Pancreatic Head Resection

Pancreatoduodenectomy (PD) for CP was described as early as 1946 by Whipple.57 In the modern era,

PD is the operation of choice for patients with complicated CP and head-dominant disease. Patients may

present with duodenal or biliary obstruction as well as obstructive pancreatopathy from an

inflammatory mass in the head of the pancreas. Outcomes for PD include pain relief in 70% to 89% of

patients, morbidity in 16% to 53%, and mortality in less than 5% in high-volume centers.58–61

The pylorus preserving pancreatoduodenectomy (PPPD) was popularized by Traverso and Longmire

in 1978 in an effort to maintain the physiologic benefits of a functional pylorus.62 PPPD has been well

adopted into pancreas surgery although the purported nutritional advantages have not been

evidenced.63–67 Some authors, however, have reported improved professional rehabilitation64 and

improved quality of life after PPPD66 as compared to classic PD.

Duodenal preserving pancreatic head resection (DPPHR) was developed by Beger and colleagues in

the 1970s in an effort to decrease the morbidity of pancreatic head resection for CP. Pain relief is

reported in 77% to 88% of patients, with professional rehabilitation rates of 63% to 69%. Morbidity and

mortality are acceptable at 28.5% and 1%, respectively.67–71 Multiple prospective randomized trials in

comparing the various methods of pancreatic head resection in CP have been undertaken mostly in

Germany over the past couple of decades, with no discernable advantage determined between them

(Table 54-4).71–76 A modification of the Beger procedure was described by the group in Berne in which

the neck of the pancreas is left intact in its course over the portal vein thereby diminishing the risk of

portal venotomy (Fig. 54-4).77,78

Distal Pancreatectomy

In patients with CP and disease localized to the body and tail of the pancreas or in patients with a main

pancreatic duct stricture in the neck or body, distal pancreatectomy (DP) can be an effective means of

pain relief. The majority of CP patients who are candidates for DP have severe inflammatory changes in

the region of the splenic hilum, making concomitant splenectomy the most prudent course. Pain-relief

rates of 57% to 84% are reported with occupational rehabilitation in 29% to 73%. Morbidity and

mortality are reported in 15% to 32% and 2% to 2.2% of cases, respectively.79–81 Postoperative

pancreatic fistula after DP is the primary morbidity of this operation and appears to be related to

patient-specific factors rather than operative technique.82 DP appears to be applicable in approximately

9% to 25% of patients in larger series of patients undergoing surgery for CP.49,83

Total Pancreatectomy

TP for CP was performed as early as 1944 by Clagett at the Mayo Clinic. Perhaps tellingly, his patient

died 10 weeks after surgery of a hypoglycemic event. TP can be an effective means of pain relief in

patients with diffuse small-duct pancreatitis, patients who have failed lesser surgeries, and patients with

hereditary pancreatitis. Excellent pain-relief rates of 72% to 100% have been described with TP, with

morbidity rates of 22% to 54% and mortality 0 to 14%. There is a requisite brittle type 3c

pancreatogenic diabetes that follows TP; however, with severe diabetic control problems in 15% to 75%

of patients, and in one series, half of late postoperative deaths were due to hypoglycemia.84,85 With TP,

there is loss of not only insulin-producing beta cells but also loss of the alpha cells and other composite

cells of the islet that produce hormones to maintain glucose homeostasis. As a result, patients may

demonstrate an unpredictable response to exogenous insulin and importantly may develop

hypoglycemic unawareness, which can be morbid.86 Thus, TP is a good option for pain relief but the

resultant diabetes is exceptionally morbid.

5 TP with islet autotransplantation (TPIAT) was described by Sutherland and colleagues at the

University of Minnesota in 1978, with the goal of ameliorating the brittle diabetes after extensive

pancreatectomy.87 TPIAT has really only been performed with any regularity, however, over the past

decade, and understanding of long-term outcomes is evolving. Pain-relief rates of 72% to 86% have

been reported and patients have a significantly improved quality of life. Morbidity rates of 47% to 55%

are reported, with 1.4% to 6% mortality, and insulin independence in 10% to 40% after islet

transplant.88–91 Insulin independence after TPIAT correlates with the number of islet equivalents per

kilogram harvested89,91 and transplanted islet function appears to be durable, with outcomes reported

for more than 13 years.92 TPIAT has been safely and effectively performed in children with hereditary

pancreatitis, with insulin independence in 55%.93 While this therapy holds promise, long-term outcomes

data are currently lacking.

1390

Figure 54-4. Schematic drawings of extent of resection (A), and method of reconstruction (B) for a Beger procedure (1), Frey

procedure (2), and a Berne modification of the Beger procedure (3). Reproduced from Muller MW, Freiss H, Leitzbach S, et al.

Perioperative and follow-up results after central pancreatic head resection (Berne technique) in a consecutive series of patients

with chronic pancreatitis. Am J Surg 2008;196:364–372.

Table 54-4 Comparative Randomized Controlled Trials of Pancreatic Head

Resection

Laparoscopic Surgery for Chronic Pancreatitis

Laparoscopy began in pancreas surgery with laparoscopic staging for pancreatic cancer. The

development of endoscopic stapler technology in the mid-1990s allowed for pancreatic resections to be

developed. In 1996, Gagner reported his experience with laparoscopic distal pancreatectomy.94 Due to

the recent epidemic of incidentally discovered low-grade pancreatic neoplasms, experience with

laparoscopic DP has matured rapidly, and now it is currently the most commonly performed

laparoscopic pancreatic resection. A large multicenter group reported on 667 distal pancreatectomies

with 159 (24%) laparoscopic, and 14 (9%) were for CP. The authors reported lower blood loss, length

of stay and morbidity with laparoscopy, and equivalent operative times and pancreatic fistula rates.95 A

recent meta-analysis of studies reporting experience with laparoscopic DP, including greater than 1,800

cases, showed similar advantages with laparoscopy, while maintaining quality.96 While laparoscopic DP

is arguably now the standard approach to resection of benign or low-grade neoplasms its wide

application in patients with CP is still in evolution, as these cases are more technically challenging due

to the distorted anatomy and loss of tissue planes in CP. Laparoscopic LPJ has been described by several

authors and is technically feasible.97 Success rate for the minimally invasive approach in this operation

increases as the size of the pancreatic duct increases. The laparoscopic PD is being performed at many

1391

academic centers, mostly for malignant disease, but in a few with CP. The authors report reasonable

operative times (median 357 to 368 minutes), blood loss (75 to 240 cc), morbidity (26.7% to 42%), and

pancreatic fistula rates (6.7% to 18%).98–100 The limitations of laparoscopic PD in CP are similar to

those with laparoscopic DP, with the associated technical challenges of operating on a fibrotic gland.

CONCLUSIONS

CP is a complex disease, challenging in diagnosis and management. Notable recent progress has been

made in understanding the underlying pathophysiology, including genetic causes and cellular and

biochemical mechanisms, with much still to be learned. Surgery can be beneficial in many patients with

debilitating pain from CP. Evolving surgical therapies, such as TPIAT and minimally invasive

techniques, are promising.

References

1. Rickels MR, Bellin M, Toledo FG, et al. Detection, evaluation, and treatment of diabetes mellitus in

chronic pancreatitis: recommendations from Pancreasfest 2012. Pancreatology 2013;13(4):336–342.

2. Levy P, Barthet M, Mollard BR, et al. Estimation of the prevalence and incidence of chronic

pancreatitis and its complications. Gastroenterol Clin Biol 2006;30:838–844.

3. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: liver, biliary tract,

and pancreas. Gastroenterology 2009;136:1134–1144.

4. Schneider A, Lohr JM, Singer MV. The M-ANNHEIM classification of chronic pancreatitis:

introduction of a unifying classification system based on a review of previous classifications of the

disease. J Gastroenterol 2007;42:101–119.

5. Layer P, Yamamoto H, Kalthoff L, et al. The different courses of early and late onset idiopathic and

alcoholic chronic pancreatitis. Gastroenterology 1994;107:1481–1487.

6. Dani R, Penna FJ, Nogueira CE. Etiology of chronic calcifying pancreatitis in Brazil: a report of 329

consecutive cases. Int J Pancreatol 1986;1:399–406.

7. Marks IN, Bank S, Louw JH. Chronic pancreatitis in the Western Cape. Digestion 1973;9:447–453.

8. Cote GA, Yadav D, Slivka A, et al. Alcohol and smoking as risk factors in an epidemiology study of

patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2011;9:266–273.

9. Whitcomb DC. Genetics of alcoholic and nonalcoholic pancreatitis. Curr Opin Gastroenterol

2012;28:501–506.

10. Cavallini G, Talamini G, Vaona B, et al. Effect of alcohol and smoking on pancreatic lithogenesis in

the course of chronic pancreatitis. Pancreas 1994;9:42–46.

11. Maisonneuve P, Lowenfels AB, Mullhaupt B, et al. Cigarette smoking accelerates progression of

alcoholic chronic pancreatitis. Gut 2005;54:510–514.

12. Yadav D, Hawes RH, Brand RE, et al. Alcohol consumption, cigarette smoking, and the risk of

recurrent acute and chronic pancreatitis. Arch Int Med 2009;169:1035–1045.

13. Nojgaard C, Becker U, Matzen P, et al. Progression from acute to chronic pancreatitis: prognostic

factors, mortality and natural cause. Pancreas 2011;40:1195–1200.

14. Comfort MW, Steinberg AG. Pedigree of a family with hereditary chronic relapsing pancreatitis.

Gastroenterology 1952;21:54–63.

15. Whitcomb DC, Gorry MC, Preston RA, et al. Hereditary pancreatitis is caused by a mutation in the

cationic trypsinogen gene. Nat Genet 1996;14:141–145.

16. Witt H, Luck W, Hennies HC, et al. Mutations in the gene encoding the serine protease inhibitor,

Kazal type 1 are associated with chronic pancreatitis. Nat Genet 2000;25:213–216.

17. Szmola R, Sahin-Toth M. Chymotrypsin C promotes degradation of human cationic trypsin: identity

with Rinderknecht’s enzyme Y. Proc Natl Acad Sci U S A 2001;104:11227–11232.

18. Felderbauer P, Hoffman P, Einwachter H, et al. A novel mutation of the calcium sensing receptor

gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations. BMC

Gastroenterol 2003;3:34.

19. Brand H, Diergaarde B, O’Connell MR, et al. Variation in the gamma-glutamyltransferase 1 gene

1392

and risk of chronic pancreatitis. Pancreas 2011;40:1188–1194.

20. Whitcomb DC. Genetic risk factors for pancreatic disorders. Gastroenterology 2013;144:1292–1302.

21. Apte MV, Haber PS, Darby SJ, et al. Pancreatic stellate cells are activated by proinflammatory

cytokines: implications for pancreatic fibrogenesis. Gut 1999;44:534–541.

22. Shek FW, Benyon RC, Walker FM, et al. Expression of transforming growth factor beta 1 by

pancreatic stellate cells and its implications for matrix secretion and turnover in chronic

pancreatitis. Am J Pathol 2002;160:1787–1798.

23. Bockman DE, Buchler M, Malfetheiner P, et al. Analysis of nerves in pancreatitis. Gastroenterology

1988;94:1459–1469.

24. Buchler M, Weihe E, Fries H, et al. Changes in peptidergic innervation in chronic pancreatitis.

Pancreas 1992;7:183–192.

25. Michalski CW, Shi X, Reiser C, et al. Neurokinin-2 receptor levels correlate with intensity,

frequency, and duration of pain in chronic pancreatitis. Ann Surg 2007;246:786–793.