Intraoperative Chemotherapy Research Articles

Treatment of Malignant Mesothelioma: Extrapleural Pneumonectomy with Intraoperative Chemotherapy

Extrapleural pneumonectomy (EPP) is a radical en bloc resection of the lung, pleura, diaphragm, and pericardium. The inability to separate the fused pleural envelope from the central tendon of the diaphragm and the lateral portion of the pericardium also mandates resection of these structures to preserve the intact pleural envelope. EPP was originally developed to treat tuberculous empyema and now it has become the cornerstone of treatment for select patients undergoing multimodality therapy for malignant pleural mesothelioma (MPM). MPM is an uncommon disease with only 3000 cases in the US each year. 1 Esophageal and lung cancer are, respectively, at least 4 and 50 times more common. Few surgeons will treat more than a handful of cases over their careers. The Brigham and Women’s Hospital (BWH) and Dana Farber Cancer Institute (DFCI) in Boston, Massachusetts have gained a large amount of experience in the treatment of this malignancy. Early application of EPP to the treatment of MPM was disappointing. Worn 2 reported an early series in 1974, but with median survival of only 19 months and 5-year survival of 10%. In 1976, Butchart and coworkers 3 reported a series with a perioperative mortality rate of 31%, median survival of 10 months, and 5-year survival of 3.5%. Operative mortality after EPP at BWH declined with increasing experience, from an initial perioperative mortality of 6% after the first 18 patients in 1991 4 to 3.4% after 328 patients reported in 2004. 5 Despite advances in surgical technique, the unfortunate fact remains that nearly all patients eventually die of recurrent disease within 10 years, although more than 50% of patients with favorable prognostic variables live at least 5 years. Analysis of our late results reveals that most recurrences occur in either the abdomen or the ipsilateral hemithorax. 6 The dose limitation of most adjuvant therapies is systemic toxicity to the patient. Intraoperative intracavitary heated cisplatin chemotherapeutic lavage (IOHC) has the advantage of permitting higher chemotherapy doses than are possible by systemic administration. Studies of IOHC in abdominal malignancies, including peritoneal mesothelioma, have been effective. 7,8 Ongoing phase I and II studies of IOHC in combination with EPP at our institution have shown encouraging

Pseudomyxoma Peritonei: Diagnosis and Management

Pseudomyxoma peritonei is a rare disease characterized by a large amount of mucinous ascites with peritoneal and omental implants. The etiology of the disease remains unclear. Different histological categories have been described: the benign, malignant, and the intermediate forms. It is commonly diagnosed incidentally at laparotomy. Most investigators agree that radical surgical debulking and appendectomy is the cornerstone of treatment, but the optimal management of the disease remains controversial. The role of intraoperative and intraperitoneal chemotherapy has been evaluated by a number of authors. The clinical outcomes vary widely between the different histological types and treatment modalities.

Pseudomyxoma peritonei and the urinary tract: Involvement and treatment related complications

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterized by intraperitoneal accumulation of mucus produced by neoplastic cells of mostly appendiceal origin. The aim of this study was to analyze primary and secondary involvement and treatment-related complications of the urinary tract in PMP. A retrospective study of 92 patients with PMP, treated by cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) at The Netherlands Cancer Institute between 1996 and 2004. Seven patients presented with involvement of the urinary tract. Major urologic complications occurred in five patients, of which two had secondary involvement of the urinary tract. Major urologic complications consisted predominantly of surgical complications related to the bladder. All patients with secondary involvement and/or urologic complications had undergone previous pelvic surgery. The urinary tract is rarely involved in patients with PMP. Secondary involvement is mostly observed and may be a result of seeding of PMP of pelvic origin after prior pelvic surgery. There is a low urologic complication risk of treatment with cytoreduction and HIPEC. The combination of secondary involvement and previous pelvic surgery is an omen of treatment-related urologic complications, necessitating (surgical) re-interventions and further management in close collaboration with urologists.

Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei—a report of 103 procedures

AimsTo report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors. MethodsA review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality. ResultsThe median hospital stay was 21 days (4–149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality. ConclusionsCytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.

Preoperative computed tomography and selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Aim A survival benefit has been observed for colorectal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment modality is associated with a considerable morbidity and mortality and in a significant number of patients survival is not improved. We studied whether poor survivors could be identified on preoperative computed tomography (CT), in order to avoid unnecessary surgery. Patients and methods Films of abdominopelvic CT scans from 25 such patients treated by cytoreductive surgery and HIPEC were retrospectively analysed by two radiologists separately. A simplified peritoneal cancer index (SPCI) was used to determine the extent of peritoneal involvement. Correlation between the on preoperative CT based SPCI-scores as well as number of involved abdominopelvic areas ( N) and survival was examined with the log-rank test. The relation between each affected region and survival was evaluated with Cox regression analysis. Results The preoperative SPCI- and N-scores of one of the radiologists had no statistically significant prognostic value, while for the second radiologist SPCI≥7 and N≥4 were associated with particularly poor outcome. Additionally, the presence of ileocaecal region involvement and, depending on the radiologist, the occurrence of tumour deposits in the left subdiaphragmatic area on CT appeared to be unfavourable prognostic signs. Conclusions The prognostic value of preoperative conventional CT appeared to be radiologist dependent and may, therefore, be of limited value in selecting colorectal cancer patients with peritoneal carcinomatosis who will not benefit from extensive cytoreductive surgery followed by HIPEC.

Radiotherapy Following Extrapleural Pneumonectomy(EPP) for Mesothelioma: The Brigham and Women’s Hospital Experience

Purpose/Objective: We have previously published the world’s largest series of patients undergoing EPP for malignant pleural mesothelioma (MPM). (Sugarbaker et al. JCTS 99’) Building on those results we have published the patterns of failure of patients treated with low dose hemithoracic radiation of 30-40Gy (Baldini et al. Ann Thor Surg 97’) demonstrating a benefit to post-operative RT but with a high local failure rate of 65%. Following that publication, two attempts at the BWH/DFCI have been made to improve local control. The first was moderate dose RT 40Gy with concurrent platinum based chemotherapy and the second was high dose hemithoracic RT alone to 54Gy as per the technique of Yajnik et al.(IJROBP 03′) from MSKCC. We report the treatment details and outcome of those patients. Materials/Methods: Between 1999 and 2004, 68 patients were referred to our department following EPP for adjuvant therapy. We reviewed their treatment as part of an IRB approved study. Forty-three patients were treated closer to home and twenty-five patients received adjuvant RT @ BWH/DFCI. Of the 25 patients Median age was 57 years (44–75). 19 patients were male and six were female. 16 patients had epithelial histology with seven patients having mixed and two patients with sarcomatoid histology. Brigham stage 1 in 11 patients, ten had stage 2 and four stage 3. Ten patients were treated with APPA fields to 30Gy to the entire hemithorax with a limited chest wall boost to 40Gy and any grossly positive nodes were boosted to 54Gy. All of these patients received concurrent cisplatin chemotherapy at 50mg/m2 weekly. A second cohort of patients was treated with high dose RT to 54 Gy as per the study of Yajnik et al. The high dose cohort were treated with either sequential adjuvant,(5 patients with pemetrexed based), or neoadjuvant, (9 patients with gemcitabine and platinum)chemotherapy. Results: With a median potential follow-up of 30 months, the median survival of the entire group is 17.5 (95% CI 12.3–22.8) months. Eight patients (32%) remain alive and disease free, seven of these patients were treated with high dose hemithoracic RT and sequential chemotherapy. All had epithelial histology, and 3/8 were node positive. Of the remaining 17 patients who have experienced disease failure, 6 patients have experience death from distant failure alone, 5/6 with diffuse peritoneal disease. 11/25 (44%) patients have had documented local failure. Three patients have experience local only failure 2/3 died of local recurrence in the ipsilateral mediastinum alone. All three failures were in the radiation field. Eight patients experienced local and distant failure with in-field local failure occurring as the first site of failure in 6/8 patients. Of the eleven local in-field failures all were in an areas of the chest that received 30Gy or less because of normal tissue constraints. Conclusions: High dose hemithoracic radiation appears to benefit patients with favorable histology following EPP for MPM. In-field local failure remains a significant obstacle to improvement in outcome for these patients. Alternatives such as IMRT, intraoperative chemotherapy and concurrent RT and pemetrexed regimens are being pursued.

Inguinal canal as an anatomic sanctuary site of relapse in peritoneal carcinomatosis previously treated with intraperitoneal chemotherapy

Early postoperative intraperitoneal chemotherapy (EPIC) and intraoperative peritoneal hypertermic chemotherapy (IPHC) are used in addition with cytoreductive surgery to treat with curative intent peritoneal carcinomatosis arising from colorectal adenocarcinomas. Three patients with such a disease were treated with perioperative intraperitoneal chemotherapy in addition to cytoreductive surgery and presented isolated local recurrence located in the inguinal canal (round ligament in two and spermatic cord in one). All these patients were treated by local surgical excision. No patient showed evidence of intra-abdominal recurrence at the last follow-up, but one developed pulmonary metastasis. When communicating with the peritoneal cavity, the inguinal canal may act as a sanctuary site for peritoneal carcinomatosis, since it is not totally soaked by the intraperitoneal chemotherapy solution. A local recurrence is thus possible. New clinical presentations such as this one have first to be described in order to improve patient follow-up.

Chemotherapy for malignant mesothelioma

0 d er to identify single drugs or combinations that how any activity in malignant pleural mesotheioma (MPM). In general, the reported level of acivity of these drugs was low, for which different easons could be given. Many of the phase II studies ave been poorly designed with too few patients nd many studies did not have standard review of he pathology specimen to rule out patients with ther types of cancer. Furthermore, mixtures of the ifferent types of mesotheliomas within studies ocurred, which also lead to a statistical bias of the esults. Response measurements in MPM are conidered difficult because the tumor grows along the horacic wall and significant amounts of connective issue limits the measurement of response with cerainty. CT scanning is used as follow-up but a reponse of a pleural thickness of ≤1 cm is difficult to stablish and also the usefulness of the RESIST crieria has been challenged. The presence of pleural uid makes the analysis difficult especially when it ecomes organized. A new development is the use of resection and intra-operative chemotherapy has attracted much attention. After aggressive tumor resection a lavage with chemotherapeutic drugs under hyperthermic conditions can be performed in order to kill the remaining microscopic tumor cells [1,2]. Details of this approach however will be discussed elsewhere. For many years, chemotherapy using single agents has been tested to select promising drugs and to evaluate their toxicity. Some studies with single agents have reported overall response rates in the range of 10—20% and were the basis for combination therapies. The anthracyclines (doxorubicin, epirubicin), the antifolates (high-dose methotrexate, MTX) and cisplatin are examples of such agents. In Table 1, the response rates and median survival times achieved with single agent chemotherapy are presented. A large variation in overall response rate between different researchers using the same drug is probably due to the relative small number of patients and the variation f FDG PET scanning but this approach has not yet een fully validated. Chemotherapy can be administered systemically in patient selection criteria. Therefore, the number of patients treated with comparable schedules has been pooled.

Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation?

The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, alpha-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m2) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m2. Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA.

Hepatectomy plus intraoperative radiofrequency ablation and chemotherapy to treat technically unresectable multiple colorectal liver metastases

Results and indications of intra-operative radiofrequency (RF) ablation of liver metastases (LM) are not well defined in the literature. To appreciate the survival rate of patients with strictly unresectable LM (defined on technical but not oncological criteria) when undergoing liver resection plus RF, along with optimal systemic chemotherapy. Sixty three patients with technically unresectable LM (either >5, or bilateral with no sparing of at least one sector of the liver, or with tumor proximity to central major vascular structures) were treated. Extrahepatic metastases were also resected in 27% of patients. All patients received perioperative chemotherapy. The median follow-up was 27.6 months (range: 15-74). There was no postoperative mortality and the morbidity rate was 27%. The 2-year overall survival rate of the 63 patients was 67% with a median survival of 36 months. The local recurrence rates were similar for the three types of local treatments: 7.1% for the 154 RF ablations, 7.2% for the 55 wedge resections, and 9% for the 44 segmental anatomic resections (P = 0.216). Hepatic recurrences occurred in 71% of patients. The combination of anatomic segmental and wedge resections, RF ablation, and optimal chemotherapy in patients with technically unresectable LM results in a median survival of 36 months.

Hepatic segmentectomy under ultrasound-guided segmental staining and intraoperative chemotherapy for liver cancer

目的 比较B超引导下肝段门静脉阻断灌注化疗并肝段染色后肝切除术与常规肝切除术的临床疗效.方法 41例肝癌病人术中应用B超引导肝段门静脉阻断灌注化疗并肝段染色后肝切除术,35例应用常规肝切除术,术后定期复查肝功能、AFP,CT及MRI变化,并随访.结果 B超引导下肝段门静脉阻断灌注化疗并肝段染色后肝切除组较常规肝段切除组术中出血少,对肝功能影响小,其术后5年生存率分别为37.8%和24.3%(P＝0.040);局部复发率分别为31.7%和57.1%(P＝0.037).结论 B超引导下肝段门静脉阻断灌注化疗并肝段染色后肝切除术的临床疗效优于常规肝切除术。

Cytoreductive surgery and intraperitoneal chemotherapy for pseudomyxoma peritonei

Surgical improvement can be achieved in selected patients with pseudomyxoma peritonei (PMP) by major cytoreductive surgery and intraperitoneal chemotherapy (IPEC). The purpose of this retrospective study was to analyze morbidity, mortality, and survival following therapy. Between July 1995 and September 2003, 28 patients (mean age 56 years, range 28-79) with PMP were operated on with the aim of complete macroscopical cytoreduction. Surgery was followed by IPEC. A macroscopically complete cytoreduction was achieved in 11 patients (40%). The mean operating time was 6 h with a mean of three peritonectomy procedures per patient. Cisplatin (15 out of 28), mitomycin C (6 out of 28) and 5-FU (7 out of 28) were used for the intraoperative chemotherapy. Overall morbidity was 36%. Most frequent surgical complications were digestive fistulae (3 out of 28), abscesses (5 out of 28) and bleeding (2 out of 28). Two patients died postoperatively. Patients with low tumor volume (mean survival time 78+/-11 vs. 37+/-9 months, p=0.05) and complete cytoreduction (73+/-10 vs. 24+/-8 months, p<0.05) had an improved prognosis. Cytoreductive surgery combined with IPEC is associated with acceptable morbidity and mortality. Complete cytoreduction may improve survival, particularly in selected patients with PMP who have a low tumor volume, complete cytoreduction, and no organ metastases.

Noninvasive cardiac monitoring by aortic blood flow determination in patients undergoing hyperthermic intraperitoneal intraoperative chemotherapy (HIIC)

Noninvasive cardiac monitoring by aortic blood flow determination in patients undergoing hyperthermic intraperitoneal intraoperative chemotherapy (HIIC)

Hyperthermia modifies pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rat model.

Peritoneal surface malignancy is a common manifestation of failure of treatment for abdominal cancers. Best results of treatment have been achieved with complete cytoreduction followed by heated intraoperative chemotherapy. Melphalan is a chemotherapeutic agent that shows increased pharmacological activity with heat. But the combination of intraperitoneal administration and heat have never been tested for this drug. The purpose of this study was to evaluate the effect of hyperthermia on the pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rodent model. Melphalan was given by the intraperitoneal route to 20 Sprague-Dawley rats at a dose of 12 mg/kg over 90 min. Rats were randomized into two groups according to the temperature of the peritoneal perfusate: group NT received normothermic (33.5 degrees C) melphalan; group HT received hyperthermic (42 degrees C) melphalan. During the course of intraperitoneal chemotherapy, peritoneal fluid and blood were sampled at 5, 15, 30, 60 and 90 min. At the end of procedure, the rats were killed and tissues samples (heart, liver, ileum, jejunum, colon, omentum, and abdominal wall) were collected. Concentrations of melphalan were determined in peritoneal fluid, plasma, and tissues by high-performance liquid chromatography. The area under the curve (AUC) of peritoneal fluid melphalan was significantly lower in the HT group than in the NT group ( P=0.001), whereas no significant difference in plasma AUC was found. AUC ratios (AUC peritoneal fluid/AUC plasma) were 12.1 for the NT group and 12.3 for the HT group. The mean time to reach the plasma peak was shorter in the HT group than in the NT group ( P=0.004). The HT group exhibited increased melphalan concentrations in all intraabdominal tissues. These differences were significant for the ileum ( P=0.03) and jejunum ( P=0.04). Hyperthermia affected the pharmacokinetics of intraperitoneal melphalan by decreasing the AUC of peritoneal fluid melphalan without increasing the plasma AUC. It increased intraabdominal tissue concentrations.

Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy.

During recent years, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin has been used for various malignancies. To characterise the population pharmacokinetics and pharmacodynamics of mitomycin during HIPEC. Forty-seven patients received mitomycin 35 mg/m2 intraperitoneally as a perfusion over 90 minutes. Mitomycin concentrations were determined in both the peritoneal perfusate and plasma. The observed concentration-time profiles were used to develop a population pharmacokinetic model using nonlinear mixed-effect modelling (NONMEM). The area under the plasma concentration-time curve (AUC) was related to the haematological toxicity. Concentration-time profiles of mitomycin in perfusate and plasma were adequately described with one- and two-compartment models, respectively. The average volume of distribution of the perfusate compartment (V1) and rate constant from the perfusate to the systemic circulation (k12) were 4.5 +/- 1.1L and 0.014 +/- 0.003 min(-1), respectively (mean +/- SD, n = 47). The average volume of distribution of the central plasma compartment (V2), clearance from the central compartment (CL) and volume of distribution of the peripheral plasma compartment (V3) were 28 +/- 16L, 0.55 +/- 0.18 L/min and 36 +/- 8L, respectively. The relationship between the AUC in plasma and degree of leucopenia was described with a sigmoidal maximum-effect (Emax) model. The pharmacokinetics of mitomycin during HIPEC could be fitted successfully to a multicompartment model. Relationships between plasma exposure and haematological toxicity were quantified. The developed pharmacokinetic-pharmacodynamic model can be used to simulate different dosage schemes in order to optimise mitomycin administration during HIPEC.

Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum

The aim of this study was to review the long-term results of cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Our goal was to identify clinical factors by which to select patients likely to benefit from a comprehensive management plan.Clinical data of 28 females who underwent surgery were retrieved from a prospective database. Major cytoreductive procedures were possible in 25 patients. Heated intraoperative or early postoperative intraperitoneal chemotherapy was also used where appropriate. The median follow-up after cytoreduction was 26.9 months. The overall median survival after cytoreduction was 45.8 months. The prognostic indicators associated with a statistically significant impact on survival were the prior surgery score (P &lt; 0.001), the completeness of cytoreduction score (CC; P = 0.037), and response to chemotherapy prior to surgery (P = 0.012).Our findings suggest that cytoreductive surgery can be effective when combined with perioperative intraperitoneal chemotherapy. Results can be improved by excluding cases where CC seems unlikely. Extensive prior surgery without the protection of adjunctive intraperitoneal chemotherapy is associated with a poor prognosis. This may be due to disruption of anatomical planes leading to deep abdominal and pelvic dissemination intractable to further treatment.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer

BackgroundIn selected patients with peritoneal carcinomatosis from ovarian cancer prognosis can be improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsBetween September 1995 and February 1999, 19 patients (mean age 52 years, range 30–72 years) with peritoneal carcinomatosis from primary or recurrent epithelial ovarian carcinoma were operated with the aim of complete macroscopical cytoreduction. Surgery was followed by intraoperative HIPEC. The data was analyzed retrospectively.ResultsEleven patients had recurrent and 8 primary ovarian cancer. The median progression free interval was 18 months (range 6–36 months). Macroscopically complete cytoreduction was achieved in 9 patients. Cisplatin (n = 16) or mitoxantrone (n = 3) were used for the intraoperative chemotherapy. The median intraabdominal inflow temperature was 41.5°C. Complications occurred in seven patients. Most frequent complications were anastomotic leakage (2/19) and intraabdominal abscess formation (2/19). One patient died postoperatively. The mean (± SD) overall survival time was 33(± 6) months with a 5-year survival rate of 15%. The survival was found to be influenced by the completeness of cytoreduction (44 ± 11 vs. 25 ± 6 months, p = 0.40), tumor volume (54 ± 10 versus 16 ± 4, p = 0.002) and presence of lymph node (38 ± 8 vs. 20 ± 8 months, p= 0.2) or liver metastases (51 ± 9 vs. 21 ± 6 months, p = 0.06).ConclusionsCytoreductive surgery combined with HIPEC is feasible and is associated with a reasonable morbidity and mortality. Complete cytoreduction may improve survival in select group of patients with low tumor volume and no organ metastases.

Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum.

The aim of this study was to review the long-term results of cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Our goal was to identify clinical factors by which to select patients likely to benefit from a comprehensive management plan. Clinical data of 28 females who underwent surgery were retrieved from a prospective database. Major cytoreductive procedures were possible in 25 patients. Heated intraoperative or early postoperative intraperitoneal chemotherapy was also used where appropriate. The median follow-up after cytoreduction was 26.9 months. The overall median survival after cytoreduction was 45.8 months. The prognostic indicators associated with a statistically significant impact on survival were the Prior Surgery Score (P < 0.001), the Completeness of Cytoreduction Score (P = 0.037) and response to chemotherapy prior to surgery (P = 0.012). Our findings suggest that cytoreductive surgery can be effective when combined with perioperative intraperitoneal chemotherapy. Results can be improved by excluding cases where completeness of cytoreduction seems unlikely. Extensive prior surgery without the protection of adjunctive intraperitoneal chemotherapy is associated with a poor prognosis. This may be due to disruption of anatomic planes leading to deep abdominal and pelvic dissemination intractable to further treatment.

Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum

The aim of this study was to review the long-term results of cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Our goal was to identify clinical factors by which to select patients likely to benefit from a comprehensive management plan. Clinical data of 28 females who underwent surgery were retrieved from a prospective database. Major cytoreductive procedures were possible in 25 patients. Heated intraoperative or early postoperative intraperitoneal chemotherapy was also used where appropriate. The median follow-up after cytoreduction was 26.9 months. The overall median survival after cytoreduction was 45.8 months. The prognostic indicators associated with a statistically significant impact on survival were the Prior Surgery Score (P&lt; 0.001), the Completeness of Cytoreduction Score (P= 0.037) and response to chemotherapy prior to surgery (P= 0.012). Our findings suggest that cytoreductive surgery can be effective when combined with perioperative intraperitoneal chemotherapy. Results can be improved by excluding cases where completeness of cytoreduction seems unlikely. Extensive prior surgery without the protection of adjunctive intraperitoneal chemotherapy is associated with a poor prognosis. This may be due to disruption of anatomic planes leading to deep abdominal and pelvic dissemination intractable to further treatment.

Cytoreductive Surgery Combined With Intraoperative Hyperthermic Intrathoracic Chemotherapy for Stage I Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a disease mostly confined to the thoracic cavity. Untreated, the median survival is <1 year. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy is used to kill residual tumor cells on the surface of the thoracic cavity while having limited systemic side effects. From August 1998 to August 2001, 22 patients with stage I MPM were included in this study. Two patients were irresectable at operation because of extrathoracic tumor growth. Twenty procedures were performed. After cytoreduction, a perfusion was performed with cisplatin and doxorubicin at 40 degrees C to 41 degrees C for 90 minutes. Adjuvant radiotherapy was given to surgical scars and drainage tracts. There was no perioperative mortality, but significant morbidity was seen in 13 patients (65%), including bronchopleural fistula, diaphragm rupture, wound dehiscence, persistent air leakage, and chylous effusion. No hair loss or leucopenia was noticed. The median follow-up was 14 months. The median survival (Kaplan-Meier) was 11 months, with a 1-year survival of 42%. A favorable pharmacokinetic ratio was observed for both cisplatin and doxorubicin. Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy for stage I MPM is feasible. However, this treatment is accompanied by considerable morbidity. Survival data were less encouraging.