Incomplete Cytoreduction Research Articles

The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal carcinomatosis (PC) of appendiceal origin (AO).

707 Background: Peritoneal carcinomatosis of mucinous appendiceal tumor origin is a rare condition which has poor prognosis if treated with limited surgery or systemic chemotherapy. Several publications show that CRS/HIPEC gives a significant survival benefit for patients with PC of AO. However, many patients do not get appropriate treatment. We show data from our 17-year experience using CRS/HIPEC in PC of AO. Methods: Retrospective analysis of a prospective database of 251 patients with PC of AO was performed. Peritoneal cancer index (PCI), completeness of cytoreduction (CC), lymph node (LN) status, and histopathology data was collected. The impact of each variable evaluated by Hazard ratio analysis. Overall survival (OS) estimated by Kaplan-Meier curves. Results: Mean age 53 years (range 23-81). 251 patients underwent 290 CRS/HIPEC procedures. 31 patients had 2, and 4 patients had 3 CRS/HIPEC. A total of 149 patients (59%) had peritoneal mucinous carcinomatosis (PMCA) and 102 (41%) had disseminated peritoneal adenomucinosis (DPAM) (Ronnett classification). Mean follow-up 4.8 years with a median of 4.7 years. Complete cytoreduction was achieved in 84% (89% DPAM, 80% PMCA; p = 0.047). Mean length of surgery 11.3 hours, mean hospital stay 14 days. No in-hospital or 30-day mortality. 73% had PCI > 20 (78% DPAM; 68% PMCA). LN metastasis in 42% with PMCA. OS from date of HIPEC was 93%, 86%, 81% in DPAM and 90%, 60%, 44% in PMCA for 1, 3, and 5 years, respectively. With CC, the 5-year OS was 84% in DPAM and 49% in PMCA. All PMCA patients with incomplete cytoreduction (n = 30) had PCI ≥ 20 (p < 0.001). Hazard ratios were 2.5 (95% confidence interval [95% CI] 1.3-4.5), 3.1 (95% CI 2.0-4.9), 3.6 (95% CI 2.1-6.2), for PCI < 20, complete cytoreduction, and histopathology (DPAM vs. PMCA), respectively. Hazard ratio (for LN status in patients with PMCA was 3.0 (95% CI 1.8-5.1). Conclusions: Meaningful survival could be achieved in PC of AO even with extensive peritoneal disease (PCI > 20). We consider CRS/HIPEC a standard of care for these patients. CRS/HIPEC should be provided in specialized centers by trained surgeons where complete cytoreduction could be frequently accomplished.

Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer.

Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy. Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence. A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (<1 cm of residual tumor) or incomplete cytoreduction fully abrogated the prognostic effect of CD8(+) TIL. Subsequent analysis of primary TIL by flow cytometry and immunofluorescence identified CD27 as a key marker for a less-differentiated, yet antigen-experienced and potentially tumor-reactive CD8(+) TIL subset. In line with this, CD27(+) TIL were associated with an improved prognosis even in incompletely cytoreduced patients. Neither CD8(+) nor CD27(+) cell infiltration was of prognostic benefit in patients treated with neoadjuvant chemotherapy. Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials.

Oncologic Risk Stratification Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendiceal Carcinomatosis.

Patients with peritoneal carcinomatosis (PC) of appendiceal origin demonstrate variable oncologic outcomes, despite aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We sought to devise a prognostic risk stratification system for oncologic outcomes following CRS-HIPEC. A total of 197 patients undergoing CRS-HIPEC for the treatment of appendiceal PC were reviewed from a prospective database. Kaplan-Meier survival curves and multivariate Cox regression models were used to identify prognostic factors affecting oncologic outcomes. Clinicopathologic variables affecting overall survival (OS) were utilized to develop a prognostic staging system and nomograms. Univariate and multivariate Cox regression analysis indicated that high-grade tumor histology, lymph node metastasis, and incomplete cytoreduction were high-risk features, adversely affecting OS. Patients were stratified on the presence of high-risk features as follows: low-risk patients had no risk factors (n=102); intermediate-risk patients had one risk factor (n=49); and high-risk patients had more than one risk factor (n=46). Median OS for low-risk patients was not reached, and was 43 and 22months for intermediate-risk and high-risk patients, respectively. Five-year OS was 72, 43, and 13% for low-, intermediate- and high-risk patients, respectively (p<0.0003 for low vs. intermediate risk, and p=0.06 for intermediate vs. high risk). We propose a three-tier staging system for appendiceal PC following CRS-HIPEC, based on histologic grade, lymph node involvement, and completeness of cytoreduction. The presence of any one or more of these high-risk features significantly decreased survival in our single-institution database and provided the basis for a prognostic staging system and corresponding nomograms.

Which Surgical Attitude to Choose in the Context of Non-Resectability of Ovarian Carcinomatosis: Beyond Gross Residual Disease Considerations

In ovarian cancer, the increased rate of radical surgery comprising upper abdominal procedures has participated to improve overall survival (OS) in advanced stages by increasing the rate of complete cytoreductions. However, in the context of non-resectability, it is unclear whether radical surgery should be considered when it would lead to microscopic but visible disease (≤1 cm). We aimed to compare the survival outcomes among patients with incomplete cytoreduction according to the extent of surgery. Overall, 148 patients presenting with advanced stage ovarian carcinomas were included in this retrospective study, regardless of treatment schedule. These patients were stratified according to the extent of surgery (standard or radical). Complete cytoreduction at the time of debulking surgery could not be carried out in all cases. Among our study population (n = 148), 96 patients underwent standard procedures (SPs) and 52 underwent radical surgeries (RP). Patients in the SP group had a lower Peritoneal Index Cancer (PCI) at baseline (12.6 vs. 14.9; p = 0.049). After PCI normalization, we observed similar OS in the SP and RP groups (39.7 vs. 43.1 months; p = 0.737), while patients in the SP group had a higher rate of residual disease >10 mm (p < 10(-3)). Patients in the RP group had an increased rate of relapse (p = 0.005) but no difference in disease-free survival compared with the SP group (22.2 for SP vs. 16.3 months; p = 0.333). Residual disease status did not impact survival outcomes. In the context of non-resectable, advanced stage ovarian cancer, standard surgery seems as beneficial as radical surgery regarding survival outcomes and should be considered to reduce surgery-associated morbidity.

Pseudomyxoma peritonei - a report of two cases and a review of the literature

Introduction: PMP is a rare disease with a slow but progressive course leading to death. According to the literature PMP encompass wide variety of conditions. To avoid the confusion and to facilitate the treatment and comparison of the results several authors suggested that the term `PMP` should include only the cases with appendiceal origin. Case report: We report two cases with low-grade paseudomyxoma peritonei. The first case was managed by debulking surgery alone with survival 2 years. The second case underwent complete cytoreduction plus HIPEC and 3 years later is still alive and free of disease. There was one patient with a benign appendiceal mucocele treated by appendectomy, who is free of disease 3 years later. Introduction: PMP is a rare disease with a slow but progressive course leading to death. According to the literature PMP encompass wide variety of conditions. To avoid confusion and to facilitate treatment and comparison of the results several authors suggested that the term `PMP` should include only the cases with appendiceal origin. Case report: We report two cases with low-grade paseudomyxoma peritonei. The first case was managed by debulking surgery alone with survival 2 years. The second case underwent complete cytoreduction plus HIPEC and 3 years later is still alive and free of disease. There was one patient with a benign appendiceal mucocele treated by appendectomy, who is free of disease 3 years later. Conclusion: Despite the high complication rate, cytoreductive surgery with HIPEC remains the gold standard in the treatment of pseudomyxoma peritonei. The tumor grade and completeness of cytoreduction are the main prognostic factors. Due to the rarity of the condition most of the surgeons are not experienced enough to manage these patients. Additionally, the incomplete cytoreduction is associated with poorer prognosis and significantly hampers the subsequent interventions. Thus, in the cases when it is found incidentally, the best strategy is the taking of biopsy, appendectomy and subsequent referral to a specialized center for a treatment by multidisciplinary team.

Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Patients with High-Grade, High-Volume Disseminated Mucinous Appendiceal Neoplasms.

High-grade (HG) mucinous appendiceal neoplasms (MAN) have a worse prognosis than low-grade histology. Our objective was to assess the safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) in patients with high-grade, high-volume (HG-HV) peritoneal metastases in whom the utility of this aggressive approach is controversial. Prospectively collected perioperative data were compared between patients with peritoneal metastases from HG-HV MAN, defined as simplified peritoneal cancer index (SPCI) ≥12, and those with high-grade, low-volume (HG-LV; SPCI <12) disease. Kaplan-Meier curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. Overall, 54 patients with HG-HV and 43 with HG-LV peritoneal metastases underwent CRS/HIPEC. The HG-HV group had longer operative time, increased blood loss/transfusion, and increased intensive care unit length of stay (p < 0.05). Incomplete macroscopic cytoreduction (CC-1/2/3) was higher in the HG-HV group compared with the HG-LV group (68.5 vs. 32.6 %; p = 0.005). Patients with HG-HV disease demonstrated worse survival than those with HG-LV disease (overall survival [OS] 17 vs. 42 m, p = 0.009; time to progression (TTP) 10 vs. 14 m, p = 0.024). However, when complete macroscopic resection (CC-0) was achieved, the OS and progression-free survival of patients with HG-HV disease were comparable with HG-LV disease (OS 56 vs. 52 m, p = 0.728; TTP 20 vs. 19 m, p = 0.393). In a multivariate Cox proportional hazard regression model, CC-0 resection was the only significant predictor of improved survival for patients with HG-HV disease. Although patients with HG-HV peritoneal metastases from MAN have worse prognosis compared with patients with HG-LV disease, their survival is comparable when complete macroscopic cytoreduction is achieved.

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.

Evaluation of the efficiency of combination palliative treatment in patients with metastatic clear-cell renal cell carcinoma

Background. Experience with combination treatment, i.e. systemic therapy in combination with palliative surgery, in the treatment of metastatic kidney cancer is very rarely described in world literature. Objective: to evaluate the efficiency of combination treatment in combination with palliative cytoreductive surgery and targeted therapy and to define optimal indications for combination treatment. Subjects and methods . Data on 47 patients with metastatic renal cell carcinoma (mRCC) who received systemic (targeted) therapy in combination or after incomplete cytoreduction (iCR) were analyzed in this retrospective study. The proportion of men and women was 72.3 % and 27.7 %, respectively; their ratio was 2.6:1. All the patients (100%) underwent surgical treatment as nephrectomy or kidney resection for primary tumor. In the patients who had received radical treatment in different periods, the median relapse-free survival was 25.3 (0-187) months; the mean follow-up duration in the study was 33.2 (27.4–39.0) months. Out of the histological characteristics of a primary tumor, its Fuhrman grade was studied. Prior to initiation of mRCC therapy, Memorial Sloan Kettering Cancer Center (MSKCC) prognosis groups were assessed; the patients were divided into good (n = 9 (19.1 %)), interim (n = 28 (59.6 %)), and bad (n = 10 (21.3 %)) prognosis groups. Their total somatic status was separately rated using the ECOG scale: 0, (n = 10 (21.3%)), 1 (n = 24 (51.1 %)), and 2, (n = 13 (27.6 %)). The sites of metastases were as follows: the lung (n = 29), bones (n = 18), adrenals (n = 11), recurrence in the removed kidney bed (n = 10), and liver (n = 10). Multiple organ involvements were detected in 22 (46.8 %) patients. There were more than 5 metastases in one organ in 18 (40.0 %) patients and only 15 (33.3 %) were found to have a single focus in one organ. Whether iCR might be used as a separate line treatment was studied. A comparative analysis was made between 2 groups of patients with mRCC: 1) 20 patients who underwent iCR and 2) 27 patients who received systemic therapy (immunotherapy (n = 12), sorafenib (n = 8), and sunitinib (n = 7)). The control points were estimation of overall survival (OS), optimal indications for iCR in patients with mRCC, and time to progression (TTP) during first- and second-line systemic treatment. Resuts. The median OS duration in Group 1 was longer: 46 months versus 31 months (p = 0.09). TTP was comparable: 9 and 6 months, respectively. Comparison of first-line systemic treatment showed that the median TTP was twice longer (13 and 17 months in the targeted (sorafenib and sunitinib) therapy group than that in the cytokine therapy group (6 months) (p = 0.0174). TTP during second-line therapy was 10 months. Median OS after immunotherapy, sorafenib and sunitinib therapy demonstrated no differences and was 34.2, 36.5, and 39.2 months (р = 0.8). Conclusion. This investigation suggests that the comprehensive approach in effective in treating mRCC. iRC may be used as an individual treatment in a certain patient group. However, survival rates in the examined group of patients can be increased only when targeted drugs are necessarily used in both first- and second-line treatment regimens. In spite of the metastatic pattern of RCC, the treatment algorithm for these patients should estimate the possibilities of using palliative cytoreductive treatment since its use may provide a median TTP of as many as 9 months. Just the same, over 30-month survival rates may be obtained when the latter is used in combination with systemic treatment.

Pretreatment with VEGF(R)-inhibitors reduces interstitial fluid pressure, increases intraperitoneal chemotherapy drug penetration, and impedes tumor growth in a mouse colorectal carcinomatosis model.

Cytoreductive surgery combined with intraperitoneal chemotherapy (IPC) is currently the standard treatment for selected patients with peritoneal carcinomatosis of colorectal cancer. However, especially after incomplete cytoreduction, disease progression is common and this is likely due to limited tissue penetration and efficacy of intraperitoneal cytotoxic drugs. Tumor microenvironment-targeting drugs, such as VEGF(R) and PDGFR inhibitors, can lower the heightened interstitial fluid pressure in tumors, a barrier to drug delivery. Here, we investigated whether tumor microenvironment-targeting drugs enhance the effectiveness of intraperitoneal chemotherapy. A mouse xenograft model with two large peritoneal implants of colorectal cancer cells was developed to study drug distribution and tumor physiology during intraperitoneal Oxaliplatin perfusion. Mice were treated for six days with either Placebo, Imatinib (anti-PDGFR, daily), Bevacizumab (anti-VEGF, twice) or Pazopanib (anti-PDGFR, -VEGFR; daily) followed by intraperitoneal oxaliplatin chemotherapy. Bevacizumab and Pazopanib significantly lowered interstitial fluid pressure, increased Oxaliplatin penetration (assessed by laser ablation inductively coupled plasma mass spectrometry) and delayed tumor growth of peritoneal implants (assessed by MRI). Our findings suggest that VEGF(R)-inhibition may improve the efficacy of IPC, particularly for patients for whom a complete cytoreduction might not be feasible.

2204 Predicting incomplete cytoreduction and aborted hyperthermic intraperitoneal chemotherapy procedures in patients with peritoneal carcinomatosis

2204 Predicting incomplete cytoreduction and aborted hyperthermic intraperitoneal chemotherapy procedures in patients with peritoneal carcinomatosis

Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of a concept

ObjectiveTo develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT>0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal surgery (UAS). Patients and methodsThe presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity≥75%, PPV≥50%, and NPV≥50% received 1 point score, with an additional one point in the presence of an accuracy of ≥60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. ResultsNo-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV≥10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC=0.885). ConclusionsS-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.

Incorporation of diagnostic laparoscopy in the management algorithm for patients with peritoneal metastases: A multi-institutional analysis.

Diagnostic laparoscopy (DL), which can predict complete cytoreduction (CC), is often considered unfeasible in patients with Peritoneal metastases (PM) due to a hostile abdomen, prior surgeries, incomplete assessment or risk of port site recurrence. We hypothesized that DL can be successfully incorporated into the management of patients with PM. Retrospective review and data analysis of prospectively maintained databases from two high volume institutions was performed between 2007 and 2013. DL was successfully completed in 211/217 (92.6%) patients with PM. The technique for entry was the Hasson in 57%, optical trocar in 38% and Veress needle in 5%. Serosal injury from DL occurred in one patient (0.4%). Predominant histology included appendiceal (40%) and colorectal primaries (34%). Exclusion from cytoreduction by DL occurred in 68 (31.3%). Among those excluded, 7 (of 68, 10.3%) subsequently underwent CRS + HIPEC after receiving systemic chemotherapy. Overall survival (from laparoscopy) for those that underwent CRS + HIPEC at the original operation was 36 versus 12.7 months among those who were excluded by laparoscopy. There were no cases of port site recurrence. Diagnostic laparoscopy can be safely incorporated in the management of patients with peritoneal metastases, and can be especially beneficial in excluding patients from attempted incomplete cytoreduction.

Complete versus incomplete cytoreduction in peritoneal carcinosis from gastric cancer, with consideration to PCI cut-off. Systematic review and meta-analysis

IntroductionThe completeness of cytoreduction has been considerated as fundamental in increasing the life expectancy in patients with peritoneal carcinosis (PC) in gastric cancer. However no defintive data about the real effect of complete cytoreduction (CC) have still been published. Moreover the PCI cut-off to attempt CC with a reasonable risk-benefit ratio still lacks. Material and methodsA systematic review with meta-analysis of trials of complete vs incomplete cytoreduction in patients with peritoneal carcinosis from GC was performed. ResultsNine trials have been included (748 patients: 417 with CC0-CC1 and 324 with CC2-CC3 cytoreduction). 1, 2, 3 and 5 years survival is favorable to CC0-CC1 (Risk Ratio: 2.41, 8.18, 8.66, and 7.96 respectively). CC0 vs. CC1 survival benefit at 1 and 3 years: RR 2.28 and 6.36 respectively, favoring CC0. 1, 2, 3 and 5 years survival changes significantly above and below a PCI of 12. Conclusions1, 2, 3 and 5-year overall survival is increased by CC0-CC1 cytoreduction in patients with PC from gastric origin. Moreover CC0 increases the 1 and 3 years survival when compared to CC1 cytoreduction.

Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of concept

Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of concept

A Simplified Preoperative Assessment Predicts Complete Cytoreduction and Outcomes in Patients with Low-Grade Mucinous Adenocarcinoma of the Appendix.

BackgroundComplete cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve survival in patients with low-grade mucinous adenocarcinoma (LGMA). However, incomplete cytoreduction exposes patients to significant morbidity without a similar survival benefit. Preoperative assessment of the ability to achieve CRS is therefore a critical step in selecting patients for CRS/HIPEC.ObjectiveThe aim of this study was to develop and validate a preoperative scoring system to accurately predict the ability to achieve complete cytoreduction in patients with LGMA of the appendix.MethodsA simplified preoperative assessment for appendix tumor (SPAAT) score was developed based on computed tomography scan findings thought to predict incomplete cytoreduction. We applied the SPAAT score to patients with LGMA to determine the ability of the score to predict complete cytoreduction. This scoring system was then applied to a separate cohort of patients from a different institution. Sensitivity and specificity were determined for the SPAAT score. Survival was calculated and correlated with the SPAAT score and the completeness of cytoreduction score.ResultsA SPAAT score of <3 is a significant predictor of complete cytoreduction in the derivation cohort. In the validation cohort, 40 of 42 patients with a SPAAT score <3 achieved a complete cytoreduction, for a positive predictive value of 95.2 % and a negative predictive value of 100 %. Additionally, the SPAAT score was a significant predictor of disease-free survival.ConclusionsThe SPAAT score is a useful tool in the preoperative assessment of patients with LGMA who are under consideration for cytoreductive surgery. Prospective analysis of this scoring system is warranted to appropriately select patients who will benefit from CRS/HIPEC.

Outcome following incomplete surgical cytoreduction combined with intraperitoneal chemotherapy for colorectal peritoneal metastases.

Cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectable disease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, PubMed and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732 (62%) underwent a complete cytoreduction while 986 (35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.

Nomogram for predicting incomplete cytoreduction in advanced ovarian cancer patients

ObjectiveAccurately predicting cytoreducibility in advanced-ovarian cancer is needed to establish preoperative plans, consider neoadjuvant chemotherapy, and improve clinical trial protocols. We aimed to develop a positron-emission tomography/computed tomography-based nomogram for predicting incomplete cytoreduction in advanced-ovarian cancer patients. MethodsBetween 2006 and 2012, 343 consecutive advanced-ovarian cancer patients underwent positron-emission tomography/computed tomography before primary cytoreduction: 240 and 103 patients were assigned to the model development or validation cohort, respectively. After reviewing the detailed surgical documentation, incomplete cytoreduction was defined as a remaining gross residual tumor. We evaluated each individual surgeon's surgical aggressiveness index (number of high-complex surgeries/total number of surgeries). Possible predictors, including surgical aggressiveness index and positron-emission tomography/computed tomography features, were analyzed using logistic regression modeling. A nomogram based on this model was developed and externally validated. ResultsComplete cytoreduction was achieved in 120 patients (35%). Surgical aggressiveness index and five positron-emission tomography/computed tomography features were independent predictors of incomplete cytoreduction. Our nomogram predicted incomplete cytoreduction by incorporating these variables and demonstrated good predictive accuracy (concordance index=0.881; 95% CI=0.838–0.923). The predictive accuracy of our validation cohort was also good (concordance index=0.881; 95% CI=0.790–0.932) and the predicted probability was close to the actual observed outcome. Our model demonstrated good performance across surgeons with varying degrees of surgical aggressiveness. ConclusionWe have developed and validated a nomogram for predicting incomplete cytoreduction in advanced-ovarian cancer patients which may help stratify patients for clinical trials, establish meticulous preoperative plans, and determine if neoadjuvant chemotherapy is warranted.

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.

Peritoneal surface disease (PSD) from appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): overview of 481 cases.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) used to treat peritoneal surface disease (PSD) from appendiceal cancer have shown variability in survival outcomes. The primary goal of this study was to determine predictors of surgical morbidity and overall survival. The secondary goal was to describe the impact of nodal status on survival after CRS/HIPEC for PSD from low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primary lesions. A retrospective analysis of 1,069 procedures from a prospective database was performed. Patient characteristics, tumor grade, nodal status, performance status, resection status, morbidity, mortality, and survival were reviewed. The study identified 481 CRS/HIPEC procedures: 317 (77.3 %) for LGA and 93 (22.7 %) for HGA lesions. The median follow-up period was 44.4 months, and the 30-day major morbidity and mortality rates were respectively 27.8 and 2.7 %. Major morbidity was jointly predicted by incomplete cytoreduction (p = 0.0037), involved nodes (p < 0.0001), and comorbidities (p = 0.003). Multivariate negative predictors of survival included positive nodal status (p = 0.003), incomplete cytoreduction (p < 0.0001), and preoperative chemotherapy (p = 0.04) in LGA patients and incomplete cytoreduction (p = 0.0003) and preoperative chemotherapy (p = 0.0064) in HGA patients. After complete cytoreduction, median survival was worse for patients with positive nodes than for those with negative nodes in LGA (85 months vs not reached [82 % alive at 90 months]; p = 0.002) and HGA (30 vs 153 months; p < 0.0001). Positive nodes are associated with decreased survival not only for HGA patients but also for LGA patients even after complete cytoreduction. Nodal status further stratifies histologic grade as a prognostic indicator of survival. Patients with node-negative HGA primary lesions who receive a complete cytoreduction may experience survival comparable with that for LGA patients.

Significance of diaphragmatic resections and thoracic chemoperfusion on outcomes of peritoneal surface disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Diaphragmatic resection (DR) during CRS/HIPEC exposes the thoracic cavity to direct contamination from the peritoneal cavity. The effect of thoracic chemoperfusion in combination with HIPEC in these patients is unknown. A prospective database of 1,077 procedures was analyzed. Type of malignancy, thoracic perfusion, resection status, comorbidities, morbidity, mortality, and overall survival were reviewed. DR was a component of 102 CRS/HIPEC procedures performed for 57 (55.9 %) appendiceal and 22 (21.6 %) colon primary lesions. DR was associated with higher volume of disease as evidenced by more organ resections (3.7 vs. 2.8, p < 0.001) and increased rates of incomplete cytoreduction (67 vs. 52 %, p = 0.004). Patients with and without DR had similar 30-day major morbidity (23.5 vs. 16.8 %, p = 0.1) and worse 90-day mortality (12.8 % vs. 6.12 %, p = 0.03), respectively. Multivariate analysis showed DR (p = 0.01) and diabetes (p = 0.005) to be associated with worse mortality. Nineteen (20 %) DR patients underwent synchronous abdominal and thoracic chemoperfusion. Intrathoracic recurrence following DR with thoracic perfusion was 17 % (3/18) vs. 2.3 % (2/85) without perfusion (p = 0.04). Median survival following complete cytoreduction was similar for patients with low-grade appendiceal (LGA) (not reached with DR and 175 months without DR, p = 0.17) and colorectal cancer (23 months with and 31 months without DR, p = 0.76). Diaphragmatic resection during CRS/HIPEC is an independent predictor of surgical mortality. Intrapleural perfusion was associated with more thoracic recurrence; however, complete cytoreduction with or without DR can achieve similar survival for patients with LGA and colorectal primary lesions. DR should be performed only if careful inspection deems all peritoneal disease resectable.