Hyperthermic Perioperative Chemotherapy Research Articles

Long-term outcomes after cytoreductive surgery and hyperthermic perioperative chemotherapy for morcellated uterine leiomyosarcoma: case series

<h3>Objectives:</h3> Uterine leiomyosarcoma (uLMS) is a rare aggressive malignant mesenchymal tumor with high risk of recurrence and poor prognosis regardless of stage. If the tumor was morcellated, the oncologist will encounter special problems that require aggressive management of peritoneal metastases. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an intraoperative intraperitoneal chemotherapy administration under hyperthermic condition. Early postoperative intraperitoneal chemotherapy (EPIC) is a second perioperative regional chemotherapy with a goal to eradicate peritoneal metastatic disease. These treatments are possible following a complete cytoreduction surgery (CRS). Only few studies have evaluated outcomes in patients with morcellated uLMS who underwent HIPEC and/or EPIC following CRS. The purpose of the study is to evaluate the long-term outcomes in patients with morcellated uLMS who underwent CRS and HIPEC plus EPIC. <h3>Methods:</h3> We previously reported short-term outcomes (median 14.5 months) in six patients who underwent CRS and HIPEC in an attempt to successfully manage the disseminated disease following morcellation. We reviewed patient demographics, tumor characteristics, treatment history, perioperative complications and outcomes. The grade of the malignancy, peritoneal cancer index (PCI), and completeness of cytoreduction score (CC score) were available for all patients. <h3>Results:</h3> Six patients with morcellated uLMS who underwent CRS and HIPEC were identified in our database. HIPEC was used for 90 minutes following the CRS in the operating room. The regimen consisted of cisplatin 50 mg/m² and doxorubicin 15 mg/m² by intraperitoneal instillation that was manually distributed into the abdominal and pelvic space and maintained at 42.5?. Of the six patients, five patients also received EPIC.Mean age at CRS followed by HIPEC was 49 years (range 40-62) and mean interval from the initial surgery was 17 months (range 1 month to 7 years). The mean PCI was 18 and a CC-0 cytoreduction was achieved in all patients. The 3-year overall survival was 50% and 5-year overall survival was 33% with the median follow-up of 30 months (range 5 months to 73 months). A low grade of sarcoma and a low PCI suggested a favorable outcome. <h3>Conclusions:</h3> Our case series suggests that CRS and HIPEC plus EPIC is well-tolerated and may be a therapeutic option for newly diagnosed uterine leiomyosarcoma following morcellation. Therapeutic options for patients with uLMS post-morcellation are limited and further research to eliminate disease dissemination is needed.

Treatment of Malignant Peritoneal Mesothelioma.

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.

Prevention and Treatment of Peritoneal Metastases: a Comprehensive Review.

Peritoneal metastases may occur from a majority of cancers that occur within the abdomen or pelvis. When cancer spread to the peritoneal surfaces is documented, a decision regarding palliation versus an aggressive approach using cytoreductive surgery (CRS) and hyperthermic perioperative intraperitoneal chemotherapy (HIPEC) must be made. This decision is dependent on a well-defined group of prognostic indicators. In addition to treatment, prevention of peritoneal metastases may be an option. The clinical and pathologic features of a primary cancer can be used to select perioperative treatments that may prevent cancer cells within the abdomen and pelvis from progressing to established peritoneal metastases. In some clinical situations with appendiceal and colorectal cancers, the clinical or histopathologic features may indicate that second-look surgery plus perioperative chemotherapy should occur. Peritoneal metastases should always be considered by the multidisciplinary team for treatment or prevention.

Concerning CT features used to select patients for treatment of peritoneal metastases, a pictoral essay

Background: During the Fifth International Workshop on Peritoneal Surface Malignancy in Milan in 2008, a consensus was reached that contrast-enhanced CT (ceCT) was the principal imaging modality for patients being evaluated for treatment of peritoneal metastases. This fact being accepted, the radiologic criteria for that may exclude patients from a high value cytoreductive surgery (CRS) plus hyperthermic perioperative chemotherapy (HIPEC) have not been reliably determined.Methods: From a consensus of surgeons and radiologists, radiologic images were selected and their determinant radiologic characteristics described. The anatomic pathology causing the abnormal images were identified and characterised. The cytoreductive surgical procedures that may, in selected patients, result in a complete resection of the pathology identified were presented.Results: Radiographs of 15 CT images that cause concern when a patient is being evaluated for CRS were listed. The anatomic pathology these images define and possible surgical resections they require were reviewed. The surgical implications of the absence or presence of a single, or of multiple concerning CT features was extracted from the surgical and radiologic literature.Conclusions: There is a definite need to identify new pre-operative imaging parameters to define optimal indication of CRS with HIPEC. The presence of a single concerning radiologic feature is associated with the possibility of an adverse outcome or technically more complex resections associated with increased morbidity and mortality. If two or more of the concerning radiologic features are described from the CT, suboptimal cytoreduction will usually occur.

When and When Not to Perform a Right Colon Resection with Mucinous Appendiceal Neoplasms.

Mucinous appendiceal neoplasms (MAN) with peritoneal dissemination is treated as a standard of care using cytoreductive surgery and hyperthermic perioperative chemotherapy. The extent of the resection of peritoneal surfaces and visceral structures is generally well defined. Exception to this consensus regarding structures to be removed are the right colon and adjacent ileocolic lymph nodes. From a prospectively maintained database, all patients with a histologic diagnosis of peritoneal mucinous carcinoma (PMCA) who underwent complete cytoreductive surgery were assessed for the presence versus absence of adenocarcinoma in lymph nodes within the appendiceal mesentery and/or in the lymph nodes of the ileocolic group. The histologic grade of the PMCA was correlated with the incidence of lymph node invasion. Also, in those PMCA patients who had no evidence of lymph node invasion, recurrence within the ileocolic lymph nodes was determined by computed tomography or second look. In a database of MAN patients, 299 had a histologic diagnosis of PMCA. In well-differentiated (n=44), moderately differentiated (n=107), and poorly differentiated (n=148) PMCA specimens, there were 6.8, 5.6, and 29% positive lymph nodes, respectively. None of these 151 patients with well- or moderately differentiated PMCA had a computed tomographic scan or clinical evidence by second-look surgery of recurrence within the ileocolic lymph nodes. There is a low incidence (6.0%) of positive lymph nodes in patients with low or moderately differentiated PMCA. With high-grade disease, lymph node invasion increased to 29.0%. Right colectomy is indicated in patients with high-grade PMCA.

Management of Malignant Peritoneal Mesothelioma Using Cytoreductive Surgery and Perioperative Chemotherapy.

Malignant peritoneal mesothelioma is a rare disease, with approximately 800 new patients per year in the United States. Its natural history is defined by progression restricted to the peritoneal space. In the past, patients with this disease had a limited lifespan of approximately 1 year. Numerous single-institution studies as well as a systematic review have reported median survival of 3 to 5 years with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy. These markedly improved survival statistics were achieved in experienced centers with 1% mortality and 20% morbidity rates. Data have shown that knowledgeable patient selection is required to prevent patients unlikely to benefit from undergoing these interventions. The conclusion is that patients with peritoneal mesothelioma can experience long-term progression-free survival or significant palliation with cytoreductive surgery plus hyperthermic perioperative chemotherapy. This management plan should be considered the standard of care for properly selected patients with malignant peritoneal mesothelioma at experienced centers around the world.

Cytoreductive Surgery and HIPEC as a Treatment Option for Laparoscopic Resection of Uterine Leiomyosarcoma with Morcellation: Early Results.

A new and frequently utilized treatment option for symptomatic uterine leiomyoma is laparoscopic resection with morcellation so the specimen can be extracted through a small abdominal incision or through the vagina. Some of these tumors (approximately 0.2%) have malignant foci of uterine leiomyosarcoma (ULMS) that is widely disseminated in the process of resection. These patients are in need of effective additional treatments. Patients with ULMS were treated with a standardized cytoreductive surgery (CRS), hyperthermic perioperative chemotherapy (HIPEC), and early postoperative intraperitoneal chemotherapy (EPIC) specifically designed for sarcomatosis. Distribution of disease by Peritoneal Cancer Index was recorded by preoperative computed tomography or magnetic resonance imaging and at the time of CRS. Completeness of cytoreduction score was determined after completion of CRS. Morbidity and mortality, as well as interval to start systemic chemotherapy, were prospectively recorded. Six patients with disseminated ULMS after morcellation or slicing underwent CRS and HIPEC plus EPIC. All six patients had complete visible clearing of sarcoma prior to perioperative chemotherapy. Early intervention after morcellation was associated with a lesser extent of disease. No serious morbidity or mortality was observed in early referral patients, and patients eligible for systemic chemotherapy were treated with perioperative chemotherapy within 6weeks of the CRS. The future use of laparoscopic resection of ULMS with morcellation is currently under debate. However, patients after laparoscopic resection and morcellation have CRS and HIPEC plus EPIC as a treatment option. Results regarding short-term benefit are suggested by these early data, especially with early referral.

Avoiding Diverting Ileostomy in Patients Requiring Complete Pelvic Peritonectomy.

In performing cytoreductive surgery with hyperthermic perioperative chemotherapy, a rectosigmoid colon resection is frequently required. To reduce the incidence of anastomotic leakage at the colorectal anastomoses, a diverting ileostomy has been recommended in these patients. Stripping of mesorectal fat from the rectum up to the peritoneal reflection allows transection of the rectum at the junction of the upper and middle rectum. A suture pulls in the lateral aspects of the rectal staple line so that this staple line is included within the barrel of the stapler. After the circular-stapled anastomoses is complete, a second layer of silk sutures is used to invert the staple line. In 31 stapled colorectal anastomoses, three rectal transections were so low that a layer of sutures was not possible. In the 29 two-layer colorectal anastomoses, no anastomotic leakages were observed. The incidence of diverting ileostomy was reduced from 50 to 7%. These results suggest that preservation of a 10-15cm length of rectum allows a second layer of sutures to be placed over the stapled colorectal anastomoses. This is a safe alternative to a diverting ileostomy in selected patients.

Surgical technology and pharmacology of hyperthermic perioperative chemotherapy.

Although cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) have not been shown to be effective by themselves, as a combined treatment they are now standard of care for peritoneal metastases from appendiceal cancer and from colorectal cancer as well as peritoneal mesothelioma. The timing of the HIPEC in relation to the CRS is crucial in that the HIPEC is to destroy minimal residual disease that remains following the CRS and prevent microscopic tumor emboli within the abdomen and pelvis from implanting within the resection site, within fibrinous clot, or within blood clot. Proper selection of chemotherapy agents is crucial to the long-term benefit of CRS and HIPEC. One must consider the response expected with the cancer chemotherapy agent, its area under the curve (AUC) ratio indicating the amount of dose intensity within the peritoneal space, and the drug retention within the peritoneal space for a prolonged exposure. Hyperthermia will augment the cytotoxicity of the cancer chemotherapy agents and improve drug penetration. Irrigation techniques should not be overlooked as an important means of reducing the cancer cell burden within the abdomen and pelvis. Multiple technologies for HIPEC exist and these have advantages and disadvantages. The techniques vary from a totally open technique with a vapor barrier over the open abdominal space to a totally closed technique whereby the HIPEC is administered at the completion of the surgical procedure. The open techniques depend on a table-mounted retractor for suspension of the skin edges allowing a reservoir to occur within the abdomen and pelvis. There are nearly a dozen commercially available hyperthermia pumps, all of which seem to perform adequately for HIPEC although there is a variable degree of convenience and documentation of the HIPEC procedure. As the management of peritoneal metastases has progressed over three decades, early cases are now seen in which a laparoscopic CRS and HIPEC may be appropriate. Also, prophylactic use of laparoscopic HIPEC with perforated appendiceal malignancies and T4 colon cancers may be appropriate.

Theoretical Considerations for Optimal Cytoreductive Surgery Plus Hyperthermic Perioperative Chemotherapy

Background: The concepts regarding the definitive management of peritoneal metastases seems straightforward in that surgery is to remove all visible disease and then intraperitoneal chemotherapy is used to eradicate minimal residual disease. However, implementation of this management strategy presents numerous patient-related, methodologic, and pharmacologic variables. Methods: In order to optimize cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC), important theoretical considerations for implementation of this management strategy are presented. The aim of the study is to integrate these modifications in the treatment of abdominal and pelvic malignancy into practice and thereby improve outcomes. Results: Surgical technology to achieve a complete response is necessary but not sufficient to optimally pursue a curative treatment option. Strategies to initiate treatments with the lowest possible peritoneal cancer index (PCI) involve proactive treatments of the primary gastrointestinal cancer, neoadjuvant chemotherapy, initiation of treatments at the first diagnosis of peritoneal metastases, and the use of laparoscopy and radiology to select patients. Tumor cell entrapment should be avoided. Mechanical removal of cancer cells by vigorous irrigation techniques carries minimal risk and may reduce residual disease. Chemotherapy agents that cause a response, result in prolonged intraperitoneal drug retention and show a high peritoneal to plasma concentration ratio are recommended. Finally, long-term bidirectional adjuvant normothermic chemotherapy (BANC) has been shown in randomized trials in ovarian cancer to improve survival and may be of value in other diseases. Conclusions: Despite the complexity of patient management using CRS and HIPEC, application of six basic principles promise to contribute to the results of treatment of peritoneal metastases.

Two Decades of Progress in the Management of a Rare Disease—Peritoneal Mesothelioma

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare but aggressive disease with a poor sustained response to systemic chemotherapy. Historically, the median survival has been less than 1 year. The disease rarely disseminates outside of the peritoneal space suggesting that local-regional treatment options may be effective in the long-term control of this malignancy. Establishment of a referral center to concentrate experience with the management of this disease has contributed greatly to progress in its management.Materials and methods:Through a series of Institutional Review Board-approved protocols, a long-standing morbidity/mortality assessment, numerous manuscripts published in the peer-reviewed literature, and participation in numerous national and international workshops, a new standard of care with expectations of long-term survival in a majority of patients has evolved.Results:The surgery for this disease has evolved through a sequence of peritonectomy procedures and visceral resections whose goal is to remove all visible evidence of disease. The first step in successful treatment is a complete cytoreduction. After the cancer resection in the operating room, hyperthermic perioperative chemotherapy (HIPEC) is used. A three-drug protocol combines heat-augmented chemotherapy within the peritoneal space and systemic chemotherapy that is heat-augmented as a continuous infusion intravenously. Catheters are placed for early postoperative intraperitoneal chemotherapy using paclitaxel for 5 days. Also placed at the time of the cytoreductive surgery is an intraperitoneal port for long-term combined intraperitoneal and systemic chemotherapy using cisplatin and pemetrexed for 6 months. Patients having the long-term bidirectional chemotherapy have shown statistically significant improved survival compared with those patients who had surgery alone plus the perioperative chemotherapy. There have been no mortality and the grade 4 adverse events have been prospectively accumulated as 12 %.Conclusions:With continued effort, the surgery and long-term regional chemotherapy for DMPM has continued to improve over 20 years. Currently, a management plan that involves cytoreductive surgery, perioperative chemotherapy, and long-term bidirectional chemotherapy has changed the natural history of this disease. A global registry has been initiated to confirm the benefits of these extended treatments.

Peritoneal metastases from mucinous endocervical adenocarcinoma

Pseudomyxoma peritonei is a clinical condition characterized by mucinous tumors and mucinous ascites that accumulates in large volume and over time will interrupt gastrointestinal function. Pseudomyxoma peritonei most commonly arises from a mucinous neoplasm of the appendix (Sugarbaker et al., 1996). Also, occasionally this syndrome may arise from the colon or rectum, gallbladder, small intestine, ovarian teratoma, lung, breast, pancreas, fallopian tube, and urachus (Sugarbaker, 2012a). Described here are three patients presenting with mucinous peritoneal metastases arising from an adenocarcinoma of the endocervix. This cause of this rare condition is unclear; it may be caused by retrograde menstruation. Evaluation of these patients for cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) at a peritoneal surface oncology treatment center early in the natural history of the disease is recommended. Patient presentation 1 A 33 year old woman presented in May of 2011 with chief complaints of abdominal distention and pain. A past history of cone biopsy of the cervix in 2002 showed pre-cancerous cells with no invasive malignancy. CT of the chest, abdomen, and pelvis showed a large volume of intraabdominal fluid consistent with combined mucinous and serous ascites (Fig. 1). Laparoscopy was performed showing bilateral adnexal masses, copious mucinous fluid, and peritoneal metastases on the abdominal wall, the right hemidiaphragm, and greater omentum. Pathology showed mucinous adenocarcinoma and immunostains suggested a cervical origin with P16 and CK7 positive and CK20 negative. Fig. 1 Abdominal and pelvic CT on a patient with adenocarcinoma of the endocervix. Paracentesis resulted in the drainage of 10 l of ascites. Upper and lower gastrointestinal endoscopy was not revealing of a cancerous process. She underwent a 9-hour complete CRS with greater omentectomy, appendectomy, right upper quadrant peritonectomy, lesser omentectomy, pelvic peritonectomy, hysterectomy, and bilateral salpingo-oophorectomy (Sugarbaker, 2012b). Pathology showed in-situ and invasive mucinous adenocarcinoma of the endocervix with metastases to ovaries, fallopian tubes, omentum, and peritoneum. The appendix was normal except for overlying extracellular mucin. She was treated with HIPEC and early postoperative intraperitoneal chemotherapy (EPIC) (Sugarbaker, 2012b). The patient was treated with a single cycle using cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) by intraperitoneal administration at 42 °C. Continuous infusion intravenous ifosfamide was given over the 90 min of HIPEC. Fifteen minutes prior to infusion 2-mercaptoethane sulfonate NA (MESNA) at 260 mg/m2 was given as a bolus. The MESNA was repeated at 4 and 8 h after initiation of the HIPEC. Early postoperative intraperitoneal chemotherapy (EPIC) with paclitaxel at 20 mg/m2 in one liter of 1.5% dextrose peritoneal dialysis solution was used postoperative days one through five (Sugarbaker, 2012b). Systemic chemotherapy was given over five months using paclitaxel at 135 mg/m2 administered over 24 h on day one plus cisplatin 50 mg/m2 administered on day two. Treatment was every 21 days for six cycles. She remains asymptomatic on 6 monthly CT follow-up at 3 years.

Update on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer.

The prevention of a disease process has always been superior to the treatment of the same disease throughout the history of medicine and surgery. Local recurrence and peritoneal metastases occur in approximately 8% of colon cancer patients and 25% of rectal cancer patients and should be prevented. Strategies to prevent colon or rectal cancer local recurrence and peritoneal metastases include cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These strategies can be used at the time of primary colon or rectal cancer resection if the HIPEC is available. At institutions where HIPEC is not available with the treatment of primary malignancy, a proactive second-look surgery is recommended. Several phase II studies strongly support the proactive approach. If peritoneal metastases were treated along with the primary colon resection, 5-year survival was seen and these results were superior to the results of treatment after peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look has been shown to be effective in two published manuscripts. Unpublished data from MedStar Washington Cancer Institute also produced favorable date. Rectal cancer with peritoneal metastases may not be so effectively treated. There are both credits and debits of this proactive approach. Selection factors should be reviewed by the multidisciplinary team for individualized management of patients with or at high risk for peritoneal metastases.

Optimization of Patient Selection for Surgical Approach to Peritoneal Metastases from Gastrointestinal Cancer Using Cytoreductive Surgery and Perioperative Chemotherapy

Gastrointestinal cancer can metastasize by hematogenous routes to the liver, by lymphatic channels to regional lymph nodes, and by penetration of the bowel wall to the peritoneal surfaces. For patients who have isolated peritoneal metastases, a new management plan with curative intent has evolved over the last 30 years. Now patients with peritoneal dissemination are evaluated by the multidisciplinary team for treatment by cytoreductive surgery plus perioperative chemotherapy. Major progress in the treatment of peritoneal metastases has occurred as a result of more clearly defined selection criteria. Now it is possible to identify patients who are likely to benefit and exclude those who may undergo extensive surgery with little or no added longevity or improved quality of life. Success with the combined treatment is dependent on complete cytoreductive surgery (CRS) before initiation of the perioperative chemotherapy. The large variations in success with peritoneal metastases treatment is dependent upon the success of hyperthermic perioperative chemotherapy (HIPEC) and early postoperative chemotherapy (EPIC) to maintain the absence of intraperitoneal cancer achieved by the surgical complete response. Prevention of a recurrence of peritoneal metastases after complete cytoreduction can be divided into two distinct time periods. Secondary prevention involves the peritoneal metastases diagnosed in follow up. The selection factors important in assessment of secondary prevention include the peritoneal cancer index (PCI), histological assessment of biological aggressiveness, lymph node status, distribution of peritoneal metastases, prior surgical score (PSS), and response to neoadjuvant chemotherapy. A new and promising investigation is prevention of peritoneal metastases as part of management of the primary malignancy. This use of CRS and HIPEC is referred to as primary prevention. The clinical features that suggest the need for CRS and perioperative chemotherapy are peritoneal nodules detected at the time of primary cancer resection, ovarian metastases, perforation through the primary cancer, adjacent structure or organ invasion, signet ring histology, fistula formation, or obstruction. The histopathologic features suggesting the need for CRS and perioperative chemotherapy available at the time of primary cancer resection include positive peritoneal cytology, positive imprint cytology, lymph nodes positive at or near the margin of resection, and T3/T4 mucinous cancer. The selection factors for secondary and primary prevention must be considered by the multidisciplinary team in the management of peritoneal metastases.

Colorectal cancer: prevention and management of metastatic disease.

This paper compared the similarities and differences of the two most common types of colorectal cancer metastases. The treatment of liver metastases by surgery combined with systemic chemotherapy was explained. The different natural history of liver metastases as compared to peritoneal metastases and the possibility for prevention of peritoneal metastases were emphasized. Perioperative cancer chemotherapy or second-look surgery must be considered as individualized treatments of selected patients who have small volume peritoneal metastases or who are known to be at risk for subsequent disease progression on peritoneal surfaces. However, the fact that peritoneal metastases, when diagnosed in the follow-up of colorectal cancer patients, can be cured with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy cannot be ignored. Careful follow-up and timely intervention in colorectal cancer patients with progressive disease are a necessary part of the management strategies recommended by the multidisciplinary team. After a critical evaluation of the data currently available, these strategies for prevention and management of colorectal metastases are presented as the author's recommendations for a high standard of care. As more information becomes available, modifications may be necessary.

HIPEC: standard of care or an experimental approach?

We applaud the recent report of the debate about the role of cytoreductive surgery plus hyperthermic perioperative chemotherapy (HIPEC) in the treatment of peritoneal metastases.1 Irrespective of opinion about the efficacy of HIPEC and whether this procedure is a standard of care or an experimental approach, until data from a randomised trial are available, this approach must be regarded as experimental. Indeed, the report in 2007 of the consensus for HIPEC as a reference treatment2 was presented as being supported by data from 11 phase 2 trials.

205. The influence of sound pharmacologic studies in hyperthermic perioperative chemotherapy – Development and practice for peritoneal metastases from gastrointestinal and ovarian cancer

Background: A combined treatment strategy which employs cytoreductive surgery (CRS) with peritonectomy and visceral resections along with hyperthermic perioperative chemotherapy (HIPEC) is used in order to help gain control of the peritoneal surface component of metastatic gastrointestinal and ovarian cancer. The rationale for HIPEC is the preservation of the surgical complete response within the abdomen and pelvis brought about as a result of the cytoreductive surgery.

129. Technical aspects of hyperthermic perioperative chemotherapy

Background: Chemotherapy focused on the abdominal and pelvic surfaces following cytoreductive surgery is administered in hopes of maintaining the surgical complete response that is provided by an optimal cytoreduction. The chemotherapy is initiated in the operating room after complete clearing of all visible malignancy using peritonectomy procedures and visceral resections.

Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach?

Peritoneal carcinomatosis is a common presentation in patients with metastatic colorectal cancer and the overall survival is poor. In most patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery and hyperthermic perioperative chemotherapy as the standard approach for selected patients with peritoneal metastases from colorectal cancer. Overall, very promising long-term survival has been shown in a subset of patients with a limited extent of peritoneal disease before treatment. Whether randomised, controlled trials are needed to definitively show the magnitude of benefit, if any, of this approach is an important question. This Debate outlines the arguments on each side of this issue.

Pulmonary Complications following Cytoreductive Surgery and Perioperative Chemotherapy in 147 Consecutive Patients

Cytoreductive surgery (CRS) with hyperthermic perioperative chemotherapy (HIPEC) has become a treatment option for selected patients with peritoneal metastases (PMs) from gastrointestinal malignancies. The purpose of this study is to evaluate our most recent data regarding pulmonary complications (respiratory distress, pleural effusion, and pneumonia) and attempt to identify risk factors associated with this management plan. This study includes the most recent 4-year experience with appendiceal and colorectal carcinomatosis patients treated in a uniform manner between January 1, 2006 and December 31, 2009. A prospective morbidity and mortality database was maintained and pulmonary adverse events were analyzed with special attention to subphrenic peritonectomy. There were 147 consecutive patients with a mean age of 49.9 years. Fourteen patients (10%) presented grades I–IV pulmonary complications for a total of 26 events. The peritonectomy of right upper quadrant was performed in 74% and right plus left in 49% of the patients. Statistically, there were no more pulmonary complications among patients submitted to peritoneal stripping of right or right and left hemidiaphragm as compared to no subdiaphragmatic peritonectomy (P = 1.00 and P = 0.58, resp.). In an analysis of 18 quantitative indicators and clinical variables with pulmonary adverse events, only blood replacement greater than six units showed a significant correlation (P = 0.0062). Pulmonary adverse events were observed in 10% of patients having CRS and HIPEC. Subphrenic peritonectomy was not a specific risk factor for developing these adverse events.