Risk-adjusted Sequential Probability Ratio Test Research Articles

Cytoreductive surgery with a hyperthermic intraperitoneal chemotherapy program: Safe after 40 cases, but only controlled after 140 cases

BackgroundCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), used to treat peritoneal surface malignancies (PSM), is a complex procedure with significant major morbidity (MM). ObjectiveTo investigate the learning curve (LC) of CRS with HIPEC in a new specialized surgical unit with a fully trained senior surgeon and individualize the variables associated with morbidity and oncological results. MethodsA total of 290 consecutive patients with PSM were included. Complete CRS with HIPEC was performed in 204 patients. A risk-adjusted sequential probability ratio test was used to assess the LC on the basis of rates of incomplete cytoreduction (IC) and MM. ResultsComplete CRS, MM, and mortality rates were 70.4%, 30.4%, and 2.5%, respectively. Tumor histotype, a high peritoneal cancer index (PCI) and the invaded region were the major independent risk factors for IC, whereas previous surgery, high PCI, stomia realization and blood transfusion were predictors of MM. RA-SPRT showed that 140 and 40 cases were needed to achieve the lowest risk of IC and MM, respectively. ConclusionCRS with HIPEC to treat PSM has a steep LC. Drastic selection has to be made at the beginning, excluding high PCI, rare peritoneal disease and patients previously operated on.

Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemoperfusion (HIPEC) is routinely used to treat certain peritoneal carcinomatoses (PC), but it can be associated with relatively high complication rates, prolonged hospital length of stay, and potential mortality. Our objective was to determine the learning curve (LC) of CRS/HIPEC in our high-volume institution. A total of 370 patients with PC from mucinous appendiceal neoplasms (MAN=282), malignant peritoneal mesothelioma (MPM=60), and gastric cancer (GC=24) were studied. Outcomes analyzed included incomplete cytoreduction (IC), severe morbidity (SM), 60-day mortality, progression-free survival (PFS), and overall survival (OS). Risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of CRS/HIPEC for IC and SM using prespecified odds ratio (OR) boundaries derived from previously published data. Risk adjusted-cumulative average probability (RA-CAP) was used to analyze 1-year PFS and 2-year OS. Complete cytoreduction, severe morbidity, and 60-day mortality were84.2, 30, and 1.9% respectively. Higher simplified peritoneal cancer index was the major independent risk factor for IC, whereas high-grade histology, IC, and diagnosis of MPM and GC (compared with MAN) were predictors of SM after CRS/HIPEC (p<0.05). RA-SPRT showed that approximately 180 cases are needed to achieve the lowest risk of IC and SM. Ninety cases were needed to achieve a steady 1-year PFS and 2-year OS in RA-CAP plots. The completeness of cytoreduction, morbidity, and mortality rates for CRS/HIPEC at our institution are comparable to previously reported data. Approximately 180 and 90 procedures are required to improve operative and oncologic outcomes respectively.

Multicentre study of the learning curve and surgical performance of cytoreductive surgery with intraperitoneal chemotherapy for pseudomyxoma peritonei.

The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal.

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

We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process. Six hundred and forty-one cases submitted to CRS using peritonectomy procedures and HIPEC were considered. After having overcome its own LC, the NCI of Milan has provided technical assistance to Bentivoglio's centre for the development of a new PSM program since 2003. The risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of the two centers. Outcomes were incomplete cytoreduction, G3-5 morbidity (NCI-CTCAE.v3) and procedure-related mortality (PRM). Rates of incomplete cytoreduction, G3-5 morbidity, and PRM were 8.4%, 30.1%, and 3.9%, respectively, in the entire series. The breaking points of the LC concerning incomplete cytoreduction, G3-5 morbidity, and PRM were achieved at 141, 158, and 144 cases, in the Milan's experience, and at 126, 134, and 60 cases in the Bentivoglio's experience. Surgical tutoring could substantially shorten the steep LC associated with CRS and HIPEC. Our data should be confirmed by further studies on LC focusing oncological outcomes. Other factors that could influence the length of learning process should be identified.

Multidimensional Analysis of the Learning Curve for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Peritoneal Surface Malignancies

To evaluate the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM). CRS and HIPEC to treat PSM is a complex procedure with a significant morbidity. A long-lasting training program is required to acquire expertise in this type of operation. We performed CRS using peritonectomy procedures. HIPEC through the closed abdomen technique employed cisplatin and mitomycin-C or cisplatin and doxorubicin. Risk-adjusted sequential probability ratio test was used to assess the learning curve on a series of 420 cases of PSM on the basis of rates of incomplete cytoreduction and G3-5 morbidity (NCI-CTCAE v3). We determined control limits setting the type I/II error rates and unacceptable odds ratios (ORs) for the outcomes being studied. We performed the risk adjustment using logistic regression model. Rates of incomplete cytoreduction, G3-5 morbidity, and postoperative mortality rates were 10.2%, 28.5%, and 2.1%, respectively. The risk-adjusted sequential probability ratio test curve crossed the lower control limit at the 137 th and 149 th case, respectively, for incomplete cytoreduction and G3-5 morbidity. At those points, the actual ORs are lower than the prespecified ORs for outcomes being studied. Therefore, we estimated that approximately 140 cases are necessary to ensure surgical proficiency in CRS and HIPEC. CRS and HIPEC to treat PSM has a steep learning curve requiring 140 procedures to acquire expertise.

Using statistical process control (SPC) charts for monitoring of surgical performance in vascular surgery: A case study and comparison of two monitoring methods

Background: the technique of prospective monitoring of surgical performance has replaced the traditional audit models in different clinical settings. Risk-adjusted cumulative sum (CUSUM)-type charts and variable life-adjusted display (VLAD) charts are of special interest for quality improvement Method: some 25129 patients on the national vascular database who underwent abdominal aortic aneurysm repair were analysed. A riskadjusted CUSUM chart, a risk-adjusted sequential probability ratio test (SPRT) chart and a VLAD chart with prediction limits chart were used to detect excess deaths. Results: control charts from two centres are shown in order to illustrate the main features of SPC monitoring systems. A risk-adjusted CUSUM model is shown and is comparedwith non-risk adjusted CUSUM and VLAD techniques. Selecting the control limit based on the simulation results of average run length using the method of fractional polynomials to produce a closed-form relationship between the average run length, control limit, and acceptable rate of failure are also described. Conclusion: risk-adjusted CUSUM technique are shown to be reliable, accurate and intuitive technique that can reliably detect outliers in major vascular surgery.

Risk-adjusted sequential probability ratio test control chart methods for monitoring operator and institutional mortality rates in interventional cardiology

The objective of this study was to evaluate risk-adjusted sequential probability ratio test control charts for the detection of significant discrepancies between institution or individual interventional cardiologist postprocedural mortality rates and national or local event rate expectations. Eight thousand nine hundred forty-two percutaneous coronary interventional procedures were performed by 27 operators between January 1, 2002, and November 30, 2006. The institution-based evaluation included all procedures, and the individual-based evaluations included 8750 procedures performed by 18 operators who had each done at least 100 PCI procedures. Risk-adjusted sequential probability ratio test control charts were developed to assess whether the odds ratios (ORs) for death were >2.0 for alpha = beta = 0.10. The American College of Cardiology 1.1 prediction model was used to risk-adjust both the institution and individuals, and an additional local model was used for individuals. After national risk adjustment, the local institution did not show mortality of more than a 1.5 OR. Two operators had a >2.0 mortality OR after national risk adjustment, and one of those remained elevated after local risk adjustment. Of 18 operators, 10 had insufficient data to allow us to accept or reject the hypothesis of increased risk. The local institution performed within national expectations, but 1 operator was identified as having poor performance, which prompted an in-depth review of that operator's cases. The review revealed that the operator had an unusually high number of patients who presented with risk factors not included in the risk-adjustment models. This study highlights the utility of risk-adjusted sequential probability ratio test as a method for outcomes monitoring and quality control in interventional cardiology.

Monitoring the performance of residents during training in off-pump coronary surgery

Objective Control charts (eg, cumulative sum charts) plot changes in performance with time and can alert a surgeon to suboptimal performance. They were used to compare performance of off-pump coronary artery bypass surgery between a consultant and four resident surgeons and to compare performance of off-pump coronary artery bypass surgery and conventional coronary artery bypass grafting within surgeons. Methods Data were analyzed for consecutive patients undergoing coronary artery bypass grafting who were operated on by one consultant or one of four residents. Conversions were analyzed by intention to treat. Perioperative death or one or more of 10 adverse events constituted failure. Predicted risks of failure for individual patients were derived from the study population. Variable life-adjusted displays and risk-adjusted sequential probability ratio test charts were plotted. Results Data for 1372 patients were analyzed; 769 of the procedures were off-pump coronary artery bypass operations (56.0%). The consultant operated on 382 patients (293 off-pump, 76.7%), and the residents operated on 990 (474 off-pump, 47.9%). Patients operated on by residents tended to be older, more obese, more likely to require an urgent operation, and more likely to need a circumflex artery graft but less likely to have triple-vessel disease. There were 7 conversions (consultant 5, residents 2). The overall failure rate was 8.5% (9.2% for consultant's operations and 8.2% for residents' operations), including 10 deaths (0.7%). Predicted and observed risks of failure were similar for all five surgeons. After 100 off-pump coronary artery bypass operations, performance was the same or better for the residents as for the consultant. For all surgeons, performance was the same or better for off-pump as for conventional coronary artery bypass grafting. Conclusions Off-pump coronary artery bypass surgery can be safely taught to cardiothoracic residents. Implementation of continuous performance monitoring for residents is practicable.