Small Duct Chronic Pancreatitis Research Articles

CLINICAL COURSE OF MEDICALLY MANAGED PATIENTS WITH LARGE AND SMALL DUCT CHRONIC PANCREATITIS.

Pancreatic duct obstruction is the primary indication for endoscopic and/or surgical therapy in patients with chronic pancreatitis (CP). However, the clinical course of medically managed patients in relation to pancreatic duct obstruction is largely unknown. This was a retrospective cohort study of medically managed CP patients. We classified patients based on pancreatic duct obstruction from a stricture or stone using cross-sectional imaging (i.e., large vs small duct CP). We compared prevalence of diabetes and exocrine insufficiency (EPI) between subgroups at inclusion and investigated risk of new onset diabetes, EPI, and all-cause mortality over a follow-up period of 5 years. Changes in pancreatic morphology were studied in patients who underwent follow-up imaging. A total of 198 patients (mean age 58 ± 12 years, 70% male, 60% alcoholic aetiology, 38% large duct CP) were evaluated. At inclusion, patients with large vs small duct CP had a higher prevalence of both diabetes (43% vs 24%, P=0.004) and EPI (47% vs 28%, P=0.007). There was an increased risk of new onset EPI in patients with large duct CP (hazard ratio 1.72; 95% CI [1.05-2.80], P=0.031) and higher rates of pancreatic atrophy (P<0.001). No differences between groups were observed for new onset diabetes and all-cause mortality. Conversion from small to large duct CP or vice versa during follow-up was observed in 14% of patients. In a medically managed cohort of patients, large duct CP was associated with increased risk of EPI and pancreatic atrophy compared to small duct CP.

369 Cost-Effectiveness of Total Pancreatectomy With Islet Cell Autotransplantation for the Treatment of Small Duct Chronic Pancreatitis

Introduction: Total pancreatectomy and islet cell autotransplantation (TPIAT) has gained popularity for managing chronic pancreatitis (CP), but a cost-benefit assessment has not been scientifically performed. We hypothesized that TPIAT decreases long-term resource utilization and improves quality-of-life, justifying the initial costs and risks of the procedure. Methods: From 1999-2013, 46 patients with small duct CP and detailed treatment and outcomes data in the perioperative period (12 months before and after TPIAT) were analyzed. These data populated aMarkovmodel comparing ongoingmedical management versus TPIAT for small duct CP. The surgery cohort included perioperativemortality and complication rates, while CT imaging, insulin use, morphine equivalent (MEQ) and endoscopic procedure (EGD, EUS, ERCP) and readmissions were used in both surgical and medical cohorts. Survival (quality adjusted life years, QALY) and cost (based on Medicare payment, 2013 US$) were discounted at 3% per year. Results: Median patient age was 36 years (range = 15-61) with a predominance of females (n=29, 63%). The etiologies of CP were primarily idiopathic (n=30, 65%) followed by genetic (n=12, 26%). In the 12 months prior to TPIAT (medical management cohort), annual mean per patient hospital admissions were 1.6 (range = 0-11), endoscopic procedures 1.3 (range = 0-6), and imaging (CT/MRI) 1.3 (range = 0-4). In the surgical cohort there were no perioperative deaths, with complication and 30-day readmission rates of 41% and 37%, respectively. 1 year after TPIAT, annual mean per patient admissions, endoscopic procedures and imaging had decreased to 0.9 (range = 0-4), 0.4 (range = 0-2) and 0.9 (range 0-5), respectively. Furthermore, monthly narcotic use in the surgical cohort decreased from 138 to 37 MEQ (p=0.012). Cost and survival for the TPIAT versus continued medical management were $153,576/14.9 QALYs and $196,042/11.5 QALYs, respectively. Sensitivity analyses with variable perioperative mortality rates, quality of life adjustment and TPIAT payment did not substantially change the cost-effectiveness analysis. Conclusions: In patients with refractory small duct CP, TPIAT is associated with both decreased cost and increased quality-adjusted survival. Because TPIAT is a cost-effective treatment for small duct pancreatitis, tertiary care centers should look for opportunities to increase the use of TPIAT, and insurers should more enthusiastically embrace its use.

Modified duval procedure for small-duct chronic pancreatitis without head dominance.

In the case of small-duct chronic pancreatitis, surgery for pain relief is broadly divided into resection and drainage procedures. These procedures should be selected according to the location of dominant lesion, diameter of the pancreatic duct and extent of the disease. The appropriate procedure for the treatment of small-duct chronic pancreatitis, especially small-duct chronic pancreatitis without head dominance, remains controversial. We developed the modified Duval procedure for the treatment of small-duct chronic pancreatitis without head dominance and determined the efficacy of this procedure. We retrospectively studied 14 patients who underwent surgical drainage with or without pancreatic resection for chronic pancreatitis with small pancreatic duct (<7mm) without head dominance. These patients were divided into 2 groups; the modified Puestow procedure group and the modified Duval procedure group. No complications occurred in the modified Duval group. In the modified Puestow procedure group, complete and partial pain relief were observed in 62.5%, and 37.5% of patients respectively. In contrast, complete pain relief was observed in all the patients in the modified Duval procedure group. Our modified Duval procedure is useful and should be considered the appropriate surgical technique for the treatment of small-duct chronic pancreatitis without head dominance.

70 Lessons from the Secretin Stimulation Test: S-MRCP May Not Be the Best Test to Diagnose Small Duct Chronic Pancreatitis

70 Lessons from the Secretin Stimulation Test: S-MRCP May Not Be the Best Test to Diagnose Small Duct Chronic Pancreatitis

Small Duct Chronic Pancreatitis and the Results of Endoscopic Therapy Using Serial Stents

Small Duct Chronic Pancreatitis and the Results of Endoscopic Therapy Using Serial Stents

Long-term Follow-up in Small Duct Chronic Pancreatitis

A pancreatic duct diameter (PDD) ranging from 4 to 5 mm is regarded as "normal." The "large duct" form of chronic pancreatitis (CP) with a PDD >7 mm is considered a classic indication for drainage procedures. In contrast, in patients with so-called "small duct chronic pancreatitis" (SDP) with a PDD <3 mm extended resectional procedures and even, in terms of an "ultima ratio," total pancreatectomy are suggested. Between 1992 and 2004, a total of 644 patients were operated on for CP. Forty-one prospectively evaluated patients with SDP underwent a new surgical technique aiming at drainage of the entire major PD (longitudinal "V-shaped excision" of the anterior aspect of the pancreas). Preoperative workup for imaging ductal anatomy included ERCP/MRCP, visualizing the PD throughout the entire gland. The interval between symptoms and therapeutic intervention varied from 12 to 120 months. Median follow-up was 83 months (range, 39-117 months). A pain score as well as a multidimensional psychometric quality-of-life questionnaire was used. Hospital mortality was 0%. The perioperative (30 days) morbidity was 19.6%. Postoperative, radiologic imaging showed an excellent drainage of the entire gland and the PD in all but 1 patient. Global quality-of-life index increased in median by 54% (range, 37.5%-80%). Median pain score decreased by 95%. Twenty-seven patients (73%) had complete pain relief. Sixteen patients (43%) developed diabetes, while the exocrine pancreatic function was well preserved in 29 patients (78%). "V-shaped excision" of the anterior aspect of the pancreas is a secure and effective approach for SDP, achieving significant improvement in quality of life and pain relief, hereby sparing patients from unnecessary, extended resectional procedures. The deterioration of exocrine and endocrine pancreatic functions is comparable with that observed during the natural course of the disease.

Effect of NCPB and VSPL on pain and quality of life in chronic pancreatitis patients

To compare the effects of neurolytic celiac plexus block (NCPB) and videothoracoscopic splanchnicectomy (VSPL) on pain and quality of life of chronic pancreatitis (CP) patients. Forty-eight small duct CP patients were treated invasively with NCPB (n = 30) or VSPL (n = 18) in two non-randomized, prospective, case-controlled protocols due to chronic pain syndrome, and compared to a control group who were treated conservatively (n = 32). Visual analog scales were used to assess pain and opioid consumption rate was evaluated. In addition, the quality of life was measured using QLQ C-30 for NCPB and FACIT for VSPL. Although both questionnaires covered similar problems, they could not be compared directly one with another. Therefore, the studies were compared by meta-analysis methodology. Both procedures resulted in a significant positive effect on pain of CP patients. Opioids were withdrawn totally in 47.0% of NCPB and 36.4% of VSPL patients, and reduced in 53.0% and 45.4% of the respective patient groups. No reduction in opioid usage was observed in the control group. In addition, fatigue and emotional well-being showed improvements. Finally, NCPB demonstrated stronger positive effects on social support, which might possibly be attributed to earlier presentation of patients treated with NCPB. Both invasive pain treatment methods are effective in CP patients with chronic pain.

Chronic pancreatitis: controversies in etiology, diagnosis and treatment

The pathogenesis of idiopathic chronic pancreatitis remains poorly understood despite the high expectations for ascribing the pancreatic damage in affected patients to genetic defects. Mutations in the cationic trypsinogen gene, pancreatic secretory trypsin inhibitor, and the cystic fibrosis conductance regulator gene do not account for the chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis. Small duct chronic pancreatitis can be best diagnosed with a hormone stimulation test. Endoscopic ultrasonography can detect abnormalities in both the parenchyma and ducts of the pancreas. The true value of endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains to be fully defined and is under active investigation. It is not clear whether endoscopic ultrasonography is more sensitive for early structural changes in patients with small duct disease or is over diagnosing chronic pancreatitis. Pancreatic enzyme supplementation with non-enteric formulation along with acid suppression (H2 blockers or proton pump inhibitors) is an effective therapy for pain in patients with small duct chronic pancreatitis. The role of endoscopic ultrasonography-guided celiac plexus block should be limited to treating those patients with chronic pancreatitis whose pain has not responded to other modalities. Total pancreatectomy followed by autologous islet cell autotransplantation appears to be potential therapeutic approach but for now should be considered experimental.

Prevalence of gastroparesis in patients with small duct chronic pancreatitis.

The most common symptoms of chronic pancreatitis are abdominal pain, diarrhea, and weight loss. The abdominal pain has no consistent pattern, and nausea and vomiting commonly occur simultaneously. Gastroparesis may produce similar symptoms. These similar symptoms may cause diagnostic confusion, particularly with regard to patients with small-duct chronic pancreatitis, for whom diagnosis of chronic pancreatitis is most difficult. We have observed that coexistent gastroparesis may also interfere with the effectiveness of pancreatic enzyme therapy by failing to deliver proteases into the duodenum and therefore not restoring feedback control of pancreatic secretion. To estimate the prevalence of gastroparesis in patients with minimal-change chronic pancreatitis. Patients with chronic pancreatitis diagnosed on the basis of secretin test results but with otherwise normal pancreatic imaging (ultrasonographic or computed tomographic) findings who had also undergone a gastric emptying study were retrospectively identified. An abnormal secretin test value was defined as a peak bicarbonate concentration in pancreatic secretions of <80 mEq/L after secretin stimulation. Gastroparesis was defined as an emptying half-time greater than 90 minutes. Fifty-six patients were identified. Twenty-five of the 56 patients (44%) had concomitant gastroparesis and small-duct chronic pancreatitis. Twenty-four of these 25 were women, and 22 of the 25 had idiopathic small-duct chronic pancreatitis. In our referral population, gastroparesis is frequently seen in patients with small-duct chronic pancreatitis. For patients with small-duct disease whose abdominal pain does not respond to pancreatic enzyme therapy, clinicians should consider an evaluation for gastroparesis.

Quality of Life After Bilateral Thoracoscopic Splanchnicectomy: Long-Term Evaluation in Patients With Chronic Pancreatitis

We prospectively evaluated quality of life and visual analogue scale pain scores after bilateral thoracoscopic splanchnicectomy in 55 patients with small-duct chronic pancreatitis and abdominal pain. The perioperative morbidity rate was 11% and there were no perioperative deaths. Four late deaths occurred (7%), and three patients were lost to follow-up. Patients were divided into those who had prior operative or endoscopic interventions (N = 38) and those who did not (N = 17). Preoperatively there were no significant differences between the two groups with regard to age, sex, etiology, pain score, or narcotic use. Pain score, narcotic use, and symptoms scales improved significantly in both groups at 3 and 6 months postoperatively ( P < 0.0001). The group with no prior surgical or endoscopic intervention did significantly better initially ( P < 0.007), and the improvements in their quality-of-life and pain scores continued for the remainder of the study. In contrast, quality-of-life and pain scores in patients who had undergone prior surgical or endoscopic intervention returned to baseline by 12 months postoperatively and remained poor throughout the remainder of the study. Bilateral thoracoscopic splanchnicectomy appears to work best in patients who have had no prior operative or endoscopic interventions. ( J Gastrointest Surg 2002;6:845–854.)

Chronic pancreatitis

The pathogenesis of idiopathic chronic pancreatitis remains poorly understood despite the high expectations for ascribing the pancreatic damage in affected patients to genetic defects. Neither mutations in the cationic trypsinogen gene nor mutations of the cystic fibrosis conductance regulator gene account for the chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis. Attempts to find an autoimmune basis for the pancreatitis in these patients have not been very successful. The diagnosis of small duct idiopathic chronic pancreatitis remains a great source of frustration for clinicians. Such patients with negative results of radiographic studies often cannot be diagnosed unless a hormone stimulation test such as a secretin test is performed. Although the porcine biologic form of secretin, which has been used to diagnose chronic pancreatitis, became unavailable because of widespread use in the treatment of children with autism, a synthetic form of porcine secretin has now been approved by the US Food and Drug Administration and is available. The true value of endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains to be fully defined. Endoscopic ultrasonography is becoming the test of choice in detecting radiographic abnormalities in both the parenchyma and ducts of the pancreas. Endoscopic ultrasonography-guided celiac plexus block can be performed relatively easily and very safely. It can provide excellent short-term pain relief in some patients, but reliable predictors of which patients will be successful with this therapy are not yet available. Because long-term follow-up data on the use of endoscopic ultrasonography in this respect are not available, and because the pain of chronic pancreatitis is, indeed, chronic, the role of endoscopic ultrasonography-guided celiac plexus block should be limited to treating those patients with chronic pancreatitis whose pain has not responded to other modalities.

Pancreatoduodenectomy for Chronic Pancreatitis

For patients with head-dominant, small-duct chronic pancreatitis who require operative intervention, pancreatoduodenectomy can be performed safely and affords satisfactory pain relief in most. Retrospective case series. Follow-up was complete in 86% of study subjects (average, 6.6 years). Tertiary care center. Among 484 consecutive cases of chronic pancreatitis treated surgically from January 1976 through April 1997, 105 (22%) in which pancreatoduodenectomy was performed were reviewed with regard to criteria for selection, operative procedure, postoperative course. and long-term outcome. The main outcome measure was degree of pain relief. Additionally, late mortality, cause of death, the presence of endocrine and exocrine insufficiency, and quality of life were recorded. There were 72 men (69%) and 33 women (31%) with a mean age of 51 years (range, 24-77 years). The cause of chronic pancreatitis was alcohol related in 58 patients (55%) and idiopathic in 41 (39%). Clinical manifestations included abdominal pain in 86 patients (82%), obstructive jaundice in 27 (26%), and vomiting in 11 (11%). Suspicion of malignant neoplasm was a concern in 67 patients (64%). Operative morbidity was 32%, and mortality, 3%. Mean hospital stay was 16 days (range, 12-82 days). Survival was significantly lower than that of age-matched controls. Among 66 patients with preoperative pain, pain relief was achieved in 59 (89%); it was complete in 44 patients (67%) and partial in 15 (23%). Operation resulted in a significant increase in patients with normal functional status (73 patients [81%] vs 51 [49%]; P<.001). Forty patients (48%) had diabetes. Steatorrhea was observed in 39 patients (43%), while weight maintenance or gain occurred in 59 (66%). Pancreatoduodenectomy achieves pain relief and good quality of life in a large percentage of selected patients with small-duct, head-dominant disease and is especially useful when a malignant neoplasm must be excluded. Morbidity and mortality are acceptable in experienced hands. Onset of diabetes and steatorrhea, while reflecting the natural course of the disease, is likely accelerated by pancreatoduodenectomy.

Distant processing of pancreas islets for autotransplantation following total pancreatectomy

background: Small duct chronic pancreatitis is associated with intractable pain and failure to thrive, usually unresponsive to conventional management approaches. Total pancreatectomy is considered after failure of medical intervention. The major morbidity following total pancreatectomy is diabetes mellitus with its associated complications. This adverse outcome can be mitigated through autotransplantation of islets recovered from the pancreatectomy specimen. This approach has been limited historically owing to the absence of an on-site islet processing facility. We present the results from 5 pancreatectomized patients whose islets were prepared 1,500 miles away. methods: Five patients (4 women, 1 man, average age 42 years) who failed medical therapy and were not candidates for longitudinal pancreaticojejunostomy underwent total/completion pancreatectomy (4 total, 1 completion) for intractable symptoms from idiopathic small duct chronic pancreatitis. The resected pancreata were preserved in ViaSpan solution and were transferred to an islet processing laboratory by commercial airliner and returned. The dispersed pancreatic islet tissue was infused into a portal vein tributary through an operatively placed catheter after systemic heparinization. results: All 5 patients experienced complete relief from pancreatic pain; 2 had significant residual discomfort from underlying Crohn’s disease. Three of the 5 patients had minimal or no insulin requirement after autotransplantation (median follow-up of 23 months); 1 patient continued with glycemic control difficulties related to Crohn’s disease. One patient died 17 months following autotransplantation from an unrelated pneumonia. conclusion: Total pancreatectomy with autologous islet transplantation can offer patients with idiopathic small duct chronic pancreatitis pain relief without the sequelae of diabetes mellitus and can be performed without an on-site islet processing facility. All patients undergoing total/completion pancreatectomy should be considered candidates for this procedure.

Incapacitating pain of chronic pancreatitis: a surgical perspective of what is known and what needs to be known

Gastrointest Endosc 1999;49:S85-9.

Longitudinal V-shaped excision of the ventral pancreas for small duct disease in severe chronic pancreatitis: prospective evaluation of a new surgical procedure.

The technique of longitudinal V-shaped excision of the ventral pancreas for small duct chronic pancreatitis is presented and its efficacy in terms of pain relief and improvement of quality of life is evaluated. Small duct chronic pancreatitis has been regarded as a classical indication for more or less extensive resection, in which the therapeutic success of pain relief is offset by the considerable risk of significant perioperative mortality and morbidity and the burden of substantial loss of pancreatic function. Thirteen patients with severe pain who were diagnosed with small duct pancreatitis (defined as maximal Wirsungian ductal diameter of 2 mm) underwent longitudinal V-shaped excision of the ventral pancreas. In addition to routine pancreatic workup, a multidimensional psychometric quality-of-life questionnaire and a pain score were used. Assessment of exocrine and endocrine function included fecal chymotrypsin and the pancreolauryl test as well as oral glucose tolerance, serum concentrations of insulin, C-peptide, and hemoglobin A1c. The interval between symptoms and surgery ranged from 12 months to 10 years (mean, 5.4 years). Median follow-up was 30 months (range, 12-48 months). There were no deaths. Overall morbidity was 15.4%. In 92% of patients, complete relief of symptoms was obtained. Median pain score decreased by 95%. Physical status, working ability, and emotional and social functioning scores improved by 40%, 50%, 67%,, and 75%, respectively. Global quality-of-life index increased by 67%. Occupational rehabilitation was achieved in 69% of patients. Exocrine and endocrine pancreatic function was well preserved. In small duct chronic pancreatitis, longitudinal V-shaped excision of the ventral pancreas is a safe and effective alternative to resection procedures. The new technique provides pain relief and improvement of quality of life, thus offering the benefit of a resection procedure without its burden.

Autologous Islet Transplantation to Prevent Diabetes After Pancreatic Resection

Background Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. Objective Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. Patients and Methods Of the 48 patients, 43 underwent total or near-total (>95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. Results One perioperative death occurred, Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received >300,000 islets, 74% were insulin independent at >2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = −0.52, p = 0.006) and the dispersion method (p = 0.005). Conclusion Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

Autologous islet transplantation to prevent diabetes after pancreatic resection.

Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.