Minimal Change Chronic Pancreatitis

Posted by Robin H. (CA) on August 23, 2007 at 12:46:37:


DEAR LISTMATES: Here is a written response by Dr. Sutherland himself and an article by Dr. Sutherland's research group about "minimal change CP". It clearly states that you can have "microscopic CP" that causes horrible pain, yet does not yield positive diagnostic results on an EUS. I am posting this in response to recent posts that have suggested that THERE IS A PREVAILING MOVEMENT TO PUSH THE TP/ICT and that it is better to wait for emerging diagnostic criteria on an EUS, which for those patients like me, who had "Minimal Change CP", would have resulted in a less than beneficial islet cell yield.
I enclose an excerpt (below) from an email from Dr. Sutherland himself regarding this matter.
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There are articles on minimal change CP that I will send you the references. We also have an abstract showing that the traditional view that an EUS has to show 5 of 9 criteria for CP to be diagnosed is not correct, even one criteria has been associated with documented CP under the microscope.

Many patients have had acute relapsing pancreatitis for years, pain free between episodes, and now began go have constant pain and go on daily narcotics. At 6 months of narcotics and pain getting worse, what would one propose even if imaging shows only minimal changes.

The fact is that 95% of our patients say they are better off, whether done early or late, and all done late wish they had done it earlier. Ann Marie can give you names of patients who might be interested n chiming in in.

Attached is an abstract summarizing outcomes with TP/IAT at Minnesota, along with a review article we have written on the topic, and you should feel free to share these on the web.

Pancreas Club, Inc. 41st Annual MeetingSunday, May 20, 2007Washington, DC

ABSTRACT FORM

Abstract Revised: July 31, 2007
Title of abstract: Pancreatectomy and autologous islet transplantation: a study of long-term outcomes
Authors: Annelisa M. Carlson MD, Juan J. Blondet MD, Angelika Gruessner PhD, Melena Bellin MD, Greg Beilman MD, David E.R. Sutherland, MD, PhD
Institution: University of Minnesota, Departments of Surgery and Pediatrics
Presentation of abstract, if accepted: (please choose one)
0 Oral presentation 0 Poster presentation x Oral or Poster presentation
Corresponding Author: Annelisa M. Carlson, MD
Presenting Author: David E.R. Sutherland, MD, PhD
Mailing address: Department of SurgeryUniversity of Minnesota Medical SchoolMMC 280, 420 Delaware Street S.E.Minneapolis, MN 55455
TEL: 612-625-7600 FAX: 612-624-7168 EMAIL: dsuther@umn.edu

Program Chairman: William H. Nealon, MDUTMB Department of Surgery6.112 John Sealy HospitalGalveston, TX 77555-0544Tel: (409) 772-6582 Fax: (409) 747-2253E-mail: wnealon@utmb.edu
For more information, please visit our website at www.pancreasclub.com.
ABSTRACT(Not to exceed 1 full page. May include graphs, charts, and/or images.)


Pancreatectomy and autologous islet transplantation: a study of long-term outcomes Annelisa M. Carlson, Juan J. Blondet, Angelika Gruessner, Melena D. Bellin, Greg Beilman, David E.R. Sutherland Departments of Surgery and Pediatrics, University of Minnesota Minneapolis,

MN 55455
INTRODUCTION
Pancreatectomy with autologous islet transplantation (TP/IAT) is performed to alleviate pain and improve quality of life of patients with severe chronic pancreatitis who have failed prior medical and oftentimes surgical therapies; the islet autograft is performed with a goal of preventing post-surgical diabetes.

The aim of this study was to examine long-term outcomes with regard to pain, quality of life, and graft function.

METHODS
We performed 188 pancreatectomies with islet autografts (25 children, 5-18 yrs) during the period from Feb,1977-Sep,2006. Medical records were reviewed, and patients were contacted to complete a telephone survey. Patients were classified as having full graft function if they reported complete insulin-independence;
partial graft function if on a once-daily long-acting insulin;
and graft failure if on a full diabetic regimen.

Islet function rates were computed using Kaplan-Meier estimates.RESULTSIn the entire series, patient survival rates after TP/IAT were 98% at 1 yr, 92% at 3 yrs, 87% at 5 yrs and 73% at 10 years. Eighty-three adult patients were able to be reached for the telephone survey (71% female, 29% male; mean age 37 +/- 10 years), at a median of 42 months post-TP/IAT (range 2-330 months). Etiologies of pancreatitis included idiopathic (60%), alcohol (17%), pancreas divisum (12%), biliary (7%), and hereditary (5%). Total pancreatectomy was performed in 68%, partial or distal in 11%, completion in 17%, and near-total in 4%.
One-hundred percent of adult patients stated they had pancreatitis pain prior to undergoing TP/IAT;
93% stated they were on daily narcotics prior to TP/IAT.
Ninety-four percent reported an improvement in pain following the procedure, and 49% of patients have been able to discontinue daily narcotic pain medications.
Ninety-six percent of patients would recommend the procedure.
Eighty-five percent of adult patients stated their quality of life has significantly improved compared to the time before their TP/IAT, while 8% state their quality of life is the same, and 5% (n=4) stated it is worse.

In the overall series, full and partial graft function was seen in 74% of adult patients at 1 year and 70% at 5 years; full graft function alone was seen in 55% of patients at 1 year, 40% at 5 years and 34% at 10 years.
Patients who had undergone a previous pancreatic resection had a significantly lower islet yield than those who had not (2712 IEQ/kg versus 4077 IEQ/kg, p=0.0.03). When adjusted according to islet mass (IE) transplanted, there were virtually no adult cases of insulin-independence when <2500 IE/kg were transplanted, while it was 47% with 2500-5000 IE/kg (n=27) and 75% with >5000 IE/kg (n=21).
IAT function for more than 16 hears has been documented in at least 2 adult cases, showing the potential for durable engrafment.Of the pediatric patients, all had been on narcotics preoperatively, while only 39% were on at follow-up. 94% reported improvement in pain, and 67% were entirely pain free. At 1 yr after TP/IAT, 78% had full or partial islet function and 56% were insulin-independent. The mean islet yield (IEQ/kg) was 7467 for those with full, 4066 with partial and 2890 with poor/no graft function, but there was considerable overlap and some low yields functioned well. The likelihood of insulin-independence was 67% in those without and only 33% in those with previous direct surgery on the pancreas.

CONCLUSIONS
TP/IAT can ameliorate pain and improving quality of life long term in most patients with CP in whom other interventions have failed. The islet autograft prevents or minimizes post-surgical diabetes in about 2/3 of patients and insulin-independence is sustained long-term in about 1/3. Narcotic induced hyperalgesia from prolonged use prior to TP/IAT prevents a substantial proportion of patients from withdrawing even when the pancreatic pain is relieved. Islet yield and function and ease of narcotic withdrawal may be improved if patients are referred for TP/IAT earlier in the course of their disease. Patients with chronic pancreatitis who have persistent pain after standard interventions should be considered for TP/IAT, and ideally should not be on narcotic analgesics for > 6 months without being referred..

CONTROL ID: 317038
CATEGORY: Endoscopic Ultrasound
PRESENTATION TYPE: ASGE Oral or Poster
PRESENTER: Kapil Gupta
PRESENTER (E-MAIL ONLY): gupta078@umn.edu
Abstract
TITLE: EUS early chronic pancreatitis: Comparison with histopathology in patients undergoing total pancreatectomy with autologous islet cell transplantation

AUTHORS (LAST NAME, FIRST NAME): Gupta, Kapil1, 2; Carlson, Annelisa3; Kobayashi, Takashi3; Manivel, Carlos4; Lai, Rebecca1, 2; Mallery, Shawn1, 2; Sutherland, David E.3; Freeman, Martin L.1, 2
INSTITUTIONS (ALL): 1. Gastroenterology, University of Minnesota, Minneapolis, MN, USA. 2. Gastroenterology, Hennepin County Medical Center, Minneapolis, MN, USA. 3. Surgery, University of Minnesota, Minneapolis, MN, USA. 4. Pathology, University of Minnesota, Minneapolis, MN, USA.

ABSTRACT BODY:
Background: The diagnosis of minimal change chronic pancreatitis (CP) is challenging. The role of endoscopic ultrasonography (EUS) is controversial. At least 3-5 out of 9 possible EUS criteria are generally required to suggest this diagnosis. No previous series comparing EUS with histopathology has included significant numbers of patients with minimal change or non-calcific CP.Aim: To compare EUS imaging to histology in patients with clinically suspected CP undergoing total pancreatectomy with autologous islet cell transplantation (TP/ AIT).Methods: All patients who underwent EUS prior to TP/ AIT for intractable abdominal pain and suspected minimal change chronic pancreatitis were reviewed. EUS was performed by two expert endosonographers. Pancreatic histology was analyzed by a gastrointestinal pathologist with expertise in pancreatic pathology. Results: Of the 15 patients studied, 14 (93%) were women. Ages ranged from 14 to 44 years (mean 33). Histologic exam revealed fibrosis in 14/15 (93%) [7 mild, 5 moderate, 2 severe]; parenchymal atrophy in 9/15 (60%) [4 mild, 3 moderate, 2 severe]; inflammation in 10/15 (67%) [7 mild, 1 moderate, 2 severe]. All 15 patients had at least one of the above histopathologic abnormalities, and all patients responded clinically with improvement or resolution of pain after TP/AIT. Three or more criteria for CP on EUS were present in 10 (67 %); all 10 of these patients had fibrosis [6 mild, 4 moderate to severe]; 7 had atrophy (3 mild, 4 moderate to severe); inflammation in 5 (4 mild, 1 severe). Less than 3 criteria were present in 5 patients; fibrosis was present in 4, all of moderate severity; atrophy in 2, and inflammation in 5. In the one patient with no EUS criteria, the only histopathologic finding was mild acute inflammation. There was no apparent or statistically significant association between mean number of EUS criteria and severity of histological changes (Table 1). Conclusion: In our pilot study there is a subset of patients who have clinical and histological evidence of chronic pancreatitis with minimal (<3) EUS criteria. The severity of histological changes did not correlate with number of EUS criteria. These preliminary findings bring into question the sensitivity and clinical utility of EUS for the diagnosis of minimal change or non-calcific CP. A prospective study evaluating the role of EUS in diagnosis of CP, and its correlation with histopathology is ongoing.
Table 1: Mean number of EUS criteria None or Mild/Minimal changes Moderate to severe changes
Fibrosis 3.6 (0-6) 3.3 (2-5)
Atrophy 3.5 (0-6) 3.4 (2-5)
Inflammation 3.6 (0-6) 3 (2-4)

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ASGE Questions
ASGE Minority or Gender Study: No
NASPHGAN Pediatric Endoscopy Award: No
Disclosures
ASGE - Disclosure Form:
Kapil Gupta: No financial interests exist.
Annelisa Carlson: No financial interests exist.
Takashi Kobayashi: No financial interests exist.
Carlos Manivel: No financial interests exist.
Rebecca Lai: No financial interests exist.
Shawn Mallery: No financial interests exist.
David Sutherland: No financial interests exist.
Martin Freeman: No financial interests exist.