Surgical treatment of chronic pancreatitis - a 14 years experience

Of the organ preserving proximal resections, six patients had Beger procedure and four had Frey operation. All patients had a favorable outcome with an adequate control of postoperative pain.
Rare cases of CP in the pancreatic body and/or tail can be successfully treated by distal pancreatectomy if the disease is confined to the pancreatic tail. In our series distal pancreatectomy with splenectomy was performed in 38 (25,33%) patients and only 4 patients had spleen preserving resection.
As shown in fig. 2 and 5, the number of resections decreased in the second half of the studied period as more conservative procedures were adopted. There was one case of laparoscopic distal resection with spleen preservation.

We had three patients which required different resections: one total pancreatectomy carried out 12 months after a drainage procedure for a pseudocyst, one near total pancreatectomy in a patient with previous splanchnicectomy and reccurence of pain (no pancreatic duct dilatation) and one central pancreatectomy. In this series we only had one case of malignancy developing in a chronic pancreatitis patient.
3. By-pass procedures
Because of the low percent of minimally invasive procedures (endotherapy -papillotomy, stone removal, dilation of strictures and/or stent implantation) carried out in our hospital there was a high number of by-pass procedures.
· Derivations for pseudocysts (65 patients):
a. Internal - digestive diversion (cystgastrostomy - 14, or Roux-en=Y cystjejunostomy - 33) 47 patients;
b. External drainage 18 patients.
· Procedures for jaundice 40 patients;
· Derivations for upper GI stenosis (9 patients).
4. Denervation alone procedures
c. 5 left thoracoscopic splanchnicectomies;
d. 2 bilateral thoracoscopic splanchnicetomies;
e. 1 celiac plexus block.
One patient required a biliary-digestive diversion after Frey procedure (2 years).
Most patients underwent cholecystectomy as part of their operative procedure. Ten patients underwent a second surgical procedure during a separate hospitalization. Except the three cases mentioned above, there was one cases of spleen preserving distal pancreatectomy after a cystjejunostomy, two redo gastrojejunostomy and two hepaticojejunostomy after PD, one splanchnicectomy after Whipple procedure (7 years) and left and right splanchnicectomy 4 months away (pain free after the last procedure).
The overall complication rate was 22 %, with no significant differences being observed for the different procedures. Twelve patients required reoperation in the immediate post-operative period with the indications: hemorrhage in 9 patients, abscess or intra-abdominal sepsis, as shown in Table 2 .
Length of hospital stay average was 16,4 days with 18,21 days in the resected group and 14,15 days for the non-resected group.
Seven deaths occurred in the series for an overall perioperative mortality rate of 2,64%, with three deaths in the resected group 2% ( 3/150), and four deaths in the non-resected group. (Table 3 ) Three of the seven deaths occurred in patients requiring reoperation for abscess, with 2 cases of postoperative pneumonia, one case of massive pulmonary trombembolism in the third postoperative day and one case of disseminated intravascular coagulation in a patient that first presented with GI hemorrhage from a SMA fistula that required emergency operation. Also we had 4 cases of emergency operation for perforated pancreatic pseudocysts with peritonitis, all with favorable outcome.
Survival information was available for 137 patients (69%), all operated after 2002. The median follow-up was 40 months, with a mean follow-up of 39, 37 months. For this cohort of patients, the 5- year actuarial survival rate was 74, 7%. The survival curve is depicted in Fig. 6.
Of the twenty seven late deaths (19, 7%) eleven occurred in alcoholic patients.
No difference in survival was observed for patients undergoing resection or other derivative procedure. (Fig. 7)
Of the 110 patients alive at the time of the survey, 85 responded to the Quality of Life Questionnaire (QLQ) regarding status of pain, diabetes, the necessity for enzyme supplementation and employment.
Patients showed dramatic improvement after surgery on all questions regarding subjective perception of quality of life, especially pain (mainly in the resected group). However, surgery often exacerbated the pathophysiologic consequences of chronic pancreatitis. (Fig. 8) A portion of patients developed insulin-dependent diabetes and required pancreatic exocrine supplementation after surgery. In addition, the rate of unemployment increased after surgical intervention, all these more frequently observed in the resected group (Fig. 9).

Discussion
CP is a slow process evolving clinically in two stages, i.e. early-stage CP with recurrent clinical acute pancreatitis, and late-stage CP with exocrine insufficiency, diabetes and calcification. The pathogenesis of chronic pancreatitis and predictors of long-term success after operative treatment of the disease are poorly understood.
The incidence and prevalence of CP varies between different countries. Most European studies show comparable incidence and prevalence rates around 8 per 100,000 and 28 per 100,000, respectively. (12-14) Higher rates have been reported in other countries, for example in Japan (incidence of 14.4 per 100,000 inhabitants and a prevalence of 35.5 per 100,000 in 2002 (14)). Interestingly, these numbers show a marked increase compared to a 1999 survey in the same country. (15)
The etiologic factors associated with CP are commonly summarised using the TIGAR-O classification meaning they can be Toxic–metabolic (e.g. alcohol and tobacco), Idiopathic (early-onset; late-onset and tropical), Genetic (mutations in the PRSS1, CFTR, or SPINK1 gene), Autoimmune, Recurrent and severe acute pancreatitis or Obstructive (e.g. pancreas divisum or pancreatic neoplasm; reviewed in Stevens et al (16)). In Western industrialized countries alcohol over-consumption is the leading cause of CP (varying between 65% and 90% among different studies) followed by idiopathic (20–25%) and other rare aetiologies (5%). (13;14;17-20)
In the current series, the cause was thought to be alcohol related in 66 % of patients, with the cause being idiopathic in an additional 32, 5%. The disease is frequently the result of chronic alcohol abuse, and patients are often addicted to narcotics at the time of presentation to a surgeon. According to a recently established hypothesis, chronic pancreatitis results from relapsing acute pancreatitis that causes interstitial acinar and fatty tissue necrosis, inducing a perilobular fibrosis, and consequently results in stenosis and dilatations of the pancreatic main duct. In about 30%–50% of the patients with chronic alcoholic pancreatitis an inflammatory mass in the head of the pancreas develops, leading to a head enlargement. Besides local complications (such as stenosis of the pancreatic main duct, the common bile duct or the duodenum) the area of inflammation leads to a pancreatitis-specific neuritis which contributes to the clinical pain syndrome via local release of pain hormones, such as substance P and CGRP (21;22). Although conservative management may be successful in some patients, the remission of pancreatic pain is uncommon and not consistently observed. (23). The medical management of chronic pancreatitis remains a difficult therapeutic problem.
Notably, partial to complete pain relief is a common feature in 50% - 80% of patients with late-stage CP irrespective of surgery and about 50% of CP patients never need surgery (or endoscopic intervention). (24;25) The origin of pain in CP is incompletely understood and likely multifactorial. Contributing factors are neuro-immunological interactions, (21;26-28) inflammation, increased intraductal and/or intraparenchymal pressure, (29) pancreatic duct stenosis/dilation, and ischemia.
Complications of CP arise from the formation of pseudocysts, calculi (pancreaticolithiasis) and inflammatory masses which can lead to portal or splenic vein thrombosis, obstruction of the duodenum, the pancreatic duct and/or the common bile duct with cholestasis, jaundice and cholangitis. Nevertheless, anatomical, embryological and pathomorphological findings point to the head of the pancreas as a “pacemaker” of the disease, as postulated by Beger and Longmire (30;31). Excision of the body and distal pancreas used to be a commonly performed procedure during 1960-1970, but, with the development of better imaging facilities it was noted that disease in the body and the tail is often secondary to disease in the head of the pancreas, thereby limiting its role. This procedure is still indicated when the disease is confined to the body and tail e.g., pseudocyst, failed pancreaticojejunostomy, non-dilated duct, pseudo-aneurysm and when there is suspicion of a malignant lesion in the body and tail.
The operative treatment selected is tailored to the individual patient’s overall health status, with consideration for disease severity and location, ductal anatomy, presence of complications, such as pancreatic duct disruption, biliary, duodenal and splanchnic venous obstruction.
Whether endotherapy or surgery is superior to treat symptoms in CP remained illusive until recently, when two prospective randomized clinical trials addressed this question. Dite et al (32) included 140 patients into their study, of which 72 were randomized either to surgery (resection 80%, drainage 20%) or endotherapy (sphincterotomy and stenting 52% and/or stone removal 23%). While after one year pain relief was similar in both groups, at 5 years more patients who had undergone surgery had complete absence of pain and greater weight gain than endoscopically treated patients (34 vs 15% and 47% vs 29%, respectively) . Cahen et al (33) reported even more convincing results: of 39 randomised patients 19 underwent endotherapy (16 after lithotripsy) and 20 surgical drainage by pancreaticojejunostomy.
Current indications for surgery are:
· Intractable pain;
· Suspicion of malignant neoplasm (CA19-9, PET-SCAN sensitivity 91%);
· Ductal stenosis;
· Common bile duct stenosis;
· Upper GI stenosis;
· Pseudo-aneurysms or vascular erosions not controlled by radiological intervention.
Depending on the morphology of the lesions, two principal types of surgical interventions are available for CP patients: drainage and resection procedures
1. Drainage:
· A –> Puestow, Partington-Rochelle
2. Resection:
· Proximal resection
- B -> Whipple, Traverso
- C -> Beger
- D -> Frey
- E -> Berne procedure
- F -> Izbicki operation
· Distal resection
- With or without splenectomy
· Total or subtotal pancreatectomy with or without duodenum/spleen preservation.
Drainage procedures
The most common drainage procedure is the side-to-side pancreaticojejunostomy as described by Partington-Rochelle. (34) However, a number of patients are suffering from additional problems due to an inflammatory mass in the head of the pancreas, e.g. common bile duct stenosis, duodenal stenosis, and vascular stenosis with compression of the portal vein and portal hypertension. Consequently, long-term results of drainage procedures are rather discouraging. Whereas early postoperative results were good, they had deteriorated during the following 5 years to 55% good or fair pain relief (35). In our series we only had 3 cases of drainage using the modified Puestow procedure as described by Partington and Rochelle, the patients having a significant improvement concerning their pain status in the long-term follow-up. All three patients had documented dilatation of the Wirsung duct. The single use of a drainage operation is limited to patients without inflammatory mass in the pancreatic head, but with dilatation of the main pancreatic duct.
Proximal resection procedures
The classical pancreatic head resection procedures are the Whipple operation (PD) in which a duodenectomy, pancreatic head resection, partial resection of the extrahepatic bile duct as well as resection of the distal stomach is performed and the Traverso-Longmire pylorus-preserving pancreaticoduodenec-tomy (ppPD). Resection procedures are indicated in the presence of an inflammatory mass of the pancreatic head irrespective of the duct diameter. The Whipple PD was the standard surgical resection procedure for CP of the pancreatic head. Although it was associated with high postoperative morbidity and mortality after its introduction, it is now a safe and efficient procedure, especially at high volume centers where mortality rates for PD in CP patients are less than 3%. (36)
However, the Whipple procedure, although successful in achieving the goal of pain relief and removing complications to neighbouring organs, is associated with poor long-term results in CP patients and morbidity rates range between 30% and 50%. (36) Especially with regard to quality of life (QoL), endocrine and exocrine as well as digestive function PD has shown disappointing results compared to other resection procedures and is thus no longer the operation of choice in patients with CP. To address the drawbacks of the Whipple procedure, the pylorus-preserving pancreaticoduodenectomy was introduced. (37) In preserving the stomach, the pylorus and the first part of the duodenum, the ppPD was thought to protect against delayed gastric emptying (DGE), gastric dumping, and bile-reflux gastritis. Results, however, are mixed concerning the actual benefits of this procedure. (1; 5; 30; 36; 37)
One should keep in mind, however that both procedures, the PD as well as the ppPD, were originally developed to treat malignant diseases of the pancreatic head and the periampullary region, whereas CP is a benign disorder of the pancreas in which radical resection might be counterproductive.
In our series the choice of procedure was based on presenting symptoms, radiological findings and intraoperative findings. If a patient had no evidence of pancreatic ductal dilatation, an ablative procedure such as pancreaticoduodenectomy or distal pancreatectomy was preferred, with PD being performed for disease thought to be centered in the pancreatic head. Ablative procedures were performed when malignancy was suspected.
Most resections were Whipple, 47, 33 % (71) of all patients resected, 5 procedures including portal vein resection; we also had an increasing number of ppPD, especially after 2002, with 18 procedures, compared to 6 performed in 2000-2001. Portal vein resection was performed whenever there was a suspicion of malignancy with vascular invasion, or in cases when dissection of the portal vein was too difficult because of the inflammatory pancreatic tissue and there was a risk of massive bleeding form disruption of the vein.
The duodenum preserving pancreatic head resection introduced by Beger et al (DPPHR) (31) was the first resection procedure specifically designed for CP. In resecting the pancreatic head subtotal and preserving the body and tail of the organ it can alleviate common bile duct obstructions, pancreatic duct stenosis and obstruction of the retropancreatic vessels by an inflammatory pancreatic head mass. Several studies have established that the DPPHR is a safe procedure (mortality rates 0–2%, morbidity rates between 15% and 54%) resulting in long-term pain relieve in approx. 80% of patients (at 5 years follow-up) and a low long-term endocrine insufficiency rate. (1;5) Furthermore, in terms of quality of life 69% of patients were professionally rehabilitated after DPPHR and in 72% of patients the Karnofski index was between 90% and 100%. (38). Still, this procedure is preferred by the German authors, while the ppPD is the procedure of choice for the American authors. (39-41). The Beger technique (DPPD) was first introduced in Romania by Popescu et al (42) and it was performed in 6 patients in this series.
The Frey procedure has been introduced primarily as a drainage procedure with an additional minor resection of part of the pancreatic head and is therefore a modified Partington-Rochelle procedure, which leaves the major part of the inflammatory mass in the pancreatic head. In contrast to Beger operation with a weight of the resected tissue of about 25–45 g, the Frey procedure is a coring out of part of the pancreatic head with an average specimen weight of less than 6 g (43). In our series the number of Frey procedures was limited to four patients (44), one of which required re-operation after 2 years for decompression of the main bile duct also. Consequently this procedure is not effective against cholestasis, because the resection is not appropriate to decompress the common bile duct in the intra-pancreatic segment.
The above mentioned procedures are suited to treat CP originating in the head of the pancreas which is by far the most common location of CP.
Distal resection procedures
Distal resections are indicated when the disease is confined to the body and tail e.g., pseudocyst, failed pancreatico-jejunostomy, non-dilated duct, pseudo-aneurysm and when there is suspicion of a malignant lesion in the body and tail (a predominant inflammatory lesion that is located in the left pancreas). Splenic preservation may be possible in 20-34% of patients, with or without ligation of the splenic vessels. (39) (6) (45) (46).The procedure described by Warshaw, in which spleen preservation is achieved by preservation of the short gastric vessels has an early mortality of 0- 4% (47) and pain relief is 70-88%. About 20% develop diabetes in the early postoperative period. (47) (6)
We performed 42 cases of distal pancreatectomy, 4 with preservation of the spleen, for disease located in the pancreatic tail, mainly presented as large pseudocysts or inflammatory mass of the pancreatic tail. (48) A concomitant splenectomy was unavoidable in the majority of patients because of dense fibrosis precluding the isolation of the splenic vessels and also because of the suspicion of malignancy.
Total or subtotal resections
The indications for total or near total pancreatectomy are involvement of the entire pancreas, a small duct or a failure of other procedures, and the willingness to accept diabetes for relief of pain.(47). Total or near total pancreatectomy is the surest way to relieve the pain of chronic pancreatitis but is rarely applied because the metabolic consequences are severe (when more than 95% of a gland is removed, all patients become insulin dependent). Two series by Braasch et al and Cooper et al studied total pancreatectomy in CP patients yielding, however, poor results concerning the number of patients acquiring pain relief (54% and 84%, respectively) underlining the complexity of treating pain in CP. (49) The most serious complications of diabetes in individuals pancreatectomized because of chronic pancreatitis, however, are in those with an alcoholic origin. They are usually non-complying patients or they manage their diabetes poorly, and hypoglycemia from insulin reactions are as much a threat as ketoacidosis. (50) So TP must be undertaken only in selected patients and with the acceptance of diabetes as a tradeoff for pain relief and for the chance to discontinue narcotics.
Islet autotransplantation offers a valuable addition to surgical resection of the pancreas for the treatment for CP and although there is a notable decline in islet function after islet auto transplant, there is still evidence of significant long-term insulin secretion and possible protection against diabetic complications. (51; 52)
Only one patient in this series was treated with total pancreatectomy. The patient had a previous cystjejunostomy for pseudocyst of the distal pancreas, now with recurrence of the pain. The CT scan and MRI showed diffuse inflammation of the pancreas with multiple strictures of the Wirsung duct. The pathology report revealed cystadenocarcinoma of the pancreas, with poor results concerning the quality of life after surgery.
Also, there was one case of subtotal resection of the pancreas (95% pancreatic tissue resected) with preservation of the spleen. This was a young patient, with idiopathic chronic pancreatitis, previously diabetic insulin dependent. His main symptom was pain not alleviated by narcotics or left splanchnicectomy, no dilatation of the Wirsung, persistent high levels of CA 19-9. The postoperative result was a significant reduction of pain with no need for narcotics with good control of the diabetes –single insulin dose/day- and exocrine pancreatic enzyme substitution (Kreon). (53)
Duodenum- and spleen-preserving total pancreatectomy has a role in selected patients with medically intractable pain and complications resulting from chronic pancreatitis. The results showed successful outcome with increased quality of life, particularly in reducing hospital admission rates, promoting weight gain, improving pain relief and reducing analgesic consumption. (54)
Minimally invasive procedures for the treatment of pain were designed for patients who have no dilatation of the Wirsung duct and those who may not be candidates for major abdominal surgery. (50) Ideal treatment options would have a limited risk of drug addiction and would leave the functional capacity of the gland unaffected. The rationale for neurotomy in this symptom is based on the fact that sensory nerves from the pancreas run along the hepatic, splenic, and superior mesenteric arteries to the semilunar ganglion, where they become incorporated in the greater and lesser splanchnic nerves, which arise from the 5th to the 11th thoracic ganglia on both sides of the vertebrae. Afferent sympathetic fibers follow the same route, whereas extrinsic parasympathetic innervation is supplied by the vagus. Thoracoscopic splanchnicectomy has targeted the greater splanchnic nerve. In our series we had 5 cases of left thoracoscopic splanchnicectomy and two cases requiring a bilateral procedure, with good pain control. It is well known that pain relief with minimally invasive procedures (nervous block) has better results in pancreatic cancer patients (90%) compared to CP (70%) which is probably due to the difference in survival, hence follow-up period is longer in CP patients. Also, it is important to know that in CP patients the procedure usually needs to be bilateral. (56).
In regards to postoperative morbidity our results are comparable with other series (7;9;17;39). Our late results are limited in value due to the low number of patients responding to the QLQ questionnaire (85/265). In this series, most patients had a marked reduction in pain immediately after surgery which was maintained. This was associated with a significant reduction in the use of all types of analgesia including opiates, and by 2 years after surgery almost two thirds of patients were taking no regular analgesia.
Left resection has been associated with a high incidence of IDDM (Insulin Dependent Diabetes Mellitus) between 32 and 72% (55) after surgery perhaps because of the said relative preponderance of islets of Langerhans within the body and tail of the pancreas. Standard pancreaticoduodenectomy is associated with loss of the normal enteroinsular axis and typically results in a 20 % increase in the incidence of IDDM. In contrast, Beger and colleagues (38) reported no significant deterioration in glucose metabolism after duodenum-preserving resection of the head of the pancreas. Higher levels of exocrine insufficiency have also been reported after left resection compared with the Whipple operation and minimal exocrine disturbance occurred after duodenum-preserving resection of the head of the pancreas. The preservation of endocrine and exocrine function corresponds to the improvement in nutritional status after surgery, with Beger et al (38) reporting an increase in weight in 80 per cent of patients after duodenum-preserving resection of the head of the pancreas. In this series, however, all types of procedures were associated with an increase in IDDM and an increase in exocrine insufficiency.
Our series is comparable with others published in terms of number of patients, surgical procedures and postoperative results. Multiple studies demonstrate that pancreatic surgery for benign disease can be performed safely. (39; 40)
The data we present suggests that surgery for chronic pancreatitis can be performed safely, with acceptably low morbidity and mortality. As shown in our study, the number of organ preserving interventions has increased in the recent years due to the introduction of new techniques (42;44;56) and the on growing experience of our surgeons. This led to increasingly better results in terms of blood loss, duration of surgery and postoperative immediate complications. The mortality registered in our study 2, 64% is comparable with those published by other authors with large experience in CP surgery. (7;10;17;23;41). Despite increases in endocrine and exocrine insufficiency, patients enjoyed acceptable long-term survival following operative intervention, with improved quality of life. The current analysis evaluates pain control and other subjective aspects of quality of life in a disease specific and standardized fashion, with highly significant improvement reported in all quality-of-life measures.

Conclusions
The goals of surgical management of chronic pancreatitis are control of pain and preservation of exocrine and endocrine function. The choice of surgical therapy should be based on the individual’s symptom complex and pattern of disease on radiographic studies. With careful patient and procedure selection, surgery is associated with improved quality of life and long-term survival and remains an excellent option for patients with chronic pancreatitis.

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