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Medicine » Surgery » "Abdominal Surgery", book edited by Fethi Derbel, ISBN 978-953-51-0691-3, Published: August 14, 2012 under CC BY 3.0 license. © The Author(s).

Chapter 6

Abdominal Advanced Oncologic Surgery

By Enrico Maria Pasqual and Serena Bertozzi
DOI: 10.5772/48155

Article top


Mechanisms of peritoneal cancer cells seeding.
Figure 1. Mechanisms of peritoneal cancer cells seeding.
Omental cake.
Figure 2. Omental cake.
Hyperthermia effects on tumour cells.
Figure 3. Hyperthermia effects on tumour cells.
Peritoneal cancer index to map carcinosis localization.
Figure 4. Peritoneal cancer index to map carcinosis localization.
Surgical cytoreduction.
Figure 5. Surgical cytoreduction.
Hyperthermic intraperitoneal chemotherapy
Figure 6. Hyperthermic intraperitoneal chemotherapy
Invasion of the gastric serosa.
Figure 7. Invasion of the gastric serosa.
Ovarian cancer survival in compete and non complete cytoreduction.
Figure 8. Ovarian cancer survival in compete and non complete cytoreduction.

Abdominal Advanced Oncologic Surgery

Enrico Maria Pasqual1, 1

1. Introduction

1.1. The peritoneal cavity, locoregional area

The peritoneal cavity, enclosed by visceral and parietal peritoneum, is the largest potential space in the body. With its own vascularization and lymphatic drainage, is anatomically separated from the general body system and other body compartments.


Figure 1.

Mechanisms of peritoneal cancer cells seeding.

Any pathological process involving the peritoneal cavity can easily disseminate throughout this space by means of unrestricted movement of fluid and cells. Accordingly malignant intraperitoneal tumour progression, before reaching the circulation system and developing distant metastases (pulmonary, brain and bone metastases) diffuses within and through the peritoneal cavity (Fig. 1). At this step intraperitoneal tumours must be considered in locoregional stage.

Peritoneal neoplasia can originate de novo from the peritoneal tissues (primary tumour) or invade or metastasize into the peritoneum from adjacent or remote organs (metastases).

Rare are the primitive tumours of the peritoneum: they include malignant mesothelioma, peritoneal primary carcinoma and sarcoma.

Malignant peritoneal mesothelioma is a rare but aggressive tumor derived from the peritoneal mesothelium accounting for 2 cases per 1 million population reported each year in USA. Association of malignant peritoneal mesothelioma and asbestos exposure has been reported to be as high as 83%. This locally aggressive disease is difficult to treat or palliate. Commonly, treatment regimens combine aggressive cytoreductive surgery with intraperitoneal chemotherapy. Cytoreductive surgery is the cornerstone of current treatment, while hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is a promising strategy in suitable patients (Deraco et al., 2002) (Fig. 2).


Figure 2.

Omental cake.

Primary peritoneal carcinoma is a very rare tumour and (ie, serous surface papillary carcinoma) arises primarily from peritoneal cells. This malignancy predominantly affects postmenopausal women and typically displays multicentric peritoneal and omental involvement. Pathologically and clinically, it resembles papillary serous ovarian carcinoma.

Many primary tumours, arising from organs placed within the peritoneal cavity, disseminate through it, leading patients to death. Peritoneal cavity represents the site of metastases in 50% of colorectal cancer, 50% of gastric cancer and 75% of ovarian advanced cancer. It represents the sole site of intraperitoneal metastasis in 20-25% of colorectal cancer, 30% of gastric cancer and 70% of ovarian cancer (Koppe et al., 2006; Randall and Rubin, 2001; Sadeghi et al., 2000). Intraperitoneal drug administration studies confirmed the existence of a peritoneal-plasma barrier which allows to concentrate the antiblastic drug within the cavity even 100-1000 times compared with that of the same drug infused through systemic circulation. Therefore a high antiblastic tumour tissue concentration and a low systemic toxicity can be achieved (Flessner, 2005). In association with intraperitoneal chemotherapy, hyperthermia has been demonstrated to enhance drug diffusion within the tumour tissue and also to have a direct antitumour activity (Issels, 2008) (Fig. 3)


Figure 3.

Hyperthermia effects on tumour cells.

Therefore cytoreduction and HIPEC procedure have been suggested to treat metastases from colorectal, gastric and gynaecological tumors (Sugarbaker, 1995). Results after treatment are encouraging in particular in cases of colorectal and gynaecological cancer with median 5 years survival respectively of 40% and 45%. Less satisfactory results have been obtained in case of gastric and pancreatic cancer with a minimal percentage of patient still living far from initial diagnosis (Elias et al., 2006; Roviello et al., 2011). The aggressive tumour surgical removal (tumour cytoreduction) coupled with intraperitoneal chemotherapy nowadays represents the cornerstone of advanced abdominal oncologic surgery (Glehen et al., 2006; Glockzin et al., 2009). A large international experience was therefore made through the last decades with the goal of allowing treatment and possibly cure of intraperitoneal tumours in advanced stage (Levine et al., 2007; Roviello et al., 2011).


Figure 4.

Peritoneal cancer index to map carcinosis localization.

2. Cytoreduction and intraperitoneal hyperthermic chemotherapy (HIPEC)

Advanced metastatic tumour can therefore be treated with surgery and hyperthermic chemotherapy contemporarily, during the same surgical operating work up. The first step is to carry out an aggressive cytoreduction in order to remove the whole macroscopic intracavitary tumour tissue and then to complete the procedure with HIPEC, to kill residual neoplastic cells floating within the peritoneal cavity or adherent to intraperitoneal tissue.

2.1. Cytoreduction

The surgical procedure of cytoreduction is now well standardized. Sugarbaker’s classification is still the reference for abdominal oncologic surgery and goes under the definition of peritonectomy. The surgical procedure was classified according to specific different areas of the abdominal cavity and it has been tailored by Milan ‘s panel workshop, defining (Fig. 4):


Figure 5.

Surgical cytoreduction.

  1. Upper RightPeritonectomy: right diaphragmatic peritonectomy with Glisson’s capsule dissection; lesser omentectomy, stripping of the omental bursa and cholecystectomy plus gastric antrectomy or total gastrectomy.

  2. Upper Left Peritonectomy: left diaphragmatic and parietal peritonectomy with splenectomy and greater omentectomy.

  3. Pelvic Peritonectomy: pelvic parietal peritonectomy, sigmoidectomy, hysterectomy and salpingo-ovariectomy.

  4. Right Parietal Peritonectomy, right/total colectomy; left parietal peritonectomy.

  5. Mesenteric implants on visceral surfaces could be removed surgically or by electrosurgical local dissection. Performing cytoreduction for peritoneal tumour dissemination, not all the procedures are necessary and made, usually necessitating one – three of the different peritonectomy procedures (Fig. 4 and 5).

2.2. Intraperitoneal hyperthermic chemotherapy

After having made complete surgical cytoreduction with an absent or minimal residual disease (less than 2.5 mm tumour diameter) some catheters are inserted into the abdominal cavity and a perfusion of 2 liters of a saline solution with a determined quantity of antiblastic drug (Mytomycin, Oxaliplatin for digestive cancer and Cisplatin, Taxol for ovarian cancer) is made. The peritoneal perfusion may lasts 30-90 minutes and it can be performed in condition of closed abdomen or open abdomen (Coliseum technique) or a compromise between the two, with an abdominal- wall small entrance suitable for the handling by the operator. (Fig. 6).


Figure 6.

Hyperthermic intraperitoneal chemotherapy

Hyperthermic perfusion can be obtained by heating the perfusion medium with a heat exchanger connected to the perfusion pump. The peritoneal cavity temperature considered optimal in terms of antitumor activity and antiblastic tumour tissue diffusion is 41,5-42,5 °C (Sugarbaker and Chang, 1999; Sugarbaker, 1996; Van der Speeten et al., 2009). It is of absolute importance to control the temperature of organs and bowels during the procedure. Excessive temperature of intraperitoneal tissue, more than 43 °C, is strongly correlated with lesions of the bowel wall and perforation, and also with necrosis of nerves, bladder or vases. To prevent excessive intraperitoneal temperature multiple temperature probes are placed within the peritoneal cavity to monitorate the temperature. At the end of the procedure the perfused medium is usually removed from the peritoneal cavity.

3. Advanced oncological surgery in colorectal cancer

Every year about 400.000 new cases of colorectal cancer (CRC) are diagnosed in Europe and 210.000 are believed to die of disease (Boyle and Ferlay, 2005). Peritoneal carcinosis (PC) has an incidence about 13% of CRC, in 58% of cases is synchronus with primary disease and in most cases is not diffused to the entire abdominal cavity but limited to an area (Jayne et al., 2002). Peritoneal cavity recurrence is the only site of relapse in about 25% of cases (Chu et al., 1989). The principal mechanism of peritoneal cancer diffusion through the abdominal cavity is the esfoliation of cancer cells following bowel-serosa tumour infiltration. Also lymphatic channel infiltration by the tumour followed by breaking of the lymphatic channel wall and subsequently loss of neoplastic cells within the abdominal cavity is a mechanism of PC formation. Furthermore at the time of surgical work up tumour manipulation and blood loss are also intracavitary mechanism of PC formation. Facing PC, both synchronous or metachronous, the usual treatment is systemic chemotherapy but median survival is usually not longer than 6 months even after the advent of new drugs and treatment scheme (Sadeghi et al., 2000). More recently Dominique Elias has published an experience with patients with PC and absence of extra-abdominal disease by using modern scheme of chemotherapy FOLFOX (5-FU, AF and oxaliplatin) and FOLFIRI (5-FU, AF and irinotecan) obtaining a median survival of 23,9 months and a 2 and 5 years survival of 65% and 13% respectively (Elias et al., 2009). The advent of CRS with HIPEC have ameliorated the prognosis in these patients (Elias et al., 2006; Verwaal et al., 2005; Yan and Morris, 2008).

During the last decade a randomized study, two multicentric comparative studies and a numbers of observational studies have tested the CRS and HIPEC activity against PC from CRC with encouraging results: mortality and postoperative morbidity of 0-8% and 39-72% respectively and 5 years survival of 40-51% (Verwaal et al., 2003, 2005; Elias et al., 2009, 2006; Franko et al., 2010). Main indications for application of the procedure are the presence of PC both synchronous or metachronous, therefore defining it a therapeutic procedure. But recent experiences also suggest the possible use of HIPEC in adjuvant setting after radical surgery work up. Not all patients with CRC could benefits from this approach. A number of risk factors for PC development have been demonstrated: minimal PC which was macroscopically visible, completely resected or ovarian metastasis (also resected), synchronous with the primary tumour or a perforated primary tumor inside the peritoneal cavity, primary CRC presenting with occlusion or haemorrhagia. Patients bearing these risk factors and treated with cytoreduction and HIPEC at the end of cytoreduction (no residual tumour disease was present - R0 resection) showed, in preliminary experiences, impressive results with a 5 years survival percentage reaching 90% and a 5 years disease free survival of more than 40% (Elias et al., 2009). This preliminary experience supports a large number of multi-istitutional ongoing worldwide studies to confirm the role of cytoreduction and hyperthermic intraperitoneal chemoperfusion in adjuvant setting at the same time of primary surgery or after a planned second look exploration. This new therapeutic approach even if after a long maturation phase lasting more than a decade, now seems to be accepted as a new frontier to treat advanced CRC and world wide surgical units have been created to coordinate and carry on the associated medical activity.

4. Advanced oncological surgery in gastric cancer

PC from gastric cancer arises following tumours invasion of the gastric serosa as depicted in Fig. 7. Also histological type can be crucial in PC gastric developing. Gastric tumours of the diffused type seems to represent a risk factor for PC and it has been demonstrated to relapse in about 50% of cases even after curative surgical resection (Marrelli et al., 2002). It has been shown that the serosal tumor invasion is correlated to the detection rate of intraperitoneal free cancer cells. The treatment of peritoneal carcinomatosis from gastric cancer by peritonectomy and HIPEC has demonstrated not so good long-term results when compared with the treatment of PC from other causes (Stewart et al., 2005). Anyway conventional treatment using palliative systemic chemotherapy showed a very dismal prognosis (Hanazaki et al., 1999). Long survival after peritonectomy and HIPEC for carcinomatosis arising from gastric cancer are possible if the extension of the carcinosis is low and the cytoreduction is complete. 3-year survival of 41% and 5-year survival rates of 11% was reported (Sayag-Beaujard et al., 1999; Yonemura et al., 2001, 1996). CRS and HIPEC of the PC seems to allow longer survival even if hyperthermic intraperitoneal chemoperfusion role is still under evaluation.


Figure 7.

Invasion of the gastric serosa.

Recent experiences with HIPEC have shown quite encouraging results in case of prevention of peritoneal recurrence after radical surgery for primary carcinoma, the adjuvant role. When curative gastrectomy is performed, in fact, peritoneal recurrence develops in nearly 50% of patients, therefore prevention of PC developing represent a fundamental goal in this setting (Yonemura et al., 2001, 1996; Fujimoto et al., 1999; Shen et al., 2009). Worldwide experiences are ongoing to ascertain the role of HIPEC in adjuvant setting and definitive results will be available in a short time.

5. Advanced oncological surgery in ovarian cancer

Epithelial ovarian cancers account for 80% to 90% of all ovarian malignancies and are the main cause of death for all gynaecological tumors (Yancik, 1993). Despite being diagnosed frequently at an advanced stage, dissemination is often confined to the peritoneal cavity (Randall and Rubin, 2001). It presents with vague gastrointestinal and constitutional symptoms of abdominal bloating, distension, weight loss, and fatigue (Goff et al., 2000). Late presentation results in the majority of patients being diagnosed with advanced disease (Stage III/IV). The 5-year survival rate of patients with advanced ovarian cancer is <25% (Ozols, 2005). In the final stages of this disease, patients suffer from severe anorexia, dyspnea and pain from malignant bowel obstruction, ascites, and pleural effusion as a result of the extensive burden of tumor.

Epithelial ovarian tumor arises from the serosal lining of the ovary. This covering of the ovary communicates with the serosal lining of the abdominopelvic cavity, and is known as the peritoneum. Tumor growth results in the exfoliation of malignant cells into the peritoneal fluid. They circulate freely and typically implant in the pelvis and subdiaphramatic recesses owing to gravity and the incumbent position. Intraoperatively, it is characterized by the extensive presence of macroscopic whitish tumor nodules of variable sizes and consistency that may coalesce to form plaques or masses within the abdominopelvic cavity.

Tumor dissemination from the primary tumour may also occur through the lymphatic channel disrupted by the tumour and the direction of neoplastic cell diffusion is all through the abdominal cavity.

CRS using limited peritonectomy procedures to resect peritoneal implants and HIPEC aims to allow both macroscopic cytoreduction through surgery and cytotoxic cytoreduction through loco-regional administration of heated chemotherapy. Cytoreduction and HIPEC has been tested in different routes; front line when treating the primary cancer, as interval surgery after neoadjuvat chemotherapy in case of unresectable cancer, as treatment of ovarian cancer relapses and even in case of salvage therapy (Look et al., 2004).


Figure 8.

Ovarian cancer survival in compete and non complete cytoreduction.

The largest experience to date was reported by Bereder who reported a median overall survival of 46 months in patients with first relapsed ovarian cancer of which a proportion are chemoresistant. In their institutions, the mortality rate was under 1% and the morbidity rates were about 10%.The treatment related complications is considered acceptable and further large volume peritonectomy units have low morality rates that range from 0 to 2% (Raspagliesi et al., 2006; Bereder et al., 2009; Look et al., 2004). Nowadays there is large agreement on the role of extreme cytoreduction of peritoneal carcinosis in case of ovarian cancer. Two groups of patients are then obtained: those with residual disease no more than 2.5 mm in diameter corresponding to the completeness cytoreduction rate CC0-1 and those with residual disease more than 2.5 mm CC2-3. The first group with a complete tumour eradication shows a significative better survival (Fig. 8).

Promising results have been published during this decade improving survival and disease free survival. This particular indication for this complex procedure represents a very promising but also conflicting tool because of the high drug Platinum sensitivity of ovarian cancer which makes medical oncologist to be confident with systemic chemotherapy results. Unfortunately despite a great number of patients optimally treated in this way a significant fraction of them relapse (50-70%) and in this case it is reasonable to think that extreme cytoreduction and HIPEC can be helpful.

6. Advanced oncological surgery in malignant peritoneal mesothelioma

Diffuse malignant peritoneal mesothelioma (DMPM) is a relatively uncommon peritoneal malignancy, representing 20-30% of 2.200-2.500 new cases diagnosed every year in USA, but its incidence has been rising worldwide since 1970s and is not expected to peak for another 5 to 20 years. The reason lays in its recognized association with asbestos exposure, which has been extensively used in the past as building material (Battifora, 1995; Robinson and Lake, 2005). Along with the occupational exposure, DMPM has been reported following radiation therapy, mica exposure, recurrent peritonitis and thorium dioxide administration (Maurer and Egloff, 1975; Antman et al., 1983; Chahinian et al., 1982; Riddell et al., 1981).

It is characterized macroscopically by thousands of whitish tumor nodules of variable size and consistency that may coalesce to form plaques or masses that may layer out to uniformly cover the entire peritoneal surface. Traditionally, DMPM was considered a preterminal condition, as the majority of patients died from intestinal obstruction or terminal starvation within the first year from the diagnosis (Yan et al., 2007). Despite its generally local spread without lymphoadenopathy or distant organ metastases, its poor prognosis may be explained by late diagnosis, due to the aspecificity of presenting symptoms (abdominal pain, girth, ascitis,...) and the inadequateness of most imaging tools in detecting small nodules on the whole peritoneal surface. Furthermore, no uniform treatment was initially suggested for this kind of malignancy, systemic chemotherapy and abdominal radiation therapy showed scarce results and were used only in selected patients, and surgery had only a palliative role to resolve intestinal obstruction in urgency without any significant effect on patients prognosis (Chailleux et al., 1988; Antman et al., 1983; Eltabbakh et al., 1999; Markman and Kelsen, 1992; Neumann et al., 1999; Sridhar et al., 1992; Yates et al., 1997). Recently, diagnostic and therapeutic aspects of the disease have been re-evaluated as encouraging reports from several centers worldwide on a combined locoregional treatment approach that uses cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have emerged. This new treatment strategy has shown favorable prognosis and has achieved in selected patients a median survival of up to 60 months and a 5-year survival of 50% using different antiblastic sequence (Deraco et al., 2006; Nonaka et al., 2005; Park et al., 1999; Sugarbaker et al., 2003; Yan et al., 2007).

Given its tendency to remain confined to the peritoneal surface, the prognosis of DMPM has been significantly improved by the combined treatment with CRS and HIPEC. In particular, while CRS reduces the tumoral mass (an optimal cytoreduction aims to residual disease smaller than 2,5mm), HIPEC maximizes loco-regional chemotherapy cytotoxicity while limiting the systemic side effects (Vlasveld et al., 1991; Markman, 1990; Markman and Kelsen, 1992). In this perspective, some encouraging experiences in numerous centers demonstrated a median survival of 40 to 90 months and a 5-ys-OS of 30 to 60% (Yan et al., 2007; Brigand et al., 2006; Deraco et al., 2006; Feldman et al., 2003; Loggie et al., 2001; Nonaka et al., 2005; Park et al., 1999; Sugarbaker et al., 2003). All peritonetomy center agree that complete cytoreduction is the prognostic principal factor for clinical success and that complete cytoreduction is correlated to the initial extent of intrabdominal disease and to the ability of the surgical team. Despite the data available, the role of HIPEC in this setting represents one of the strongest indications, particularly in view of considerable survival improvement over the best systemic therapy to date offered (Munkholm-Larsen et al., 2009; Shen et al., 2009).

7. Advanced oncological surgery in pseudomyxoma peritonei

Appendiceal tumors are uncommon neoplasms accounting for about 1% of all colorectal malignancies.

The majority of appendix cancers are carcinoid tumors; the second most common are epithelial neoplasms. The latter frequently present with mucinous ascites and mucinous tumor implants throughout the abdominal cavity. Such rare condition, with an incidence of approximately 1/1,000,000/year, is known as pseudomyxoma peritonei (PMP). Mucinous adenocarcinoma originating from large bowel, ovary, or other intra-abdominal sites may mimic PMP (Baratti et al., 2008). According to Ronnett, PMP was histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and intermediate or discordant feature group (ID). Appendiceal tumors were classified into low-grade appendiceal mucinous neoplasm (LAMN) and mucinous adenocarcinoma (MACA) (Misdraji). Pseudomyxoma peritonei (PMP) represents a rare peritoneal malignancy with a controversial bordeline behavior. Although a possible ovarian origin was initially suggested in the female sex, the over-expression of determined molecular markers has finally demonstrated a more probable PMP origin from a perforated appendiceal epithelial tumor. Undoubtedly, a small proportion of cases originate anyway from other organs, which ovarian primary is likely to be the more commonest of, followed by colon and rectum, stomach, gallbladder and biliary ducts, small bowel, urinary bladder, lung, breast, falloppian tube and pancreas (Smeenk et al., 2006, 2007; de Bree et al., 2000).

PMP is clinically characterized by diffuse intra-abdominal gelatinous collections with mucinous implants on peritoneal surfaces. Its pathognomonic accumulation at specific abdominal and pelvic sites is due to the so-called phenomenon of “redistribution” within the peritoneal cavity, which is determined by physical factors, such as the movement and absorption of peritoneal fluid and gravity (Sugarbaker, 1994). Despite its usually indolent behavior, its natural history is characterized by a slow progression to terminal starvation through intestinal obstruction by mucinous ascitis. Recent pathological (Ronnett et al., 1995) molecular genetic (Szych et al., 1999) and immunohistochemical studies (Carr et al., 2002) have provided substantial evidence that most cases of PMP originate from ruptured low grade appendiceal tumors and that mucin-producing epithelial cells accumulate into the abdominal cavity as a result of a distribution process.Therefore, surgical management consisted in repeated interval debulking for symptomatic relief (Sugarbaker, 1996). Based on recent prospective trials, CRS and HIPEC has been proposed as the standard of care for PMP. Results are encouraging with a 5-ys-OS ranging from 62.5 to 100% for low grade PMP and from 0 to 65% for high grade disease. This differentiation is crucial for the evolution of disease; low grade tumours are slow growing and indolent differently from those high grade, fast growing and aggressive (Sugarbaker and Chang, 1999; Witkamp et al., 2001; Güner et al., 2005; Moran et al., 2008; Moran and Cecil, 2003; Murphy et al., 2007; Baratti et al., 2008; Elias et al., 2008; Loungnarath et al., 2005; Smeenk et al., 2007; Stewart et al., 2005; Yan et al., 2006). The goal of the surgical cytoreduction is to remove all the visible tumor by the following procedures: right subdiaphragmatic and parietal peritonectomy, left subdiaphragmatic and parietal peritonectomy,greater omentectomy with splenectomy, lesser omentectomy and stripping of the omental bursa, andpelvic peritonectomy with salpingo-oophorectomy in women. Depending on disease extent, implants on visceral serosa were removed by electrosurgical local dissection or multivisceral resections including Glisson’s capsule dissection, cholecystectomy, partial or total gastrectomy, sigmoid, right or total colectomy. According to several phase I and II prospective trials, 5-year survivals have ranged between 66% and 97% (Stewart et al., 2005). It must be taken in mind that, because of the limited data on prognostic factors for this procedure in the setting of appendiceal primary tumors, further well designed, prospective, multi-institutional study are required (Bevan et al., 2010; Roviello et al., 2011).

8. Conclusion

CRS and HIPEC is a complex therapeutic systems which require highly specialized human resources, complex technological facilities, very much depending from expertize of the team involved. Literature refers to a learning curve of more than 100 procedures underscoring the crucial importance of treatment center experience. A continuous comparison must be done with new systemic and locoregional treatment possibility in order to verify new advantages in term of patient survival. This is the reason why a biannual international meeting is planned for comparing results, verify indications and planning of further studies regard to indications, duration and temperature of the perfusion, open or closed perfusion models or type and dosage of chemotherapeutic agents.

The future of treatment of peritoneal carcinosis appears correlated to the strong cooperation with medical oncologists to select patients and focusing on the timing of treatment which in our experience is crucial. The development of new scheme treatment must be approached as in treating ovarian peritoneal carcinosis with front line, interval, or salvage procedures. Therefore creating regional centers dedicated to peritoneal carcinosis treatment that investigate not only response and survival, but also standardization of technique and methods to do CRS and deliver HIPEC remains crucial.


1 - K. Antman, R. Shemin, L. Ryan, K. Klegar, R. Osteen, T. Herman, G. Lederman, J. Corson, mesothelioma. Malignant, variables. prognostic, a. in, registry, 180 180 patients, the Dana-Farber Cancer Institute and Brigham and Women’s Hospital experience over two decades, 1965-1985. J Clin Oncol 1988; 6 147153 ;
2 - K. H. Antman, J. M. Corson, F. P. Li, J. Greenberger, A. Sytkowski, D. E. Henson, L. Weinstein, Malignant mesothelioma following radiation exposure. J Clin Oncol 1 695700 1983
3 - D. Baratti, S. Kusamura, D. Nonaka, M. Langer, S. Andreola, M. Favaro, C. Gavazzi, B. Laterza, M. Deraco, peritonei. Pseudomyxoma, pathological. clinical, prognostic. biological, in. factors, treated. patients, cytoreductive. with, surgery, intraperitoneal. hyperthermic, . H. I. P. E. C. chemotherapy, Ann Surg Oncol 15 526534 2008
4 - H. Battifora, Tumors of the serosal membranes. Armed Forces Institute of Pathology under the auspices of Universities Associated for Research and Education in Pathology, Washington, D.C, 1995
5 - J. Bereder, O. Glehen, J. Habre, M. Desantis, E. Cotte, N. Mounier, I. Ray-Cocquard, B. Karimdjee, N. Bakrin, J. Bernard, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management 246 peritoneal carcinomatosis from ovarian cancer: a multiinstitutional study of 246 patients. In J Clin Oncol (Meeting Abstracts), 27 2009; 5542.
6 - K. E. Bevan, F. Mohamed, B. J. Moran, peritonei. Pseudomyxoma, J. World, Gastrointest, Oncol 2 4450 2010
7 - P. Boyle, J. Ferlay, Cancer incidence and mortality in europe, 2004 Ann Oncol 2005;16 481488 .
8 - C. Brigand, O. Monneuse, F. Mohamed, A. C. Sayag-Beaujard, S. Isaac, F. N. Gilly, O. Glehen, Peritoneal mesothelioma treated by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy: results of a prospective study. Ann Surg Oncol 13 405412 2006
9 - Carr NJ, Emory TS, Sobin LH. Epithelial neoplasms 53 the appendix and colorectum: an analysis of cell proliferation, apoptosis, and expression of 53 cd44, bcl-2. Arch Pathol Lab Med 2002;126:837-841.
10 - A. P. Chahinian, T. F. Pajak, J. F. Holland, L. Norton, R. M. Ambinder, E. M. Mandel, malignant. Diffuse, mesothelioma, prospective evaluation 69 69 patients. Ann Intern Med 1982;96 746755 .
11 - E. Chailleux, G. Dabouis, D. Pioche, M. de Lajartre, A. Y. de Lajartre, A. Rembeaux, P. Germaud, Prognostic factors in diffuse malignant pleural mesothelioma. a study 167 167 patients. Chest 1988;93 159162 .
12 - D. Z. Chu, N. P. Lang, C. Thompson, P. K. Osteen, K. C. Westbrook, Peritoneal carcinomatosis in nongynecologic malignancy. a prospective study of prognostic factors. Cancer 63 364367 1989
13 - E. De Bree, A. J. Witkamp, F. A. Zoetmulder, Peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer. Eur J Surg Oncol 26 630632 2000
14 - M. Deraco, A. Gronchi, V. Mazzaferro, M. G. Inglese, E. Pennacchioli, S. Kusamura, M. Rizzi, R. A. Anselmi, M. Jr Vaglini, Feasibility of peritonectomy associated with intraperitoneal hyperthermic perfusion in patients with pseudomyxoma peritonei. Tumori 88 370375 2002
15 - M. Deraco, D. Nonaka, D. Baratti, P. Casali, J. Rosai, R. Younan, A. Salvatore, Ad. A. D. Cabras, S. Kusamura, Prognostic analysis of cl49icopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Ann Surg Oncol 2006;13 229237 .
16 - D. Elias, C. Honoré, R. Ciuchendéa, V. Billard, B. Raynard, Dico. R. Lo, C. Dromain, P. Duvillard, D. Goéré, pseudomyxoma. Peritoneal, of. a. results, policy. systematic, complete. of, surgery. cytoreductive, intraperitoneal. hyperthermic, chemotherapy, Br J Surg 95 11641171 2008
17 - D. Elias, J. H. Lefevre, J. Chevalier, A. Brouquet, F. Marchal, J. M. Classe, G. Ferron, J. M. Guilloit, P. Meeus, D. Goéré, J. Bonastre, Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 27 681685 2009
18 - D. Elias, B. Raynard, F. Farkhondeh, D. Goéré, D. Rouquie, R. Ciuchendea, M. Pocard, M. Ducreux, Peritoneal carcinomatosis of colorectal origin. Gastroenterol Clin Biol 30 12001204 2006
19 - Eltabbakh GH, Piver MS, Hempling RE, Recio FO, Intengen ME. Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. J Surg Oncol 70 612 1999
20 - Feldman AL, Libutti SK, Pingpank JF, Bartlett DL, Beresnev TH, Mavroukakis SM, Steinberg SM, Liewehr DJ, Kleiner DE, Alexander HR. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol 21 45604567 2003
21 - Flessner MF. The transport barrier in intraperitoneal therapy. Am J Physiol Renal Physiol 433 2005
22 - J. Franko, Z. Ibrahim, N. J. Gusani, M. P. Holtzman, D. L. Bartlett, H. Zeh, 3 3rd. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer 2010;116 37563762 .
23 - S. Fujimoto, M. Takahashi, T. Mutou, K. Kobayashi, T. Toyosawa, Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma. Cancer 85 529534 1999
24 - O. Glehen, E. Cotte, J. C. Lifante, C. Arvieux, N. Moles, C. Brigand, A. C. Beaujard, Y. François, F. N. Gilly, Peritoneal carcinomatosis in digestive cancers: cytoreductive surgery combined with intraperitoneal chemohyperthermia. The experience in centre hospitalier et universitaire lyon sud (chls). Acta Chir Belg 106 285290 2006
25 - G. Glockzin, N. Ghali, S. A. Lang, H. J. Schlitt, P. Piso, Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer. J Surg Oncol 100 306310 2009
26 - BA Mandel. L. Goff, H. G. Muntz, C. H. Melancon, carcinoma. Ovarian, diagnosis, Cancer 89 20682075 2000
27 - Z. Güner, U. Schmidt, M. H. Dahlke, H. J. Schlitt, J. Klempnauer, P. Piso, Cytoreductive surgery and intraperitoneal chemotherapy for pseudomyxoma peritonei. Int J Colorectal Dis 20 155160 2005
28 - K. Hanazaki, Y. Mochizuki, T. Machida, S. Yokoyama, H. Sodeyama, Y. Sode, M. Wakabayashi, N. Kawamura, T. Miyazaki, Post-operative chemotherapy in non-curative gastrectomy for advanced gastric cancer. Hepatogastroenterology 46 12381243 1999
29 - Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer 44 25462554 2008
30 - D. G. Jayne, S. Fook, C. Loi, F. Seow-Choen, Peritoneal carcinomatosis from colorectal cancer. Br J Surg 89 15451550 2002
31 - Koppe MJ, Boerman OC, Oyen WJG, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 243 212222 2006
32 - Levine EA, Stewart 4 4th, Russell GB, Geisinger KR, Loggie BL, Shen P. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg 2007;204 94353 ; discussion 953-5.
33 - Loggie BW, Fleming RA, McQuellon RP, Russell GB, Geisinger KR, Levine EA. Prospective trial for the treatment of malignant peritoneal mesothelioma. Am Surg 67 9991003 2001
34 - M. Look, D. Chang, P. H. Sugarbaker, Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Int J Gynecol Cancer 14 3541 2004
35 - R. Loungnarath, S. Causeret, N. Bossard, M. Faheez, A. C. Sayag-Beaujard, C. Brigand, F. Gilly, O. Glehen, Cytoreductive surgery with intraperitoneal chemohyperthermia for the treatment of pseudomyxoma peritonei: a prospective study. Dis Colon Rectum 48 13721379 2005
36 - M. Markman, Intraperitoneal belly bath chemotherapy. Percept Press, Chicago, 2 ed., 1990.
37 - M. Markman, D. Kelsen, Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 118 547550 1992
38 - D. Marrelli, F. Roviello, G. de Manzoni, P. Morgagni, A. Di Leo, L. Saragoni, A. De Stefano, S. Folli, C. Cordiano, E. I. R. Pinto, G. C. Gf, Different patterns of recurrence in gastric cancer depending on lauren’s histological type: longitudinal study. World J Surg 26 11601165 2002
39 - R. Maurer, B. Egloff, Malignant peritoneal mesothelioma after cholangiography with thorotrast. Cancer 36 13811385 1975
40 - B. Moran, D. Baratti, T. D. Yan, S. Kusamura, M. Deraco, Consensus statement on the loco-regional treatment of appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei). J Surg Oncol 98 277282 2008
41 - Moran BJ, Cecil TD. The etiology, clinical presentation, and management of pseudomyxoma peritonei. Surg Oncol Clin N Am 12 585603 2003
42 - S. Munkholm-Larsen, C. Q. Cao, T. D. Yan, peritoneal. Malignant, World. J. mesothelioma, Gastrointest, Surg 1 3848 2009
43 - E. M. Murphy, R. Sexton, B. J. Moran, Early results of surgery 123 123 patients with pseudomyxoma peritonei from a perforated appendiceal neoplasm. Dis Colon Rectum 2007;50 3742 .
44 - V. Neumann, K. M. Müller, M. Fischer, Peritoneal mesothelioma-incidence and etiology. Pathologe 20 169176 1999
45 - D. Nonaka, S. Kusamura, D. Baratti, P. Casali, A. D. Cabras, R. Younan, J. Rosai, M. Deraco, Diffuse malignant mesothelioma 35 the peritoneum: a clinicopathological study of 35 patients treated locoregionally at a single institution. Cancer 2005;104 21812188 .
46 - Ozols RF. Treatment goals in ovarian cancer. Int J Gynecol Cancer 2005 Suppl 1 311 .
47 - B. J. Park, H. R. Alexander, S. K. Libutti, P. Wu, D. Royalty, K. C. Kranda, D. L. Bartlett, Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (chpp). Ann Surg Oncol 6 582590 1999
48 - Randall TC, Rubin SC. Cytoreductive surgery for ovarian cancer. Surg Clin North Am 81 871883 2001
49 - F. Raspagliesi, S. Kusamura, Torres. J. C. Campos, G. A. de Souza, A. Ditto, F. Zanaboni, R. Younan, D. Baratti, L. Mariani, B. Laterza, M. Deraco, Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: The experience of national cancer institute of milan. Eur J Surg Oncol 32 671675 2006
50 - Riddell RH, Goodman MJ, Moossa AR. Peritoneal malignant mesothelioma in a patient with recurrent peritonitis. Cancer 48 134139 1981
51 - Robinson BWS, Lake RA. Advances in malignant mesothelioma. N Engl J Med 353 15911603 2005
52 - Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. a clinicopathologic analysis 109 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to "pseudomyxoma peritonei". Am J Surg Pathol 1995;19 13901408 .
53 - F. Roviello, S. Caruso, D. Marrelli, C. Pedrazzani, A. Neri, A. De Stefano, E. Pinto, Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: state of the art and future developments. Surg Oncol 38 2011
54 - B. Sadeghi, C. Arvieux, O. Glehen, A. C. Beaujard, M. Rivoire, J. Baulieux, E. Fontaumard, A. Brachet, J. L. Caillot, J. L. Faure, J. Porcheron, J. L. Peix, Y. François, J. Vignal, F. N. Gilly, Peritoneal carcinomatosis from non-gynecologic malignancies: results of the evocape 1 multicentric prospective study. Cancer 88 358363 2000
55 - A. C. Sayag-Beaujard, Y. Francois, O. Glehen, B. Sadeghi-Looyeh, J. Bienvenu, G. Panteix, F. Garbit, E. Grandclément, J. Vignal, F. N. Gilly, Intraperitoneal chemo-hyperthermia with Mitomycin C for gastric cancer patients with peritoneal carcinomatosis. Anticancer Res 19 13751382 1999
56 - P. Shen, J. Stewart, 4 4th, Levine EA. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancy: overview and rationale. Curr Probl Cancer 2009;33 125141 .
57 - R. M. Smeenk, A. Bex, V. J. Verwaal, S. Horenblas, F. A. N. Zoetmulder, Pseudomyxoma peritonei and the urinary tract: involvement and treatment related complications. J Surg Oncol 93 2023 2006
58 - R. M. Smeenk, V. J. Verwaal, N. Antonini, F. A. N. Zoetmulder, Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg 245 104109 2007
59 - K. S. Sridhar, R. Doria, W. Raub, R. J. Jr Thurer, M. Saldana, New strategies are needed in diffuse malignant mesothelioma. Cancer 70 29692979 1992
60 - Stewart 4 4th, Shen P, Levine EA. Intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: current status and future directions. Ann Surg Oncol 2005;12 765777 .
61 - P. H. Sugarbaker, peritonei. A. Pseudomyxoma, whose. cancer, is. biology, by. a. characterized, phenomenon. redistribution, Ann Surg 219 109111 1994
62 - Sugarbaker PH. Peritonectomy procedures. Ann Surg 221 2942 1995
63 - Sugarbaker PH. Pseudomyxoma peritonei. Cancer Treat Res 81 105119 1996
64 - P. H. Sugarbaker, D. Chang, Results 385 treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol 1999;6 727731 .
65 - P. H. Sugarbaker, L. S. Welch, F. Mohamed, O. A. Glehen, of. review, mesothelioma. peritoneal, The. at, cancer. Washington, institute, Surg Oncol Clin N Am 12 60521 2003 xi.
66 - C. Szych, A. Staebler, D. C. Connolly, R. Wu, K. R. Cho, BM Ronnett, Molecular genetic evidence supporting the clonality and appendiceal origin of pseudomyxoma peritonei in women. Am J Pathol 154 18491855 1999
67 - K. Van der Speeten, O. A. Stuart, P. H. Sugarbaker, Pharmacokinetics and pharmacodynamics of perioperative cancer chemotherapy in peritoneal surface malignancy. Cancer J 15 216224 2009
68 - V. J. Verwaal, S. van Ruth, E. de Bree, G. W. van Sloothen, H. van Tinteren, H. Boot, F. A. N. Zoetmulder, Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21 37373743 2003
69 - V. J. Verwaal, S. van Ruth, A. Witkamp, H. Boot, G. van Slooten, F. A. N. Zoetmulder, Long-term survival of peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 12 6571 2005
70 - L. T. Vlasveld, M. P. Gallee, S. Rodenhuis, B. G. Taal, Intraperitoneal chemotherapy for malignant peritoneal mesothelioma. Eur J Cancer 27 732734 1991
71 - A. J. Witkamp, E. de Bree, MM Boot. H. Kaag, J. H. Beijnen, G. W. van Slooten, F. van Coevorden, F. A. Zoetmulder, Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-c in patients with peritoneal carcinomatosis of colorectal origin. Eur J Cancer 37 979984 2001
72 - T. D. Yan, E. A. Brun, CA Haveric. N. Cerruto, D. Chang, P. H. Sugarbaker, Prognostic indicators for patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma. Ann Surg Oncol 14 4149 2007
73 - T. D. Yan, M. Links, Z. Y. Xu, P. C. Kam, D. Glenn, D. L. Morris, Cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal mucinous neoplasms. Br J Surg 93 12701276 2006
74 - Yan TD, Morris DL. Cytoreductive surgery and perioperative intraperitoneal chemotherapy for isolated colorectal peritoneal carcinomatosis: experimental therapy or standard of care? Ann Surg 248 829835 2008
75 - R. Yancik, cancer. Ovarian, Age contrasts in incidence, histology, disease stage at diagnosis, and mortality. Cancer 71 517523 1993
76 - D. H. Yates, B. Corrin, P. N. Stidolph, K. Browne, Malignant mesothelioma in south east England: clinicopathological experience 272 272 cases. Thorax 1997;52 507512 .
77 - Y. Yonemura, X. de Aretxabala, T. Fujimura, S. Fushida, K. Katayama, E. Bandou, K. Sugiyama, T. Kawamura, K. Kinoshita, Y. Endou, T. Sasaki, Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study. Hepatogastroenterology 48 17761782 2001
78 - Y. Yonemura, T. Fujimura, G. Nishimura, R. Falla, T. Sawa, K. Katayama, K. Tsugawa, S. Fushida, I. Miyazaki, M. Tanaka, Y. Endou, T. Sasaki, Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination. Surgery 119 437444 1996