Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma: Canadian practices and outcomes.

INTRODUCTION: Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS: A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS: A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION: CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.

Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec.

BACKGROUND: The 21-gene Breast Recurrence Score (RS) assay, "the assay", has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada. PATIENTS AND METHODS: We conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician's recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician's expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results. RESULTS: For the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up. CONCLUSION: Altogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.

Tumor bed extending to margins in breast cancer specimens after neoadjuvant chemotherapy: Incidence and clinical significance.

BACKGROUND: Pathologic examination of post-neoadjuvant chemotherapy (NAC) breast surgical specimens includes assessment of margins. It has been recommended that tumor bed (TB) changes extending to margins should be documented; however, its' incidence and clinical significance have not yet been established. The aim of our study was to gather prognostic data on this histological finding. DESIGN: We retrospectively identified all cases where TB was reported at margin. Cases where margins were also positive for invasive carcinoma or DCIS were excluded. RESULTS: From 2016 to 2019, 115 cases of NAC treated breast cancers were identified with 21 having at least one margin positive for TB after initial surgery (incidence of 18.3 %). Five cases were estrogen receptor (ER)-/HER2-, 9 were HER2+ and 7 were ER+/HER2-. Nineteen patients underwent partial mastectomy and 2 underwent total mastectomy. Nine patients had a pathological complete response (pCR).Ten cases had more than one positive margin for TB. None of the 21 patients underwent a second surgery for margin re-excision. Twenty patients received adjuvant therapy. With an average follow-up of 28.1 months, there has been one local recurrence. Four other patients developed metastatic disease, one of which died of the disease. The rates of locoregional and distant recurrence and mortality were statistically similar to those from patients whose margins were negative for TB. CONCLUSIONS: Our results suggest low risk of local recurrence when a positive margin for TB is not re-excised. Further data and follow-up will be needed to confirm the adequacy of conservative management in this setting.

Carboplatin Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Stage IVB Endometrial Cancer.

BACKGROUND: Endometrial cancer presenting with peritoneal metastases carries a poor prognosis. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to the surgical management of these patients has been studied in recent years, but only with cisplatin. CASES: This is a series of 3 patients presenting with endometrial cancer and synchronous peritoneal metastases who underwent cytoreductive surgery and carboplatin HIPEC as primary treatment. Complete cytoreductive surgery was achieved for each patient. No grade 3-5 complications were observed. Two patients died at 12 and 18 months, respectively, and 1 patient was alive with disease at 29 months. CONCLUSION: This case series suggests that the addition of carboplatin HIPEC to the surgical management of peritoneal metastases from endometrial cancer is safe as primary treatment. However, long-term survival remains poor.

Two-step cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei with high peritoneal carcinomatosis index.

BACKGROUND: Complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only curative treatment for pseudomyxoma peritonei (PMP) arising from the appendix. High peritoneal carcinomatosis index (PCI) is associated with an increased risk of surgical complications. The objective of this study was to present the results of a planned two-step surgical strategy to decrease postoperative morbidity and improve resectability of patients with very high PCI. METHODS: All consecutive patients who underwent a planned two-step surgical approach for PMP between January 2012 and March 2020 were retrospectively included. This approach was offered for patients with low-grade PMP with PCI > 28 for which feasibility of a complete CRS in one operation was uncertain. The first surgery included a complete CRS of the inframesocolic compartment and omentectomy. HIPEC was delivered at the second surgery, after complete CRS of the supramesocolic compartment. Postoperative morbidity was assessed using the Clavien-Dindo classification and survival results were also collected. RESULTS: Eight patients underwent the two-step approach. The median PCI was 33 (29-39) and the median time between the two procedures was 111 days (90-212 days). One patient was deemed unresectable at the second surgery. The rate of major morbidity was 0% for the first step and 25% for the second step, with no mortality. Median follow-up was 53.8 months (3-73 months). CONCLUSION: A two-step surgical management for low-grade PMP patients with very high PCI is safe and feasible, with acceptable postoperative morbidity and no compromise on oncological outcomes.

Self-directed learning by video as a means to improve technical skills in surgery residents: a randomized controlled trial.

BACKGROUND: With their demanding schedules, surgical residents have limited time to practice techniques. The aim is to evaluate the pedagogic model of self-directed learning using video in surgery residents. METHODS: Informed consent was obtained from all the participants. A randomized controlled trial was conducted in 2018 at Hôpital Maisonneuve-Rosemont (University of Montreal). Participants were general surgery residents. There were 27 eligible residents; 22 completed the study. They were filmed performing an intestinal anastomosis on cadaveric pig bowel. The self-directed learning by video (SDL-V) group was given an expert video, which demonstrated the technique performed by an experienced surgeon. The control group continued with their regular duties. Three weeks later, participants performed a second filmed anastomosis. Two attending surgeons evaluated the residents' filmed anastomosis using the Objective Structured Assessment of Technical Skills scale. After their second anastomosis, all participants had access to the expert video and completed a survey. RESULTS: Score did not differ significantly between groups during the first (control: 23.6 (4.5) vs. SDL-V: 23.9 (4.5), p = 0.99, presented as mean (SD)) or second filmed anastomosis procedure (control: 27.1 (3.9) vs. SDL-V: 29.6 (3.4) p = 0.28). Both groups improved significantly from pre- to post-intervention (mean difference between the two anastomosis procedure with 95% CI for control: 3.5, [1.1; 5.9] and for SDL-V: 5.8, [3.4: 8.2]). Correlation between the evaluators for score was moderate (r = 0.6, 95% CI: [0.3: 0.8]). The pass/fail global evaluation exhibited poor inter-rater reliability (Kappa: 0.105, 95% CI: [- 0.2:0.4]). On the survey, all participants wanted more expert-made videos of specific surgical techniques. CONCLUSIONS: Despite a higher final OSATS score for the intervention group, self-directed learning by video failed to produce a statistically significant difference on the overall OSATS scores between the two groups in this small cohort.

Morbidity associated with the use of oxaliplatin versus mitomycin C in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal or appendiceal origin: a multi-institutional comparative study.

Background: The raw costs of mitomycin C (MMC) and oxaliplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) differ substantially. We sought to compare the morbidity and toxicity profiles associated with the use of oxaliplatin and MMC in patients undergoing cytoreductive surgery (CRS) and HIPEC for peritoneal carcinomatosis (PC) of colorectal or appendiceal origin, to evaluate whether the costeffectiveness of these 2 agents should dictate drug choice. Methods: We conducted a retrospective multi-institutional study of all patients with PC of colorectal or appendiceal origin treated with CRS-HIPEC using MMC or oxaliplatin from 2010 to 2015. Demographic, perioperative, morbidity, toxicity and cost data were compared between the 2 treatment groups and between cancer-origin subgroups. Results: Forty-two patients treated with MMC and 76 treated with oxaliplatin were included in the study. Baseline demographic and tumour characteristics were comparable in the 2 groups, except that the patients treated with MMC had higher Charlson Comorbidity Index scores. The MMC group had a higher rate of cancer of colorectal origin (76.2% v. 57.9%, p = 0.047) and longer operative times (553 v. 320 min, p < 0.001). In the subgroup of patients whose cancer was of colorectal origin, patients treated with MMC had a higher transfusion rate (50.0% v. 28.6%, p = 0.023) and lower postoperative baseline hemoglobin level (100 v. 119 g/L, p = 0.002) than those treated with oxaliplatin. There was no difference in hematologic toxicity scores after controlling for postoperative anemia. There was no difference in the rates of major complications and 90-day mortality. However, MMC was less costly than oxaliplatin ($724 v. $8928). Conclusion: MMC and oxaliplatin are both suitable agents for HIPEC and are associated with comparable morbidity and toxicity profiles, regardless of cancer origin. Thus, we propose that cost-effectiveness should ultimately dictate drug selection.

Contexte: Les coûts bruts de la mitomycine C (MMC) et de l'oxaliplatine pour la chimiothérapie hyperthermique intrapéritonéale (CHIP) sont très différents. Nous avons voulu comparer la morbidité et la toxicité associées à l'oxaliplatine et à la MMC chez les patients subissant une chirurgie de réduction tumorale (CRT) et une CHIP pour une carcinomatose péritonéale (CP) d'origine colorectale ou appendiculaire afin d'évaluer si le choix des professionnels de la santé devrait reposer sur le rapport coût­efficacité de ces médicaments. Méthodes: Nous avons mené une étude multicentrique rétrospective sur tous les patients qui, entre 2010 et 2015, présentaient une CP d'origine colorectale ou appendiculaire et ont subi une CRT ainsi qu'une CHIP à la MMC ou à l'oxaliplatine. Les données relatives aux caractéristiques démographiques, aux résultats périopératoires, à la morbidité, à la toxicité et aux coûts ont été comparées entre les 2 groupes de traitement et entre les sous-groupes formés en fonction de l'origine du cancer. Résultats: Au total, 42 patients traités à la MMC et 76 patients traités à l'oxaliplatine ont été inclus dans l'étude. Les caractéristiques démographiques et tumorales des 2 groupes avant le traitement étaient semblables, à l'exception de l'indice de comorbidité de Charlson, qui était plus élevé dans le groupe MMC. Le groupe MMC présentait un taux plus important de cancer d'origine colorectale (76,2 % c. 57,9 %; p = 0,047), de même qu'un temps opératoire plus long (553 min c. 320 min; p < 0,001). En ce qui concerne le sous-groupe de patients atteints d'un cancer d'origine colorectale, les personnes traitées à la MMC affichaient un taux de transfusion plus élevé (50,0 % c. 28,6 %; p = 0,023) et un taux d'hémoglobine postopératoire de référence plus bas (100 g/L c. 119 g/L; p = 0,002) que celles traitées à l'oxaliplatine. Une fois l'anémie postopératoire prise en compte, aucune différence n'a été observée quant à la toxicité hématologique. Les taux de complications majeures et de mortalité à 90 jours étaient aussi comparables. La MMC coûtait toutefois moins cher que l'oxaliplatine (724 $ c. 8928 $). Conclusion: La MMC et l'oxaliplatine conviennent à la CHIP, et la morbidité et la toxicité qui y sont associées sont comparables, quelle que soit l'origine du cancer. Nous proposons donc que le choix du médicament à utiliser repose sur le rapport coût­efficacité.

A rare case of recurrent epidermoid anal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy-case report.

BACKGROUND: Anal cancer is a rare cancer with chemoradiation being the mainstay of treatment for locoregional presentation. In North America, the most common subtype is anal squamous cell carcinoma (epidermoid). A surgical approach is considered for persistent or recurrent anal disease and systemic chemotherapy for metastatic disease. We are presenting a unique case of recurrent anal cancer with isolated peritoneal malignancy, an oligometastatic state which is rare in itself. It was treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There are currently no clear guidelines for the aforementioned presentation. The discussion drew on the feasibility and safety of this approach. CASE PRESENTATION: A 68-year-old woman diagnosed with an epidermoid anal cancer (stage 3B) was initially treated with chemoradiation therapy (Standard Nigro Protocol) in 2014. At the 5-year mark post-treatment, she was diagnosed with a recurrent anal epidermoid cancer in the form of isolated peritoneal carcinomatosis proven by biopsy. After declining systemic chemotherapy, she underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C©. Peritoneal carcinomatosis index was evaluated at 10, and intraoperative frozen sections were positive for carcinoma of epidermoid origin compatible with anal cancer. A completeness of cytoreduction score of 0 was achieved during the cytoreductive surgery, and her hospital course was unremarkable. She remains disease-free 12 months later. CONCLUSIONS: To our knowledge, this is the first case reporting the disease presentation of anal cancer with oligometastatic dissemination to the peritoneum. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were performed. Thus far, this approach seems to be a safe and feasible option for short-term control of the disease.

Evaluation of repeat cytoreductive surgery and heated intraperitoneal chemotherapy for patients with recurrent peritoneal carcinomatosis from appendiceal and colorectal cancers: a multicentre Canadian study

Background: Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin. Methods: Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery. Results: Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III­IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months. Conclusion: Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.

Contexte: Les récurrences péritonéales après une chirurgie cytoréductrice (CCR) et une chimiothérapie hyperthermique intrapéritonéale (CHIP) pour les cancers de l'appendice et colorectaux sont fréquentes. Cette étude visait à évaluer l'innocuité, la faisabilité technique et les résultats périopératoires et à long terme d'une reprise de CCR/CHIP chez les patients qui présentent une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice. Méthodes: Des données ont été recueillies sur des patients traités entre 2000 et 2016 pour une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice par CCR/CHIP dans 2 centres spécialisés. On a tenu compte des données démographiques, des détails des interventions, ainsi que de la morbidité et de la survie. Des analyses ont permis de comparer les premières et deuxièmes CCR/CHIP pour évaluer l'innocuité et l'efficacité des chirurgies répétées. Résultats: De tous les patients soumis à des CCR/CHIP dans les 2 centres, 37 ont subi l'intervention de nouveau. Le temps opératoire a été similaire pour les premières et les deuxièmes chirurgies (412,1 c. 412,5 min, p = 0,74), mais les patients présentaient un score de carcinomatose péritonéale beaucoup plus bas lors de la deuxième chirurgie (21,8 pour la première intervention c. 9,53 pour la seconde, p < 0,001) et des pertes sanguines significativement moindres (1762 mL pour la première intervention c. 790 mL pour la seconde, p = 0,001). On a noté une diminution non significative des complications de grades III­IV et on n'a déploré aucune mortalité à 30 jours en lien avec la reprise de l'intervention. Pour les patients atteints d'un cancer colorectal, la survie médiane sans maladie a été de 9,6 mois et la survie médiane globale a été de 40 mois. Pour les patients atteints d'un cancer de l'appendice, la survie médiane sans maladie a été de 15 mois et la survie médiane globale a été de 64,4 mois. Conclusion: La reprise des CCR/CHIP pour les récurrences de carcinomatose péritonéale ayant leur origine au niveau colorectal ou de l'appendice est sécuritaire chez les patients soigneusement sélectionnés, sans accroissement de la morbidité ou de la mortalité, et elles sont associées à une survie à long terme significative, particulièrement chez les patients ayant un cancer de l'appendice. Ces résultats appuient la reprise des CCR/CHIP chez ces patients.

Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli.

BACKGROUND: The Pain Monitoring Device (PMD) monitor (Medasense Biometrics Ltd., Ramat Gan, Israel) uses the Nociception Level (NOL) index, a multiple parameter-derived index that has recently shown a good sensitivity and specificity to detect noxious stimuli. The aim of this study was to assess the latest version of the device (PMD200TM) on variations of the NOL response after standardized tetanic stimuli to study the correlation between remifentanil doses and NOL. METHODS: Data from 26 patients undergoing midline laparotomy and receiving a desflurane-remifentanil-based anesthetic coupled with low thoracic epidural analgesia were analyzed. A standardized tetanic stimulus was applied to the forearm of the patients at different remifentanil infusion rates. The primary aim was to evaluate the correlation between post-tetanic stimulation NOL values from the PMD200 and remifentanil doses. The NOL index variations after experimental and clinical stimuli were also compared with heart rate (HR), mean arterial pressure (MAP), and Bispectral Index™ (BIS). RESULTS: A correlation between post-tetanic stimulation NOL values and remifentanil doses was found (r = -0.56; 95% confidence interval [CI], -0.70 to -0.44; P < 0.001). The NOL discriminated noxious from non-noxious states with the maximal Youden's index value of the NOL receiver operating characteristic (ROC) curve showing a specificity of 88% (95% CI, 69.0 to 100) and sensitivity of 79.1% (95% CI, 56.2 to 95.5). The area under the NOL ROC curve (AUC, 0.9; 95% CI, 0.84 to 0.95) was significantly different from the other variables (P < 0.001 vs HR; P < 0.001 vs MAP; P < 0.001 vs BIS). CONCLUSIONS: The NOL value after noxious stimulus decreased with incremental remifentanil doses, showing a significant inverse correlation between the NOL index and opioid doses. The sensitivity and specificity of NOL to discriminate between noxious and non-noxious stimuli suggests its interesting potential as a monitor of nociception intensity during anesthesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02884778); 27 July, 2016.

Peritoneal carcinomatosis index predicts survival in colorectal patients undergoing HIPEC using oxaliplatin: a retrospective single-arm cohort study.

BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancer is associated with poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for patients with colorectal peritoneal carcinomatosis. However, standardization of HIPEC protocols, including which chemotherapeutic agent to use, is lacking in the literature. Therefore, we sought to report survival outcomes from colorectal cancer patients undergoing CRS/oxaliplatin-based HIPEC at our institution over the last 10 years. METHODS: Colorectal PC patients treated with CRS/oxaliplatin-based HIPEC 2004-2015 were included. Demographic, clinical, and oncologic data were abstracted from the medical record. Overall (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Univariate/multivariate Cox regression analysis was done. RESULTS: Laparotomy was performed in 113 patients for colorectal PC; 91 completed a curative intent CRS/HIPEC. At 3 and 5 years, OS for the CRS/HIPEC cohort was 75% and 55%, and DFS was 50% and 25%, respectively. On multivariate analysis, incremental increases in peritoneal carcinomatosis index (PCI) were associated with worse OS (p = 0.0001) and DFS (p = 0.0001). Grade III/IV complications were also associated with worse OS. CONCLUSIONS: A standardized regimen of CRS and oxaliplatin-based HIPEC for colorectal PC is effective with favorable OS and DFS and acceptable complication rates.

Comparison of open and closed abdomen techniques for the delivery of intraperitoneal pemetrexed using a murine model.

BACKGROUND AND OBJECTIVES: Pemetrexed is an appealing agent to use for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the optimal method of pemetrexed delivery still remains undefined. Using a murine model, we compared the use of open and closed abdomen techniques on the absorption of intraperitoneal (IP) pemetrexed in different compartments. METHODS: Eleven Sprague-Dawley rats were submitted to a fixed dose of IP pemetrexed (1000 mg/m2 ) at a perfusion temperature of 40°C during 25 min according to two techniques: open and closed. At the end of perfusion, samples in different compartments were harvested and the concentrations of pemetrexed were measured by high performance liquid chromatography. RESULTS: Absorption of IP pemetrexed in portal and systemic blood was significantly higher using the open compared to the closed abdomen technique (93.17 vs 52.50 µg/mL, P < 0.001) and (76.26 vs 51.65 µg/mL, P < 0.001), respectively. No difference was found between the two techniques on the peritoneal tissue concentration of pemetrexed (18.07 vs 19.17 µg/g, P = 0.51). CONCLUSION: Peritoneal absorption of pemetrexed is not modified by the use of either technique. However, systemic concentrations of pemetrexed increased using the open technique, suggesting it could increase systemic toxicity.

Opioid prescribing and dispensing: Experiences and perspectives from a survey of community pharmacists practising in the province of Quebec.

BACKGROUND: Canada leads in opioid prescription and consumption rates, and this has resulted in high levels of opioid-related morbidity and mortality. Pharmacists' input could contribute significantly to understanding the disadvantages of opioid prescribing and dispensing and improving the service. This study aimed to examine the experiences of community pharmacists in relation to opioid prescribing and dispensing, with a focus on optimizing collaboration and communication. METHODS: An online survey was performed among pharmacists from the province of Quebec, Canada, in 2016. Pharmacists were eligible if registered and working in community pharmacies. RESULTS: In all, 542 questionnaires were analyzed (participation rate of 8.1%). Pharmacotherapy-related problems were reported in at least 50% of opioid prescriptions: additional drug(s) required (reported by 30% of pharmacists), interaction(s) between opioid(s) and other drug(s) (16%), physician did not meet the general issuing standards for opioid prescriptions (26%) and patient had mild to moderate pain that was easily managed by a nonopioid analgesic (20%). Half of the patients were reported as requesting anticipated refills, possibly indicating abuse or poor pain control. Most pharmacists (89.6%) reported needing to contact physicians in 1 to 3 out of 10 opioid prescriptions, but many pharmacists (71.8%, often or very often) reported difficulties communicating with physicians. CONCLUSIONS: Pharmacists' observations of pharmacotherapy-related problems and patients' unusual behaviours reveal a significant number of issues related to opioid prescribing and dispensing in an outpatient setting. Improved collaboration between physicians and pharmacists appears mandatory to address the issues reported in this study.

Postoperative complications affect long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis.

BACKGROUND AND OBJECTIVES: Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) for colorectal peritoneal carcinomatosis (PC) may negatively affect survival. The objective was to determine the impact of postoperative complications (CX) on survival in patients undergoing CRS + HIPEC for colorectal PC. METHODS: All patients undergoing laparotomy for planned CRS + HIPEC for colorectal PC at a single institution from 1999 to 2014 were included. Patients were divided into three groups: CRS + HIPEC without CX (+HIPEC-CX); CRS + HIPEC with postoperative complication (+HIPEC + CX); and aborted CRS and HIPEC due to unresectable disease (-HIPEC). Postoperative morbidity were defined as Clavien II+ complications. Kaplan-Meier survival analyses and multivariable Cox proportional hazard modeling were used to describe the disease-free (DFS) and overall survival (OS). RESULTS: One hundred and twenty-two patients were included in the analysis (50 +HIPEC - CX, 40 +HIPEC + CX, 32-HIPEC). Overall complication rate was 42%. OS at 1-, 3-, and 5-years in patients undergoing successful CRS + HIPEC were 97%, 67%, and 45%. CX after successful CRS + HIPEC was independently associated with worsened OS (HR1.58, 95%CI, 1.19-1.97) but not DFS (HR1.11, 95%CI, 0.56-2.20). PCI also independently predicted worsened DFS (HR1.12, 95%CI, 1.06-1.18) and OS (HR1.08, 95%CI, 1.04-1.12). Patients with unresectable disease had significantly worse OS (HR6.50, 95%CI, 1.37-7.01). CONCLUSIONS: CX after CRS + HIPEC significantly affect OS. Patient selection and perioperative care are of paramount importance in the management of CRS + HIPEC for colorectal PC.

Effect of chemotherapy and heat on biomechanical properties of absorbable sutures.

BACKGROUND: The quality of tissue repairs depends on tissue integrity, surgical technique, and material properties of the sutures used. Currently, there is no clear consensus on which is the best suture to use during cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. The aim of this study was to evaluate the impact of heat and chemotherapy on sutures' biomechanical properties. METHODS: Six different 3.0 absorbable sutures (Biosyn, Dexon II, Maxon, Monocryl, PDS II, and Vicryl Plus) were tested. All suture strands were incubated for a 24-h period in saline, mitomycin-c, and oxaliplatin at 37 and 45°C. Suture loops were then loaded to failure using a servohydraulic testing machine. Data for tensile breaking force (TBF) and elongation rate were collected for all samples. RESULTS: Under basal condition, Maxon was the strongest of all sutures with a TBF of 59.6 ± 4.3 N (P < 0.01), and no significant difference in TBF was observed between other sutures. Heat alone had no impact on sutures' biomechanical parameters. Exposition to mitomycin-c at 45°C did not significantly affect sutures' basal tensile properties, with Maxon remaining the strongest suture. When incubated in oxaliplatin at 45°C, the six suture types had a similar TBF. In all experimental conditions, multifilament sutures had a significantly lower elongation rate than monofilament sutures, and no correlations were demonstrated between elongation rate and the TBF of sutures. CONCLUSIONS: This study showed that exposition to heated chemotherapy did not significantly affect absorbable sutures biomechanical properties.

Impact of electrocautery and hyperthermic intraperitoneal chemotherapy on intestinal microvasculature in a murine model.

BACKGROUND: Electrocautery (EC) is used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Using a murine model, we studied the effect of HIPEC on small bowel EC lesions and surrounding normal tissues. METHODS: Thirty-two rats were divided into five groups: a control group with EC lesions; EC plus intraperitoneal heated 5% dextrose (D5W); EC plus oxaliplatin (OXA, 460 mg/m(2)); EC plus mitomycin C 10 mg/m(2) (MMC10); EC plus MMC 35 mg/m(2) (MMC35). EC lesions and surrounding tissue microvasculature were analysed after intravenous injection of fluorescein. RESULTS: In the ileum OXA significantly reduced EC lesions microvasculature compared with the control group; MMC10 caused greater reduction than the control, D5W and MMC35 groups. Surrounding tissue microvasculature was significantly reduced by MMC35 exposure when compared to the control, OXA or MMC10 groups. In the jejunum EC injuries exposed to OXA or MMC10 had significantly reduced microvasculature compared to the control, heated D5W and MMC35 groups. Surrounding tissue microvasculature was significantly reduced by MMC35 exposure when compared to the OXA group. There was no significant microvasculature difference between the EC lesions made before or after HIPEC. CONCLUSION: HIPEC with OXA and MMC10 potentiates small bowel wall EC injuries. MMC35 reduces surrounding unharmed tissue microvasculature. There was no effect of hyperthermia alone on microvasculature.

Electrocautery effect on intestinal vascularisation in a murine model.

BACKGROUND: The use of electrocautery devices is associated with complications such as perforation or fistulisation when used near intestinal structures. This is likely due to its effect on vascularisation of the bowel wall. To test this hypothesis we established a murine model to quantify the effect of electrocautery injury on the intestinal microvascularisation. METHODS: Sprague-Dawley rats were subjected to five electrocautery injuries on the small bowel in coagulation mode (30 W intensity) and in cut mode (40 W, 80 W and 200 W intensities) for durations of 1, 2 and 5 s. 5 mg/kg of fluorescein was injected intravenously, the injured bowel segments harvested and the rat sacrificed. The segments were analysed to measure the fluorescence of injured bowel compared to adjacent unharmed tissue. RESULTS: A significant decrease in bowel wall microvascularisation occurred with increasing intensity (coag 30 W/cut 40 W versus cut 200 W 1 s: p < 0.05) and duration of electrocautery injury (cut 40 W 1/2 s versus 5 s: p < 0.05). There was a 40% perforation rate when decreased bowel wall microvascularisation was 25% or more. Despite similar electrocautery injury, a significantly greater microvascularisation decrease was observed in jejunum compared to ileum (p < 0.05). CONCLUSION: We successfully established a murine model to quantify the decrease of bowel wall microvascularisation associated with electrocautery use. Unsurprisingly, the decrease in microvascularisation is greater with higher intensity and duration of electrocautery and is associated with more perforations in the experimental model. The jejunum seems more vulnerable to electrocautery injury than the ileum. These observations support caution when using electrocautery devices near intestinal structures.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: an emerging treatment option for advanced goblet cell tumors of the appendix.

BACKGROUND: The debate remains whether appendiceal goblet cell cancers behave as classical carcinoid or adenocarcinoma. Treatment options are unclear and reports of outcomes are scarce. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is considered optimal treatment for peritoneal involvement of other epithelial appendiceal tumors. METHODS: Prospective cohorts of patients treated for advanced appendiceal tumors from three peritoneal malignancy centres were collected (1994-2011). All patients underwent complete CRS+HIPEC, when possible, or tumor debulking. Demographic and outcome data for patients with goblet cell cancers were compared to patients with low- or high-grade epithelial appendiceal tumors treated during the same time period. RESULTS: Details on 45 goblet cell cancer patients were compared to 708 patients with epithelial appendix lesions. In the goblet cell group, 57.8 % were female, median age was 53 years, median peritoneal cancer index (PCI) was 24, and CRS+HIPEC was achieved in 71.1 %. These details were similar in patients with low- or high-grade epithelial tumors. Lymph nodes were involved in 52 % of goblet cell patients, similar to rates in high-grade cancers, but significantly higher than in low-grade lesions (6.4 %; p < 0.001). At 3 years, overall survival (OS) was 63.4 % for goblet cell patients, intermediate between that for high-grade (40.4-52.2 %) and low-grade (80.6 %) tumors. On multivariate analysis, tumor histology, PCI, and achievement of CRS+HIPEC were independently associated with OS. CONCLUSIONS: This data supports the concept that appendiceal goblet cell cancers behave more as high-grade adenocarcinomas than as low-grade lesions. These patients have reasonable long-term survival when treated using CRS+HIPEC, and this strategy should be considered.

High-accuracy measurement of the differential scalar polarizability of a 88Sr+ clock using the time-dilation effect.

We report a high-accuracy measurement of the differential static scalar polarizability Δα(0) of the 5s(2)S(1/2)-4d(2)D(5/2) transition of the (88)Sr(+) ion. The high accuracy is obtained by comparing the micromotion-induced positive scalar Stark shift to the negative time-dilation shift. Measurement of the trap drive frequency where these shifts cancel is used to determine Δα(0) without the need to determine the electric field. Δα(0) is a critical parameter for the operation of frequency standards as it determines the blackbody radiation frequency shift coefficient, the largest source of uncertainty in the (88)Sr(+) ion clock. The measured value of Δα(0) is -4.7938(71) × 10(-40) J m(2)/V(2). Taking into account the dynamic correction, the blackbody shift at 300 K is 0.247,99(37) Hz. The contribution of the blackbody shift coefficient to the uncertainty of the ion standard has been reduced by a factor of 24, from 2 × 10(-17) to 8.3 × 10(-19). The revised total uncertainty of our reference standard is 1.2 × 10(-17), limited by the blackbody field evaluation. An additional benefit of the low uncertainty of Δα(0) is the ability to suppress, by a factor of about 200, the net micromotion frequency shifts.

Hyperthermic intraperitoneal chemotherapy with oxaliplatin as treatment for peritoneal carcinomatosis arising from the appendix and pseudomyxoma peritonei: a survival analysis.

BACKGROUND: Appendiceal peritoneal carcinomatosis (PC) is rare and its long-term prognosis is poor. The aim of this study was to evaluate the results of an aggressive treatment approach used in our institution for the last eight years. METHODS: Data from all patients with PC arising from the appendix were prospectively collected and analyzed. Treatment consisted of complete surgical cytoreduction (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (460 mg/m2) at 43°C over 30 minutes. Ronnett's histologic classification was used for tumor grading. RESULTS: Between February 2003 and April 2011, 78 patients underwent laparotomy with curative intent. The mean follow-up period was 33.7 months. A total of 58 patients received HIPEC, but 11 patients could not have CRS and received no HIPEC. Nine patients with a negative second-look surgery also received no HIPEC. The five-year overall survival for the entire cohort was 66.2%; 100% for the negative second-look patients, 77% for the HIPEC patients and 9% for the unresectable patients (P<0.0001). A total of 15 patients (25.9%) had isolated peritoneal recurrence, no patient had visceral recurrence only, and five patients (8.6%) had both. In regards to the five-year disease-free survival for the HIPEC patients, histologic grade (disseminated peritoneal adenomucinosis 100%, peritoneal mucinous carcinomatosis with intermediate features 40%, peritoneal mucinous carcinomatosis 20%; p=0.0016) and completeness of cytoreduction (CCR-0 56%, CCR-1 24%; P=0.0172) were prognostic factors. There was one postoperative mortality. The major complication rate for patients treated with HIPEC was 40%, including intra-abdominal abcess (17%), hemorrhage (12%) and anastomotic leak (10%). One patient in the HIPEC group experienced temporary grade II neuropathy and grade III thrombocytopenia. CONCLUSIONS: This therapeutic approach seems both feasible and safe in selected patients. Recurrence is, however, frequent and represents a challenge.