Multicolour Versus Monocolour Specimens Inking After Pancreaticoduodenectomy for Periampullary Cancer
Condition: Stage, Pancreatic Cancer; Neoplasm, Residual; Pancreatic Neoplasm; Periampullary Cancer
MeSH terms: Neoplasms; Pancreatic Neoplasms; Neoplasm, Residual
Study type: Interventional

Summary: 
      A single-centre, randomised clinical trial of patients affected by periampullary cancer who
      underwent pancreaticoduodenectomies which included two different types of specimen
      margination: arm A (multicolour inking) and arm B (monocolour inking). The randomisation of
      the specimen was made after the resection, blinded for the surgeons involved in the
      operation. The primary endpoint was the overall R1 resection rate and its difference between
      the two arms. The secondary endpoints were the R1 resection rate in each margin and its
      difference between the two arms, and the impact of margin status on survival. A sample size
      of 18 patients was required.
    

Detailed description: 
      This study was a single-centre, prospective, controlled, open, parallel group, randomised
      clinical trial, conducted in the tertiary referral University Centre of S.Orsola-Malpighi
      Hospital, Bologna, Italy, from June 2012 to January 2016, which enrolled patients affected by
      periampullary cancer who underwent pancreaticoduodenectomy (PD). All patients with suspected
      periampullary cancer were enrolled in the study, but only patients who underwent
      pancreaticoduodenectomy were randomised and allocated to a multicolour inking specimen (arm
      A, experimental) or a monocolour inking (arm B, control) after specimen was taken out from
      the operative field. The analysis regarded only the specimens of the patients who underwent
      PD in which the final pathologic report showed a diagnosis of invasive periampullary cancer
      (pancreatic, ampullary and distal bile duct).

      After performing the pancreaticoduodenectomies, the surgeon intraoperatively inked the
      surfaces/margins of the specimen with different colours. In the multicolour arm, the
      surfaces/margins inked were the following: Anterior surface of the pancreas (yellow);
      Posterior surface of the pancreas (orange); Superior mesenteric/portal vein groove (blu);
      Superior mesenteric artery margin (retroperitoneal margin) (red); Transection margin of the
      bile duct (green).The trans-section pancreatic and gastric margins were not inked.

      In the monocolour arm, only the superior mesenteric artery margin and the pancreatic margin
      were intraoperatively indicated by the surgeon in the specimen: a single stitch to identify
      the transection pancreatic margin and a continuous suture to identify the superior mesenteric
      artery margin. Monochromatic inking of the superior mesenteric artery margin was subsequently
      carried out by the pathologist. In both arms of treatment, the macroscopic evaluation and
      slicing of the surgical specimen followed the Leeds Pathology Protocol (LEEPP), and seven
      margins, which included the anterior, posterior, superior mesenteric /portal vein groove,
      superior mesenteric artery, bile duct, pancreatic neck and stomach margins, were examined.
      The primary endpoint was to evaluate the overall R1 resection rate and its difference between
      multicolour (arm A) and monocolour (arm B) inking of the specimen. The secondary endpoints
      were to evaluate the R1 resection rate in each margin: anterior and posterior surfaces of the
      pancreatic head; superior mesenteric/portal vein groove; superior mesenteric artery margin;
      transection pancreatic and bile duct margins, and its difference between the two arms
      compared. Finally, the impact of the margin status on survival was considered for each margin
      and type of periampullary tumours.

      Calculation of the sample size was based on the literature assumption that the overall
      incidence rate expected of R1 ranged from 10 to 76% while it increased to 81-85% when a
      standardised pathological technique and margination with multicolour inking, as described in
      arm A, was performed. To detect a difference in R1 rate between these values with a 5%
      alpha-error and a 80% beta-error at a two-sided 0.05 significance level, a sample size of 18
      patients was required for each group. In relation to the fact that the patients were often
      randomised without a preoperative biopsy, and that following current literature the 5-13% of
      the presumed malignancies were benign, it was decided to randomise 25 patients in order to
      avoid a sample size smaller than expected. The sample size calculation was carried out using
      PS Power and Sample Size Calculation software (Department of Biostatistics; Vanderbilt
      University; Nashville, TN, USA).
    

Intervention name(s): Multicolour inking specimens; Monocolour inking specimens
Intervention type(s): Procedure; Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Diagnostic
Keywords: cancer; resection margin; pathology; pancreas