Annals of Surgical Oncology Sign the Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9169-7
Annals of Surgical Oncology 14:41-49 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yan, T. D.
Right arrow Articles by Sugarbaker, P. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, T. D.
Right arrow Articles by Sugarbaker, P. H.

Original Article

Prognostic Indicators for Patients Undergoing Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma{dagger}

Tristan D. Yan, BSc (Med) MBBS1, Erwin A. Brun, MD2, Carlos A. Cerruto, MD2, Namik Haveric, MD3, David Chang, MS4 and Paul H. Sugarbaker, MD1

1 Washington Hospital Center, Washington Cancer Institute, 106 Irving Street, NW, Suite 3900N, Washington, DC 20010, USA
2 Department of Pathology, Washington Hospital Center, Washington, DC, USA
3 Department of Radiology, Washington Hospital Center, Washington, DC, USA
4 Westat, Rockville, MD, USA

Correspondence: Address correspondence and reprint requests to: Paul H. Sugarbaker, MD; E-mail: Paul.Sugarbaker{at}medstar.net


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: This study evaluates clinical, radiological and histopathological prognostic indicators for survival of patients undergoing cytoreductive surgery and perioperative intra-peritoneal chemotherapy for diffuse malignant peritoneal mesothelioma (DMPM).

Methods: Sixty-two consecutive patients with DMPM underwent cytoreduction and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute. Twenty-six clinical, radiological and histopathological parameters were analyzed in univariate and multivariate analyses using overall survival as an endpoint.

Results: The overall survival was 79 months (range 1–143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (P = .045), peritoneal cancer index (P = .038), completeness of cytoreduction score (P = .010), interpretive CT findings of the small bowel and mesentery (P = .001), mesothelioma cell type (P < .001), mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion (P = .014). In the multivariate analysis, the only factor that was independently associated with an improved survival after cytoreduction and perioperative intraperitoneal chemotherapy was mesothelioma nuclear size.

Conclusions: Mesothelioma nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed.

Key Words: Peritoneal mesothelioma • Cytoreductive surgery • Intraperitoneal chemotherapy • Peritonectomy • Histopathology • Staging • Computed tomography


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Diffuse malignant peritoneal mesothelioma (DMPM) represents one-third of all mesotheliomas and the annual incidence is 300–400 cases in the United States.1–3 In the past, DMPM carried a dismal prognosis with a median survival of less than 1 year.3–9 Because DMPM tends to remain confined to the peritoneal cavity, there has been an increased recognition and usage of comprehensive local-regional treatments for this disease. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has improved survival compared to historical controls, achieving a median survival of 50–90 months in recently published series.10–15

This comprehensive treatment modality is associated with lengthy operations, long postoperative hospitalization and moderate to high morbidity and mortality rates.10–20 It is not indicated for all patients with DMPM. In order to maximize benefits and reduce morbidity and mortality, proper patient selection is important. Prior reports have attempted to describe and evaluate clinical, histopathological and radiological features of DMPM, but in general these studies have a relatively small sample size and meaningful implications of the results are limited.21–25 To date, there is no staging system that can be used to optimize patient selection for DMPM.

This current study consisted of 62 consecutive patients who underwent cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for DMPM at the Washington Cancer Institute, Washington, DC. The aims of this study were to critically evaluate this treatment alternative using 26 clinical, radiological and histopathological parameters with survival as an endpoint. These data allowed us to propose a staging system for this disease.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Between September 1989 and September 2005, 100 patients with peritoneal mesothelioma were treated with cytoreductive surgery by the same surgeon (PHS) at the Washington Cancer Institute. A thorough histopathologic review was performed on 62 patients who were treated in a uniform fashion utilizing cytoreductive surgery combined with heated intraoperative intraperitoneal chemotherapy, with cisplatin and doxorubicin, followed by early postoperative intraperitoneal paclitaxel from postoperative days 1 to 5.

Preoperative Management
All patients underwent extensive preoperative investigations, which included a review of all prior clinical information, physical examination, abdominal, pelvic and chest CT to assess the extent of the disease. The median interval between the preoperative CT and the operation was 2 days (range 1–20 days). In all patients CT was performed following the administration of oral and intravenous contrast media. All scans were assessed and reported by a hospital radiologist prior to surgery. Measurements of relevant tumor markers (e.g., CA 15-3, CA 19-9, CA 72-4, CA 125 and carcino-embryonic antigen) were also obtained.

Operative Management
All patients underwent maximal cytoreductive surgery by the same surgical team with intent to remove all visible intraperitoneal tumor deposits. The volume and extent of the tumor deposits were prospectively recorded in each of the 13 abdominopelvic regions using the peritoneal cancer index (PCI), which is an assessment combining lesion size (lesion size 0–3) with tumor distribution (abdominopelvic region 0–12), to quantify the extent of disease as a numerical score (PCI 0–39).26

The details of the surgical techniques have been described elsewhere.27 In short, a cytoreductive surgery consisted of a series of peritonectomy procedures including: anterior parietal peritonectomy, greater omentectomy with splenectomy, left upper quadrant peritonectomy, right upper quadrant peritonectomy, lesser omentectomy with cholecystectomy, and pelvic peritonectomy with rectosigmoid or total colonic resection.

All positive findings were documented by histopathological examination of each of the resected specimens. All sites and volumes of the residual disease following the cytoreductive surgery were also prospectively recorded using the completeness of cytoreduction score (CCR score).26 A CCR-0 indicated no visible evidence of mesothelioma. CCR-1 indicated residual tumor nodule <2.5 mm in diameter. CCR-2 indicated residual tumor nodule between 2.5 mm and 2.5 cm in diameter. CCR-3 indicated residual tumor modules >2.5 cm in diameter or a confluence of tumor nodules remaining at any site.

After maximal cytoreduction of peritoneal mesothelioma, the skin edges were elevated on a self-retaining retractor to make a reservoir of the abdomen and pelvis to retain the chemotherapy solution. HIIC with cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) was administrated in the operating room at approximately 41.5 °C in 3 L of 1.5% dextrose peritoneal dialysis solution for 90 min.14 The intra-peritoneal chemotherapy solution was manually distributed to facilitate uniform distribution and penetration of the chemotherapy into residual tumor.

Postoperative Management
In the early postoperative period (postoperative days 1–5), paclitaxel at 20 mg/m2 day was administered into the peritoneal cavity in 1 L of 1.5% dextrose peritoneal dialysis solution or 6% hetastarch solution.14,28 Nasogastric suctioning, thoracostomy drainage of the pleural spaces, total parental nutrition, deep venous thrombosis prophylaxis and postoperative pain control were used as indicated in the DMPM clinical pathway.

Study Methods
The clinical and radiological data were obtained prospectively and recorded on the standardized data sheets. The data were then entered regularly onto an electronic database by a research assistant. Four classes of interpretative CT appearances of the small bowel and its mesentery were described previously.29 In short, class 0 showed no evidence of abnormality; class I showed free intraperitoneal fluid only; class II showed tumor involvement of small bowel or its mesentery and the mesentery appeared stellate or pleated; class III showed an increased solid tumor involvement of small bowel and its mesentery, which appeared distorted and thickened.29

A review of the histopathological features of DMPM was performed by two experienced pathologists, who individually evaluated each case. These physicians were aware that all 62 patients in this study had clinical evidence of peritoneal mesothelioma, but were masked to all other clinical information. The mean number of specimens taken from separate anatomic sites was 11 ± 4 per patient. The mean number of slides studied was 20 ± 8 per patient. The assessment and measurement of the histopathological features were finally determined by the predominant findings throughout the multiple specimens examined in each case. Any differences in the interpretation of these slides were resolved by final consensus between the two pathologists.

The immunohistochemical studies were performed using immunostaining on formalin-fixed, paraffin-embedded sections using the avidin–biotin–peroxidase complex method. Sections were cut 3–4 µm thick, deparaffinized in xylene, and rehydrated in descending grades (100–70%) of ethanol. Endogenous peroxidase activity was blocked by a 10-min treatment with 3% hydrogen peroxide in absolute methanol. The primary antibodies used were keratin 5/6 by Boehringer–Mannheim (Indianapolis, IN), 1:25 dilution Calretinin by Zymed Laboratories, Inc. (South San Francisco, CA) pre-diluted by the manufacturer; Ber-EP4 by DakoCytomation California Inc. (Carpinteria, CA) 1:30 dilution; B72.3 by Signet Laboratories Inc. (Dedham, MA) 1:30 dilution. All cases selected were positive for Calretinin and CK 5/6 and negative for at least two epithelial markers including B72.3 and Ber-EP4.30–33 DMPM were classified into epithelial, biphasic or sarcomatoid histologic types, according to the World Health Organization classification.34

The nuclear size was determined by the measurement of the predominant nuclear size found throughout the multiple specimens examined in each case. For the purpose of this study, the size of the nucleus was categorized into four groups: nucleus size I was between 10 and 20 µm, nuclear size II was between 21 and 30 µm, nuclear size III was between 31 and 40 µm and nuclear size IV was >40 µm. Mitotic count was evaluated in 10 high-power microscopic fields (HPF) at 40x and categorized into ≤4 versus >4.

The chromatin pattern of the nucleus was evaluated by the distribution of chromatin material, which was classified into three groups: uniform granular, clear and clear with intracellular inclusions.

The predominant supporting structures (stroma) of the epithelial cells were defined as follows: an inflammatory stroma was characterized by the predominant presence of inflammatory cells. Desmoplastic stroma was characterized by a fibro-collagenous proliferation adopting a distinctive whorled or storiform pattern. Fibrous stroma was characterized by the predominant presence of a fibrous or fibroblastic proliferation arranged in bands or cords of various degree of thickness. Myxoid stroma was characterized by the presence of a myxoid substance often with some fibroblastic proliferation intermingled with the myxoid substance.

Statistical Analysis
The statistical analysis of all 26 clinical, radiological and histopathological parameters used overall survival as the endpoint, which was determined from the time of cytoreductive surgery. Institutional review board approval was obtained to review and analyze these data. Survival analysis was performed by using Kaplan–Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox-regression (Cox proportional hazards model). These statistical analyses were performed using SPSS for Windows (Version 11.5; SPSS GmbH, Munich, Germany). A significant difference was assumed for P < .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
There were 34 male patients (55%). The mean age at the time of diagnosis of DMPM was 47 ± 13 years. The mean age at the time of surgery was 49 ± 13 years. The median interval between the time of diagnosis and surgery was 4 ± 29 months. Twenty-three patients (37%) had complete cytoreduction (CCR-0/CCR-1); 21 patients (34%) had adequate cytoreduction (CCR-2); 18 patients (29%) had suboptimal cytoreduction (CCR-3). All patients were followed until 25 September 2005 or until death. The median follow-up was 37 months (range 8–143 months). The patient follow-up was complete.

Survival Analysis
The overall median survival was 79 months (range 1–143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively (Fig. 1Go). Thirty-six patients (58%) were alive at the last time of contact.


Figure 1
View larger version (5K):
[in this window]
[in a new window]

  		FIG. 1. Overall survival of 62 patients with diffuse malignant peritoneal mesothelioma who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute, Washington, DC.

 
Univariate Analysis of Clinical Factors
Seven clinical factors were analyzed in univariate analysis (Table 1Go). The following three clinical factors were significant for overall survival: gender (P = .045), PCI (P = .038) and CCR (P = .010).


View this table:
[in this window]
[in a new window]

  		TABLE 1. Univariate analysis of seven clinical factors
 
Univariate Analysis of Radiological Factors
Seven radiological factors were analyzed in univariate analysis (Table 2Go). Classification of the interpretive CT findings of the small bowel and mesentery was statistically significant for overall survival (P = .001).


View this table:
[in this window]
[in a new window]

  		TABLE 2. Univariate analysis of seven radiological factors
 
Univariate Analysis of Histopathological Factors
Twelve potentially prognostic histopathological factors were analyzed in univariate analysis (Table 3Go). The following 10 histopathological factors were significant for overall survival: histopathological type (P < .001), nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion of the serosal surface (P = .014).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Univariate analysis of 12 histopathological factors
 
Multivariate Analysis of Prognostic Factors Affecting Survival
The significant prognostic factors identified in univariate analysis were subsequently analyzed in multivariate analysis. The only factor that was independently associated with an improved survival was mesothelioma nuclear size (P < .001).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In the past DMPM carried a dismal prognosis with a median survival of less than 1 year and systemic or local-regional chemotherapy alone did not seem to alter the natural history of the disease.3–9 Cytoreductive surgery combined with perioperative intra-peritoneal chemotherapy demonstrated an improved survival in selected patients.10–15 The most recent report from the National Cancer Institute, Bethesda showed that the median survival of 49 DMPM patients was 92 months, with a 3-year survival rate of 59%, after cytoreductive surgery and HIIC.13 Nonaka et al.15 enrolled 35 patients to undergo these comprehensive treatments and the progression-free survival was 28 months. The overall median survival in this current series was 79 months (range 1–143 months) and the 5-year survival rate was 50%.

Even though these recent studies have demonstrated that cytoreductive surgery combined with perioperative intraperitoneal chemotherapy can improve the overall survival of patients with DMPM as compared to the historical data, not all patients benefit from these treatments; also the associated perioperative morbidity and mortality should not be overlooked. In the current literature, the morbidity rate varies from 30% to 50% and the mortality rate ranges from 1% to 10% after these comprehensive treatments.10–20 To the best of our knowledge there have been no clear guidelines for patient selection and no staging system for DMPM. The clarification of such issues is important in the management of these patients. Clearly, such aggressive treatment strategies should only be considered in patients who are likely to benefit.

A lack of prognostic indicators for optimal patient selection is not surprising. Cytoreductive surgery with perioperative intraperitoneal chemotherapy has only become a treatment option for DMPM over the last decade. Also the disease is rare, so that most centers do not have a sufficient number of patients. Treatments employed in these patients have varied greatly. Most studies in the current literature have a relatively small sample size (<50 cases) that have not allowed adequate clinical, radiological or pathological features of DMPM.21–25 The clinical implications of these reports, in terms of their value for patient management, are limited.

Feldman et al.13 have previously analyzed prognostic parameters on 49 patients and showed that age of <60, history of tumor debulking, lack of deep invasion and minimal residual disease after tumor resection were independently associate with a favorable prognosis in multivariate analysis. Nonaka et al.15 recently studied clinical, histopathological and biological features of DMPM on 35 patients who underwent cytoreductive surgery and HIIC and they reported that small nuclear size, low mitotic count and complete cytoreduction were significant for survival in univariate analysis.

The current study evaluated 26 clinical, radiological and histopathological parameters to identify significant prognosticators for survival, in an attempt to facilitate patient selection and patient management. Completeness of cytoreduction was prognostically significant for overall survival. It might be related to the pretreatment tumor load and the surgeon’s ability to clear gross disease. However, there are problems with using CCR for staging DMPM; this prognostic information is unavailable preoperatively in the patient selection process.

We have shown in the past that the interpretive CT findings of the small bowel and mesentery are useful in determining the operability of a patient with DMPM.29 In a class III disease, the small bowel and mesentery on CT appear so thickened and grossly distorted, which means that a complete cytoreduction is almost unable to be achieved. This current study further validated that the CT classification of small and mesentery could be used as a prognosticator for overall survival (P = .001).

The histopathological classification of DMPM consists of epithelial, sarcomatoid and biphasic types.34 In our study group, we had 57 patients (92%) with epithelial type and five patients (8%) with biphasic type. The survival of the biphasic type was extremely poor. Four of the five patients died within the first 6 months after the surgery. However, the clinical significance of this finding is restricted, due to the small number of patients with the biphasic type.

In this study, mesothelioma nuclear size was the only independent prognostic indicator for an improved survival by multivariate analysis. Goldblum and Hart35 first described a nuclear grading system for DMPM.35 They categorized the nuclear size into four grades: grade 0 = small nuclei, uniform chromatin pattern, inconspicuous or absent nucleoli; grade 1 = small nuclei, uniform chromatin pattern, small pinpoint-sized nucleoli; grade 2 = large nuclei, some chromatin irregularity, more prominent nucleoli; grade 3 = large nuclei, irregular chromatin pattern with clearing, prominent macronucleoli. Kerrigan et al.36 first tested this nuclear grading system in 25 female patients with DMPM who underwent a variety of surgical, chemotherapy or radiotherapy treatments and they found that the nuclear grading was not strongly associated with the long-term survival.36 In contrast, Nonaka et al.15 recently demonstrated that the size of the mesothelioma nucleus was prognostically significant for overall survival in 35 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. The nuclear grades used in these studies were not quantitative measurements of the actual size of the nucleus, but rather subjective interpretations of the relative size of the nucleus, be it small or large. In addition, this nuclear grading system integrated other histomorphological parameters, such as the size of the nucleoli and chromatin patterns. It remains unclear as to whether they considered one or multiple histopathological parameters, when assessing DMPM.

In our study the nuclear size was quantified by an actual measurement of the predominant nuclear size found throughout the multiple specimens examined in each case. Chromatin pattern was separated as an individual histomorphological parameter from the original nuclear grading system. The nuclear grading should be reproducible at any institutions.

With a larger sample size, uniform treatment, longer follow-up and more histopathology sections per patients studied, we found in multivariate analysis that the nuclear size was the only independent prognostic determinant for survival. The 3-year survival rates with nuclear size of 10–20, 21–30, 31–40 and >40 µm were 100%, 87%, 27% and 0%, respectively. Other histopathological parameters, such as mesothelioma cell type, nuclear/cytoplasmic ratio, mitotic count, atypical mitosis, chromatin pattern, cellular necrosis and stroma pattern were also significant for survival in univariate analysis. These findings may suggest that the prognosis of DMPM after maximal attempt of cytoreduction and perioperative intraperitoneal chemotherapy is predominantly governed by the biological aggressiveness of the mesothelioma cells (Fig. 2Go). It seemed that cytoreductive surgery with perioperative intraperitoneal chemotherapy offered little benefit to patients with a nucleus size of >40 µm. Systemic chemotherapy may be indicated in these patients.


Figure 2
View larger version (11K):
[in this window]
[in a new window]

  		FIG. 2. Survival after cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma. The prognostic significance of mesothelioma nuclear size was P < .001.

 
All six patients in our series with nuclear size less than 20 µm are long-term survivors. These patients were treated no differently than the remainder of the series in that maximal cytoreductive surgery with peritonectomy and intraoperative hyperthermic chemotherapy was utilized. By analogy with other peritoneal surface malignancies such as appendiceal epithelial malignancy, one would expect long-term benefits from these treatments in patients who have a minimally invasive disease. This long-term benefit is seen despite the very large volume of tumor as was present in the nuclear grade I patients. Unfortunately, judgments regarding the requirement for these "aggressive" local-regional treatments in these groups of patients cannot be found in our report in that all patients have been treated in a near identical fashion. A uniform treatment was necessary in this study in order to allow the clinical, radiological and histopathologic prognostic indicators to be appreciated. When a uniform treatment was not used a grading system similar to the one used in our patients did not correlate with prognosis.36

In DMPM nuclear size was the only independent prognostic factor in the multivariate analysis. Consequently it has been selected for our proposed staging system for DMPM (Table 4Go). Nuclear grading has been proposed not only for DMPM, but also for renal cell carcinoma and breast cancer.37,38 The relationship of an increasing nuclear size to tumor aggressive biological behavior has not been determined. Other significant clinical, radiological and histopathological parameters should be regarded as adjunctive criteria by which to evaluate prognosis of a patient with DMPM. The clinical implications of the histopathology of DMPM are significant in that it can be obtained by tissue biopsy during an exploratory laparoscopy or laparotomy and used to select patients to undergo cytoreduction and perioperative intraperitoneal chemotherapy.


View this table:
[in this window]
[in a new window]

  		TABLE 4. A proposed histopathological staging system for diffuse malignant peritoneal mesothelioma
 
In conclusion, this study supports prior data that suggest that an improved survival can be achieved with cytoreductive surgery and perioperative intra-peritoneal chemotherapy in patients with DMPM. The prognosis of these patients was largely dependent on the histopathological features and a histopathological staging system based on measurement of the nuclear size seemed possible.


   ACKNOWLEDGMENTS
 
The authors would like to thank Tina Sugarbaker for her maintenance of the peritoneal surface malignancy database. Tristan D. Yan, surgical oncology fellow, is sponsored by the Foundation for Applied Research in Gastrointestinal Oncology and MedStar Research Institute.


   FOOTNOTES
 
{dagger} Financial disclosure: The authors indicated no potential conflicts of interests. Back

Received for publication February 27, 2006. Accepted for publication April 5, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. McDonald AD, MacDonald JC. (1987) Epidemiology of malignant mesothelioma. In: Antman K, Aisner J (edsAsbestos-related malignancy Grune & Stratton, Orland FL, pp 31–5.
  2. Asensio JA, Goldblatt P, Thomford NR. Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature. Arch Surg 1990; 125:477–81.
  3. Sridhar KS, Doria R, Raub WA Jr, Thurer RJ, Saldana M. New strategies are needed in diffuse malignant mesothelioma. Cancer 1992; 70:2969–79.[CrossRef][Medline]
  4. Markman M, Kelsen D. Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 1992; 118(7):547–50.[CrossRef][Medline]
  5. Neumann V, Muller KM, Fischer M. Peritoneal mesothelioma—incidence and etiology. Pathologe 1999; 20(3):169–76.[CrossRef][Medline]
  6. 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 1999; 70(1):6–12.[CrossRef][Medline]
  7. Plaus WJ. Peritoneal mesothelioma. Arch Surg 1988; 123:763–6.[Abstract/Free Full Text]
  8. Janne PA, Wozniak AJ, Belani CP, et al. Open-label study of pemetrexed a lone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer 2005; 7(1):40–6.[Medline]
  9. Langer CJ, Rosenblum N, Hogan M, et al. Intraperitoneal cisplatin and etoposide in peritoneal mesothelioma: favorable outcome with a multimodality approach. Cancer Chemother Pharmacol 1993; 32:204–8.[CrossRef][Medline]
  10. Sebbag G, Yan H, Shmookler BM, Chang D, Sugarbaker PH. Results of treatment of 33 patients with peritoneal mesothelioma. Br J Surg 2000; 87(11):1587–93.[CrossRef][Medline]
  11. Sugarbaker PH, Acherman YIZ, Gonzalez-Moreno S, et al. Diagnosis and treatment of peritoneal mesothelioma: Washington Cancer Institute experience. Semin Oncol 2002; 29(1):51–61.[Medline]
  12. Park BJ, Alexander HR, Libutti SK, et al. Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP). Ann Surg Oncol 1999; 6(6):582–90.[Abstract]
  13. Feldman AL, Libutti SK, Pingpank JF, et al. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol 2003; 21(24):4560–7.[Abstract/Free Full Text]
  14. Sugarbaker PH, Welch LS, Mohamed F, Glehen O. A review of peritoneal mesothelioma at the Washington Cancer Institute. Surg Oncol Clin N Am 2003; 12(3):605–21.[CrossRef][Medline]
  15. Nonaka D, Kusamura S, Baratti D, et al. Diffuse malignant mesothelioma of peritoneum. Cancer 2005; 104(10):2181–8.[CrossRef][Medline]
  16. Jacquet P, Stephens AD, Averbach AM, et al. Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intra-operative intraperitoneal chemotherapy. Cancer 1996; 77:2622–9.[CrossRef][Medline]
  17. Stephens AD, Alderman R, Chang D, et al. Morbidity and mortality of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the Coliseum technique. Ann Surg Oncol 1999; 6(8):790–6.[Abstract]
  18. Butterworth SA, Panton ONM, Klaassen DJ, Shah AM, McGregor GI. Morbidity and mortality associated with intraperitoneal chemotherapy for pseudomyxoma peritonei. Am J Surg 2002; 183(5):529–32.[CrossRef][Medline]
  19. Glehen O, Osinsky D, Cotte E, et al. Intraperitoneal chemo-hyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol 2003; 10(8):863–9.[Abstract/Free Full Text]
  20. Ahmad SA, Kim J, Sussman JJ, Soldano DA, Pennington LJ, James LE, Lowy AE. Reduced morbidity following cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion. Ann Surg Oncol 2004; 11(4):387–92.[Abstract/Free Full Text]
  21. Swan N, Cottell D, Sheahan K. Peritoneal mesotheliomas. Am J Surg Pathol 1997; 21(1):122–3.[CrossRef][Medline]
  22. Sussman J, Rosai J. Lymph node metastasis as the initial manifestation of malignant mesothelioma. Report of six cases. Am J Surg Pathol 1990; 19:810–28.
  23. Reuter K, Raptopoulos V, Reale F, et al. Diagnosis of peritoneal mesothelioma: computed tomography, sonography, and fine-needle aspiration biopsy. Am J Roentgenol 1983; 140(6):1189–94.[Abstract/Free Full Text]
  24. Guest PJ, Reznek RH, Selleslag D, Geraghty R, Slevin M. Peritoneal mesothelioma: the role of computed tomography in diagnosis and follow up. Clin Radiol 1992; 45(2):79–84.[CrossRef][Medline]
  25. Whitley NO, Brenner DE, Antman KH, Grant D, Aisner J. CT of peritoneal mesothelioma: analysis of eight cases. Am J Roentgenol 1982; 138:531–5.[Abstract/Free Full Text]
  26. Glehen O, Gilly FN. Quantitative prognostic indicators of peritoneal surface malignancy: carcinomatosis, sarcomatosis, and peritoneal mesothelioma. Surg Oncol Clin N Am 2003; 12:649–71.[CrossRef][Medline]
  27. Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995; 221(1):29–42.[Medline]
  28. Mohamed F, Marchettini P, Stuart OA, Yoo D, Sugarbaker PH. A comparison of hetastarch and peritoneal dialysis solution for intraperitoneal chemotherapy delivery. Eur J Surg Oncol 2003; 29:261–5.[CrossRef][Medline]
  29. Yan TD, Haveric N, Carmignani CP, Chang D, Sugarbaker PH. Abdominal computed tomography scans in the selection of patients with malignant peritoneal mesothelioma for comprehensive treatment with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cancer 2005; 103:839–49.[CrossRef][Medline]
  30. Cerruto C, Brun E, Chang D, Sugarbaker P. Prognostic significance of histomorphological parameters in diffuse malignant peritoneal mesothelioma. Arch Pathol Lab Med 2006 [accepted for publication].
  31. Riera JR, Astengo-Osuna C, Longmate JA, Battifora H. The immunohistochemical diagnostic panel for epithelial mesothelioma. A reevaluation after heat-induced epitope retrieval. Am J Surg Pathol 1997; 21:1409–19.[CrossRef][Medline]
  32. Ordonez NG. Value of cytokeratin 5/6 immunostaining in distinguishing epithelial mesothelioma of the pleura from lung adenocarcinoma. Am J Surg Pathol 1998; 22:1215–21.[CrossRef][Medline]
  33. Ordonez NG. Role of immunohistochemistry in distinguishing epithelial peritoneal mesothelioma from peritoneal and ovarian serous carcinomas. Am J Surg Pathol 1998; 22:1203–14.[CrossRef][Medline]
  34. Weiss SW. (1994) World Health Organization, International Histological Classification of Tumors. Histological typing of soft tissue tumors, 2nd ed. Berlin: Springer-Verlag.
  35. Goldblum J, Hart WR. Localized and diffuse mesotheliomas of genital tract and peritoneum of women. Am J Surg Pathol 1995; 19:1124–37.[Medline]
  36. Kerrigan SA, Turrnir RT, Clement PB, Young RH, Churg A. Diffuse malignant epithelial mesotheliomas of the peritoneum in women: a clinicopathologic study of 25 patients. Cancer 2002; 94:378–85.[CrossRef][Medline]
  37. Mostofi FK, Davis CJ. (1998) Histological typing of kidney tumors, 2nd ed. New York: Springer.
  38. Hachisuga T, Kawarabayashi T, Iwasaka T, Sugimori H, Kamura T, Tsuneyoshi M. The prognostic value of semi-quantitative nuclear grading in endometrial carcinoma. Gynecol Oncol 1997; 65(1):115–20.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
J. M. Foster, Z. Gatalica, S. Lilleberg, G. Haynatzki, and B. W. Loggie
Novel and Existing Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor are Predictors of Optimal Resectability in Malignant Peritoneal Mesothelioma
Ann. Surg. Oncol., January 1, 2009; 16(1): 152 - 158.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
L. Bijelic, A. Jonson, and P. H. Sugarbaker
Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer
Ann. Onc., December 1, 2007; 18(12): 1943 - 1950.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
D. Baratti, S. Kusamura, D. Nonaka, G. D. Oliva, B. Laterza, and M. Deraco
Multicystic and Well-differentiated Papillary Peritoneal Mesothelioma Treated by Surgical Cytoreduction and Hyperthermic Intra-peritoneal Chemotherapy (HIPEC)
Ann. Surg. Oncol., October 1, 2007; 14(10): 2790 - 2797.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
T. D. Yan, J. Sim, and D. L. Morris
Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy
Ann. Surg. Oncol., June 1, 2007; 14(6): 1807 - 1817.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yan, T. D.
Right arrow Articles by Sugarbaker, P. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, T. D.
Right arrow Articles by Sugarbaker, P. H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS