1587 (retrospectively registered).

Effectiveness and failures of a fast track protocol after cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal surface malignancies.

BACKGROUND: The aim of this study was to analyze the results short term perioperative of patients with peritoneal surface malignancies undergoing cytoreduction with peritonectomy and HIPEC under a controlled fast track protocol and evaluate the factors related to the failure of implementation of the protocol. PATIENTS AND METHOD: We prospectively analyzed a consecutive series of patients (N = 156) with peritoneal surface malignancies treated by cytoreductive surgery with peritonectomy procedures and HIPEC from September 2008 until December 2014, in whom a fast track protocol was implemented. We limited the protocol to patients who had optimal cytoreduction, HIPEC administration, and not more than one digestive anastomosis. All patients signed informed consent for surgery and the perioperative multimodal recovery program. RESULTS: A total of 156 consecutive patients, with a median age of 57 years were included in the study. Median PCI was 8 (IQR: 0-32). Morbidity rate (Clavien-Dindo) was 25.6%, with a major morbidity rate (Clavien-Dindo III-IV) of 11.5%. One hundred and three patients (66%) completed the protocol. Multivariate analysis identified the following independent factors, which were related to failure of the protocol: age over 57 years (OR = 3.159, 95% CI: 1.286-7.758, p < 0.05), the realization of a digestive anastomosis (OR = 3.834, 95% CI: 1.562-9.414, p < 0.005) and occurrence of postoperative complications (OR = 18.704, 95% CI: 6.888-50.790, p < 0.001) CONCLUSIONS: Our data support the idea that in selected patients undergoing cytoreductive surgery and HIPEC, with a low PCI and especially no necessity to perform a digestive anastomosis, the implementation of a fast track program is feasible.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients. A systematic literature review.

The objective of this review was to evaluate morbidity, mortality and survival outcomes of elderly patients with peritoneal carcinomatosis. A systematic literature search and standardized data collection of primary research publications until June 2016 on morbidity, mortality and survival outcomes in adults aged 65 and older with peritoneal carcinomatosis treated with cytoreduction and HIPEC was performed, using PubMed, EMBASE, Scopus, ClinicalTrials.gov and Cochrane. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Nine studies were included. Severe morbidity of all elderly patients ranges from 17% to 56% in centers with high experience. In-hospital and 30-day mortality ranges from 0% to 8%. In only two studies were the differences in morbidity and mortality statistically significant related to the control group. However, older adults undergoing cytoreductive surgery and HIPEC consistently had lower survival rates across all study settings and procedure types than younger individuals. In studies that stratified for elderly patients, PCI, completeness of cytoreduction, tumor histology and albumin levels were predictive factors of survival. None of these studies examined quality of life, which precludes including functional outcomes in this review. Differences in exposures, outcomes, and data presented in the studies did not allow for quantification of association using a meta analysis.

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?

OBJETIVE: To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival. PATIENTS: We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m(2)O or Cisplatin (doses of 75 mg/m(2)) were used. RESULTS: A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12-96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction (HR: 6.54, 95% CI 2.98-10.17, p < 0.01) and PCI >11 (HR: 2.15, 95% CI 1.42-6.68, p < 0.05) were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis. CONCLUSION: HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.

Morbidity and mortality outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients aged 75 years and over: Spanish group of peritoneal cancer surgery (GECOP) multicenter study.

BACKGROUND: The aim of this study is to report the perioperative outcomes of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in patients ≥75 years from a Spanish multi-institutional experience. METHODS: This multi-institutional retrospectively analyzed a prospectively collected clinical data from 10 Spanish hospitals that are part of the Spanish Group Peritoneal Cancer Surgery (GECOP). We assessed postoperative morbidity rates and performed univariate and multivariate analyses of factors associated with overall (grade I-IV) and major (grade III-IV) postoperative morbidity. RESULTS: A total of 85 patients aged ≥75 years were included. Forty six postoperative adverse events were detected in 37 patients (43.5%). Twenty five complications in 20 patients (23.5%) were mild (grade I-II) and 16 complications in 12 patients (14.1%) were moderate-severe (grade III-IV). Five patients died in the first 90 days after the procedure (5.9%). After multivariate analysis, independent factors associated with postoperative complications were: PCI> 12 (OR: 4.14, 95% CI 1.22-14.12, p = 0.043) and the need for perioperative blood transfusion (OR: 14.91, 95% CI 3.87-57.46, p < 0.001). Regarding grade III-IV complications, after multivariate analysis, the presence of preoperative albumin levels <3.5 mgr/dl (OR: 9.15, 95% CI 1.38-60.57, p = 0.017), need for diaphragmatic peritonectomy procedures (OR: 11.32, 95% CI 1.40-91.32, p = 0.023) and perioperative blood transfusion (OR: 8.58, 95% CI 1.44-51.16, p = 0.018) were independent factors. CONCLUSIONS: Cytoreductive surgery and performing HIPEC by experienced groups in selected patients aged ≥75 years can be performed with morbidity and mortality similar to that described in the literature.

HIPEC in ovarian cancer: treatment of a new era or is it the end of the pipeline?

Ovarian cancer is the leading cause of death from gynecological cancer in western countries. The absence of an effective screening program as well as specific symptoms, makes the diagnosis difficult and often made in advanced stages of the disease, in the presence of peritoneal dissemination. The complete cytoreduction of the disease and tumor sensitivity to systemic chemotherapy based on platinums, are the two main prognostic factors. However in patients with complete cytoreduction the recurrence rate is high. The microscopic component of the disease at the end of the cytoreduction is responsible for these recurrences and the use of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in the same time of surgery has been proposed as a reasonable therapeutic option for treatment. However, the absence of sufficient levels of scientific evidence to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination does not allow a general recommendation outside of clinical trials. The main objective of this study is to identify the strengths and weaknesses of HIPEC treatment in ovarian cancer with peritoneal dissemination, and to know which points can be improved in the future.

The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction.

BACKGROUND: We analyzed the role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) on the microscopic component of the disease in patients with a first recurrence of platinum-sensitive ovarian cancer after complete cytoreduction (CCR). PATIENTS AND METHODS: We analyzed the data of 54 patients who were operated on between January 2001 and July 2012 with the diagnosis of platinum-sensitive recurrent ovarian cancer. In all patients, it was possible to achieve a CCR. Patients were divided into two groups: group I (cytoreduction alone) consisted of 22 surgical patients and group II (cytoreduction and HIPEC) consisted of 32 patients. RESULTS: There were no significant differences in any of the preoperative variables studied. After a multivariate analysis of factors identified in the univariate analysis, only the presence of tumors with undifferentiated histology (hazard ratio 2.57; 95% CI 1.21-5.46; p < 0.05) was an independent factor associated with a reduced disease-free survival. The 1- and 3-year disease-free survival was 77 and 23% in patients from group I and 77 and 45% in patients from group II, respectively, with a tendency, but no significant differences (p = 0.078). There was no significant difference in postoperative morbidity between the two groups. CONCLUSIONS: The administration of HIPEC in patients in whom it is possible to achieve a CCR of the disease has not increased postoperative morbidity and mortality rates in our center. HIPEC with paclitaxel is effective in the treatment of microscopic disease in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction, although with no statistically significant difference.

Protein supplementation during a short-interval prostaglandin-based protocol for timed AI in sheep.

The aim of this experiment was to improve the reproductive performance of a short-interval prostaglandin (PG)-based protocol for timed artificial insemination in sheep, using a short-term nutritional treatment. During the breeding season (March-April), 132 multiparous and 61 nulliparous Corriedale ewes grazing natural pastures (600 kg DM/ha, 8.5% CP), were allocated to two groups: 1, Control group (n=100) two injections of D-Cloprostenol (75 µg per dose, 7d apart: Synchrovine(®) protocol); and 2, Supplemented group (n=93) ewes in which stage of the oestrous cycle was synchronised with Synchrovine(®) protocol plus focus feeding of a protein supplement (33.8% CP) between PG doses (Day -7 to -2). Cervical AI was performed at fixed time (Day 0), 46 ± 1.0 h after the second PG injection using 150 million sperm per ewe. Ovulation rate (Day 10), pregnancy rate, prolificacy and fecundity at Day 69 were evaluated by ultrasonography. Ovulation rate at Day 10 (1.20 ± 0.05 vs. 1.22 ± 0.05), pregnancy (46 ± 0.05 vs. 56 ± 0.05), prolificacy (1.09 ± 0.04 vs. 1.06 ± 0.05), and fecundity (0.49 ± 0.06 vs. 0.59 ± 0.06) at Day 69, were similar between groups (P>0.05; Control and Supplemented group respectively). It is concluded that focus feeding for 6d with protein supplementation during a short-interval PG-based protocol (Synchrovine(®)) did not improve the reproductive outcome associated with this protocol.