Resection and palliation of pancreatic and periampullary carcinoma van Geenen, R.C.I.

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1 UvA-DARE (Digital Academic Repository) Resection and palliation of pancreatic and periampullary carcinoma van Geenen, R.C.I. Link to publication Citation for published version (APA): van Geenen, R. C. I. (2001). Resection and palliation of pancreatic and periampullary carcinoma General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 29 Nov 2017

2 CHAPTERR 1 Introductionn and Outline of the Thesis

3 ChapterChapter 1 Outlinee of the Thesis Periampullaryy carcinoma, including pancreatic, bile duct, and ampullary carcinoma, have a grimm prognosis with a 5-year survival between 1 and 25% for pancreatic and 6-50% for ampullaryy carcinoma. Different treatments are available for patients with these malignancies varyingg from resection with curative intent such as the pancreaticoduodenectomy (PD) to palliationn of symptoms by means of bypass surgery for biliary and gastrointestinal obstruction,, endoprostheses for biliary obstruction, pain management, and supportive therapies,, as for example nutritional support. Thee treatment of first choice is the PD, which offers the only chance for cure. There are three typess of resection according to the extent of the resection: the standard, the extended, and the regionall resection. In Amsterdam, the standard resection is performed routinely. Traditionally,, PD has been associated with a high morbidity (50-70%) and mortality (10-20%).. During the last decade morbidity and mortality decreased to acceptable levels 23. AA parallel development was the mounting evidence that hospital volume inversely related to in-hospitall mortality. This resulted in a plea for centralisation 4. However, the scientific validityy of studies on this subject is questioned and further evidence is necessary to convince surgeonss of these findings. Still other factors might also influence in-hospital mortality of the PD.. For instance, individual perioperative parameters and the experience of the individual surgeonn have been described to effect in-hospital mortality. Furthermore the expertise of the differentt disciplines, such as radiology gastroenterology, intensive care, and surgery, might effectt the treatment and outcome of these patients. These aspects need further evaluation. Differentt technical modifications of the resection have been described to improve resectability oftenn with increased morbidity and mortality. Resection is often precluded by tumour ingrowthh in to surrounding tissue such as the retroperitoneum, or the portal and superior mesentericc vein (PV/SMV). In case of PV/SMV involvement (a part of) the PV/SMV can be resected.. There is still discussion about the indication and the technique as well as the effect onn outcome of this procedure in terms of morbidity, mortality and survival 56. Differentt aspects influence the final outcome of treatment. Apart from the perioperative results,, long-term results such as functional outcome, long-term morbidity, extent of the resection,, and survival also determine the final outcome of treatment. PD may affect the complexx mechanisms that regulate nutrient digestion such as gastrointestinal motility, release off pancreatic enzymes and gastrointestinal hormones, and intraluminal ph 7 " 9. This may negativelyy affect nutrient digestion and absorption and thereby long-term outcome. There are limitedd data available on the gastrointestinal ph and hormone secretion after PD. Re-admissionss are an objective tool to measure severity of long-term morbidity. Readmissionss may be caused by sequelae of tumour recurrence and late complications of the initiall surgical procedure that require re-admission after PD. Data on re-admissions and the indicationss for re-admission after PD are limited but are needed to evaluate the long-term morbidityy of the procedure. Survivall is the most important determinant of long-term outcome. Five-year survival after PD wass poor varying from 1-25% for pancreatic carcinoma, and 6-50% for periampullary 10 0

4 Introduction Introduction carcinoma 10 '' ". Decreased operative mortality resulted in a more optimistic view towards resection,, and improved survival after PD has been reported. Patient selection as a result of a betterr diagnostic approach could have improved survival after PD. Therefore new data on survivall and risk factors for poor survival are needed to evaluate the long-term outcome of PD.. Att the time of diagnosis most patients (80%) are no candidates for resection 12. At this stage palliationn of symptoms such as jaundice or gastric outlet obstruction can be performed by bypasss surgery. A hepaticoenterostomy relieves jaundice, and duodenum obstruction can be treatedd with a gastroenterostomy. Pain is another major symptom and is mostly treated with painn medication. However other therapeutic options are available. During bypass surgery a chemicall splanchnectomy can be performed with injection of alcohol 13, or a thoracoscopic splanchnectomyy can be performed. Also radiotherapy can offer pain relief 14. It is still unclear whatt the effects and side effects of these treatment modalities are. Thee complex syndrome of cancer cachexia continues to be a major contributor to the morbidityy and mortality of patients with advanced malignancy 15; 16. Different types of nutritionall support or hormone treatment have been used in an attempt to reverse this cachecticc state and increase the lean body mass. Previous nutritional support or hormone treatmentt resulted only in an increase of weight due to an increase in fat rather than lean body mass.. A pilot study showed that administration of eicosapentaenoic acid (EPA), an omega-3 fattyy acid derived from fish oil, resulted in weight stabilisation 17 ' ' 8. However, level one evidencee is not available. Thee limited prognosis forces physicians to carefully consider the risk of postoperative complications,, mortality, long-term complications and survival of each treatment strategy in thee different stages of the disease, and to carefully select patients and also the setting in which thee different types of treatment are performed. The first part of the thesis covers issues concerningg the resection of periampullary and pancreatic carcinoma by means of PD. The secondd part of the thesis deals with aspects of long-term outcome after surgical resection, and thee third part deals with the issues in palliation of symptoms such as pain and cachexia. Partt one Inn chapter 2 the morbidity, mortality, and risk factors for complications after PD are discussedd in a single centre study performed in the Netherlands. Also the inverse relationship betweenn hospital volume and in-hospital mortality after PD in the Netherlands and its effect onn centralisation are described in this chapter. In Chapter 3 the impact of hospital and surgeonn volume on in-hospital mortality is described and the importance of a multidisciplinaryy approach in the management of complications after PD is clarified in a case history.. In chapter 4 a meta-analysis of the available literature on hospital volume and mortalityy in pancreatic surgery is presented. In chapter 5 the indication, technique and the additionall value of the PV/SMV resection in the presence of tumour invasion of this structure andd its effect on morbidity and mortality is described. 11 1

5 ChapterChapter 1 Partt two Functionall outcome in terms of intragastric and intraduodenal ph after pylorus preserving PD inn comparison with healthy control subjects is described in chapter 6. In a non-malignant setting,, functional outcome in patients after pylorus preserving PD or duodenum preserving resectionn of the head of the pancreas is analysed in comparison with non-operative chronic pancreatitiss patients in chapter 7. Changes in proximal and distal gut hormone secretion in patientss after pancreatic surgery are compared with non-operated patients with comparable exocrinee pancreatic insufficiency and with healthy controls in chapter 8. Re-admissions after PDD are an objective parameter to measure long-term outcome. Re-admission-rate and indicationss for re-admissions are discussed in chapter 9. Current survival after PD is discussedd in chapter 10, this chapter also deals with the risk factors for poor survival after PD.. Partt three Painn management is an important part in the palliative treatment of patients with periampullaryy and pancreatic carcinoma. The effect of pain medication, intraoperative chemicall splanchnectomy, and radiotherapy is discussed in chapter 11. The developments in thee treatment of cachexia were stimulated by the positive effect of EPA. Chapter 12 describess the effect of a supplement of a high caloric supplement combined with EPA on weightt loss and quality of life in pancreatic cancer cachexia. References s 1.. Pedrazzoli S, Beger HG, Obertop H, et al. A surgical and pathological based classification of resective treatmentt of pancreatic cancer. Summary of an international workshop on surgical procedures in pancreatic cancer.. Digestive Surgery 1999; 16: Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s:: pathology, complications, and outcomes. Annals of Surgery 1997; 226: Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections withoutt an operative mortality. Annals of Surgery 1990; 211: Gouma DJ, Obertop H. Centralization of surgery for periampullary malignancy. British Journal of Surgery 1999;86: Allema JH, Reinders ME, van Gulik TM, et al. Portal vein resection in patients undergoing pancreatoduodenectomyy for carcinoma of the pancreatic head. British Journal of Surgery 1994; 81: Roder JD, Stein HJ, Siewert JR. Carcinoma of the periampullary region: who benefits from portal vein resection?? American Journal of Surgery 1996; 171: Andersen JR, Bendtsen F, Ovesen L, Pedersen NT, Rune SJ, Tage-Jensen U. Pancreatic insufficiency. Duodenall and jejuna! ph, bile acid activity, and micellar lipid solubilization. Pancreatologyy 1990; 6: International Journal of 8.. DiMagno EP, Malagelada JR, Go VL, Moertel CG. Fate of orally ingested enzymes in pancreatic insufficiency.. Comparison of two dosage schedules. New England Journal of Medicine 1977; 296:

6 Introduction Introduction 9.. Regan PT, Malagelada JR, DiMagno EP, Go VL. Reduced intraluminal bile acid concentrations and fat maldigestionn in pancreatic insufficiency: correction by treatment. Gastroenterology 1979; 77: Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Lillemoe KD, Pitt HA. Periampullary adenocarcinoma: analysiss of 5-year survivors. Annals of Surgery 1998; 227: Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Americann Journal of Surgery 1993; 165: Kelly DM, Benjamin IS. Pancreatic carcinoma. Annals of Oncology 1995; 6: Lillemoe KD, Cameron JL, Kaufman HS, Yeo CJ, Pitt HA, Sauter PK. Chemical splanchnicectomy in patientss with unresectable pancreatic cancer. A prospective randomized trial. Annals of Surgery 1993; 217: Minsky BD, Hilaris B, Fuks Z. The role of radiation therapy in the control of pain from pancreatic carcinoma.. Journal of Pain & Symptomm Management 1988; 3: Inagaki J, Rodriguez V, Bodey GP. Proceedings: Causes of death in cancer patients. Cancer 1974; 33: Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients.. Eastern Cooperative Oncology Group. American Journal of Medicine 1980; 69: Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KC. Effect of oral eicosapentaenoic acid on weight losss in patients with pancreatic cancer. Nutrition & Cancer 2000; 36: Wigmore SJ, Ross JA, Falconer JS, et al. The effect of polyunsaturated fatty acids on the progress of cachexiaa in patients with pancreatic cancer. Nutrition 1996; 12:S27-S

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