ABSTRACT
INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief. METHODS: This is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival. RESULTS: Between 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients - 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31). CONCLUSION: CRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients - improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.
Subject(s)
Antineoplastic Agents/administration & dosage , Appendiceal Neoplasms/secondary , Appendiceal Neoplasms/therapy , Colorectal Neoplasms/therapy , Cytoreduction Surgical Procedures/methods , Drug Therapy/methods , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Adult , Aged , Appendiceal Neoplasms/mortality , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Hong Kong/epidemiology , Humans , Male , Middle Aged , Peritoneal Neoplasms/mortality , Survival Rate , Time Factors , Treatment OutcomeSubject(s)
Antineoplastic Agents/administration & dosage , Appendiceal Neoplasms/pathology , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/surgery , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/secondary , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Peritoneal Neoplasms/drug therapy , Pseudomyxoma Peritonei/drug therapyABSTRACT
OBJECTIVES: Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death. RESULTS: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46-77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20-52) and 0% (95% CI 0-5) respectively. CONCLUSION: One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC.
Subject(s)
Carcinoma, Ovarian Epithelial/therapy , Ovarian Neoplasms/therapy , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/surgery , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Chemotherapy, Cancer, Regional Perfusion/methods , Cytoreduction Surgical Procedures/adverse effects , Cytoreduction Surgical Procedures/methods , Female , Humans , Hyperthermia, Induced/adverse effects , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Observational Studies as Topic , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Randomized Controlled Trials as Topic , Retrospective StudiesABSTRACT
BACKGROUND: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy. OBJECTIVE: This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care. DESIGN: This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). SETTINGS: This study was conducted at 3 hospital sites in South Australia. PATIENTS: Eighty-six adults undergoing colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. INTERVENTIONS: Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. MAIN OUTCOME MEASURES: Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days; postoperative pain was assessed by using a visual analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded. RESULTS: The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent. LIMITATIONS: This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control. CONCLUSIONS: We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A698.
Subject(s)
Amides/administration & dosage , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Colectomy/adverse effects , Aged , Amides/adverse effects , Amides/pharmacology , Analgesia/methods , Analgesia/trends , Analgesics, Opioid/therapeutic use , Anesthetics, Local/pharmacology , Australia/epidemiology , Colectomy/trends , Female , Humans , Infusions, Parenteral/methods , Injections, Intraperitoneal/methods , Laparoscopy/adverse effects , Male , Middle Aged , Outcome Assessment, Health Care , Pain Management/standards , Pain Measurement/methods , Pain, Postoperative/drug therapy , Postoperative Period , Recovery of Function/physiology , RopivacaineABSTRACT
OBJECTIVES: The choice of an optimal administration route for intraperitoneal (IP) chemotherapy and a suitable chemotherapeutic regime in the treatment of ovarian cancer remains a controversy. We investigated survival outcomes according to catheter intraperitoneal chemotherapy (CIPC), normothermic and hyperthermic chemoperfusion (NIPEC and HIPEC) with cytostatic drugs dioxadet and cisplatin in rats with transplantable ascitic ovarian cancer. METHODS: Ascitic liquid containing 1 × 107 tumour cells was inoculated to female Wistar rats and 48 hours after rats received dioxadet and cisplatin at the maximum tolerated doses. Dioxadet at doses 1.5, 30 and 15 mg/kg and cisplatin at doses 4, 40 and 20 mg/kg body weight were administered for CIPC, NIPEC and HIPEC, respectively. Rats in the control groups received physiological saline and CIPC with physiological saline was regarded as the untreated control. The antitumor activity of the drugs was evaluated as an increase in average life expectancy (ALE). Analysis of the data was based primarily on Bayesian statistics and included Kaplan-Meier method, log-rank test and hazard ratio (HR) estimation. RESULTS: Compared to the untreated control CIPC, NIPEC and HIPEC with dioxadet significantly increased ALE by 101316, 61524 and 1.71735 days, whereas with cisplatin by 61013, 122437 and -13523 days, respectively. CONCLUSIONS: Dioxadet and cisplatin show similar efficacy in the CIPC route. Compared with CIPC IP chemotherapy by chemoperfusions is more effective for both the drugs. Dioxadet in HIPEC showed highest survival benefit whereas largest effect during NIPEC is achieved with cisplatin.
Subject(s)
Ascites/drug therapy , Infusions, Parenteral/methods , Ovarian Neoplasms/drug therapy , Animals , Ascites/pathology , Chemotherapy, Cancer, Regional Perfusion/methods , Disease Models, Animal , Female , Humans , Hyperthermia, Induced , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Rats , Rats, Wistar , Survival AnalysisABSTRACT
Background and aims: The optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN. Design and methods: A retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial dose of SC insulin was estimated as 50% of the daily IV insulin requirements, extrapolated from the previous 12h. A corrective dose of short-acting insulin (lispro) was used when necessary. Results: Mean blood glucose (BG) level during SC insulin treatment was 136±35mg/dL in the EN group and 157±37mg/dL in the TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first three days after switching, and a 41% increase in the glargine dose was required to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout the days of transition and the dose of glargine remained unchanged. Conclusions: In the transition from IV to SC insulin therapy, initial insulin glargine dose estimated as 50% of daily IV insulin requirements is adequate for patients on EN, but inadequate in those given TPN (AU)
Introducción y objetivo: La dosis óptima inicial de insulina subcutánea (SC) después de la infusión intravenosa (IV) es controvertida, especialmente en pacientes que reciben nutrición enteral continua (NE) o nutrición parenteral total (NPT). El objetivo de este estudio fue evaluar la estrategia utilizada en nuestra unidad de cuidados intensivos (UCI) en pacientes sometidos a transición de infusión IV a insulina glargina SC mientras recibían NE o NPT. Diseño y métodos: Se analizaron retrospectivamente 27 pacientes con NE y 14 con NPT que cambiaron de infusión IV a insulina SC. La dosis inicial de insulina SC se estimó como el 50% de los requerimientos diarios de insulina IV, extrapolado de las 12 horas anteriores. Se utilizó dosis correctiva de insulina ultrarrápida (lispro), cuando fue necesaria. Resultados: La media de glucemia plasmática (GP) con insulina SC fue de 136,35mg/dl en el grupo NE y de 157,37mg/dl en el grupo NPT, p=0.01. En el grupo de NPT la GP media fue>180mg/dL durante los tres primeros días después de la transición y fue necesario un aumento del 41% en la dosis de glargina para alcanzar la GP objetivo. En el grupo NE, la GP media permaneció<180mg/dl durante los días de transición y la dosis de glargina permaneció sin cambios. Conclusiones: En la transición de la terapia de insulina IV a insulina SC, la dosis inicial de insulina glargina estimada como el 50% de los requerimientos diarios de insulina IV es adecuada para los pacientes que reciben NE, pero insuficiente para los que reciben NPT (AU)
Subject(s)
Humans , Male , Middle Aged , Critical Care/methods , Insulin/therapeutic use , Insulin, Long-Acting/therapeutic use , Enteral Nutrition/methods , Insulin Glargine/therapeutic use , Infusions, Parenteral/methods , Administration, Intravenous , Retrospective StudiesABSTRACT
BACKGROUND: Several studies suggest that young patients may derive less oncologic benefit from surgical resection of cancers compared with older patients. We hypothesized that young patients may have worse outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for peritoneal metastases. METHODS: Perioperative and oncologic outcomes in adolescent and young adults (AYA), defined as younger than age 40 years (n = 135), undergoing CRS/HIPEC between 2001 and 2015 were reviewed and compared with middle-aged adults, defined as aged 40-65 years (n = 684). RESULTS: The two groups were similar with regards to perioperative characteristics except that AYA were more likely to be symptomatic at presentation (65.2 vs. 50.9%, p = 0.003), had lower Charleson comorbidity index (median 6 vs. 8, p < 0.001), were less likely to receive neoadjuvant chemotherapy (32.8 vs. 42.5%, p = 0.042), and had longer operative times (median 543 vs. 493 min, p = 0.010). Postoperative Clavien-Dindo grade 3-4 morbidity was lower in AYA (17 vs. 26%, p = 0.029), and they required fewer reoperations for complications (3.7 vs. 10.4%, p = 0.014). AYA had longer median overall survival (103.6 vs. 73.2 months, p = 0.053). In a multivariate Cox regression analysis, age was an independent predictor of improved overall survival [hazard ratio 0.705; 0.516-0.963, p = 0.028]. CONCLUSIONS: Young patients with peritoneal metastases derive similar benefits from CRS/HIPEC as middle-aged patients. Young age should not be a deterrent to consideration of CRS/HIPEC for peritoneal metastases.
Subject(s)
Antineoplastic Agents/administration & dosage , Appendiceal Neoplasms/pathology , Colorectal Neoplasms/pathology , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Mesothelioma/therapy , Peritoneal Neoplasms/therapy , Adolescent , Adult , Age Factors , Aged , Cytoreduction Surgical Procedures/adverse effects , Female , Humans , Infusions, Parenteral/methods , Male , Mesothelioma/pathology , Mesothelioma/secondary , Middle Aged , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Postoperative Complications/etiology , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Survival Rate , Young AdultABSTRACT
AIM: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma. MATERIAL AND METHODS: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology. RESULTS: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery. CONCLUSION: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications.
Subject(s)
Cytoreduction Surgical Procedures/methods , Peritoneal Neoplasms , Pseudomyxoma Peritonei , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Combined Modality Therapy , Female , Humans , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Male , Middle Aged , Neoplasm Staging , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/mortality , Pseudomyxoma Peritonei/pathology , Pseudomyxoma Peritonei/surgery , Retrospective Studies , Russia , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: The long-term survival of patients with peritoneal carcinomatosis of colorectal origin has been achieved with cytoreductive surgery, which removes all macroscopic implants, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The current technology for administering intraperitoneal heated chemotherapy is expensive and, for some institutions, unaffordable. We conducted this study to assess the temperature stability provided by a modified, inexpensive system, to offer a simple and low cost alternative to the standard HIPEC delivery equipment. METHODS: Ten patients with histologically diagnosed peritoneal metastases of adenocarcinoma or pseudomyxoma peritonei underwent cytoreductive surgery and received HIPEC with 5-fluorouracil for 90 min, delivered via our modified system. The temperature was recorded from two probes: one in the inflow catheter and one in the outflow catheter. The intra-abdominal temperature was monitored meticulously to maintain it at between 41 and 42 °C. RESULTS: All patients underwent cytoreductive surgery and HIPEC using our modified delivery system. Temperature stability was achieved in all patients, with a mean of 41.4°. There were no thermal injuries associated with any of the ten perfusions. The mean hospital stay was 15 days and the median survival was 30 months. CONCLUSION: Analysis of this data demonstrates that the uniform delivery of HIPEC at 41° with this modified system is feasible and safe. The outcome of the patients treated with cytoreductive surgery and HIPEC with this modified system compares favorably to other published series. Its low cost and simple design will give more patients with peritoneal carcinomatosis access to this treatment.
Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/surgery , Antineoplastic Agents/administration & dosage , Colorectal Neoplasms/pathology , Cytoreduction Surgical Procedures/methods , Fluorouracil/administration & dosage , Hyperthermia, Induced/methods , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/surgery , Adenocarcinoma/drug therapy , Adult , Aged , Combined Modality Therapy , Female , Humans , Infusions, Parenteral/methods , Male , Middle Aged , Peritoneal Neoplasms/drug therapy , Pseudomyxoma Peritonei/drug therapy , Treatment OutcomeABSTRACT
UNLABELLED: This CORCAN study is concerned with the way patients hospitalised for peritoneal carcinosis perceive surgical treatment and hyperthermic intraperitoneal chemotherapy (HIPEC). OBJECTIVES: (1) To identify and analyse, using concepts of social representation and accounts of the illness, characteristics of the way this treatment is experienced; (2) to inform doctors and healthcare workers about patients' representations, with a view to adjusting the treatment, the care and the information given to patients. METHODOLOGY: Fifty-eight directive and nondirective interviews were conducted longitudinally with 21 patients (13 women and 7 men) hospitalised for treatment by cell killing and HIPEC. RESULTS: Five important elements of concern were raised and discussed by the patients at different stages of the disease, then reported and discussed with the doctors and healthcare workers. These were patients' experiences of: the hyperthermic intraperitoneal chemotherapy (HIPEC), randomisation, intensive care, the effects of surgery on the digestive system, reorganising their diet, and returning home.
Subject(s)
Carcinoma/drug therapy , Carcinoma/psychology , Carcinoma/surgery , Hyperthermia, Induced/psychology , Infusions, Parenteral/psychology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/psychology , Peritoneal Neoplasms/surgery , Aged , Antineoplastic Agents/administration & dosage , Critical Care/psychology , Female , Humans , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Longitudinal Studies , Male , Middle Aged , Parenteral Nutrition/psychology , Patient Participation , Qualitative ResearchABSTRACT
BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.
Subject(s)
Air Conditioning/methods , Antineoplastic Agents/therapeutic use , Carcinoma/therapy , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Peritoneal Neoplasms/therapy , Personal Protective Equipment/statistics & numerical data , Practice Patterns, Physicians' , France , Humans , Occupational Health , Risk Management , Smoke , Surveys and QuestionnairesABSTRACT
Experimental perfusion system and technology for normothermic and hyperthermic intraperitoneal chemoperfusion are developed for the treatment of abdominal carcinomatosis in rats with transplanted ovarian cancer. MTD of cisplatin in normothermic intraperitoneal chemoperfusion and hyperthermic perfusion are 40 and 20 mg/kg, i.e. by 10- and 5-fold higher than the dose of this cytostatic for routine intraperitoneal injection. Normothermic intraperitoneal chemoperfusion with cisplatin increases median survival time by 200% (p=0.039) in comparison with intraperitoneal injection.
Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Ovarian Neoplasms/drug therapy , Animals , Antineoplastic Agents/administration & dosage , Cell Line, Tumor , Cisplatin/administration & dosage , Female , Neoplasm Transplantation , Peritoneal Neoplasms/drug therapy , Random Allocation , Rats , Rats, WistarABSTRACT
Peritoneal surface malignancies (PSM) include peritoneal metastases from gastrointestinal and gynecological tumor and rare primary peritoneal malignancies. PSM have been historically considered as end-stage metastatic conditions only amenable to palliative options. Only in recent years, better knowledge of their natural history and pattern of disease-progression has evolved into the concept that PSM represent a local-regional disease stage. A novel treatment approach aiming at definitive disease eradication combines aggressive cytoreductive surgery (CRS) and perioperative local-regional chemotherapy, either in the form of hyperthermic intraperitoneal chemotherapy (HIPEC), or normothermic early postoperative chemotherapy. Such a combined treatment approach has reportedly resulted in a survival improvement over historical controls, and it is gaining an increasing acceptance as standard of care for selected patients with PSM. This article reviews the most recent literature data on the surgical and comprehensive management of PSM. Epidemiology and natural history of the different disease entities are briefly discussed. Cytoreductive surgical procedures and intraperitoneal chemotherapy administration techniques are described, focusing on the technical variants adopted in our institution. Indications for combined treatment, and outcomes following CRS/HIPEC, are addressed, including peritoneal metastases from appendiceal tumors (pseudomyxoma peritonei), colorectal cancer, gastric cancer, epithelial ovarian cancer, and rare primary peritoneum based neoplasms, such as diffuse malignant peritoneal mesothelioma, and primary peritoneal (extra-ovarian) serous papillary carcinoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures , Gastrointestinal Neoplasms/therapy , Hyperthermia, Induced , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/therapy , Pseudomyxoma Peritonei/therapy , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant/methods , Evidence-Based Medicine , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Humans , Infusions, Parenteral/methods , Meta-Analysis as Topic , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Patient Selection , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Pseudomyxoma Peritonei/pathology , Randomized Controlled Trials as Topic , Risk Factors , Treatment OutcomeABSTRACT
OBJECTIVE: Our objective was to review the published experiences of the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced and recurrent ovarian cancer with a focus on survival outcomes. METHODS: A search of the PubMed database (2008-2014) for articles specifically addressing the topic "HIPEC and ovarian cancer" was performed. We found a total of 22 publications that included 1450 patients. A final group of eleven studies (248 patients with advanced ovarian cancer) and eight publications (499 patients with recurrent sensitive ovarian cancer) that included information about survival were reviewed. RESULTS: Among patients with primary ovarian cancer who were treated with primary debulking and HIPEC, the weighted median overall survival was 37.3 months (range 27-78), the median disease-free survival was 14.4 months (range 12-30), and the 5-yr-survival rate was 40% (range 28-72). In the recurrent cohort, the overall survival after HIPEC was 36.5 months (range 23-62), and the median disease-free survival was 20.2 months (range 11-29). The rates of severe morbidity were 25 and 19% in the primary and recurrent groups, respectively. CONCLUSION: Although randomized trials are ongoing, the recently published retrospective data regarding the use of HIPEC for primary advanced and for recurrent ovarian cancer do not indicate any apparent advantage of this treatment in terms of the survival outcomes in these patients. Therefore, HIPEC cannot be considered a standard treatment and should not be offered outside of clinical trials.
Subject(s)
Antineoplastic Agents/administration & dosage , Hyperthermia, Induced/methods , Neoplasm Recurrence, Local/therapy , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Carcinoma, Ovarian Epithelial , Combined Modality Therapy , Female , Humans , Infusions, Parenteral/methods , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Randomized Controlled Trials as Topic , Retrospective Studies , Survival RateABSTRACT
PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival. METHODS: A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied. RESULTS: Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months. CONCLUSION: The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.
Subject(s)
Cytoreduction Surgical Procedures , Hyperthermia, Induced , Infusions, Parenteral/methods , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Aged , Colorectal Neoplasms/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Multivariate Analysis , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Prognosis , Pseudomyxoma Peritonei/mortality , Pseudomyxoma Peritonei/therapy , Stomach Neoplasms/pathologyABSTRACT
A new intraoperative cisplatin administration method for patients with locally advanced gastric cancer (AGC) and without peritoneal metastasis, fibrin-sealant-delivered cisplatin chemotherapy, was reported, and its safety, pharmacokinetics, and efficacy were compared with cisplatin hyperthermic intraperitoneal perfusion chemotherapy. Forty-two AGC patients were randomly divided into 2 groups: fibrin-sealant-delivered cisplatin chemotherapy (FS) (n = 21) and cisplatin hyperthermic intraperitoneal perfusion chemotherapy (CHIC) (n = 21). Both groups received 120 mg cisplatin after complete cytoreductive surgery. At different time points, cisplatin concentrations in patients' sera and urine samples were measured to determine time-dependent maximal concentration (Cmax) and the area under the curve (AUC). The primary and secondary end-points were overall survival (OS) and safety profiling, respectively. Occurrence of grade-3 to grade-4 liver or kidney dysfunction was less frequent in the FS group than in the CHIC group (28.6 % vs 47.6 %). Cisplatin Cmax and AUC for the serum and urine of the FS patients were significantly lower than that of the CHIC patients. Elimination half-life of cisplatin in the FS group was significantly longer than in the CHIC group (24.1 h vs 14.2 h). After a median follow-up of 40 months, 1-, 2-, and 3-years OS were 90.5 %, 71.4 %, and 61.9 % in the FS group, and 61.9 %, 47.6 %, and 42.8 % in the CHIC group, respectively. The median OS was 35.9 months in the FS group and 29.1 months in the CHIC group. Fibrin-sealant-delivered cisplatin chemotherapy was as effective and had a favorable pharmacokinetic profile with similar survival outcomes as cisplatin hyperthermic intraperitoneal perfusion chemotherapy following complete cytoreductive surgery of locally advanced GC without peritoneal metastases.
Subject(s)
Chemoembolization, Therapeutic/methods , Cisplatin/administration & dosage , Fibrin Tissue Adhesive/administration & dosage , Hyperthermia, Induced/methods , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Combined Modality Therapy/methods , Female , Follow-Up Studies , Hemostatics/administration & dosage , Humans , Infusions, Parenteral/methods , Male , Middle Aged , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Treatment OutcomeABSTRACT
INTRODUCTION: Complete cytoreductive surgery (CRS) can achieve cure or long-term survival in selected patients with peritoneal malignancy. In selected patients, due to extensive disease, complete tumour removal is impossible and optimal strategy may be maximal tumour debulking (MTD). We analysed the stoma related outcome in a series of patients undergoing surgery in a National Peritoneal Malignancy Referral Centre. METHODS: All patients who underwent CRS, with or without, intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) between 1994 and 2012 were included. Data was collected prospectively in an institutional database and analysed retrospectively. RESULTS: CRS was performed in 958 patients (female: 595, male: 363) of whom 781 (81.5%) had a primary appendix tumour, 63 (6.6%) had a colorectal primary, 47 (4.9%) peritoneal mesothelioma, 38 (4%) an ovarian tumour and 29 patients (3%) other tumours. Complete CRS was achieved in 72% (693/958). Overall 352/958 (37%) had a stoma, which was permanent in 165/958 (17.2%). The median time interval from CRS to reversal of stoma was 4.4 months (range: 1.4-13.8). Stomas were created in 113/265 (42.6%) at MTD (permanent: n = 105 (93%), temporary: n = 8 (7%)), and 239/693 (34.5%) at complete CRS (permanent: n = 60 (25%), temporary: n = 179 (75%)) (p = 0.020). All temporary stomas in the 168/693 (24.4%) of patients who had complete CRS were subsequently reversed. CONCLUSION: To achieve complete CRS for peritoneal malignancy a stoma is often required and in a proportion this will be permanent. Overall over one third had a stoma at surgery with almost half subsequently reversed.
Subject(s)
Appendiceal Neoplasms/pathology , Carcinoma/surgery , Colorectal Neoplasms/pathology , Colostomy/statistics & numerical data , Ileostomy/statistics & numerical data , Mesothelioma/surgery , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma/secondary , Cytoreduction Surgical Procedures , Female , Humans , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Male , Mesothelioma/secondary , Middle Aged , Peritoneal Neoplasms/drug therapy , Pseudomyxoma Peritonei/drug therapy , Young AdultABSTRACT
PURPOSE: The aim of this study was to analyse feasibility, morbidity and outcome of repeat complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). CRS combined with HIPEC is becoming the gold standard treatment for resectable peritoneal carcinomatosis in highly selected patients. As yet treatment of isolated peritoneal recurrence with iterative CRS and HIPEC has not been thoroughly explored. MATERIALS AND METHODS: We selected 16 patients presenting isolated peritoneal recurrence who had undergone iterative CRS and HIPEC from a dataset of 322 CRS associated with HIPEC performed between 1996 and 2012. RESULTS: Peritoneal carcinomatosis (PC) was due to colorectal and ovarian cancer, peritoneal mesothelioma and pseudomyxoma peritonei (PMP). Disease-free survival (DFS) was 13 months after the first procedure and 13.7 months after the second one. Overall morbidity rate was 43.7% (7/16) for all patients, with grade III-IV complications in three patients (18.7%). CONCLUSIONS: Iterative procedures combining cytoreductive surgery and HIPEC are feasible with acceptable morbidity and mortality rates in strictly selected patients. DFS following repeated CRS and HIPEC is comparable to that registered after the first procedure.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced , Neoplasm Recurrence, Local/therapy , Peritoneal Neoplasms/therapy , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Doxorubicin/administration & dosage , Female , Humans , Infusions, Parenteral/methods , Male , Middle Aged , Mitomycin/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/secondary , Neoplasm Recurrence, Local/surgery , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Positron-Emission Tomography , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. OBJECTIVES: To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. SEARCH METHODS: For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). SELECTION CRITERIA: Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. DATA COLLECTION AND ANALYSIS: Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. MAIN RESULTS: Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. AUTHORS' CONCLUSIONS: Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. PLAIN LANGUAGE SUMMARY: Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth.
Subject(s)
Cross Infection/prevention & control , Enterocolitis, Necrotizing/prevention & control , Probiotics/therapeutic use , Sepsis/prevention & control , Cross Infection/mortality , Enterocolitis, Necrotizing/mortality , Humans , Infant, Newborn , Infant, Premature , Infusions, Parenteral/methods , Randomized Controlled Trials as Topic , Sepsis/mortalityABSTRACT
INTRODUCTION: Treatment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is relatively ineffective and associated with morbidity. This raises the question whether we should focus on prevention of the development of PC. We determined the feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in a short stay setting. METHODS: A prospective single centre pilot study was conducted between January 2011 and July 2012. Ten patients at risk of developing PC of CRC origin were included. Laparoscopic HIPEC using Mitomycin-C (90 min; inflow temperature 42-43 °C) was performed within several weeks after primary resection of CRC and was considered feasible when postoperative hospital stay was three days or shorter in at least six patients, and if a maximum of one conversion and one re-admission within 30 days occurred. RESULTS: HIPEC was performed after a median of 6 weeks (range 3-9 weeks). Postoperatively, five patients were discharged at day one, four patients at day two and one patient at day three. Laparoscopic adhesiolysis resulted in small bowel injury in one patient, but no conversion to open surgery and no postoperative complications were observed. One patient was readmitted within 30 days due to a clostridium infection. The postoperative course was uneventful for the remaining patients. CONCLUSION: Adjuvant laparoscopic HIPEC appeared to be feasible in a short stay setting based on this small pilot study. The necessity of adhesiolysis determines the complexity of the procedure and requires an operating team with experience in minimally invasive abdominal surgery.