壞死性胰臟炎的標準治療: 個案檢討及未來治療方針 The protocol for treatment of necrotizing pancreatitis 陳昱廷 部立雙和醫院 外科部 一般外科 第四年住院醫師

Purpose Necrotizing pancreatitis : ~20% patients in acute pancreatitis will develop necrosis of the pancreatic parenchyma, the peripancreatic tissue, or both Depending on the presence of persistent organ failure, it is considered moderately severe or severe, with mortality exceeding 30% In 2/3 the necrosis remains sterile; 1/3 develops infection Bacterial translocation from the gut Disturbed intestinal motility, small bowel bacterial overgrowth, increased mucosal permeability

Etiology

Etiopathogenesis Necrotizing pancreatitis : Unregulated activation of trypsin within the pancreatic acinar cells After activation of trypsinogen to trypsin, several enzymes such as elastase, phospholipase A2, and the complement and kinin are activated The release of these enzymes and the resulting injury to the pancreatic parenchyma triggers an inflammatory cascade resulting in additional cytokine production, including interleukin (IL)-1, -6, -8, as well as tumor necrosis factor (TNF) Additionally, activation of endothelial cells enables the migration of leukocyte with release of more injury inducing enzymes. The endpoint of this cascade is a SIRS, characterized by loss of vascular tone, systemic vascular resistance and increased capillary permeability with third spacing of plasma volume, leading to hypotension, respiratory distress, and multiple organ failure

Diagnosis Infected necrotizing pancreatitis : Gas in the necrotic collection on image (42%) Positive culture of a fine-needle aspiration (false negative: 20%) Unequivocal clinical sings of infection

Diagnosis Necrotizing pancreatitis : Parenchymal necrosis: areas not present with enhancement by the contrast agent, an index scale may be utilized to quantify: <30%, 30-50%, >50% Peripancreatic fat necrosis (steatonecrosis): peripancreatic tissue densification, heterogeneity; suggested by presence of paracolic gutters and mesentary root thickening, fat densification with involvement of anterior pararenal space Development of heterogeneous fluid collections containing solid components; as modify over time, an initial solid appearance, evolving to a more fluid status Wall-off necrosis (WON): to build a wall around a certain location; a circumscribed area containing fluid and necrotic pancreatic debri replacing part of the pancreatic parenchyma, originating from a necrosis area apper

Treatment Necrotizing pancreatitis : Working group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis (2013) The Italian Association for the study of the Pancreas (ASIP). Consensus guidelines on severe acute pancreatitis (2015)

Open surgical approach : High mortality rate up to ~65% Subcostal or midline longitudinal incision The retroperitoneum is entered through the lesser sac and the pancreas is exposed; infracolic approach as a alternative Debridement is typically performed with blunt finger dissection or ring forceps Formal resection is avoided to minimize the incidence of bleeding, fistulae, and removal of vital tissue Enterotomies are avoided to decreased to incidence of post-operative enterocutaneous fistula

Two distinct open surgical completion techniques: Marsupialization: open abdominal packing, with return to operating room every 48 hours for further debridement until granulation tissue has replaced the retroperitoneal necrosis; the so-call “sandwich technique” is that suction tubes are placed for superficial drainage and the wound was covered by protective materials (Opsite dressing); a mesh was interposed between the edges of the fascia Continuous post-operative lavage: insertion of two or more double lumen Salem sump tubes (20-24 Fr.) and single lumen silicon rubber tubes (28-32 Fr.) through separate incisions with their tips in the lesser sac and necrotic areas. The smaller lumen tubes are used as the inflow and the larger lumen tubes for outflow. 35-40 litters of fluid are used for lavage.

Treatment Necrotizing pancreatitis : Laparotomy necrosectomy “Step-up approach” First step: drainage via CT-guided route or endoscopic transluminal route Complication(28%): Colonic perforation, bleeding, fistula

Treatment Necrotizing pancreatitis : “Step-up approach” Second step: Minimal invasive interventions Parekh, 2006, 3 ports with one hand port Infra-colic approach, blunt dissection with finger, and drains left

Treatment Necrotizing pancreatitis : “Step-up approach” Second step: Minimal invasive interventions Laparoscopic approach Retroperitoneoscopic approach (VARD) Utilize a percutaneous tract, dilated, and then direct visulization of the necrosis by advancing scope Endoscopic approach Hybrid approach

Enteral nutrition Maintain gut integrity Reduced intestinal permeability Down-regulate the systemic immune response

Nutrition in acute severe pancreatitis PN should be delayed for at least 5 days after the peak of inflammation Providing EN postoperatively in those patients requiring surgical intervention dose benefit outcome compared with use of STD

Materials and Methods Necrotizing pancreatitis Sterile necrosis & infected necrosis Surgical intervention under walled-off status

Excel Data 編號 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 住院日數 手術治療 Etiology 34 O unknown 27 Alcoholism; GB stones 26 GB stones 18 22 D Alcoholism 68 33 71 CBD stone 3 CBD sludge & CBD stenosis 21 GB sludge 50 Alcoholism; GB stone 42 85 Alcoholism; Dyslipidemia 1 80+ 74+ GB sludge; Hyperlipidemia 25 12+ GB stone

Excel Data 編號 手術治療 手術術式 1 O Gastrocystotomy + feeding jejunostomy 2 Drainage of pancreatic abscess + feeding jejunostomy 3 Pancreatic abscess drainage, cholecystectomy, feeding jejunostomy 4 Cholecystectomy, choledochotomy, feeding jejunostomy 5 D Drainage of retroperitoneal abscess + feeding jejunostomy 6 Pigtail-guided pancreas abscess drainage 7 Retroperitoneal, intra-peritoneal, and pancreatic abscess drainage 8 Drainage of pancreatic and retroperitoneal abscess + feeding jejunostomy 9 Minimal invasive necrosectomy 10 Duodenum resection, duodenojejunostomy, drainage of pancreas abscess + feeding jejunostomy 11 Pancreatic necrosectomy, drainage abscess + feeding jejunostomy 12 Drainage of retroperitoneal and pancreatic abscess + feeding jejunostomy 13 Exploratory laparotomy + feeding jejunostomy (MI*2) 14 Pancreatic and retroperitoneal debridement; Hartmann procedure, loop ileostomy 15 Pigtail-guided pancreatic abscess drainage (MI*1, feeding jejunostomy) 16 Exploratory laparotomy, debridement with drainage 17 Retroperitoneal abscess drainage; segmental small bowel resection with anastomosis 18 LC + IOC; open necrosectomy + feeding jejunostomy

Excel Data 編號 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 住院日數 手術治療 Morbidity/Mortality 34 O - 27 26 18 22 D 68 33 71 3 21 50 42 85 Colocutaneous fistula 1 Expired (POD 1) 80+ Right colic artery branch bleeding; Duodenum perforation 74+ Duodenum perforation 25 Anastomosis site leakage 12+

Materials and Methods Oct. 2012 to Aug. 2017 : 18 patients Patient collection : n=18 Total (n=18) Male Female Gallstone Alcoholism Combined Hyper-TG Others 14 (77%) 4 (23%) 11 7 2 3

Materials and Methods Patient characteristics : n=18 Total Head Body Tail Necrosis index scale <30% 30~50% >50% (Image within 5 days from op) 11 8 2 5 4 2 3 4 3 3 3 2 *CTSI = CT severity index Balthazar score (A-E) + Necrosis index scale: 0-10

Materials and Methods Surgical intervention : n=18 open minimal-invasive both feeding necrosectomy (including drain-guide) jejunostomy Op only (n=11) 10 1 - 7 CT-guided drain 4* 2 1 5 then accepted op (n=7) *secondary drainage/debridement (5/18) *one case in “both” group *one case converted from scope to open accpeted MI intervention *one case performed Gastrocystotomy twice then open at third time *additional cholecystectomy (3/18)

Materials and Methods Patient characteristics : n=18 ND insertion hospitalization OPD follow-up Morbidity (days) (months) (Mortality) Op only (n=11) 2 39.8 11.5 2 (1) CT-guided drain 3 43.1 1.5 2 then accepted op (n=7) *M/M included duodenum perforation, sigmoid colon perforation, right colic artery bleeding, colo-cutaneous fistula, expired (1/18)

Case Presentation (1)

Case Presentation (2)

Case Presentation (3)

Discussion “Step-up”approach had a trend of lessen morbidity, and mortality compared to open necrosectomy for the priority treatment in necrotizing pancreatitis cases There are advantages in minimal invasive approach for necrosectomy including lesser stress induced and sessions of procedure available Of course, there are limitations in minimal invasive approach, especially the necrosis content was located more centralized

Discussion Marsupialization with continuous post-operative lavage remained the classical and valuable method for necrosectomy surgical treatment We could start enteral feeding via ND route or once feeding jejunostomy was constructed combined with necrosectomy procedure