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  Volume 96
Numero 3
maggio-giugno 2010 		I documenti sono in formato PDF, consultabili utilizzando Acrobat Reader
 
Cytoreductive surgery and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer

Antonios-Apostolos K Tentes, Odysseas S Korakianitis, Stylianos Kakolyris, Dimitrios Kyziridis, Dousan Veliovits, Chrysa Karagiozoglou, Evanthia Sgouridou, Konstantinos Moustakas
1Department of Surgery, and 2Anesthesiology Department, Didimotichon General Hospital Didimotichon; 3Clinical Oncology, Democritus University of Thrace, Alexandroupolis, Greece

Key words: cytoreductive surgery, intraperitoneal chemotherapy, morbidity-mortality, recurrent ovarian cancer, survival.

abstract

Background and aims. Cytoreductive surgery with perioperative intraperitoneal chemotherapy is another approach for recurrent ovarian cancer. The purpose of the study was to assess the feasibility and the effect of cytoreduction and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer.
Patients and methods. Twenty-nine women with recurrent ovarian cancer underwent cytoreductive surgery. Clinical variables were correlated to morbidity, hospital mortality, recurrences, and survival.
Results. Complete cytoreduction was possible in 58.6%. Extensive seeding of the small bowel and distant metastases excluded the possibility of performing complete cytoreduction. Perioperative intraperitoneal chemotherapy was given in 75.9%. Morbidity and hospital mortality rates were subsequently 24.1% and 3.4%. Recurrence was recorded in 48.3%. The extent of peritoneal dissemination was an independent variable of recurrence (P = 0.014). The 5-year survival rate was 30%. The extent of peritoneal dissemination and the completeness of cytoreduction were related to survival (P <0.05). The completeness of cytoreduction independently influenced survival (P = 0.013).
Conclusions. Secondary cytoreduction with intraperitoneal chemotherapy is feasible in most women with recurrent ovarian cancer with acceptable morbidity and mortality. Complete cytoreduction is not possible if distant and unresectable metastases are present or if the small bowel is extensively seeded. Long-term survivors are patients with limited peritoneal dissemination who may undergo complete cytoreduction. Free full text available at www.tumorionline.it

Introduction
The role of secondary cytoreduction in recurrent ovarian cancer has been strongly questioned1-5. Optimal cytoreductive surgery has been identified as one of the most powerful determinants of survival in the treatment of primary ovarian cancer, provided that the entire macroscopically visible tumor has been removed6-8.
The treatment strategies for recurrent ovarian cancer have changed over the last decade. Complete cytoreductive surgery with standard peritonectomy procedures and perioperative intraperitoneal chemotherapy is available and seems to improve long-term survival9-11. Complete cytoreduction is not always feasible. The feasibility of complete cytoreduction varies widely, ranging from 38-83% in the literature12,13.
The objectives of the study were: 1) to assess the feasibility of complete cytoreductive surgery and identify the clinical factors that exclude the possibility of complete cytoreduction, 2) to evaluate the impact of complete cytoreduction on long-term survival and identify the clinical variables related to survival, and 3) to assess the clinical factors related to hospital mortality and morbidity in women with recurrent ovarian cancer.

Patients and methods
The records of 29 women with recurrent ovarian cancer treated from 2000-2008 were retrospectively reviewed. Their mean age was 59.9 ± 9.5 years (range, 44-82). All the patients had been heavily treated with systemic combination chemotherapy consisting of carboplatin plus taxanes. The interval between the last dose of systemic chemotherapy and secondary surgery was at least 7 months. The diagnosis and staging was possible by physical examination, hematological-biochemical examinations, tumor markers, abdominal and thoracic computed tomography scan, and bone scan.
Variables such as performance status, age, extent of previous surgery, tumor volume, completeness of cytoreduction, extent of peritoneal dissemination, the presence of ascites and distant metastases, and treatment with systemic or intraperitoneal chemotherapy were evaluated and correlated to survival, morbidity, and hospital mortality.
The presence of metastatic disease in lymph nodes that had no anatomic relation to the primary site was considered as distant metastasis. The extent of peritoneal dissemination was calculated using the peritoneal cancer index (PCI)14. The extent of previous surgery was assessed using the prior surgery score, and the completeness of cytoreduction (CC) score15. Only CC-0 surgery was considered as complete cytoreduction. The Karnofsky performance scale was used to assess the physical status.
The patients received hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with the Coliseum technique14,15 after the completion of cytoreduction and before reconstruction of the gastrointestinal tract with the use of a heat exchanger, one roller pump, one reservoir, and a heater/cooler unit (ThermoChem Ht-1000, ThermaSolutions, White Bear Lake, MN, USA). Cis-platin (50 mg/m2) with doxorubicin (15 mg/m2) was used during HIPEC for 90 min at a stable mean temperature of 42-42.5 °C. Early postoperative intraperitoneal chemotherapy (EPIC) was performed during the first five postoperative days either with docetaxel (100 mg/m2) or with 5-fluorouracil (650 mg/kg body weight). The treatment plan for patients who underwent complete cytoreduction was adjuvant HIPEC only. HIPEC and EPIC was planned for patients with CC-1 or CC-2 surgery and EPIC and systemic chemotherapy for those with CC-3 surgery. Additional systemic chemotherapy was planned for patients who had systemic disease (lymph node involvement). Severe hematological toxicity was classified according to the WHO scale.
During the follow-up, patients were assessed with physical examination, hematological-biochemical examinations, tumor markers, and CT scans every 6 months.
The proportions of patients with a given characteristic were compared by chi-square analysis or by Fisher’s exact test. Differences in the means of continuous measurement were tested by Student’s t test. Survival curves were obtained using the Kaplan-Meier method, and the comparison of curves was calculated using the logrank test. Cox’s regression model was used for multiple analysis of survival. Logistic regression analysis was used for multiple analysis of recurrence. A two-tailed P value <0.05 was considered statistically significant.

Results
The physical status of most of the patients (86.2%) was excellent (90-100%). Extensive cytoreductive surgery (in more than 2-5 abdominopelvic regions) had been performed in nearly half of the patients at initial surgery. Large volume tumors were found in 75.9% of the patients. Ascites and extensive peritoneal dissemination (PCI >13) were present in nearly half of the patients. Distant metastases were found in 5 patients. Three of them had positive nodal disease and 2 had positive pleural effusion (Table 1).

Treatments
Midline laparotomy was used for maximal abdominal exposure. The patients underwent cytoreductive surgery with standard peritonectomy procedures (Table 2). Complete cytoreduction was possible in 17 patients (58.6%). Twenty-two patients (75.8%) received intraperitoneal chemotherapy. Eleven of them received EPIC, 9 HIPEC, and 2 HIPEC + EPIC. Six patients received systemic chemotherapy because of incomplete cytoreduction. In addition to perioperative intraperitoneal chemotherapy, systemic chemotherapy was administered in 13 patients for whom histologic examination revealed positive lymph nodes (Table 1). Complete cytoreduction was not feasible in 12 cases (41.4%). Extensive seeding of the small bowel was identified in 10 cases (83.2%) and nodal involvement at distant sites from the primary region which were unresectable in 2 cases (16.7%).

Table 1 - Patient characteristics

Variable

No

%

 

 

 

Performance status (Karnofsky)

 

 

 90-100%

25

86.2

 70-80%

3

10.3

 50-60%

1

3.4

PSS

 

 

 1

15

51.7

 2

7

24.1

 3

7

24.1

Tumor volume

 

 

 Small

7

24.1

 Large

22

75.9

PCI

 

 

 <13

15

51.7

 >13

14

48.3

Ascites

15

51.7

Metastases

5

17.2

Systemic chemotherapy

22

75.9

Intraperitoneal chemotherapy

 

 

 EPIC

11

37.9

 HIPEC

9

31

 HIPEC + EPIC

2

6.9

CC score

 

 

 0

17

58.6

 1, 2, 3

12

41.4

Morbidity

7

24.1

Hospital mortality

1

3.4

 

 

 

CC score, completeness of cytoreduction; EPIC, early postoperative intraperitoneal chemotherapy; HIPEC, hyperthermic intraoperative intraperitoneal chemotherapy; PCI, peritoneal cancer index; PSS, prior surgery score.

Table 2 - Peritonectomy procedures

Procedure

No

%

 

 

 

Epigastric peritonectomy

29

100

Pelvic peritonectomy

19

65.5

Subdiaphragmatic peritonectomy

 

 

 Right

4

13.8

 Bilateral

3

10.3

Cholecystectomy + resection of omental bursa

13

44.8

Greater omentectomy

 

 

 + splenectomy

5

17.2

 – splenectomy

10

34.4

Lesser omentectomy

2

6.9

Lateral peritonectomy

 

 

   Right

1

3.5

   Left

2

6.9

   Bilateral

12

41.4

Visceral peritonectomy

 

 

   Segmental small bowel resection

14

48.3

   Subtotal colectomy

6

20.7

   Antrectomy

1

3.5

   Right colectomy

2

6.9



Morbidity and hospital mortality
The hospital mortality rate was 3.4% (one patient). No clinical variable related to mortality was identified. Major morbidity was recorded in 7 patients (24.1%). One patient (3.4%) presented pulmonary failure, 3 patients (10.3%) had anastomotic failure, 2 (6.9%) had wound infection, 2 (6.9%) had grade II neutropenia, and 2 patients (6.9%) had cardiac arrhythmia. Two patients who underwent complete cytoreduction and 5 patients who underwent incomplete cytoreduction had major complications. Although no clinical factor was found to be related to morbidity, the CC score showed a trend to be adversely related to morbidity ( P = 0.064). The higher the CC score, the higher the morbidity. Severe hematological toxicity was not recorded. Grade II neutropenia was recorded in 2 patients but did not require any treatment.

Follow-up
The median follow-up was 34 months. Recurrence was recorded in 14 patients (48.3%). Distant metastases were recorded in 4 patients (13.8%) and local-regional recurrence in 10 patients (34.5%). The extent of peritoneal dissemination was found to be related to recurrence (P = 0. HR 016). By multivariate analysis, it was shown that the PCI was an independent factor of recurrence (P = 0.014; = 6.875; 95% CI, 1.348-35.059). In patients with complete cytoreduction, the recurrence rate was restricted to 29.4% (5 patients). Distant metastases were recorded in 2 of them and local-regional relapse in 3. In patients with a PCI <13, the recurrence rate was 26.7% (4 patients). Two patients were recorded with local-regional recurrence and 2 others with distant metastases.

Survival
The overall 5-year survival rate was 30%. The median survival was 34 months (95% CI, 14-54) (Figure 1). The extent of peritoneal dissemination (P = 0.0356) and the completeness of cytoreduction (P = 0.0007) were the clinical variables found to be related to survival. Physical status, the presence of metastasis, prior surgery score, the presence of ascites, treatment with systemic chemotherapy, and tumor volume were not related to survival (P >0.05). The five-year survival rate for patients with limited peritoneal spread was 68% and mean survival 66 ± 15 months (range, 37-95) (Figure 2). For patients with complete cytoreduction, the 5-year survival rate was 58% and mean survival 67 ± 12 months (range, 43-91) (Figure 3). The 5-year survival rate for patients with extensive peritoneal spread was 0% and mean survival 24 ± 7 months (range, 11-37) (Figure 2). For patients with incomplete cytoreduction, the 5-year survival rate was 0% and mean survival 16 ± 4 months (range, 7-24) (Figure 3). By multivariate analysis, the completeness of cytoreduction was identified as the single independent factor of survival ( P = 0.013; HR = 3.409: 95% CI, 1.302-8.928). At this writing, 11 (37.9%) patients were alive without evidence of disease, 4 (13.8) were alive with stable disease, 1 (3.4%) patient had disease progression, 9 (31%) patients had died for extensive disease, and 4 (13.8%) had died for reasons unrelated to the disease or treatment (including one hospital death).










Discussion
Cytoreductive surgery followed by systemic chemotherapy is the standard therapeutic approach in the management of epithelial ovarian cancer16. More than 80% of ovarian carcinomas are chemoresponsive and achieve complete remission17. Despite advances with consecutive lines of systemic aggressive che­mo­the­rapy, the recurrence rate is still high (80%)18 and 5-year survival rate is limited to 25-30%19. Systemic chemotherapy without cytoreductive surgery has a limited effect on overall survival because median survival is restricted to 11-15 months20, 21. Moreover, secondary cytoreduction alone offers a median survival of 5 to 43 months, depending on the completeness of the performed cytoreduction, and a 5-year survival rate of 28%8,12,13.
Maximal cytoreductive surgery with standard peritonectomy procedures, as originally described by Sugarbaker22, is likely to improve long-term survival from ovarian cancer6,7,10. Recently, the initially described peritonectomy procedures have been modified to: 1) epigastric peritonectomy, 2) subdiaphragmatic peritonectomy (right, left, bilateral), 3) pelvic peritonectomy, 4) cholecystectomy + resection of the omental bursa, 5) greater omentectomy (± splenectomy), 6) lesser omentectomy, 7) lateral peritonectomy (right, left, bilateral), and 8) visceral peritonectomy requiring resection of other organs (segmental resection of the small bowel, subtotal colectomy, right colectomy, gastrectomy etc) 14.
The epigastric peritonectomy procedure includes the en bloc resection of the old scar, the round and the falciform ligament of the liver and sometimes the xiphoid process. The procedure is necessary in those cases in which midline laparotomy had been used at initial surgery because a 60% recurrence rate has been reported at this site23.
The intensification of treatment during surgery using instillation of cytostatic drugs in the abdominal cavity is a challenge for ovarian cancer. Intraperitoneal chemotherapy has been proved to be another powerful tool for the eradication of microscopic tumor in pseudomyxoma peritonei24, 25, colorectal26, and gastric cancer with peritoneal spread27, peritoneal mesothelioma and sarcomatosis28, but has been sporadically used in recurrent ovarian cancer9-11. EPIC has been successfully used in gastric cancer27 but has been rarely used in ovarian cancer.
The feasibility of secondary cytoreduction in recurrent ovarian cancer varies widely from 38-83%12,13, probably because different clinical criteria are used. Extensive dissemination of the tumor at the peritoneal surfaces of the small bowel is the most important clinical factor excluding the possibility of complete cytoreduction. In addition, the presence of metastatic disease at lymph nodes that have no anatomic relation to the primary source and that cannot be resected or metastatic lesions at distant sites that are also unresectable makes complete cytoreduction impossible 7. Thus, complete cytoreduction was possible in only 58.6% of the cases.
Numerous clinical factors influencing long-term survival have been identified and consistently reproduced. The most important is the completeness of cytoreduction3,5-8. The CC score has been identified by both univariate and multivariate analysis to be related to survival. The survival of patients who underwent incomplete cytoreduction did not exceed 2 years despite further systemic chemotherapy. Various studies have reported that 5-year survival does not exceed 16% when treatment consists only of cytoreductive surgery and HIPEC11,29. Although the ideal treatment of recurrent ovarian cancer has not yet been defined, it appears reasonable to use cytoreductive surgery and HIPEC only in patients undergoing CC-0 surgery. Even after CC-1 surgery, further treatment seems to be required11. Once patients with recurrent ovarian cancer have been heavily treated with several lines of systemic chemotherapy, the ideal cytostatic drug or a chemotherapy regimen and their proper dose have not yet been standardized for use in the perioperative period.
The extent of peritoneal spread seems to play the same role in prognosis as in primary ovarian cancer30. The survival of patients with extensive peritoneal dissemination did not exceed 3 years. PCI was identified as the most important factor of recurrence. It is interesting that most recurrences develop in patients who undergo incomplete cytoreduction or in those who have extensive peritoneal spread. Consequently, it is meaningful that 29.4% of patients with CC-0 surgery and 26.7% of those with a PCI <13 developed a recurrence. Ovarian cancer is a malignancy with predominantly intracelomic spread. Therefore, most recurrences were local-regional (10 patients, 34.5%) with only 4 (13.8%) distant metastases recorded.
As reported in similar studies, hospital mortality and morbidity rates were within an acceptable range, although the morbidity rate was relatively high (24.1%)10,11,29. The most frequent postoperative complication was anastomotic leak after low anterior resection. Anastomotic failure in addition to wound infection was attributed to perioperative chemotherapy, although it could not be statistically proved. It has been well established that cytostatic drugs exert an adverse effect on wound healing31. In contrast, no severe hematological or nephrological toxicity was recorded in patients who received perioperative chemotherapy. It is also well known that severe systemic toxicity is very infrequent when cytostatic drugs are administered intraperitoneally32. Therefore, only 2 patients had mild and transient hematological toxicity.

Conclusions
Secondary cytoreduction and perioperative intraperitoneal chemotherapy is a safe and feasible method for the treatment of recurrent ovarian cancer. Significant survival benefit may be obtained in patients undergoing complete cytoreduction. Complete cytoreduction is feasible in patients with limited peritoneal dissemination at the surfaces of the small bowel who have no distant metastases. Extensive peritoneal spread is a significant caveat for the performance of complete cytoreduction.

References
 1. Chen LM, Karlan BY: Recurrent ovarian carcinoma: Is there a place for surgery? Semin Surg Oncol, 19: 62-68, 2000.
 2. Rose PG: Surgery for recurrent ovarian cancer. Semin Oncol, 27: 17-23, 2000.
 3. Eisenkop SM, Friedman RL, Spirtos NM: The role of secondary surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer, 88: 144-153, 2000.
 4. Scarabelli C, Gallo A, Carbone A: Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Gynecol Oncol, 83: 504-512, 2001.
 5. Pfisterer J, Harker P, Canzler M, Richter B, Jackisch C, Hahmann M, Hasenburg A, Burges A, Loibl S, Gropp M, Hueber J, Fink D, Bois A, AGO Ovarian Committee, AGO Ovarian Study Group (AGO-OVAR): The role of surgery in recurrent ovarian cancer. Int J Gynecol Cancer, suppl 3: 195-198, 2005.
 6. Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ: Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol, 20: 1248-1259, 2002.
 7. Tentes AA, Mirelis CG, Markakidis CK, Bekiaridou KA, Bougioukas IG, Xanthoulis AI, Tsalkidou EG, Zafiropoulos GH, Nikas IH: Long-term survival in advanced ovarian carcinoma following cytoreductive surgery with standard peritonectomy procedures. Int J Gynecol Cancer, 16: 490-495, 2006.
 8. Tay EH, Grabt PT, Gebeki V, Hacker NF: Secondary cytoreductive surgery for recurrent epithelial ovarian cancer. Obstet Gynecol, 99: 1008-1013, 2002.
 9. Deraco M, Rossi CR, Penacchioli E, Guadagni S, Somers DC, Santoro N, Raspagliesi F, Kusamura S, Vaglini M: Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion in the treatment of recurrent epithelial ovarian cancer: a phase II clinical study. Tumori, 87: 120-126, 2001.
10. Look M, Chang D, Sugarbaker PH: Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Int J Gynecol Cancer, 13: 764-770, 2003.
11. Piso P, Dahlke MH, Loss M, Schlitt HJ: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer. World J Surg Oncol, 2: 21, 2004.
12. Zang RY, Zang ZY, Li LT, Chen J, Tang MG, Liu Q, Cai SM: Effect of cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer. EJSO, 26: 798-804, 2000.
13. Eisenkop SM, Friedman RL, Wang HJ: Secondary cytoreductive surgery for recurrent ovarian cancer. A prospective study. Cancer, 76: 1606-1614, 1995.
14. Sugarbaker PH: Management of peritoneal surface malignancy: the surgeon’s role. Langenbeck’s Arch Surg, 384: 576-587, 1999.
15. Sugarbaker PH: Management of peritoneal surface malignancy using intraperitoneal chemotherapy and cytoreductive surgery. A manual for physicians and nurses. 3d ed, Grand Rapids, Michigan: Ludann Co, 1998.
16. Randall T, and Rubin S: Cytoreductive surgery for ovarian cancer. Surg Clin N Am, 81: 871-873, 2001.
17. Michel G, Zarca D, Castaigne D, Prade M: Secondary cytoreductive surgery in ovarian cancer. EJSO, 15: 201-204, 1989.
18. Neijt J: Ovarian cancer: Rethinking Prognostic Factors and Chemotherapy, ASCO Educational Book, 214-220, 1994.
19. Memarzadeh S, and Berek J: Advances in the management of epithelial ovarian cancer. J Reprod Med, 46: 621-629, 2001.
20. Meier W, du Bois A, Kuhn W, Olbricht S, Gropp M, Richter B, Luck HJ, Kimmig R, Pfisterer J: Topotecan versus treosulfan, an alkylating agent in patients with epithelial ovarin cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: A prospective randomized phase III trial by the Arbeitsgemeinschaft Gynaecologische Onkologie Ovarian Cancer Group (AGO-OVAR). Gynecol Oncol, 114: 199-205, 2009.
21. Tanguay JS, Ansari J, Buckley L, Fernando I: Epithelial ovarian cancer: role of pegylated liposomal Doxorubicin in prolonging the platinum-free interval and cancer antigen 125 trends during treatment. Int J Gynecol Cancer, 19: 361-366, 2009.
22. Sugarbaker P: Peritonectomy procedures. Ann Surg, 221: 29-42, 1995.
23. Sugarbaker TA, Sugarbaker PH: Pathophysiology of peritoneal carcinomatosis from ovarian malignancy. In: Sugarbaker PH (ed) Peritoneal Carcinomatosis: Drugs and Diseases, Norwell, MA: Kluwer Academic Publishers, pp 247-261, 1996.
24. Sugarbaker P, and Chang D: Results of treatment of 358 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol, 6: 727-731, 1999.
25. van Ruth S, Ackerman Y, van de Vijver M, Hart A, Verwaal V, Zoetmulder F: Pseudomyxoma peritonei: a review of 62 cases. EJSO, 29: 682-688, 2003.
26. Verwaal V, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA: 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: 3737-3739, 2003.
27. Yu W, Whang I, Suh I, Averbach A, Chang D, Sugarbaker P: Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer. Ann Surg, 228: 347-354, 1998.
28. Begossi G, Gonzalez-Moreno S, Ortega-Perez G, Fon L, Sugarbaker P: Cytoreduction and intraperitoneal che­mo­therapy for the management of peritoneal carcinomatosis, sarcomatosis and mesothelioma. EJSO, 28: 80-87, 2002.
29. Di Giorgio A, Naticchioni E, Biacchi D, Sibio S, Accarpio F, Rocco M, Tarquini S, Di Seri M, Ciardi A, Montruccoli D, Sammartino R: Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer. Cancer, 15: 315-325, 2008.
30. Tentes AAK, Tripsiannis G, Markakidis SK, Karanikiotis CN, Tzegas G, Georgiadis G, Avgidou K: Peritoneal cancer index: a prognostic indicator of survival in advanced ovarian cancer. EJSO, 29: 69-73, 2003.
31. Ferguson MK: The effect of antineoplastic agents on wound healing. Surg Gynecol Obstet, 154: 421-428, 1982.
32. Fernandez-Trigo F, Stuart OA, Stephens A, Hoover L, Sugarbaker PH: Surgically directed chemotherapy: heated intraperitoneal lavage with mitomycin C. In: Peritoneal Carcinomatosis: Drugs and Diseases, Sugarbaker PH (Ed), pp 51-61, Kluwer Academic, Norwell (MA), 1996.



 
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