Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy.

BACKGROUND: Pancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection. MATERIALS AND METHODS: Prospectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed. RESULTS: Between 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010). CONCLUSION: Patients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.

Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.

BACKGROUND: It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. OBJECTIVE: This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. DESIGN: This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. SETTING: The study was conducted by 1 surgical team at St. George Hospital. PATIENTS: A total of 444 patients formed the cohort of this study. MAIN OUTCOME MEASURES: Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. RESULTS: Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p < 0.001), adjusted for peritoneal cancer index >20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. LIMITATIONS: This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. CONCLUSIONS: Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.

Physical and chemical characteristics of mucin secreted by pseudomyxoma peritonei (PMP).

Background: Pseudomyxoma peritonei (PMP) is a rare disease with excess intraperitoneal mucin secretion. Treatment involves laparotomy, cytoreduction and chemotherapy that is very invasive with patients often acquiring numerous compromises. Hence a mucolytic comprising of bromelain and N-acetyl cystein has been developed to solubilise mucin in situ for removal by catherization. Owing to differences in mucin appearance and hardness, dissolution varies. Therefore the current study investigates the inter-mucin physical and chemical characteristics, in order to reformulate an effective mucolytic for all mucin. Method: PMP mucin, from the three categories (soft, semi hard and hard mucin) was solubilised and then various physical characteristics such as turbidity, density, kinematic viscosity were measured. The water content and the density of solid mucin were also determined. This was followed by the determination of sialic acid, glucose, lipid, Thiol (S-S and S-H) content of the samples. Lastly, the distribution of MUC2, MUC5B and MUC5AC was determined using western blot technique. Results: Both turbidity and kinematic viscosity and sialic acid content increased linearly as the hardness of mucin increased. However, density, hydration, protein, glucose, lipid and sulfhydryl and disulphide content decreased linearly as hardness of mucin increased. The distribution ratio of mucins (MUC2:MUC5B:MUC5AC) in soft mucin is 2.25:1.5:1.0, semi hard mucin is 1:1:1 and hard mucin is 3:2:1. Conclusion: The difference in texture and hardness of mucin may be due to cellular content, hydration, glucose, protein, lipids, thiol and MUC distribution. Soft mucin is solely made of glycoprotein whilst the others contained cellular materials.

Impacts of Preoperative Serum Albumin Level on Outcomes of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy.

BACKGROUND: Only few small studies in the literature have explored the impacts of preoperative serum albumin level and clinical outcomes of patients with peritoneal surface malignancy (PSM) who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). This study aimed to evaluate the value of preoperative serum albumin as a prognostic factor for long-term survival outcomes after CRS and PIC in a large patient cohort and to determine whether preoperative serum albumin is correlated with perioperative complications. METHODS: This retrospective study examined prospectively collected data for patients with PSM who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia. The study used 35 g/L as the cuffoff for normal serum albumin level. RESULTS: The study enrolled 591 patients. Hypoalbuminemia was found to be associated with a significantly higher rate of major morbidity (p < 0.001), a longer ICU stay (p = 0.003), a longer HDU stay (p < 0.001), a longer total hospital stay (p < 0.001), and a shorter overall survival (OS) (p = 0.016). Factor analysis showed preoperative serum hypoalbuminemia to be a prognostic factor for a poor perioperative outcome (p = 0.018) and a poor OS (p = 0.026). CONCLUSION: Preoperative hypoalbuminemia is associated with poor perioperative outcomes. More importantly, it is a predictor of poorer OS for patients with PSM independent of the PCI, age, and completeness of cytoreduction. In the future, strategies should be undertaken to improve preoperative nutrition of malnourished patients as a means of improving clinical outcomes for patients with PSM.

Prognostic significance of Ki67 expression in malignant peritoneal mesothelioma.

OBJECTIVES: Although Ki67 measurement by immunohistochemistry has been widely used as a prognostic index in cancers, it has not been reported in malignant peritoneal mesothelioma (MPM). Hence, this study examines the prognostic significance of Ki67 in MPM. METHODS: Specimens from 42 MPM patients were screened for Ki67 expression using immunohistochemistry. Ki67 expression was classified into 2 groups on the basis of expression (<25%=low; ≥25%=high) using standard methods. Using Kaplan-Meier survival analysis, the significance of Ki67 was assessed in different clinicopathologic categories. RESULTS: High expression of Ki67 (≥25% by immunohistochemical evaluation) was correlated with poor survival in the overall group (P=0.001); male sex (P=0.001); female sex (P=0.001); epithelioid tumors (P=0.001): male epithelioid (P=0.001), female epithelioid (P=0.003); peritoneal cancer index (PCI): PCI<20 (P=0.001), PCI≥20 (P=0.002); and age at diagnosis (AAD): AAD<60 years (P=0.001), AAD≥60 years (P=0.004). Independent of Ki67, male sex (P=0.007), sarcomatoid histology (P=0.001), PCI≥20 (P=0.013), and AAD≥60 years (P=0.004) correlated with poor survival. Multivariate analysis showed that only AAD≥60 years (P=0.049) and high Ki67 expression for all tumors (P=0.031), male sex (P=0.038), female sex (P=0.021), epithelioid tumors (P=0.044), and AAD<60 years (P=0.029) were statistically significant. CONCLUSIONS: Ki67 expression affects prognosis in MPM patients and helps to predict survival within the various clinicopathologic categories.

A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei.

Although numerous clinical attempts have been made to disintegrate mucin secreted by pseudomyxoma peritonei (PMP), none are clinically recommended. Through examination of the pharmacologic characteristics of two novel agents, we titrated an optimized combination of bromelain and N-acetyl cysteine (NAC) that demonstrates in vitro and in vivo efficacy in the dissolution of mucinous ascites from PMP. In the in vitro experiments, 1 g of mucin was incubated in varying concentrations of bromelain (0-400 µg/ml) and NAC (0-5%) individually followed by a combination before arriving at a therapeutic combination dose of 300 µg/ml bromelain+4% NAC. This established an effective dose of bromelain 300 µg/ml+4% NAC at pH 7.0, when tested in a rat model implanted with 3 g of mucin intraperitoneally (IP). IP administration of the drug in a rat model of PMP was shown to result in mucin disintegration within 72 hr with no toxicity observed.

Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells.

Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneum, causally related to asbestos exposure. Nonspecific symptoms with a late diagnosis results in poor survival (<1 year). Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has improved survival in some patients (median 3-5 years). Hence, new therapies are urgently needed. MUC1 is a glycosylation-dependent protein that confers tumours with invasiveness, metastasis and chemoresistance. Bromelain (cysteine proteinase) hydrolyses glycosidic bonds. Therefore, we investigated the antitumour effect of bromelain on MUC1-expressing MPM cell lines. MUC1 expressions in cells were assessed using immunofluorescent probes with cells grown on cover slips and western blot analysis on cell lysates. The cell lines were treated with various concentrations of bromelain and after 4 and 72 h, their viability was assessed using standard sulforhodamine assays. The cells were also treated with combinations of bromelain and cytotoxic drugs (cisplatin or 5-FU) and their viability was assessed at 72 h. Finally, with western blotting, the effects of bromelain on cellular survival proteins were investigated. PET cells expressed more MUC1 compared with YOU cells. The cell viability of both PET and YOU cells was adversely affected by bromelain, with PET cells being slightly resistant. The addition of bromelain increased the cytotoxicity of cisplatin significantly in both cell lines. However, 5-FU with bromelain did not show any significant increase in cytotoxicity. Bromelain-induced cell death is by apoptosis and autophagy. Bromelain has the potential of being developed as a therapeutic agent in MPM.

Cure for peritoneal metastases? An evidence-based review.

There is now a considerable body of published evidence supporting the use of a multimodal approach consisting of cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases (PM) arising from selected gastrointestinal tract malignancies. In the absence of systemic metastases, it is thought that disease confined to the peritoneum may be eradicated through optimum cytoreduction. This review critically evaluates the current body of published evidence for the use of CS/HIPEC in the treatment of advanced colorectal, appendiceal and gastric cancer. Although its role remains less defined in patients with gastric PM, current evidence provides a compelling argument for its use in PM of colorectal and appendiceal origin. With a low mortality and acceptable morbidity rate, CS/HIPEC may offer hope of long-term survival and cure in a defined group of patients with this disease.

Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves disease control within the peritoneum but recurrences occur. This study examines the outcomes of iterative CRS (iCRS) HIPEC for treatment of recurrent peritoneal metastases. METHODS: Patients who underwent iCRS in a single tertiary referral center were identified from a prospective database. Safety analysis was performed and clinicopathological variables were analyzed to assess factors predictive of major morbidity and survival. RESULTS: The demographics of patients who underwent primary cytoreductive surgery (pCRS) (n = 466) and iCRS (n = 79) were balanced between groups. pCRS was shown to require more blood transfusion (P = 0.019) and albumin use (P = 0.013). The mortality and major complication rates were comparable (1.2% vs. 0%; P = 0.600, and 42% vs. 41%; P = 0.806). Residual pneumothorax occurred more frequently after pCRS (12% vs. 4%; P = 0.030). Factors associated with major complications after iCRS include use of HIPEC (P = 0.042) and length of hospital stay (P = 0.024). The overall median survival was 48 months and 5-year survival was 34%. By cancer type, the 3-year survival was 0%, 74%, 80%, and 72% for colorectal, appendiceal pseudomyxoma, peritoneal mesothelioma, and appendix cancer, respectively. Independent predictors of survival include age (P = 0.049), interval between pCRS and iCRS (P = 0.008), small bowel resection (P < 0.001), and use of HIPEC (P = 0.005). CONCLUSION: Iterative CRS achieved further peritoneal disease control without adverse effects on morbidity. Patients with appendiceal tumors and peritoneal mesothelioma appear to benefit most after iCRS. Intraoperative HIPEC remains important in the repetoire of managing these patients.

Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma.

Bromelain is a mixture of proteolytic enzymes that is capable of hydrolyzing glycosidic linkages in glycoprotein. Glycoprotein's are ubiquitously distributed throughout the body and serve a variety of physiologic functions. Faulty glycosylation of proteins may lead to cancer. Antitumor properties of bromelain have been demonstrated in both, in vitro and in vivo studies, along with scanty anecdotal human studies. Various mechanistic pathways have been proposed to explain the anticancer properties of bromelain. However, proteolysis by bromelain has been suggested as a main pathway by some researchers. MUC1 is a glycoprotein that provides tumor cells with invasive, metastatic, and chemo-resistant properties. To date, there is no study that examines the effect of bromelain on MUC1. However, the viability of MUC1 expressing pancreatic and breast cancer cells are adversely affected by bromelain. Further, the efficacy of cisplatin and 5-FU are enhanced by adjuvant treatment with bromelain, indicating that the barrier function of MUC1 may be affected. Other studies have also indicated that there is a greater accumulation of 5-FU in the cell compartment on treatment with 5-FU and bromelain. Malignant peritoneal mesothelioma (MPM) expresses MUC1 and initial studies have shown that the viability of MPM cells is adversely affected by exposure to bromelain. Further, bromelain in combination with either 5-FU or cisplatin, the efficacy of the chemotherapeutic drug is enhanced. Hence, current evidence indicates that bromelain may have the potential of being developed into an effective anticancer agent for MPM.

Secondary cytoreductive surgery and peri-operative intraperitoneal chemotherapy for peritoneal recurrence of colorectal and appendiceal peritoneal carcinomatosis following prior primary cytoreduction.

PURPOSE: Primary cytoreductive surgery (CRS) and peri-operative intraperitoneal chemotherapy (PIC) is the only curative option for patients with colorectal cancer peritoneal carcinomatosis (PC). A significant proportion of patients develop peritoneal recurrence. Outcomes of patients undergoing secondary CRS and PIC for recurrent PC were examined. METHODS: All patients undergoing second procedures with curative intent for recurrent appendiceal or colorectal cancer PC in three centers were included. Patients with recurrent pseudomyxoma peritonei (PMP) were excluded. Morbidity and mortality, overall survival, and disease-free survival were primary outcome parameters. RESULTS: The study included 18 patients (13 colorectal and 5 appendiceal cancer). At primary CRS, mean Peritoneal Cancer Index (PCI) was 9.1. In 13 patients complete resection was achieved. Median time to recurrence was 14 months (range: 1-33). At secondary CRS, mean PCI was 6.3 and CRS was complete in 13 patients. There was no 30-day mortality and 1- and 2-year survival were 74% and 50%, respectively. In 14 patients a recurrence after the second procedure was diagnosed. CONCLUSIONS: A secondary CRS for recurrent colorectal or appendiceal cancer PC is safe and feasible, however, relapse is frequent. Further investigations are required to critically assess the efficacy of a secondary procedure and to define optimal patient selection criteria in the era of effective modern chemotherapy.

Summary of current therapeutic options for peritoneal metastases from colorectal cancer.

BACKGROUND: Peritoneal metastases remain an under addressed problem for which this review serves to investigate the efficacy of systemic chemotherapy and radical surgical treatments in this disease entity. METHODS: The literature between 1995 and June 2009 was surveyed systematically through a review of published studies on the treatment outcomes of metastatic colorectal cancer to the peritoneum on the Medline and PubMed databases. RESULTS: A total of 2,492 patients from 19 studies were reviewed. One thousand and eighty-four patients treated with complete cytoreductive surgery (CCS) and hyperthermic intraperitoneal chemotherapy (HIPEC) and 1,408 patients were treated with palliative surgery and/or systemic chemotherapy. For CCS HIPEC, the overall survival ranged between 20 and 63 (median 33) months, and 5-year survival ranged between 17% and 51% (median 40%). For palliative surgery and/or systemic chemotherapy, the overall survival ranged between 5 and 24 (median 12.5) months, and 5-year survival ranged between 13% and 22% (median 13%). CONCLUSION: Systemic therapies have not proved effective and randomised clinical trials have not sufficiently addressed patient subpopulations with metastatic disease of this entity. Current evidence have demonstrated the efficacy associated with CCS HIPEC for which should now be embraced as the standard of care.

Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

PURPOSE: Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. PATIENTS AND METHODS: A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International. RESULTS: Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival. CONCLUSION: The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.

Surgery for colorectal peritoneal carcinomatosis.

Peritoneal carcinomatosis occurs in patients with advanced gastrointestinal and gynecological malignancies and also in patients who experience recurrence after treatment failure of the primary tumor. Malignant disease in the peritoneal cavity is a morbid and significant predictor of a diminished survival in a cancer patient. Systemic chemotherapy alone will not be adequate to palliate or treat patients with peritoneal carcinomatosis. Cytoreductive surgery is a new surgical technique that is performed using peritonectomy procedures to allow total eradication of peritoneal tumors. Intraperitoneal chemotherapy regimens such as intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) are effective adjuvant treatment to treat the minimal residual disease after cytoreductive surgery to reduce the risk of locoregional recurrence. A substantial body of evidence available in the current literature has documented the survival benefits of combining cytoreductive surgery and intraperitoneal chemotherapy to treat a previously fatal phase of malignancy. This review provides a summary of the developments in the understanding and treatment of peritoneal surface malignancy from colorectal cancer.

Mucolysis by ascorbic acid and hydrogen peroxide on compact mucin secreted in pseudomyxoma peritonei.

BACKGROUND: This study examines the potential efficacy of hydrogen peroxide and ascorbic acid in the dissolution of mucinous ascites from pseudomyxoma peritonei. METHODS: The mucolytic action of both ascorbic acid (0%-0.2%) and hydrogen peroxide (0%-3%) are investigated as single agent on mucin samples derived from patient. This was followed by examining the joint action of ascorbic acid (0.2%) and hydrogen peroxide (0%-3.0%) on mucin. To lower the concentration of hydrogen peroxide in the mixture, the action of equal concentration of ascorbic acid/hydrogen peroxide ranging from 0%-0.3% are then examined. Finally, the pH (4.5-7.0) effect on mucolytic properties of equal concentration (0.2%) of ascorbic acid/hydrogen peroxide was studied. RESULTS: At the concentrations examined (0%-0.2%), ascorbic acid showed highest mucolytic activity at 0.2%. Similarly, hydrogen peroxide as a single agent (0%-3.0%) showed highest mucolytic activity at 3.0%. The mucolytic action of hydrogen peroxide (0%-3.0%) containing 0.2% ascorbic acid demonstrated synergistic effects. At equal concentration of the two agents, ranging from 0%-0.5%, maximal mucolytic action was observed at 0.2%. The mucolytic property of the final mixture (0.2% ascorbic acid/0.2% hydrogen peroxide) was pH-dependent and showed maximal degradation at pH 4.5 and declined as it reached towards neutral pH. CONCLUSION: The current study introduces the potential applicability of a formulation that holds promise as a mucolytic agent in patients with mucinous ascites from pseudomyxoma peritonei.

Outcomes of elderly patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal cancer peritoneal carcinomatosis.

BACKGROUND: The combined treatment of cytoreductive surgery (CRS) and perioperative chemotherapy (PIC) for colorectal peritoneal carcinomatosis (PC) is a rigorous surgical treatment most suited for fit and young patients. With technical maturity and improved perioperative care, we examined the outcomes of elderly patients undergoing CRS and PIC for colorectal PC. METHODS: All consecutive patients treated in two tertiary centers for PC of colorectal cancer who were 70 years of age or older at the time of surgery were included. Data on patient characteristics, concomitant diseases, operation details, perioperative course, and follow-up were retrieved from medical charts. Primary outcomes were perioperative morbidity and mortality. Secondary outcomes were disease-free and overall survival. RESULTS: Twenty-four patients (11 male) were included in this study (mean age 73.5 years). In eight patients major complications occurred. In six patients the postoperative course was complicated by minor adverse events. There was no perioperative mortality. Median overall survival was 35 months with a 6, 12, and 18 months survival rate of 94%, 83%, and 68%, respectively. CONCLUSIONS: CRS and PIC for colorectal PC may be safely performed with acceptable morbidity in selected elderly patients. When considering patients for surgery, performance status, and the disease extent should be used as eligibility criteria rather than age.

Development of a Bayesian Belief Network Model for personalized prognostic risk assessment in colon carcinomatosis.

Multimodality therapy in selected patients with peritoneal carcinomatosis is gaining acceptance. Treatment-directing decision support tools are needed to individualize care and select patients best suited for cytoreductive surgery +/- hyperthermic intraperitoneal chemotherapy (CRS +/- HIPEC). The purpose of this study is to develop a predictive model that could support surgical decisions in patients with colon carcinomatosis. Fifty-three patients were enrolled in a prospective study collecting 31 clinical-pathological, treatment-related, and outcome data. The population was characterized by disease presentation, performance status, extent of peritoneal cancer (Peritoneal Cancer Index, PCI), primary tumor histology, and nodal staging. These preoperative parameters were analyzed using step-wise machine-learned Bayesian Belief Networks (BBN) to develop a predictive model for overall survival (OS) in patients considered for CRS +/- HIPEC. Area-under-the-curve from receiver-operating-characteristics curves of OS predictions was calculated to determine the model's positive and negative predictive value. Model structure defined three predictors of OS: severity of symptoms (performance status), PCI, and ability to undergo CRS +/- HIPEC. Patients with PCI < 10, resectable disease, and excellent performance status who underwent CRS +/- HIPEC had 89 per cent probability of survival compared with 4 per cent for those with poor performance status, PCI > 20, who were not considered surgical candidates. Cross validation of the BBN model robustly classified OS (area-under-the-curve = 0.71). The model's positive predictive value and negative predictive value are 63.3 per cent and 68.3 per cent, respectively. This exploratory study supports the utility of Bayesian classification for developing decision support tools, which assess case-specific relative risk for a given patient for oncological outcomes based on clinically relevant classifiers of survival. Further prospective studies to validate the BBN model-derived prognostic assessment tool are warranted.

Surgical therapies in metastatic colorectal cancer with a potential for cure.

Metastatic colorectal cancer has evolved from a paradigm that was previously centered upon the use of systemic chemotherapy to one of multimodality therapy. Hepatectomy, pulmonary metastasectomy, and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy are surgical procedures that are now routinely performed in specialized institutions treating patients with metastatic colorectal cancer. Emerging evidence suggests that in selected patients, these procedures are safe and may be beneficial in contributing to long-term survival.

Evolution of locoregional treatment for peritoneal carcinomatosis: single-center experience of 308 procedures of cytoreductive surgery and perioperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis imposes an enormous clinical burden to the oncologic community. This study reports the patterns of care of the locoregional approach of cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy as a curative procedure for peritoneal carcinomatosis from the experience of a single tertiary center in Australia. METHODS: We performed a review of clinical records from a prospective database of patients who were treated at the St George Hospital Peritoneal Surface Malignancy Program according to a standard protocol. RESULTS: A total of 308 CRS were performed in 249 patients with peritoneal surface malignancy; the mean age was 53 years and 55% were women. Over the years, we expanded the age limit for treatment (P = .03), reduced intensive care unit stays (P = .04), reduced amount of blood transfusion (P = .03), treated patients with a higher peritoneal cancer index (P < .001), achieved higher rates of complete cytoreduction (P = .003), increased use of PIC (P < .001), and improved complication rate (P = .02) and mortality rate (P = .01). The median survival of patients treated over the years also improved (P = .001). CONCLUSIONS: We show the maturity of the treatment of peritoneal carcinomatosis with CRS and perioperative intraperitoneal chemotherapy in our institution after an initial learning curve with expansion of the selection criteria, improved perioperative outcomes, improved surgical results, and long-term survival outcomes.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. PATIENTS AND METHODS: All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. RESULTS: Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. CONCLUSION: The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.