head of the pancreas: a randomized study. Chirurg1997;68: 369–377. Izbicki JR, Bloechle C, Broering DC, Kuechler T, Broelsch CE. Longitudinal V-shaped excision of the ventral pancreas for small duct disease in severe chronic pancreatitis: prospec- tive evaluation of a new surgical procedure. Ann Surg 1998;227:213–219. Jalleh RP, Aslam M, Williamson RC. Pancreatic tissue and ductal pressures in chronic pancreatitis. Br J Surg 1991; 78:1235–1237. Kahl S, Zimmermann S, Genz I et al. Risk factors for failure of endoscopic stenting of biliary strictures in chronic pancre- atitis: a prospective follow-up study. Am J Gastroenterol 2003;98:2448–2453. Lowenfels AB, Maisonneuve P, Cavallini G et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993;328:1433–1437. Martin RF, Rossi RL, Leslie KA. Long-term results of pylorus- preserving pancreatoduodenectomy for chronic pancreati- tis. Arch Surg 1996;131:247–252. Nealon WH, Matin S. Analysis of surgical success in prevent- ing recurrent acute exacerbations in chronic pancreatitis. Ann Surg 2001;233:793–800. Nealon WH, Thompson JC. Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pan- creatic duct decompression. A longitudinal prospective analysis of the modified Puestow procedure. Ann Surg 1993;217:458–466. Nealon WH, Townsend CMJ, Thompson JC. Operative drainage of the pancreatic duct delays functional impair- ment in patients with chronic pancreatitis. A prospective analysis. Ann Surg 1988;208:321–329. Rattner DW, Fernandez-Del CC, Warshaw AL. Pitfalls of dis- tal pancreatectomy for relief of pain in chronic pancreatitis. Am J Surg 1996;171:142–145. Rosch T, Daniel S, Scholz M et al. Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up. Endoscopy 2002;34:765–771. Sakorafas GH, Sarr MG, Farley DR, Farnell MB. The signifi- cance of sinistral portal hypertension complicating chronic pancreatitis. Am J Surg 2000;179:129–133. Strasberg SM, Drebin JA, Soper NJ. Evolution and current status of the Whipple procedure: an update for gastroen- terologists. Gastroenterology 1997;113:983–994. Trede M, Carter DC. Preoperative assessment and indications for operation in chronic pancreatitis. In: M Trede, DC Carter (eds) Surgery of the Pancreas. Edinburgh: Churchill Livingstone, 1997: 313–328. PART II 314 Chronic pancreatitis is an irreversible patchy inflam- mation of the pancreatic tissue that progresses to fibrosis due to duct changes subsequent to the necrotic–inflammatory processes in the pancreas. In industrialized countries, chronic alcoholic pancreatitis is the most frequent etiology; in Asian countries, the nutritional tropical pancreatitis prevails (Table 39.1). From a pathomorphologic point of view, patients with an inflammatory mass in the head of the pancreas fre- quently show focal necrotic lesions, small pseudocystic cavities, calcifications of the pancreatic parenchyma, and duct stones in the head area. Considering the head of the pancreas as the pacemaker, but not the cause, of chronic pancreatitis, the inflammatory mass in the head of the gland is the result of a variety of factors deriving from the anatomy (Table 39.2). In epidemiologic terms, chronic pancreatitis is a risk factor for the development of ductal pancreatic cancer. In the subset of patients suf- fering from chronic pancreatitis with an inflammatory mass, ductal pancreatic cancer was found in the pan- creatic head in 6% of patients undergoing pancreatic head resection for long-lasting chronic pancreatitis (see Fig. 39.1). In addition to the main abdominal symptoms of chronic pancreatitis, such as exocrine insufficiency and, in 20–40% of patients, endocrine insufficiency, pain is the decisive symptom, causing discomfort and limitations in daily life. Pain is considered to be a multifactorial process in chronic pancreatitis. Ductal and tissue hypertension, as well as chronic pan- creatitis-associated neuritis with perineural inflamma- tion and increased sensory neurotransmitters in the tissue–nerve environment, are the main factors (see Fig. 39.2). Indications for surgery The most important clinically relevant local complica- tion in patients with chronic pancreatitis is stenosis of the main pancreatic duct, frequently caused by pan- creatic duct stones. On the basis of investigations with endoscopic retrograde cholangiopancreatography (ERCP), common bile duct stenosis in the intrapancre- atic segment of the duct is observed in about every second patient. One-third of these patients suffer some degree of cholestasis and around 15% develop clinical jaundice. Pseudocystic lesions are frequent in chronic pancreatitis; however, the indication for surgical drainage is mandatory in persistent large pseudocystic lesions not responding to interventional or endoscopic drainage. Severe duodenal stenosis has been document- ed in about 5–10%; portal vein compression, some- times with the consequence of portal vein and/or splenic vein thrombosis, is observed in 12–20% of pa- tients (Table 39.3). A difficult indication for surgery is inflammatory mass in the head of the pancreas which is not discriminable from a malignant process. Patients who suffer daily pain with the need for analgesic treat- ment should have surgical treatment (Table 39.4; see also Fig. 39.3). There are three surgical principles for treatment: duct drainage, local excision of the pancreatic head using duodenum-preserving pancreatic head resection, and the major surgical procedure pylorus-preserving head resection. Only a minority of patients benefit from total pancreatectomy, in cases where exocrine and en- docrine insufficiency are found in combination with a severe pain syndrome without an inflammatory mass in the head of the pancreas. The Whipple procedure, a 315 39 Surgical approaches to chronic pancreatitis: technical implications and outcome Hans G. Beger, Bernd Mühling, Naoki Hiki, Zhengfei Zhou, Zhanbing Liu, and Bertram Poch PART II 316 Table 39.1 Etiology of chronic pancreatitis. Alcoholic (60–90%) Idiopathic (20%) Hereditary (< 10%) Tropical Associated with hyperparathyroidism Pancreas divisum (< 1%) Table 39.2 Head of the pancreas is the pacemaker of chronic pancreatitis: factors likely to be involved in causing inflammatory mass of the pancreatic head (IMH). Anatomy of the pancreatic head: 40–50% of the pancreatic tissue Embryologically two parts: dorsal and ventral pancreas Two ductal systems with different drainage capacities: duct of Santorini, duct of Wirsung Pancreas divisum Development of IMH has been observed combined with a marked alteration of the ducts up to the confluence (“knee”) of the ducts Papilla–duct connections Pancreaticobiliary maljunctions Table 39.3 Chronic pancreatitis: frequency of local complications. Results in the Authors’ literature experience* Common bile 23% (Frey 1990) 43% duct stenosis Main pancreatic < 90% (Nagai 1989) 20% duct stones Pseudocysts 40–60% (Grace 1993) 32% Necroses 49% (Amman 1996) 9% Obstruction of 0.8% (Frey 1990) 23% duodenum Portal vein and 10–20% (Warshaw 1997) 16% superior mesenteric vein, splenic vein obstruction/ thrombosis * Department of General Surgery, University of Ulm, Germany, 1972–1998. Table 39.4 Surgical options in chronic pancreatitis. Duct drainage Partington–Rochelle procedure Coring-out modification of Frey Gastrointestinal drainage of pseudocysts Local resection Duodenum-preserving pancreatic head resection Spleen-preserving left resection Major resection Pylorus-preserving head resection Total pancreatectomy Historical Whipple resection Bypass procedure Sphincteroplasty Resection of splanchnic nerves bypass operation, or sphincteroplasty are historical. A Whipple resection of the pancreatic head is an overtreatment of this benign disease and results in long- lasting disadvantages regarding maintenance of en- docrine function and late morbidity. In case of a suspected malignancy, a pylorus-preserving head resec- tion is indicated. The most frequently used duct drainage procedure is pancreatic duct drainage accord- ing to Partington–Rochelle, with a duct opening from the prepapillary area of both papillas up to the tail of the pancreas. The coring-out technique, described by Frey as a modification of the Partington–Rochelle/Frey procedure, removes a minor part of the ventral pan- creas, but is different from duodenum-preserving pancreatic head resection, which results in subtotal re- section of the pancreatic head. The aims of surgical treatment for chronic pancreati- tis are (i) pain relief, (ii) control of pancreatitis-associ- ated complications of adjacent tissue, (iii) preservation of exocrine and endocrine pancreatic function, (iv) so- cial and occupational rehabilitation, and (v) improve- ment of quality of life. The frequency of the surgical techniques currently used in the first author’s institu- tion are given in Table 39.5. Drainage procedure Pancreatic duct drainage using the Partington– Rochelle modification of the Puestow technique results in a ventral incision of the dilated main pancreatic duct. A drainage procedure is most beneficial in patients with chronic pancreatitis who have a dilated main pancrea- tic duct without multiple stenosis of the side branches and who lack an inflammatory mass in the head of the pancreas. A critical point of the Partington–Rochelle modification is the excision of the ventral pancreatic tissue in the head of the pancreas at the level of the prepapillary ducts. The Frey modification of coring-out is similar to the Partington–Rochelle drainage proce- dure. The excised tissue has a wet weight of about 5 g. The Izbicki–Frey modification of the coring-out tech- nique is equivalent to a duodenum-preserving subtotal head resection if the coring-out results in subtotal excision of the pancreatic head tissue. Long-lasting pain relief after pancreatic duct drainage using the Partington–Rochelle procedure (i.e., pancreaticoje- junostomy) is achieved in only about 50% of patients. The figures given in Table 39.6 show that in patients un- dergoing a duct drainage procedure, 20% failed to gain relief from pain while 25% suffered further pain but a little less than preoperatively. Failure to control pain with the use of a duct drainage procedure is caused by tissue changes outside the duct system, mostly in patients with chronic pancreatitis and an inflammatory process in the head of the pancreas. Duct drainage into the jejunum is an inadequate treatment in these cases. It has been demonstrated that reappearance of pain after a duct drainage procedure is caused by an inflamma- tory mass; resection of this mass leads to a long-lasting pain-free status and improvement of the quality of life if the head of the pancreas is resected in a second surgical procedure. Furthermore, lateral duct-to-jejunum anastomosis is ineffective in chronic pancreatitis with side-duct stenosis through the pancreas. Duodenum-preserving pancreatic head resection The rationale for duodenum-preserving pancreatic head resection in chronic pancreatitis is removal of the main inflammatory process, considered to be the pace- maker of the disease, while preserving the upper gas- trointestinal tract. The surgical procedure preserves the stomach, duodenum, and biliary tree. Preservation of the duodenum is superior to Whipple-type resection, which includes duodenectomy. Preservation of the duodenum has been shown to be very important because the duodenum is essential for the regulation of glucose metabolism and gastric emptying. The duodenum-preserving head resection is based on two principal steps: (i) subtotal resection of the pancre- atic head with removal of the inflammatory mass, while preserving the duodenum, extrahepatic common bile duct, gallbladder, and stomach, as well as the pancrea- tic parenchyma to a large extent; and (ii) restoration of the flow of pancreatic juice from the left pancreas, in- cluding neck, body, and tail, to the upper gastrointesti- nal tract by the use of a Roux-en-Y excluded upper jejunal loop. There are three technical steps in the pro- cedure, starting with exposure of the head of the pan- creas (Fig. 39.1). After tunneling of the pancreatic neck ventrally to the portal vein along the portal groove, CHAPTER 39 317 Table 39.5 Surgery in chronic pancreatitis: Ulm experience (905 patients). Duct drainage: 121 patients (13%) Left resection: 83 patients (9%) Duodenal-preserving pancreatic head resection*: 548 patients (61%) Pylorus-preserving head resection: 78 patients (9%) Kausch–Whipple: 12 patients (1%) Others: 63 patients (7%) * Department of General Surgery, Free University of Berlin, November 1972 to April 1982, and Department of General Surgery, University of Ulm, May 1982 to September 2000. Table 39.6 Pain relief after pancreatic duct drainage by pancreaticojejunostomy: results after more than 5 years of follow-up of 582 patients.* Complete pain relief in 55% Pain, but improved in 25% Failure of pain control in 20% Unsatisfactory long-term results in 25 + 20 = 45% * Sources: Leger (1974), White (1979), Prinz (1981), Morrow (1984), Bradley (1987), Drake (1999), Greenie (1990), Wilson (1992), Adams (1994), Kestens (1996), Gonzales (1997), Shama (1998), Sidhu (2001). transection of the pancreas along the duodenal border of the portal vein is performed. After transection of the pancreas, the pancreatic head and the duodenum are rotated by 90° to a ventral–dorsal position (Fig. 39.2). Subtotal resection of the pancreatic head along the in- trapancreatic segment of the common bile duct leads in most cases to decompression of the narrowed common bile duct without opening the duct. The wet weight of an operative specimen after subtotal head resection with duodenum-preserving head resection is between 25 and 45 g; in 54 patients, the median was 28 g. After completion of the subtotal resection, a shell-like rest of the pancreatic head along the duodenal C-line is pre- served. The dorsal pancreaticoduodenal arteries are preserved, whereas in most cases the ventral branch of the gastroduodenal artery has to be ligated. To restore flow of pancreatic juice into the upper intestine, a jeju- nal loop is separated and interposed (Fig. 39.3). Two pancreatic anastomoses have to be performed. In cases with stenosis of the common bile duct, due to inflam- mation of the duct wall, an additional internal biliary anastomosis between the bile duct and jejunal loop has to be carried out (Fig. 39.4). In cases with a biliary anas- tomosis, three connections to the jejunal loop are estab- lished: two pancreatic and one biliary anastomoses. In patients with multiple stenosis and dilatation of the main pancreatic duct in the body and tail, a side-to-side PART II 318 Figure 39.1 Duodenum-preserving pancreatic head resection: the first step is transection of the neck of the pancreas; resection line is along the mass of the pancreatic head. Figure 39.2 Duodenum-preserving pancreatic head resection: dorsal view of the pancreas. The dorsal capsule of the head of the pancreas is preserved. The dorsal pancreaticoduodenal arcades are intact. Figure 39.3 Duodenum-preserving head resection: reconstruction with a jejunal loop. CHAPTER 39 319 Figure 39.4 Duodenum-preserving pancreatic head resection with intrapancreatic stenosis of the common bile duct: additional biliary drainage into the jejunal loop has to be performed. Table 39.7 Duodenum-preserving pancreatic head resection in chronic pancreatitis: early postoperative results (504 patients).* Hospitalization (postoperative): 14.5 (7–87) days Relaparotomy: 28 patients (5.6%) Hospital mortality: 4 patients (0.8%) * Department of General Surgery, Free University of Berlin, November 1972 to April 1982, and Department of General Surgery, University of Ulm, May 1982 to December 1998. Figure 39.5 Multiple stenosis of the main pancreatic duct in the body and tail: duodenum-preserving pancreatic head resection is combined with a pancreaticojejunostomoses lateral-lateral. anastomosis has to be performed additionally (Fig. 39.5). Early postoperative results after duodenum-pre- serving head resection in chronic pancreatitis are given in Table 39.7. Using the duodenum-preserving head resection, con- trol of pain is achieved in about 90% of patients in the late follow-up (Table 39.8). With regard to endocrine function, the duodenum-preserving head resection re- sults in improvement of glucose metabolism in 8–15% of patients. In the long-term follow-up, however, an Table 39.8 Late postoperative pain after duodenum-preserving pancreatic head resection in chronic pancreatitis (Beger 1999). * Median years of follow-up. Late postoperative follow-up 1984 1988 1997 2.0 years* 3.6 years* 5.7 years* 57 patients 109 patients 303 patients Pain-free 92.8% 89% 91.3% Continuing abdominal pain 7.2% 11% 8.7% Abdominal complaints — 12% 12% Hospitalization due to attacks of pancreatitis 14% 11% 9% increase in insulin-dependent diabetes occurs; after a median follow-up of 5.7 years, about 50% of patients are diabetic (Table 39.9). Table 39.10 shows the results of randomized clinical trials that compared duodenum- preserving pancreatic head resection with pylorus- preserving (Kausch–Whipple) resection and with the Izbicki–Frey modification.Duodenum-preserving head resection is superior or equal to the other procedures with regard to postoperative morbidity, postoperative maintenance of glucose metabolism, delay of gastric emptying, and low level of rehospitalization, as well as restoration of quality of life. In the long-term outcome after surgical treatment, it has been convincingly demonstrated that in a small group of patients the Partington–Rochelle procedure (i.e., duct drainage procedure) using the modification of Izbicki–Frey PART II 320 Table 39.9 Duodenum-preserving pancreatic head resection changes the natural course of chronic pancreatitis. 1972–83 1972–87 1972–94 1982–96 58 patients* 128 patients† 298 patients‡ 368 patients§ Follow-up 2.8 years (median) 3.6 years 6.0 years 5.7 years (median) 57 patients 109 patients 258 patients 303 patients Follow-up rate 100% 96% 87% 94% Pain-free 93% 89% 88% 91% Continuing abdominal pain 7% 11% 12% 9% Hospitalization for acute episode 14% 11% 10% 9% Late death rate 3.6% 4.7% 8.9% 13% Endocrine functions improved 15.8% 5.5% 11% Professional rehabilitation 89% 67% 63% 69% Quality of life/Karnorfsky 80–100 82% * November 1972 to October 1983. † November 1972 to December 1987. ‡ November 1972 to December 1994. § May 1982 to October 1996. Table 39.10 Duodenum-preserving pancreatic head resection (DPPHR) versus Whipple resection in chronic pancreatitis: results of randomized trials. Study Procedures compared Results Buechler et al. (1995) DPPHR vs. pylorus-preserving DPPHR much superior with regard to postoperative Whipple resection morbidity, glucose metabolism, gastric emptying, and rehospitalization Klempa et al. (1995) DPPHR vs. Whipple resection DPPHR superior with regard to postoperative morbidity, glucose metabolism, and rehospitalization Izbicki et al. (1995) DPPHR vs. Beger–Frey DPPHR* Both methods equal with regard to pain control, glucose metabolism, postoperative morbidity, and quality of life Izbicki et al. (1998) Frey DPPHR* vs. pylorus-preserving DPPHR superior with regard to postoperative Whipple resection morbidity, gastric emptying, and quality of life Witzigmann et al. (2003) DPPHR vs. Whipple resection DPPHR superior with regard to postoperative morbidity, maintenance of endocrine function, rehospitalization, and quality of life * Frey, modified by Izbicki. delays deterioration of function (Table 39.10). Duodenum-preserving pancreatic head resection is the surgical technique of choice in patients suffering chron- ic pancreatitis with an inflammatory mass in the head. Pylorus-preserving pancreatic head resection in chronic pancreatitis A complete pancreatic head resection is mandatory in chronic pancreatitis suspected to be associated with pancreatic cancer. In patients suffering long-lasting chronic pancreatitis, a malignant lesion is observed in 4–6%. The cancer risk in chronic pancreatitis is predicted to be increased 16-fold after 20 years. The criteria for malignancy inlude the double-duct sign and continuously increasing CA-19-9 and/or CEA in the peripheral blood after biliary stenting of jaun- diced patients. Most suggestive of cancer is positive cancer cell staining of biopsy material or of intraopera- tively obtained frozen sections. Infiltration of the portal or superior mesenteric vein wall develops rarely in chronic pancreatitis but is more frequent in cancer. Increased mutations of K-ras, p53, p16, and DPC4 can be used as markers of carcinogenic process in the pancreas. Conclusion In chronic pancreatitis complicated by medically intractable pain, common bile duct stenosis, main pancreatic duct stenosis, portal vein compression, and duodenal stenosis, and in pancreas divisum, the application of duodenum-preserving pancreatic head resection with or without lateral duct drainage offers the benefits of low postoperative morbidity, pain-free status in 90% of patients, reduction in pancreatitis-re- lated hospitalization to less than 5%, postoperative maintenance of endocrine status, professional rehabili- tation in more than 60% of patients, and significant im- provement in quality of life. In patients with main pancreatic duct dilatation without multiple main- and side-duct stenoses and without an inflammatory mass in the head, a Partington–Rochelle procedure or a Frey modification is the first choice for surgical treatment. 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Detection of point mutation of K-ras gene codon 12 in biliary tract and am- pullary carcinoma by modified two-step polymerase chain reaction. Nippon Shokakibyo Gakkai Zasshi 1993;90: 789–794. Weihe E, Nohr D, Müller S, Büchler M, Friess H, Zentel HJ. The tachykinin neuroimmune connection in inflammatory pain. Ann NY Acad Sci 1991;632:283–295. Widmaier U, Schmidt A, Schlosser W, Beger HG. Die duode- numerhaltende Pankreaskopfresektion in der Therapie des Pancreas divisum. Chirurg 1997;68:180–186. PART II 322 Introduction Pancreatic pseudocysts are chronic inflammatory fluid collections associated with pancreatitis. Pseudocysts are the most common complication of acute and chron- ic pancreatitis and nearly one-third of patients with pancreatitis will develop a pseudocyst. Because the fluid cavities are not lined with an epithelium, they are not true cysts. The cavities are instead lined with a reactive granulation tissue that surrounds a collection of enzyme-rich fluid, debris, and necrotic tissue. The treatment of pancreatic pseudocysts is highly variable, ranging from observation to surgical drainage. Drainage procedures via radiologic or endo- scopic approaches are also an important option. An understanding of the pathogenesis of pseudocysts associated with chronic pancreatitis will aid the clinician in the selection of proper treatment. Pathophysiology of pancreatic fluid collections and pseudocysts Pseudocysts associated with chronic pancreatitis Pseudocysts are chronic fluid collections that consist of pancreatic secretions and inflammatory debris and contain large concentrations of active proteolytic enzymes. The fluid collections may develop after an episode of acute pancreatitis or insidiously in the set- ting of chronic pancreatitis. Small pancreatic pseudo- cysts are usually intrapancreatic and have a thin wall. Large pseudocysts may be so large that they occupy areas remote from the pancreas. The histologic features of pseudocyst walls are similar in all types of pseudo- cysts, consisting of fibrosis and inflammatory tissue. Most pancreatic pseudocysts originate from large or small leaks from the ductal system and this feature can be demonstrated with endoscopic retrograde cholan- giopancreatography (ERCP). Focal fluid collections arising in the setting of acute pancreatitis Acute peripancreatic fluid collections commonly arise during episodes of acute pancreatitis. The fluid collec- tions may accumulate as a result of ductal disruptions or the liquefaction of necrotic pancreatic tissue. Simple fluid collections as a result of ductal leaks are usually unilocular and filled with pancreatic secretions that contain high concentrations of enzymes. Early in the formation of these fluid collections, the fluid is not well contained in the peripancreatic space and may spread throughout the peritoneal and retroperitoneal spaces. Early fluid collections located adjacent to organs such as the stomach, colon, liver, and mesentery are the source of older mature pseudocysts. Chronic fluid col- lections are contained by thick walls of fibrotic inflam- matory tissue that often include the serosa of adjacent organs. Complex fluid collections often originate from pan- creatic tissue necrosis during acute pancreatitis. These focal fluid collections or phlegmons contain semisolid debris, inflammatory fluid, and high concentrations of pancreatic enzymes and can be divided into loculations by fibrotic septations. Complex fluid collections are particularly prone to infection and often require sampling and drainage. 323 40 Management of chronic pancreatic pseudocyst: when to observe, when and how to drain William R. Brugge [...]... gallstones 1 977 –89 60 176 patients, follow-up until death or 1993 No increased risk Retrospective case–control study Abdominal ultrasound of 100 consecutive cases of pancreatic cancer and that of 140 age- and gender-matched controls Population-based cohort: 62 615 patients with cholecystectomy Follow-up for pancreatic and periampullary cancer up to 23 years Cholecystectomy at least 20 years ago: 70 % increased... Iowa women Partanen et al (19 97) Fuchs et al (1996) Population-based case–control study 118 339 women aged 30–55 years, 49 428 men aged 40 75 years without cancer, 2 116 229 person-years of follow-up, pancreatic cancer diagnosed in 186 participants Retrospective study 282 inpatients with pancreatic cancer vs 282 age- and sex-matched controls Case–control study: 451 vs 1552 controls Interview RR for current... et al (1995) Case–control study: 570 pancreatic cancers vs 570 controls; 14 centers in Italy Data on coffee consumption 20 years prior to diagnosis of cancer obtained from the next of kin of 662 cases of pancreas cancer and 177 0 reference (stomach, colon, and rectum) cancers 10-year complete follow-up of 21 73 5 men and 21 238 women aged 35–54 years in Norway Population-based case–control study: 149 from... Prospective cohort study of 33 976 postmenopausal Iowa women No effect Ki-ras mutations in tumors: 77 .7% Mutations more common among regular coffee drinkers: 82.0% vs 55.6%, P = 0.018 Dose relation between Ki-ras mutation and number of cups of coffee per week No effect Elevated risk for those who drank > 17. 5 cups of coffee per week compared with those who consumed < 7 cups per week CHAPTER 41 Table... decreased risk of pancreas cancer, SMR 72 for men, 90 for women, not statistically significant Risk increased: higher consumption of fried, grilled meat, RR 1 .7 (CI 1.1–2 .7) for weekly intake; RR 13.4 (CI 2.4– 74 .7) for associations found with other fried or grilled foods, not with meat other than fried or grilled Risk increased with the intake of margarine, RR 9 .7 (CI 3.1–30.2) No excess risk associated... intake: 0.52 (CI 0.31, 0. 87) ; P-trend 0.05 RR reduction with any current use of aspirin vs no use: 0. 57 Reduced risk: multivariate OR 0 .76 for intermediate and 0.60 for highest score of intake Vegetables, traditional Japanese foods, e.g., tofu, deep-fried tofu, raw fish, and tempura: reduced risk Risks inversely associated: vegetables, fruits, dietary fiber, eggs No associations for total energy, total... males; 1 .7 (CI 0.84–3.3) in females Increased risk (highest compared with lowest quintile, cigarettes per day: HR 1.82; CI 1.10, 3.03; P-trend 0.05) Increased risk Males: OR 1.8 (CI 1.2–2.8) Females: OR 2.1 (CI 1.4 – 3.1) Twofold increased risk among current smokers Dose–response association: number of cigarettes (P for trend, 0.02) and number of pack-years (P for trend, 0.02 for men and 0.01 for women)... cancer was 4 .7% for first-degree relatives of pancreatic cancer cases The risk increased up to 7. 2% for relatives of cases diagnosed before age 60, and was 12.3% for relatives of patients with multiple primary cancers In another study, the risk of pancreatic cancer in the sporadic pancreatic cancer kindreds was not significantly greater than expected However, there was a significantly increased 18-fold risk... a 5 7- fold increased risk When stratified by age, the risk was mainly confined to relatives over the age of 60 For many decades, the incidence of pancreatic cancer has been 50–90% higher among blacks than among whites in the USA Established risk factors such as cigarette smoking, long-term diabetes mellitus, and family history of pancreatic cancer account for 46% of the disease in black men and for 37% ... consumption and elevated BMI According to this study, in the absence of these risk factors, 3 47 PART III Table 41.6 Factors reducing risk of pancreatic cancer Study Study design Risk Aspirin Menezes et al (2002) Hospital-based case–control study Not reduced Energy-adjusted carbohydrate intake Stolzenberg-Solomon Prospective study, 27 111 male smokers aged et al (2002) 50–69 years: Alpha-Tocopherol, Beta-Carotene . 1993;328:1433–14 37. Matsubara T, Sakurai Y, Funabiki T et al. K-ras point muta- tions in cancerous and noncancerous biliary epithelium in patients with pancreaticobiliary maljunction. Cancer 1996 ;77 : 175 2– 175 7. Oertel. Scandina- vian and East European descent. In all countries inci- dence almost equals mortality. The incidence rate between the ages of 40 and 44 is 19/100 000 and be- tween the ages of 75 to 79 . than surgical treatment in unselected pa- tients. Ann Surg 1999;229 :78 1 78 7; discussion 78 7 78 9. Mori T, Abe N, Sugiyama M, Atomi Y. Laparoscopic pancre- atic cystgastrostomy. J Hepatobiliary