Pseudomyxoma Peritonei: Clinical Pathological and Biological Prognostic Factors in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background Surgical cytoreduction combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been recently advocated as the standard of care for pseudomyxoma peritonei (PMP). We reviewed our 10-year monoinstitutional case series to identify selection factors predicting postoperative outcome. Methods One hundred and four patients with PMP were operated on with the aim of performing adequate cytoreduction (residual tumor nodules ≤2.5 mm) and closed-abdomen HIPEC with mytomicin-C and cisplatin. Previously, 26 patients had systemic chemotherapy. PMP was histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and intermediate/discordant group (ID). Immunohistochemical stains were performed for cytokeratin (CK)-7, CK-20, CDX-2, MUC-2, MUC-5AC, CD-44s. The significance of 22 potential clinical, pathological, and biological prognostic variables was assessed by multivariate analysis. Results Adequate cytoreduction was performed in 89 patients, suboptimal cytoreduction in six, palliative surgery in nine. Operative mortality was 1%. Seventy-eight patients were diagnosed with DPAM, 26 with PMCA, and none with ID. Median follow-up was 37 months (range, 1–110) for the overall series. Five-year overall survival (OS) and progression-free survival (PFS) were 78.3% and 31.1%, respectively. At multivariate analysis, adequate cytoreduction, no previous systemic chemotherapy, and DPAM correlated to better OS and PFS, elevated serum CA19.9 correlated only to better PFS. In most cases, CK20, CDX-2, and MUC-2 were diffusely positive, while CK-7, MUC-5AC, and CD44s were variably expressed. CK20 expression correlated to prognosis at univariate analysis. Conclusions Favorable outcome after comprehensive treatment can be expected in patients with DPAM, not treated with preoperative systemic chemotherapy and amenable to adequate cytoreduction. MUC-2, CK-20, and CD44s expression may be related to PMP unique biologic behavior.     

Bowel Complications in 203 Cases of Peritoneal Surface Malignancies Treated With Peritonectomy and Closed-Technique Intraperitoneal Hyperthermic Perfusion

Background Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP) are increasingly used in the management of carcinomatosis of various sites of origin. We analyzed the risk factors for bowel complications with primary anastomoses and the closed technique for IPHP. Methods From 1995 to 2004, 203 consecutive procedures were performed at the National Cancer Institute of Milan. We retrospectively analyzed this series of patients. Treated pathologies included peritoneal mesothelioma; pseudomyxoma peritonei; colorectal, ovarian, or gastric carcinomatosis; and abdominal sarcomatosis. All digestive anastomoses were performed before the IPHP. Only one defunctioning stoma was used. Results We found a bowel complication rate of 10.8%. The bowel complications:anastomoses ratio was 11.3%. On univariate analysis we found a statistically significant association between bowel complications and the following variables: sex, previous systemic chemotherapy status, number of anastomoses ( fewer than two vs. two or more), duration of the procedure (<8.7 vs. ≥8.7 hours), and extent of cytoreduction. After multivariate analysis, male sex (odds ratio [OR], 4.2), no previous systemic chemotherapy (OR, 3.5), and duration of the procedure ≥8.7 hours (OR, 6.3) were considered independent risk factors for bowel complications. Conclusions Bowel complications are not increased when primary unprotected anastomoses are performed during peritonectomy and IPHP when the closed technique is used. Male sex, duration of the procedure, and no previous systemic chemotherapy are independent unfavorable risk factors.     

Prognostic Value of Circulating Tumor Markers in Patients with Pseudomyxoma Peritonei Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background Encouraging results have been recently reported in selected patients affected by pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The selection factors predicting clinical outcome are still a matter of clinical investigation. We assessed the prognostic reliability of serum tumor markers in a large series of patients with PMP undergoing CRS and HIPEC. Methods Sixty-two patients with PMP were operated on at a single institution with the intent of performing adequate CRS (residual tumor nodules ≤2.5mm) and HIPEC. Baseline and serial marker measurements were prospectively collected and tested by multivariate analysis with respect to adequate cytoreduction, overall (OS) and progression-free (PFS) survival, along with the following variables: age, sex, performance status, prior surgical score, histological subtype, prior systemic chemotherapy, disease extent, completeness of cytoreduction. Results Baseline diagnostic sensitivity was 72.6% for CEA, 58.1% for CA19.9, 58.7% for CA125, 36.1% for CA15.3. Fifty-three patients underwent adequate CRS and HIPEC; gross residual tumor was left after surgery in nine. Adequate CRS was performed in 19/27 patients with elevated and in 19/19 with normal baseline CA125 (P = .0140). The other markers were unable to predict the completeness of CRS by univariate analysis. Baseline elevated CA19.9 was an independent predictor of reduced PFS; inadequate CRS and aggressive histology were independent prognostic factors for both reduced OS and PFS. Conclusion Normal CA125 correlated to the likelihood to achieve adequate CRS, which is a significant prognostic factor for PMP. Increased baseline CA19.9 was an independent predictor of worse PFS after CRS and HIPEC.     

Circulating CA125 in Patients with Peritoneal Mesothelioma Treated with Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

Background Recent phase I/II trials report encouraging results in selected patients with peritoneal mesothelioma (PM) treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Circulating tumor markers have never been extensively investigated in the management of PM. We assessed the clinical role of markers in a large series of patients with PM undergoing CRS and IPHP. Methods Clinical data on 60 patients with PM operated with the intention to perform adequate CRS (residual tumor nodules ≤ 2.5mm) and IPHP were prospectively collected. Marker levels were determined pre-operatively, post-operatively, and routinely during long-term follow-up. Baseline diagnostic sensitivity, accuracy in monitoring response to treatment or tumor progression and prognostic significance were determined. Results Baseline diagnostic sensitivity was 53.3% for CA125, 0 for CEA, 3.8% for CA19.9 and 48.5% for CA15.3. Forty-six patients underwent adequate cytoreduction and IPHP; gross residual tumor was left after the operation in fourteen. Postoperatively, CA125 became negative in 21/22 patients with elevated baseline levels undergoing adequate CRS and IPHP, while remained elevated in 9/9 patients with persistent macroscopic disease. CA125 became positive in 12/12 patients with elevated baseline levels developing disease progression after adequate CRS and IPHP. Baseline CA125 showed borderline prognostic significance only among patients not previously treated with systemic chemotherapy. Conclusions CA125 was elevated in the majority of patients with PM in the present series. Serial maker measurements paralleled tumor growth or regression after CRS and IPHP, suggesting the need of further studies to assess the role of CA125 in this clinical setting.     

A Systematic Review on the Efficacy of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei

Background The efficacy of cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) for patients with pseudomyxoma peritonei (PMP) remains to be established. Methods Searches for all relevant studies prior to March 2006 were performed on six databases. Two reviewers independently appraised each study using a predetermined protocol. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. Results Ten most recent updates from each institution were included for appraisal and data extraction. There were no randomized controlled trials or comparative studies. All included articles were observational studies without control groups. Five studies were relatively large series (n≥100). Two studies had relatively long-term follow-up (48 months and 52 months). The median follow-up in the remaining eight studies was shorter than 3 years (range 19–35 months). The median survival ranged from 51 to 156 months. The 1-, 2-, 3- and 5-year survival rates varied from 80 to 100%, 76 to 96%, 59 to 96% and 52 to 96%, respectively. The overall morbidity rate varied from 33 to 56%. The overall mortality rates ranged from 0 to 18%. Conclusions This study reviewed current evidence on CRS and PIC for PMP. Only observational studies were available for evaluation, which demonstrated some promising long-term results, as compared to historical controls. Due to the rarity of this disease, a well-designed prospective multi-institutional study would be meaningful.     

Laparoscopic Mucin Removal in Patients with Pseudomyxoma Peritonei

Background and Objectives:

Pseudomyxoma peritonei results from ovarian and appendiceal mucinous tumors. Cyst rupture results in intraabdominal mucin accumulation, leading to abdominal distension. No effective treatment has yet been established. Pseudomyxoma peritonei is generally associated with a poor prognosis. In a recent Mayo Clinic report, the 5-year survival rate for this disease was 53% and the 10-year survival rate was 32%, while the Memorial Sloan-Kettering Cancer Center reported 5- and 10-year survival rates of 75% and 10%.

Methods and Results:

In this report, we describe 4 patients with a laparoscopically confirmed recurrence of pseudomyxoma peritonei who subsequently underwent repeated laparoscopic mucin removal.

Conclusion:

Because laparoscopic surgery can be performed frequently, it appears that laparoscopic surgery, a minimally invasive procedure, greatly improves the quality of life of patients with pseudomyxoma peritonei.     

Treatment of Primary Peritoneal Mesothelioma by Continuous Hyperthermic Peritoneal Perfusion (CHPP)

Background: Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate. Continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin (CDDP) allows uniform, high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface for the treatment of peritoneal tumors. This article summarizes the results of 18 patients with peritoneal mesothelioma treated with CHPP.Methods: From June 1993 through April 1998, 18 patients with primary peritoneal mesothelioma (13 male, 5 female; median age, 51 years) underwent surgical exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at the National Cancer Institute. Seventeen of 18 patients had malignant peritoneal mesothelioma, 13 with associated ascites. One patient had a symptomatic, multiply recurrent, benign, cystic peritoneal mesothelioma. Three patients who had a recurrence after a prolonged progression-free interval (>6 months) after CHPP underwent re-treatment. CHPP parameters included median cisplatin dose of 530 mg (range, 187–816), perfusate volume 6.0 liter (range, 4–9), flow 1.5 liter/min (range, 1–2), intraperitoneal temperature 41°C (range, 38.7–43.2), and central temperature 38.6°C (range, 36.8–39.7).Results: Median follow-up after CHPP is 19 months (range, 2–56) with no operative or treatment-related mortality. Overall operative morbidity was 24% and included two patients with superficial wound infection and one patient each with atrial fibrillation, pancreatitis, fascial dehiscence, ileus, line sepsis, and clostridium difficile colitis. The major treatment-related toxicity was systemic renal toxicity at doses above what was defined as the maximum tolerated dose of cisplatin. Nine of 10 patients had resolution of their ascites postoperatively. Three patients who developed recurrent ascites (27, 22, and 10 months after initial treatment) were re-treated and had resolution of their ascites with ongoing responses at 24, 6, and 4 months after the second perfusion. The median progression-free survival was 26 months, and the overall 2-year survival was 80%. The median overall survival has not been reached.Conclusions: CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the abdomen and long-term survival, compared with historical controls, can be achieved with aggressive surgical debulking and CHPP. Re-treatment after initial response can result in a second long-term response.     

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.     

Sclerosing Encapsulating Peritonitis (SEP) as a Delayed Complication of Continuous Hyperthermic Peritoneal Perfusion (CHPP): Report of a Case

A 47-year-old woman underwent curative resection of advanced gastric cancer, followed by continuous hyperthermic peritoneal perfusion (CHPP). She was readmitted to our hospital 6 months after the operation with a diagnosis of postoperative adhesional ileus. An exploratory laparotomy revealed that the small intestine, which had normal serosa, was folded and enveloped in thickened peritoneum like a "cocoon," suggesting sclerosing encapsulating peritonitis (SEP). Because of tight adhesion in the ileocecal region, resection of the membrane was performed only in the feasible areas, followed by side-to-side anastomosis between the ileum and ascending colon. The patient has remained well for 15 months since this operation with no radiological signs or laboratory findings of recurrence. When small bowel obstruction does not show improvement with conservative treatment, and if the possibility of peritoneal cancer recurrence is excluded by thorough examinations, it is important to perform laparotomy early to resolve the symptoms of bowel obstruction and restore the patient's quality of life.     

Failure Analysis of Recurrent Disease Following Complete Cytoreduction and Perioperative Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis from Colorectal Cancer

Background The aim of this study was to analyze the anatomic distribution, timing, and outcomes of recurrent disease after complete cytoreduction and perioperative intraperitoneal chemotherapy (PIC) for peritoneal carcinomatosis of colorectal origin. Methods Data regarding all patients who underwent complete cytoreduction and PIC for carcinomatosis from colorectal cancer were extracted from a prospectively collected database. The information regarding recurrent disease found on diagnostic evaluation and/or abdominal exploration was analyzed. Results Seventy patients underwent complete cytoreduction and perioperative intraperitoneal chemotherapy, and 49 of them had documented recurrent disease. The median time to progression for these 49 patients was 9 months while their median survival was 30 months. Eighteen patients had a localized intra-abdominal recurrence, 10 had diffuse intraperitoneal recurrence, 10 had isolated distant metastases, and 11 had a combination of distant metastases and intra-abdominal recurrence. There was a statistically significant difference in survival for patients with different patterns of recurrence (P = .012). Twenty-six patients underwent a second operation. The median survival of these patients was significantly longer than that of patients who did not have a second operation (39 vs 20 months, P = .0003). Four of the 49 patients with recurrences were still alive at the time of last follow-up, and three of them have no evidence of disease 73, 96, and 206 months after the diagnosis of recurrence. Conclusions Recurrence is a frequent event after optimal cytoreduction and PIC for carcinomatosis from colorectal cancer. Surgical treatment for a selected group of patients with recurrent disease may result in long-term survival.     

Cytoreductive Surgery with Selective Versus Complete Parietal Peritonectomy Followed by Hyperthermic Intraperitoneal Chemotherapy in Patients with Diffuse Malignant Peritoneal Mesothelioma: A Controlled Study

Background  

Combined treatment involving peritonectomy procedures, multivisceral resections, and hyperthermic intraperitoneal chemotherapy (HIPEC) has reportedly resulted in survival benefit for peritoneal surface malignancies, including diffuse malignant peritoneal mesothelioma (DMPM). Many unanswered questions remain regarding the surgical options in the management of DMPM. The aim of this case–control study was to assess the impact of the type and extent of parietal peritonectomy on survival and operative outcomes.     

Safety and Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with High-Dose Oxaliplatin in Patients with Peritoneal Carcinomatosis

Background Cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma. Methods Following complete cytoreduction, HIPEC was performed using 460 mg/m² oxaliplatin in 5% dextrose for 30 min at a temperature of 41–42°C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival. Results From July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year. Conclusion Cytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival.     

Toxicity and Outcomes Associated with Surgical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Patients with Sarcomatosis

Background Treatment of peritoneal recurrence following surgical resection of intra-abdominal sarcomas presents a significant challenge to clinicians. Historically, treatment with systemic chemotherapy has been ineffective and surgical resection alone has not been durable. We prospectively evaluated the feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with mitoxantrone (MITOX) for the treatment of sarcomatosis. Methods Two phase I trials of HIPEC were conducted (1998–2003). Eligible patients with evidence of sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first trial, CDDP dosing was established as 90 mg/m² with a perfusate time of 90 minutes and temperature of 41°C. In the second trial, MITOX (20 mg/m²) was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of life (QOL) were evaluated. Results A total of 28 patients were enrolled in the two trials. We noted a higher overall toxicity score and complication rate with combination CDDP/MITOX versus CDDP alone and shorter overall survival duration (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores at 6–8 weeks following HIPEC were 15–25% lower than the baseline scores; however, they returned to baseline at 3–6 months. Conclusions Although the HIPEC technique is feasible for patients with sarcomatosis, it is associated with significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed to demonstrate any benefit over CDDP alone; moreover, there was an increase in toxicity.     

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.     

Anesthetic Management and Renal Function in Pediatric Patients Undergoing Cytoreductive Surgery with Continuous Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cisplatin

Background

Extensive tumor implants secondary to sarcoma, sarcomatosis, or mesothelioma in children is rare. We conducted the first phase 1 trial of escalating doses of cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) in children with sarcomatosis. The most devastating complication of cisplatin therapy is nephrotoxicity. Here we present the anesthetic management and analysis of the impact of intraoperative fluid management on the incidence of renal failure.

Methods

Of the 10 patients under 18?years of age who underwent HIPEC in the context of our phase 1 trial, six patients were under the age of 10?years. We reviewed the anesthetic management, intraoperative fluid and blood administration, and postoperative renal function in these patients.

Results

The average age and weight were 6?years and 20.9?kg, respectively. To avoid renal toxicity, urine output was maintained at an average of 3?ml/kg/h. Crystalloid and colloid were transfused at an average rate of 9?ml/kg/h. Percentage increase in creatinine postoperatively varied from 33 to 500 %. Volume of fluid administered did not correlate with percentage increase in creatinine. All patients had a temporary increase in their serum creatinine, but none required dialysis.

Conclusions

Fluid administration at an average rate of 9?ml/kg/h was required to maintain satisfactory urine output. This rate of intraoperative fluid administration is similar to what is provided to adult HIPEC patients. There was no significant correlation in the volume or type of fluid delivered and the increase in serum creatinine. More studies are needed to determine optimal fluid management in children undergoing HIPEC with cisplatin.     

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Persistent and Recurrent Advanced Ovarian Carcinoma: A Multicenter, Prospective Study of 246 Patients

Background

Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed.

Results

An optimal cytoreductive surgery was possible in 92.2?% of patients. Mortality and morbidity rates were 0.37?% and 11.6?%, respectively. The overall median survival was 48.9?months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10).

Conclusions

Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.     

Outcomes of Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients Older Than 70 Years; Survival Benefit at Considerable Morbidity and Mortality

Background

Cytoreductive surgery (CRS)/Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is associated with prolonged survival in selected patients with peritoneal surface disease. Yet, for elderly patients (older than 70 years of age) CRS/HIPEC is controversial, due to associated morbidity.

Methods

A retrospective analysis of a prospective database of 950 procedures was performed. Type of malignancy, demographics, performance and resection status, hospitalization, morbidity, mortality, and survival were reviewed.

Results

A total of 81 patients (median age 73, range 70–87) underwent CRS/HIPEC between 1991 and 2011. Median follow-up was 48.1 months. Complete cytoreduction was achieved in 44 %. Median survival was 31.8 months for appendiceal cancer, 41.5 for mesothelioma, 54.0 for ovarian cancer, 13.2 for colon cancer, and 7.6 for gastric cancer. The 30-day mortality was 13.6 %. The combined grade III and IV morbidity was 38 %. Median ICU and hospital stay for uncomplicated patients was 1 and 8 days, respectively. The 3-month mortality was 27.4 %. There were no deaths in the octogenarian group. In stepwise multivariate analysis, type of primary (p = 0.03), albumin (p = 0.02), and R status (p = 0.007) were predictive of survival only in the absence of complications. Splitting the data at the midpoint of surgical experience, there was a drop in 1- and 3-month mortality over time to 9.5 and 19.3 %, respectively, while the median survival increased from 11.2 (N = 39) to 46.9 months (N = 42).

Conclusions

HIPEC in the elderly is associated with a steep learning curve and considerable morbidity and mortality. However, age alone is not a contraindication for the procedure. Institutional experience and stringent patient selection are key factors for prolonged survival.     

Peritoneal Carcinomatosis in Digestive Cancers: Cytoreductive Surgery Combined with Intraperitoneal Chemohyperthermia. The Experience in Centre Hospitalier et Universitaire Lyon Sud (CHLS)

Intraperitoneal chemohyperthermia (IPCH) with Cytoreductive surgery (CS) has been used in Centre Hospitalier et Universitaire Lyon Sud (CHLS) since 1989. Up to 2005· 420 patients were involved in different phase II studies for peritoneal carcinomatosis (PC) from colorectal· gastric or ovarian origin· as well as for pseudomyxoma peritonei and peritoneal mesothelioma. Encouraging results were achieved in case of optimal PC cytoreduction. The CHLS experience· as well as the Dutch randomized trial and the international registration· underline the advantage of such an aggressive combined therapy for selected patients in experienced multidisciplinary centers.     

Percutaneous Hepatic Perfusion in Patients with Metastatic Liver Cancer: Anesthetic, Hemodynamic, and Metabolic Considerations

Background Percutaneous hepatic perfusion (PHP), a regional cancer therapy, entails insertion of percutaneous catheters to isolate hepatic vasculature and enable simultaneous hepatic venous hemofiltration of high-dose chemotherapy. PHP has been shown to be safe and to benefit some patients with liver metastases. Methods We examined hemodynamic and metabolic changes as well as anesthetic implications during PHP in patients with metastatic liver cancer enrolled in clinical trials of escalating doses of melphalan between 2001 and 2006. Results Fifty-one patients underwent 136 PHPs with general anesthesia. Diagnoses included neuroendocrine tumors, melanoma, and metastatic carcinomas. Based upon available data derived from all procedures, incorporating multiple procedures per patient, after occlusion of the inferior vena cava and during hepatic perfusion, there were decreases in mean arterial (−15.4 ± 1 and −7.4 ± 1 mmHg, respectively) and central venous pressure (−5.4 ± 0.3 and −5.6 ± 0.3 mmHg) and increases in heart rate (11 ± 1 and 13.4 ± 0.9 bpm) (all p < 0.0001) which resolved with completion of the procedure. During vascular isolation, patients received norepinephrine (13% of procedures), phenylephrine (70%), or both agents (11%). During hepatic perfusion with melphalan, compared to baseline, there were decreases in pH (−0.09 ± 0.01) and bicarbonate (−3.3 ± 0.6 mmol/L) (both p < 0.0001) and, upon completion of procedure, increases (2.6 ± 0.4 mmol/L) in bicarbonate, compared to values during hepatic perfusion (p < 0.0001). Conclusions PHP therapy can be associated with transient but significant hemodynamic and metabolic perturbations. In order to assure patient comfort and facilitate timely diagnosis and treatment of associated hemodynamic and metabolic changes, we favor administration of general anesthesia, rather than sedation, for patients undergoing PHP.