Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Improves Survival of Patients with Peritoneal Carcinomatosis from Gastric Cancer: Final Results of a Phase III Randomized Clinical Trial

Background

This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer.

Methods

Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60–90 min. The primary end point was overall survival, and the secondary end points were safety profiles.

Results

Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2–36 (median 15) in the CRS + HIPEC and 3–23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0–1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5–83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8–8.2 months) in CRS and 11.0 months (95% confidence interval 10.0–11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0–1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival.

Conclusions

For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.     

Impact of Aggressive Histology and Location of Primary Tumor on the Efficacy of Surgical Therapy for Peritoneal Carcinomatosis of Colorectal Origin

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) of colorectal origin increases survival (OS) compared to systemic chemotherapy alone. Signet ring histology demonstrates aggressive behavior with poor survival. We sought to determine whether CRS/HIPEC increases survival in this subset of patients.

Methods

We reviewed 67 patients with PC of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology from a prospective database between May 2001 and August 2011. Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival.

Results

Complete CRS (CC-0/1) was achieved in 77 % (CRC) and 73 % (AP) of patients. Progression-free survival (PFS) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients. In the CRC group, univariate predictors of poor survival included female gender, age, American Society of Anesthesiologists score, preoperative albumin, completeness of cytoreduction, and morbidity. In a multivariate Cox regression model, incomplete cytoreduction (CC-2/3) and female gender were joint significant predictors of poor survival. In the AP group, significant univariate predictors of poor survival included higher EBL and PCI score. In a multivariate Cox regression model, blood loss of >500 ml and a body mass index of <25 kg/m² were joint significant predictors of poor survival.

Conclusions

AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis, suggesting an underlying difference in biology. CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved, whereas appendiceal signet ring carcinomatosis may benefit, regardless of resectability.     

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m²) or mitomycin C (35 mg/m²). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.     

Outcome Data of Patients with Peritoneal Carcinomatosis from Gastric Origin Treated by a Strategy of Bidirectional Chemotherapy Prior to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a Single Specialized Center in Japan

Background

Management of peritoneal disseminated gastric cancer (GC) remains a challenging problem. The purpose of our study was to evaluate the outcome of bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC) arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Patients and Methods

Overall, 194 patients with PC arising from GC were treated with BIPSC comprising intraperitoneal docetaxel at a dose of 20 mg/m² and cisplatin at a dose of 30 mg/m² followed by four cycles of oral S-1 at a dose of 60 mg/m². CRS and HIPEC were performed in responders to BIPSC.

Results

Of these 194 patients, 152 (78.3 %) underwent CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality was 3.9 %, and major complications occurred in 23.6 % of patients. The median survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32 and 10.7 %, respectively, in the patients treated with combined treatment. Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low tumor burden [peritoneal cancer index (PCI) ≤ 6] (p = 0.001), and completeness of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis.

Conclusion

As a viable option, BIPSC with CRS and HIPEC for patients with PC arising from GC may be performed safely, with acceptable morbidity and mortality, in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal dissemination seem to be essential to achieve the best outcomes in these patients.     

Cytoreduction and HIPEC in The Netherlands: Nationwide Long-term Outcome Following the Dutch Protocol

Purpose

This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol.

Methods

In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival.

Results

Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III–V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0–166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36–46 months). Median progression-free survival was 15 months (95 % CI 13–17 months) for CRC patients and 53 months (95 % CI 40–66 months) for PMP patients. Overall median survival was 33 (95 % CI 28–38 months) months for CRC patients and 130 months (95 % CI 98–162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients.

Conclusions

The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.     

Preoperative Carcinoembryonic Antigen Level Predicts Prognosis in Patients with Pseudomyxoma Peritonei Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

Even though management of pseudomyxoma peritonei (PMP) was improved with cytoreductive surgery (CRS) and hyperthermic chemotherapy (HIPEC), several aspects of PMP still need to be optimized, including patient selection for surgery and prognostic factors. We assessed the role of preoperative carcinoembryonic antigen (CEA) levels in PMP patients treated with CRS and HIPEC.

Methods

A total of 449 PMP patients with documented preoperative CEA levels referred to our center between 2005 and 2011 underwent CRS and HIPEC. The association between CEA levels and characteristics of patients with PMP was assessed with χ ² test, linear correlation, and logistic regression analyses. Survival analysis was performed with Cox proportional hazard model.

Results

Median age was 55 (range 19–84) years. There were 245 (54.5 %) females and 204 (45.5 %) males. Preoperative CEA levels were elevated in 328 (73 %, sensitivity) patients with PMP. Preoperative CEA levels were also related to peritoneal cancer index (P < 0.0001), cytoreductive surgery scores (P < 0.0001), progress free survival (P < 0.001) and overall survival (P < 0.001) in patients with PMP.

Conclusions

Our results indicated that preoperative CEA levels are useful in predicting the extent of disease and surgical success as well as progress-free and overall survival in patients with PMP treated with cytoreductive surgery and HIPEC.     

Cytoreductive Surgery Under Aminolevulinic Acid-Mediated Photodynamic Diagnosis Plus Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis from Ovarian Cancer and Primary Peritoneal Carcinoma: Results of a Phase I Trial

Background

We conducted a phase I clinical trial to evaluate the sensitivity, specificity, and safety of cytoreductive surgery (CRS) under aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on 20 patients with peritoneal carcinomatosis (PC) from ovarian cancer and primary peritoneal carcinoma (PPC).

Patients and Methods

Patients took 5-aminolevulinic acid (5-ALA) at a dose of 20 mg/kg orally with 50 mL of water 2 h before surgery. During surgery, the abdominal cavity was observed under blue light (wavelength of 440 nm) before and after CRS plus HIPEC. Specimens were excised and submitted for pathological examination to evaluate the specificity of ALA-PDD. Postoperative course was closely monitored and detailed information was recorded.

Results

CRS under ALA-PDD plus HIPEC was performed 21 times in 20 patients with PC (16 ovarian cancer, 4 PPC) between June 2011 and October 2013. With the exception of 1 (5 %) patient, strong red fluorescence was detected in 19 patients with ovarian cancer, with a sensitivity of 95 %. All specimens from red fluorescent lesions were invaded by cancer cells, with a specificity of 100 %. No severe adverse events occurred during the perioperative period, with the exception of some abnormal laboratory results and mild complications. All patients were alive until the last follow-up.

Conclusion

ALA-PDD provided a high sensitivity and specificity in detecting peritoneal metastasis in patients with PC from ovarian serous carcinoma and PPC. CRS under ALA-PDD plus HIPEC was a feasible and safe treatment option for patients with PC from ovarian cancer and PPC.     

Predictive and Prognostic Survival Factors in Peritoneal Carcinomatosis from Appendiceal Cancer After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy

Background

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefit in the treatment of selected patients with peritoneal carcinomatosis (PC) from appendiceal cancer (AC). We evaluated factors affecting the survival of patients with PC from AC after CRS/HIPEC.

Methods

A retrospective analysis of 387 CRS/HIPEC procedures performed between February 1998 and February 2013 identified 202 patients with PC from AC. Tumor histopathology, complete cytoreduction (CC 0–1), Peritoneal Cancer Index (PCI), and lymph node (LN) status were related to overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier method.

Results

Overall, 129 women (64 %) and 73 men (36 %), mean age 54 years (range 25–81), with a mean follow-up of 36 months were included in the study. Seventy-seven low-grade tumors (disseminated peritoneal adenomucinosis [DPAM]; 38 %) and 125 high-grade tumors (peritoneal mucinous carcinomatosis [PMCA]; 62 %) were identified. Five- and 10-year OS was 56 % and 47 %, respectively, with PFS of 44 % at 5 and 10 years. Five-year OS in DPAM patients was 83 %, with a 5-year OS significant difference related to CC 0–1 versus CC 2–3 (incomplete cytoreduction) [p = 0.021]. Five-year OS in PMCA patients was 41 %, with a 5-year OS significant difference related to CC 0–1 versus CC 2–3 (p < 0.001), PCI <20 versus PCI ≥20 (p = 0.002), and (–)LN versus (+)LN (p < 0.001). Grade III/IV complications were 16 %. No perioperative mortality was reported.

Conclusion

Positive LN, PMCA histopathology, and PCI ≥20 are negative prognostic factors, while CC 0–1 is a positive survival predictor in PC from AC treated with CRS/HIPEC. However, in patients with PMCA and PCI ≥20 in whom CC 0–1 was a potential outcome should not be denied CRS/HIPEC.     

Extensive Cytoreductive Surgery for Appendiceal Carcinomatosis: Morbidity, Mortality, and Survival

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis.

Methods

We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes.

Results

Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS.

Conclusions

Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.     

Does Obesity Affect Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Disseminated Mucinous Appendiceal Neoplasms?

Background

Obesity has been described as a risk factor for surgical complications and may play a prominent role in the progression, recurrence, and survival rates of various cancers. Our objective was to investigate the impact of being overweight or obese on perioperative and oncologic outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) from mucinous appendiceal neoplasms (MAN).

Methods

From a prospectively maintained database (2001–2010) of CRS/HIPEC for PC from MAN, we evaluated the body mass index (BMI) of patients, categorizing them into normal weight (NW < 25 kg/m²), overweight (OW = 25 to 29.9 kg/m²), and obese (OB ≥ 30 kg/m²). We compared the perioperative and oncologic outcomes among groups.

Results

Of the 282 patients in the database, 234 had BMI data available, and 81, 79, and 74 patients were categorized as NW, OW, and OB, respectively. Although there was a trend toward increased risk of overall complications, wound infections, deep vein thrombosis, respiratory and renal complications, and anastomotic leaks in the OW and OB groups, these differences only achieved statistical significance for renal (p = 0.03) and pulmonary (p = 0.02) complications in the OW and OB groups, respectively. The 5-year survival rate for NW, OW, and OB patients was 63.9, 48, and 54.4 %, respectively (p = 0.63). The median time to progression was 21.1 (NW), 21.7 (OW), and 23.9 (OB) months (p = 0.83).

Conclusions

OW and OB patients may have an increased risk of renal and pulmonary complications, respectively. Obesity has no major impact on perioperative mortality and long-term oncologic outcomes in patients undergoing CRS/HIPEC for MAN.     

Morbidity Associated with Colostomy Reversal After Cytoreductive Surgery and HIPEC

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival in selected colorectal cancer patients with peritoneal metastases. In these patients, the risk of a low anastomosis is sometimes diminished through the creation of a colostomy. Currently, the morbidity and mortality associated with the reversal of the colostomy in this population is unknown.

Methods

Our study involved two prospectively collected databases including all patients who underwent CRS–HIPEC. We identified all consecutive patients who had a colostomy and requested a reversal. The associations between four clinical and ten treatment-related factors with the outcome of the reversal procedure were determined by univariate analysis.

Results

21 of 336 patients (6.3 %) with a stoma with a mean age of 50.8 (standard deviation 10.2) years underwent a reversal procedure. One patient was classified as American Society of Anesthesiologists (ASA) grade III, 6 as ASA grade II, and the remaining as ASA grade I. Median time elapsed between HIPEC and reversal was 394 days (range 133–1194 days). No life-threatening complications or mortality were observed after reversal. The reversal-related morbidity was 67 %. Infectious complications were observed in 7 patients (33 %). Infectious complications after HIPEC were negatively correlated with the ultimate restoration of bowel continuity (P = 0.05). Bowel continuity was successfully restored in 71 % of the patients.

Conclusions

Although the restoration of bowel continuity after CRS–HIPEC was successful in most patients, a relatively high complication rate was observed. Patients with infectious complications after HIPEC have a diminished chance of successful restoration of bowel continuity.     

The American Society of Peritoneal Surface Malignancies (ASPSM) Multiinstitution Evaluation of the Peritoneal Surface Disease Severity Score (PSDSS) in 1,013 Patients with Colorectal Cancer with Peritoneal Carcinomatosis

Background

Extensive clinical experience suggests that hyperthermic intraperitoneal chemotherapy (HIPEC) may play an important role in the management of colorectal cancer patients with peritoneal carcinomatosis (CRCPC). However, there remains no established nonsurgical process to rationally select patients for this management, either for inclusion/stratification in clinical trials or as a component of standard of care. The Peritoneal Surface Disease Severity Score (PSDSS) was introduced as a basis to improve patient selection.

Methods

The American Society of Peritoneal Surface Malignancies conducted a retrospective review of 1,013 CRCPC patients. The PSDSS was evaluated on 3 specific criteria obtained before surgery (symptoms, extent of peritoneal dissemination, and primary tumor histology). Overall survival was analyzed according to four tiers of disease severity, and a comparison was made between patients who underwent cytoreductive surgery + HIPEC and those who did not.

Results

The PSDSS was calculated on 884 patients (87 %). The median survival of 275 patients not undergoing CRS/HIPEC based on their PSDSS—I (n = 8), II (n = 80), III (n = 55), and IV (n = 132)—was 45, 19, 8, and 6 months, respectively. The median survival of 609 patients who underwent CRS/HIPEC based on their PSDSS—I (n = 75), II (n = 317), III (n = 82), and IV (n = 135)—was 86, 43, 29, and 28 months, respectively.

Conclusions

These data support that the PSDSS, undertaken before surgery, is capable of defining CRCPC populations who have a statistically defined high or considerably lower likelihood of long-term survival after CRS/HIPEC. The PSDSS can be quite useful in the decision to enter CRCPC patients into, and their stratification within, clinical trials.     

Safety of Epidural Analgesia in the Perioperative Care of Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy

Background

The perioperative coagulopathy, hemodynamic instability, and infectious complications that may occur during cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has raised concerns about the safety of epidural analgesia in patients undergoing such procedures.

Methods

We conducted a retrospective review of the perioperative anesthetic management of 215 adult patients who had undergone CRS with HIPEC with epidural analgesia. We reviewed epidural-related complications and analyzed the effect of early initiation of continuous epidural analgesia on estimated blood loss, intraoperative fluid administration, blood transfusion and vasopressor requirements, time to extubation, and length of stay.

Results

No epidural hematomas or abscesses were reported. Two patients (0.9 %) had delays in epidural removal because of thrombocytopenia, and two had epidural-site erythema (0.9 %). The majority of postoperative epidural-related hypotensive episodes were successfully treated with fluid boluses. Early initiation of epidural analgesic infusions (before HIPEC) was associated with significantly less surgical blood loss and fluid requirements (P = 0.005 and 0.02, respectively). Pre-HIPEC initiation of epidural infusions was not associated with a statistically significant difference in the following: volume of blood transfused, intraoperative vasopressors use, time to extubation, and length of hospital stay.

Conclusions

With close hematologic monitoring and particular attention to sterility, epidural analgesia can be safely provided to patients undergoing CRS with HIPEC. Early initiation of continuous epidural infusions during surgery could lead to decreased blood loss and less intraoperative fluid administration. Prospective randomized studies are required to further investigate these potential benefits.     

Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis

Background

Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM.

Methods

We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes.

Results

Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001).

Conclusions

Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.     

Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin

Background

The significance of tumor markers in patients with appendiceal carcinomatosis is poorly defined. We determined preoperative and postoperative tumor marker levels in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemoperfusion (HIPEC) and examined their association with clinicopathologic features and survival.

Methods

A total of 176 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis had at least 1 tumor marker measured. Marker levels were correlated with tumor characteristics and oncologic outcomes. Kaplan–Meier curves and multivariate Cox regression models were used to identify prognostic factors affecting progression and survival.

Results

At least 1 marker was elevated prior to CRS/HIPEC in 70 % of patients (CEA, 54.1 %; CA19-9, 47.7 %; CA-125, 47.2 %). Among patients with elevated preoperative marker levels, normalization occurred postoperatively in 79.4 % for CEA, 92.3 % for CA19-9, and 60 % for CA-125. Absolute preoperative tumor marker levels correlated with peritoneal carcinomatosis index (PCI) (p < .0002), and the number of elevated markers was associated with PCI and progression-free survival (PFS). Elevated postoperative CEA level was associated with decreased PFS (median, 13 vs 36 months, p = .0008). On multivariate Cox regression analysis, elevated preoperative CA19-9 was associated with shorter PFS (hazard ratio [HR] 2.9, 95 % confidence interval [95 % CI] 1.5–5.3, p = .0008), whereas elevated CA-125 was associated with shorter overall survival (HR 2.6, 95 % CI 1.3–5.4, p = .01).

Conclusions

Most patients with appendiceal carcinomatosis will have at least 1 elevated tumor marker and will normalize following CRS/HIPEC, allowing for ongoing surveillance. CA19-9 is a promising biomarker for early progression following CRS/HIPEC, whereas CA-125 is associated with shorter survival.     

Complications and Toxicities After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Introduction

The purpose of our study was to evaluate the perioperative complications, toxicity, mortality rates after cytoreductive surgery (CRS), and effects of hyperthermic intraperitoneal chemotherapy (HIPEC) used in the treatment of peritoneal surface malignancies.

Methods

Between September 2007 and March 2012, we performed 118 CRS and HIPEC with the closed abdominal technique on 115 patients with peritoneal carcinomatosis (PC). Systemic toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria and were analyzed from a prospectively collected database.

Results

The mean age of patients was 53.4 (range, 20–82) years; 76.3 % were female. PC was synchronous to primary cancer in 53.4 % of patients, metachronous in 41.5 %, and recurrent in 5.1 % of the patients. PCI was ≥15 in 53.4 % of the patients, and CC-0 cytoreduction was achieved in 68.5 % of the patients. Perioperative mortality was observed in 9 (7.6 %) patients. A total of 98 complications were observed in 46 (39.0 %) patients, and 4 patients underwent 6 reoperations for perioperative surgical complications. We observed toxicity in 25.4 % of the patients, nephrotoxicity in 18.6 %, and hematological toxicity in 13.6 % of patients. No significant difference was observed among age, gender, PCI and CC scores, origin of the primary tumor, and occurrence of toxicity and surgical complications. Prolonged operation times resulted in higher complication and/or toxicity rates (P < 0.01).

Conclusions

Cytoreductive surgery and HIPEC is a combined treatment strategy for peritoneal surface malignancies with acceptable complication and toxicity rates.     

Significance of Urinary Tract Involvement in Patients Treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background

Urinary tract involvement in patients with peritoneal surface disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often requires complex urologic resections and reconstruction to achieve optimal cytoreduction. The impact of these combined procedures on surgical outcomes is not well defined.

Methods

A prospective database of CRS/HIPEC procedures was analyzed retrospectively. Type of malignancy, performance status, resection status, hospital and intensive care unit stay, morbidity, mortality, and overall survival were reviewed.

Results

A total of 864 patients underwent 933 CRS/HIPEC procedures, while 64 % (550) had preoperative ureteral stent placement. A total of 7.3 % had an additional urologic procedure without an increase in 30-day (p = 0.4) or 90-day (p = 1.0) mortality. Urologic procedures correlated with increased length of operating time (p < 0.001), blood loss (p < 0.001), and length of hospitalization (p = 0.003), yet were not associated with increased overall 30-day major morbidity (grade III/IV, p = 0.14). In multivariate analysis, independent predictors of additional urologic procedures were prior surgical score (p < 0.001), number of resected organs (p = 0.001), and low anterior resection (p = 0.03). Long-term survival was not statistically different between patients with and without urologic resection for low-grade appendiceal primary lesions (p = 0.23), high-grade appendiceal primary lesions (p = 0.40), or colorectal primary lesions (p = 0.14).

Conclusions

Urinary tract involvement in patients with peritoneal surface disease does not increase overall surgical morbidity. Patients with urologic procedures demonstrate survival patterns with meaningful prolongation of life. Urologic involvement should not be considered a contraindication for CRS/HIPEC in patients with resectable peritoneal surface disease.     

Aggressive Locoregional Surgical Therapy for Gastric Peritoneal Carcinomatosis

Background

Peritoneal carcinomatosis from gastric cancer (GPC) responds poorly to systemic chemotherapy. Limited published data demonstrate improved outcomes after aggressive locoregional therapies. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in GPC.

Methods

We prospectively analyzed 23 patients with GPC undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes.

Results

CRS/HIPEC was performed for synchronous GPC in 20 patients and metachronous GPC in 3 patients. Adequate CRS was achieved in 22 patients (CC-0 = 17; CC-1 = 5) and median peritoneal cancer index was 10.5. Most patients received preoperative chemotherapy (83 %) and total gastrectomy (78 %). Pathology revealed diffuse histology (65 %), signet cells (65 %) and LN involvement (64 %). Major postoperative morbidity occurred in 12 patients, with 1 in-hospital mortality at postoperative day 66. With median follow-up of 52 months, median overall survival (OS) was 9.5 months (95 % confidence interval 4.7–17.3), with 1- and 3- year OS rates of 50 and 18 %. Median progression-free survival (PFS) was 6.8 months (95 % confidence interval 3.9–14.6). In a multivariate Cox regression model, male gender [hazard ratio (HR) 6.3], LN involvement (HR 1.2), residual tumor nodules (HR 2.4), and >2 anastomoses (HR 2.8) were joint significant predictors of poor OS (χ ² = 18.2, p = 0.001), while signet cells (HR 8.9), anastomoses >2 (HR 5.5), and male gender (HR 2.4) were joint significant predictors of poor progression (χ ² = 16.3, p = 0.001).

Conclusions

Aggressive CRS/HIPEC for GPC may confer a survival benefit in select patients with limited lymph node involvement and completely resectable disease requiring less extensive visceral resections.     

Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Asian Perspective

Background

Data on quality of life (QOL) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is scarce in the Asian population. This study assesses QOL outcomes after CRS and HIPEC in an Asian cancer center.

Methods

Patients who completed CRS + HIPEC 6–18 months ago (27 patients) were enrolled in the study. QOL was measured via the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaires. The scores were compared with a group of 393 disease-free cancer patients, not on active treatment, who had ECOG scores of either 0 or 1. The 1-sample t test was used to compare differences in QOL scores between the 2 groups.

Results

A total of 27 patients were analyzed, of which 22 (81 %) were females. Median age was 51 years (15–59 years). CRS + HIPEC were performed for ovarian cancer in 15 patients (55 %), appendiceal carcinoma in 5 patients (19 %), and colorectal carcinoma in 4 patients (15 %). The median intraoperative peritoneal carcinomatosis index (PCI) score was 15 (2–31) while the completeness of CC score was 0 and 1 in 25 and 2 patients, respectively. The median duration after CRS + HIPEC was 10 months (6–16 months). Global health status and functional and symptom scores were largely similar between patients after CRS + HIPEC and the control group. Cognitive functioning scores and fatigue scores were significantly better in the group after CRS + HIPEC (p = 0.014 and 0.04).

Conclusions

QOL after CRS and HIPEC can be equivalent to that of well-functioning, disease-free cancer patients.     

Melphalan: A Promising Agent in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for peritoneal carcinomatosis (PC). Frequently, these patients have failed systemic chemotherapies and surgeries, including CRS/HIPEC with traditional regimens (mitomycin-C or platinum based). An alternative agent for failed or repeated CRS/HIPEC is unknown. We hypothesize that melphalan is an alternative agent in patients with PC from aggressive primaries, including recurrences following failed regional therapies.

Methods

A retrospective review of a prospective database of 247 patients revealed 25 patients (9 male and 16 female) who received intraperitoneal melphalan (50 mg/m²) in 31 CRS/HIPEC procedures, of which 19 were repeated. Primary malignancies included 17 appendiceal, one colorectal, two ovarian, two uterine sarcomas, two primary peritoneal and one mesentery sarcoma.

Results

PC index (PCI) was ≥20 in 76 % of patients (19/25). 88 % of patients (22/25) had complete cytoreduction. Seventeen patients were alive, with mean survival of 63.6 months, and eight patients are deceased. Overall survival (OS) for the entire group since diagnosis was 95.8, 84.5, 50.9, and 38.2 % at 1, 3, 5, and 10 years, respectively; OS since melphalan HIPEC was 89.4, 45, and 30 % at 1, 3, and 5 years, respectively; and OS in patients with appendiceal malignancies was 91.7, 48.1 and 32.1 % at 1, 3 and 5 years, respectively. There was no postoperative mortality. Grade III–IV morbidity was 23 % (7/31). Nine patents had neutropenia, controlled with filgrastim.

Conclusions

Melphalan is an efficacious alternative agent in patients undergoing CRS/HIPEC for aggressive and recurrent peritoneal surface malignancies. Its postoperative significant myelosuppression effect should be addressed.