Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Pancreatic Neoplasms

Fistula

Gastroparesis

Anastomotic Leak

Pancreatic Fistula

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pathological Conditions, Anatomical

Digestive System Fistula

Postoperative Complications

Stomach Diseases

Paralysis

Neurologic Manifestations

Pancreatic Cancer

Intravenous human albumin 1g/kg at skin incision running at 100ml/hour

Intravenous human albumin given at a maximum dose of 1g/kg at skin incision which is infused at 100ml/hour

Human albumin

Ian Chik

Sarah I Liew

Sarah I Liew, MBBS

Farrah-Hani Imran

Azarinah Izaham

Zamri Zuhdi

Azlanuddin Azman

Razman Jarmin

Fahrol F Jaafar

Pancreaticoduodenectomy (PD), more commonly known as Whipple's surgery is the mainstay treatment for pancreatic head and periampullary cancer. Factors contributing to PD outcomes are broadly categorized to disease-related, patient-related and operative factors. Whereas an inexhaustible list of study exists on looking at reducing PD complication rates with respect to the above-mentioned factors, it was only recently that more attention has been given to the impact of perioperative and intraoperative fluid regimes on PD outcomes. This study takes interest in the impact of intraoperative fluid regimes on PD outcomes. The objective of this investigation is to compare the outcomes with the use of intraoperative intravenous human albumin versus standard intraoperative fluid regimes.

This is a randomized controlled trial being conducted at the Universiti Kebangsaan Malaysia Medical Center (UKMMC) with two arms; the control and treatment arms. The treatment arm will receive intravenous human albumin intraoperatively whilst the control arm will receive standard intraoperative fluid regimes. Primary endpoint will be overall complication rates whilst secondary endpoints are length of hospitalization, length of ICU care, duration of gastroparesis, pancreatic fistula rates, surgical site infection rates, duration of surgery and intraoperative bleeding.

Beyond the intraoperative fluid regimes, postoperative care follows the standardised UKMMC Enhanced Recovery After Surgery (ERAS) protocols which saw an improvement in overall outcomes in patients who underwent pancreaticoduodenectomies (PD). Preoperative care will include nutrition optimisation, counselling, antimicrobial prophylaxis, perioperative glycemic control and near-zero fluid balance.

Data collection will include:

i. preoperative data: age, sex, ethnicity, BMI on admission, date of admission, comorbidities and the New York Heart Association (NYHA) functional status classification. Further information will include biochemical markers such as serum albumin albumin, white cell count (WCC), renal functions.

ii. Intraoperative information: duration of surgery, estimated blood loss, pancreatic duct size, pancreatic texture, amount and type of fluid administered, fluid balances and type of anastomoses.

iii. postoperative data: fluid balances and renal function of postoperative day 1 to 3, duration of ICU stay, readmission to ICU, length of hospital stay, duration to standard feeds, grading of pancreatic fistula (where relevant), surgical site infection, duration to removal of urinary catheter, cardiac complications, renal and pulmonary complications, deep vein thrombosis, re-operation, and mortality.

This is a randomized controlled trial conducted at the University Kebangsaan Malaysia Medical Center (UKMMC) with two arms; a control a treatment arm. The treatment arm will receive intravenous human albumin intraoperatively whilst the control arm will receive standard intraoperative fluid regimes.

Intravenous Human Albumin In Improving Pancreaticoduodenectomy Outcomes

Complications are defined as any deviation from the normal postoperative course, graded from I to V following the Clavien-Dindo classification of complications whereby Grade I are mild complications not needing any additional interventions and Grade V equates to the most severe complication which is death.

Duration of stay in ICU (in days), where relevant

Rates of postoperative pancreatic fistula

Measured in duration of surgery (in hours \& mins)

Universiti Kebangsaan Malaysia Medical Centre

Blood Substitutes

All Drugs and Chemicals

Polygeline

Plasma Substitutes

10 patients with pancreatic cancer will receive human albumin 5% in a restrictive goal directed fluid regime preoperatively for the first 24 hours.

10 patients with pancreatic cancer will receive gelofusine in a restrictive goal directed fluid regime preoperatively for the first 24 hours.

Human Albumin 5% will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.

human albumin 5%

Gelofusine will be given as fluid management for this group in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. This percentage of SVV has been validated as a threshold above which fluid administration increases stroke volume with an area under the receiver operating characteristics curve reported at 0.87. If the SVV remains more than 15% for more than 2 minutes, 250ml of fluid replacement according to patient group will be given. These boluses are given in aliquots over 30 min to avoid effects of rapid volume expansion. and the same fluid and technique will be carried out within 24 hours intra and post operatively in the Intensive Care Unit (ICU). All clinical parameters and fluids including blood that will be given will be recorded.

gelofusine.

Pui San Loh, MBBS, MMed

Sook Hui Chaw, MD

Pui San Loh, FANZCA

Wen Ben Lim

Sook Hui Chaw

Naidu Sitaram Premala

Peng Soon Koh

Rajadram Retnagowri

Dublin Norman

Background:

On the surface of every healthy cellular membrane resides a layer known as the glycocalyx. This structure consists of extracellular domains of receptor, adhesion and transmembrane molecules such as syndecan-1 covalently bound to highly negatively charged glycosaminoglycans, heparan sulfates. It has a principal role to maintain wall integrity, avoid inflammation and tissue oedema in vessels but in contrast, glycocalyx is robust and elevated on cancer cells. This study examines whether the endothelial glycocalyx layer is preserved in patients undergoing pancreatectomy with human albumin 5% vs. gelofusine in a restrictive goal directed fluid regime perioperatively for the first 24hours. Degradation of glycocalyx will be investigated by analyzing basic levels of the core protein syndecan-1 and heparan sulfates with post-operative samples.

This is a prospective study that will be conducted in the Main Operating theatres of UMMC on patients with pancreatic cancer undergoing elective pancreatectomy (includes all forms of pancreatectomy such as Whipple's procedure, total or distal pancreatectomy).

This study aim to determine the association of glycocalyx degradation by measuring levels of syndecan-1 and heparan sulfate with type of colloidal fluid given, human albumin 5% versus gelofusine in a restrictive goal directed fluid therapy in pancreatectomy.

Institutional ethics approval and registration in Clinical Trial Registry will be obtained before recruiting the first case.

Recruited patients will be randomly allocated to either the group receiving human albumin 5% or gelofusine.

Sample size:

There is no previously published literature related exactly to the pathology and methods of this proposed study. Therefore, a preliminary sample size calculation will be based on the closest study on fluids with a two-sided confidence interval of 0.95 and a desired power of 0.80 to yield a result that investigators need nine patients in each group. After adjusting for drop out rate of 10%, investigators will recruit ten in each group for human albumin 5% and gelofusine respectively within the study period of 2 years.

Data collection:

1. Intraoperative phase All preoperative preparation including fasting will be done in accordance to UMMC protocol. Intraoperative monitoring includes standard routine monitoring as per American Society of Anaesthesiologist Guidelines, invasive haemodynamic monitoring with arterial blood pressure incorporating FloTrac, BIS and neuromuscular monitoring. All patients will be under general anesthesia.

   Fluid management for both groups are in accordance to goal directed therapy and guided by stroke volume variation of approximately 12-15%. If SVV is \> 15%, 250ml of fluid replacement according to patient group will be given over 30 min within 24 hours intra and post operatively in the Intensive Care Unit (ICU). In both groups, all clinical parameters and fluids including blood that will be given will be recorded.
2. Post-operative phase:

   The allocated colloid fluid will be continued.

   Patients will be assessed for pancreatic fistula leak. The grading of pancreatic fistula will be defined according to the guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF).

   Reviews will be done on post op days 1, 3, 5 and 30. Amylase levels from drain tube post-op Day 3, 5 and 7 will be measured. The total duration of stay in intensive care, hospital and rate of mortality/ morbidity (re-laparotomy/ re-admission to ICU/ sepsis) within 30 days after surgery will be assessed and recorded.
3. Laboratory phase Blood samples are collected at 5 time points, a) preoperative, b) immediate postoperative and c) 24 hours postoperative d) Day 3 and e) Day 7 postoperative from both groups. The serum fraction will be frozen and stored at -80°C until assayed. Syndecan 1 concentrations and heparan sulfate concentrations are quantified using special enzyme-linked immunosorbent assay kit as previously reported. Inflammatory markers Interleukin-1 and CRP and any blood investigations as per hospital sepsis protocol will be determined as well.

Randomized control trial with Albumin 5% given as the intervention and Gelofusine as active control.

Randomized concealed assignment into 2 groups in opaque envelopes will be opened by care provider. Anaesthetic and ICU notes must not be revealed to outcome assessor.

Glycocalyx Levels in Patients Undergoing Pancreatectomy

Glycocalyx Levels in Patients Undergoing Pancreatectomy With Human Albumin 5% vs. Gelofusine

Review will be done according to guideline of Revised 2016 International Study Group on Pancreatic Fistula (ISGPF)

Blood samples are collected to check for syndecan 1 concentrations in serum

Blood samples are collected to check for heparan sulfate concentrations in serum

Blood samples are collected to check level of the Inflammatory markers Interleukin-1 and CRP

University of Malaya

Consultant Anaesthesiologist

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharmaceutical Solutions

Gastrointestinal Agents

Pancrelipase

Pancreatin

Patients benefited from total pancreatectomy for resectable adenocarcinoma of the cephalic region at high risk of postoperative pancreatic fistula, with intaportal/intramuscular islet autotransplantation

The total pancreatectomy will be performed in two steps: The pancreatectomy will begin by a standard pancreaticoduodenectomy procedure.

The section margin will be sent for intraoperative histological analysis to confirm the absence of invasion of the left remnant pancreas.

When absence of tumor invasion is confirmed and the high-risk of postoperative pancreatic fistula is validated intraoperatively, the extended left distal pancreatectomy will be performed, with splenic preservation when possible.

Then, the left side of the pancreas will be resected and cooled (4-6°) in the preservation solution and shipped to Lille Biotherapy platform to perform islet isolation and purification. The reconstruction after total pancreatectomy will be done as usually performed by center expert surgeon.

total pancreatectomy

The final islet preparation will be cultured and shipped 48 hours after total pancreatectomy from the Lille laboratory to the surgical center, and finally transplanted into the patient through a venous catheter placed in the portal trunk (91% of the total islet mass) and at the same time, a small fraction of the isolated islet (5% of the total islet mass) will be transplanted into the forearm muscle.

intraportal islet autotransplantation

François PATTOU, MD,PhD

Curative management of locally resectable invasive adenocarcinomas located in the cephalic region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major surgery that often leads to major complications including approximately 20% of relevant clinical postoperative pancreatic fistula.

Postoperative complications following pancreaticoduodenectomy can lead to early discontinuation of the complete oncologic strategy, i.e., chemotherapy for malignancy is performed in only about a third of patients who experienced a grade C fistula.

A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that involves the complete and definitive resection of all pancreatic tissue, eliminating any risk of postoperative pancreatic fistula but is associated with unavoidable endocrine insufficiency and potentially severe metabolic complications, such as "brittle diabetes".

Total Pancreatectomy following by intraportal Islet AutoTransplantation (TPIAT) can prevent "brittle diabetes" and improve the quality of life. The endocrine islets can be isolated from the pancreatic surgical specimen with standardized procedures and transplanted in the liver through intraportal infusion, in absence of immunosuppression and allow adequate control of glucose metabolism with a reduced need for exogenous insulin and an effective graft function in 70% of cases at 3 years Thereby, the investigators hypothesize that total pancreatectomy with intraportal Islet autotransplantation rather than classical pancreaticuduodenectomy, in patients with high-risk of postoperative fistula will increase the rate of complete access to adjuvant chemotherapy, while maintaining an adequate metabolic control.

Curative management of locally resectable invasive adenocarcinomas located in the cephalic region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major surgery that often leads to major complications including approximately 20% of relevant clinical postoperative pancreatic fistula. Severe postoperative pancreatic fistulas (grade C) require reoperation or lead to organ failure and/or mortality. In an extensive international registry study of pancreaticoduodenectomy procedures, chemotherapy for malignancy was performed in only about 33% (on time in 7% and delayed in 25.6 % of patients) and never delivered in about 67,4 % of patients who experienced a grade C fistula. Therefore, postoperative complications following pancreaticoduodenectomy can lead to early discontinuation of the complete oncologic strategy.

A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that involves the complete and definitive resection of all pancreatic tissue, eliminating any risk of postoperative pancreatic fistula.

Total pancreatectomy could represent a major shift in the surgical management of patients with a high-risk of postoperative fistula by eliminating the life-threatening risk associated with fistula and by increasing the opportunity to initiate and to complete adjuvant chemotherapy without delay.

However, total pancreatectomy is associated with unavoidable endocrine insufficiency and potentially severe metabolic complications, such as "brittle diabetes".

Total Pancreatectomy with intraportal Islet AutoTransplantation (TPIAT) is currently performed in patients with chronic pancreatitis under chronic pain failing endoscopic treatment and dependent on long-term opioid treatment.

Therefore, islet autotransplantation following total pancreatectomy can prevent "brittle diabetes" and improve the quality of life.

The endocrine islets can be isolated from the pancreatic surgical specimen with standardized procedures and transplanted in the liver through intraportal infusion, in absence of immunosuppression and allow adequate control of glucose metabolism with a reduced need for exogenous insulin and an effective graft function in 70% of cases at 3 years

Thereby, the investigators hypothesize that total pancreatectomy with intraportal Islet autotransplantation rather than classical pancreaticuduodenectomy, in patients with high-risk of postoperative fistula will increase the rate of complete access to adjuvant chemotherapy, while maintaining an adequate metabolic control.

Efficacy and Safety of TPIAT for Resectable Adenocarcinoma of the Pancreas Region at High Risk of Postoperative Fistula

Efficacy and Safety of Total Pancreatectomy With Intraportal Islet Autotransplantation for Resectable Adenocarcinoma of the Cephalic Region of the Pancreas at High-risk of Postoperative Fistula and Requiring Systemic Adjuvant Chemotherapy

success is defined when patients treated with TPIAT will have completed the adjuvant systemic chemotherapy initially approved and planned by the local multidisciplinary expert team according to current international guidelines

postoperative complication will be evaluated with Dindo Clavien classification

complications related to islet transplantation will be reported according to CTCAE v5.0.

the time in weeks between TPIAT procedure and the adjuvant systemic chemotherapy will be reported

The cancer recurrence will be assessed according standard of care imaging (Thorax multi-detection Computed Tomography, Abdomino-pelvis imaging : Mutli-detection Computed Tomography OR Magnetic Resonance Imaging) through the follow up using the Recist 1.1 criteria

Postopeartive diabetes and exocrine insufficiency will be evaluated with clinical examination (symptoms, Pancreatic enzyme replacement therapy dosage, Diabetes medication : non insulin medication, insulin (daily insuline dosage UI/kg); blood samples (Fasting C-peptide and glycemia, Post-prandial C-peptide and glycemia, HbA1C (%))

EORTC QLQ-C30 and QLQ -PAN26 are self-completion questionnaires specific to cancer patients quality of life and pancreatic cancer patients quality of life

adverse events will be reported according to CTCAE v5.0 and classified according to their suspected or confirmed reason (i.e. chemotherapy, intraportal islet transplantation, pancreatic surgery)

Islet transplantation succes status is defined by HbA1C \< 7% AND no severe hypoglycemic event

Islet transplantation succes status is defined by HbA1C \< 7% AND no severe hypoglycemic event AND C-peptide ≥ 0.2 ng/mL

Defined by the Beta 2 score calculated at 1 month post TPIAT using blood sample with fasting C peptide and glycemic, HbA1c and exogenous insuline requirement

Serious Hypoglycemic Event is defined as one requiring third-party assistance or resulting in hospitalization in an intensive care unit

Ministry of Health, France

University Hospital, Lille

Anti-Dyskinesia Agents

Coagulants

Levodopa

Hemostatics

Thrombin

Dihydroxyphenylalanine

Patients who were applied flowable thrombin containing collagen hemostat matrix after pancreatectomy

Patients who were applied thrombin coated L-dopa contained collagen patch after pancreatectomy

A 5 ml flowable hemostat matrix (CollaStat®) was applied to the stump or anastomosis site after pancreatectomy.

flowable thrombin containing collagen hemostat matrix

A 5x2.5cm sized thrombin coated L-dopa contained collagen patch (CollaSeal®) was applied to the stump or anastomosis site after pancreatectomy.

thrombin coated L-dopa contained collagen patch

Song Cheol Kim, MD, PhD

Yejong Park, MD, PhD

Under the hypothesis that collagen-based hemostatic agents improve the suppression of leakage of hemostatic pancreatic fluid at the surgical site during surgery, thrombin-containing collagen-based hemostatic agents are applied in surgery in patients with pancreatectomy. The investigators intend to evaluate the effectiveness of collagen-based hemostatic agents containing thrombin through clinical evaluation of hemostatic effect and anti-leakage effect of pancreatic fluid.

This clinical study is a study for comparative evaluation of hemostasis and anti-leakage effect of bile or pancreatic fluid when applied after pancreatic resection of a collagen-based hemostatic agent containing thrombin. It is prospective, single center, randomized, and non-inferiority test. Participants are patients who are diagnosed with pancreatic disease and other diseases, and plan to undergo pancreatectomy. Through the randomization, in the case of the intervention group, after the pancreatectomy, the Collastat (CollaStat®, Dalim Tissen. Co., Ltd., Korea) is applied to the cut surface, and in the case of the control group, Collaseal (CollaSeal®, Dalim Tissen. Co., Ltd., Korea) is applied. In this study, 30 participants were required for each intervention group and control group.

After surgery, the participants is hospitalized for 7 days and undergoes follow-up observation. Pancreatic leakage is measured through the drainage tube before discharge and evaluated as biochemical leakage (BL), B, or C according to the definition of International Study Group for Pancreatic Fistula (ISGPS).

The primary endpoint of this study was the prevention rate of leakage. The postoperative pancreatic fistula (POPF) was defined according to the definition of ISGPS. Secondary end point was assessed as the difference between groups of total number of collagen hemostatic agents used, hospital length of stay and number of patient who received RBC transfusion. Safety was assessed based on the incidence of adverse events occurred.

1. Synopsis

   * Title: Randomized controlled Study to evaluate the Effect of Thrombin-containing Collagen-based Hemostatic Matrix on Prevention of Pancreatic fistula after Pancreatectomy
   * Study center: Single center from Korea
   * Study type: Single center prospective randomized controlled study
   * Planned study dates: February 2018 to September 2020
2. Objectives

   ■ The aim of this study was to evaluate the safety and efficacy of flowable thrombin containing collagen hemostat matrix (T-C matrix) over the thrombin coated L-dopa contained collagen patch (T-CD patch) on clinical outcomes including PPH and POPF as a randomized controlled clinical trial.
3. Background

   * Hemostasis is the most basic and important procedure as a treatment for bleeding that inevitably follows most surgical procedures. Recently, with the development of pancreatic surgery and postoperative management, the mortality rate associated with surgery has decreased significantly, but the rate of complications due to massive bleeding or leakage of pancreatic fluid during surgery has not changed significantly. In hepatobiliary and pancreas (HBP) surgery, post-pancreatectomy hemorrhage (PPH) and postoperative pancreatic fistula (POPF) are both the main source of major morbidity and mortality.
   * Collagen is a natural substrate for various kinds of animal cells, and contains a relatively large amount compared to other proteins in animal tissues, and can be easily extracted and purified from animal tissues. Collagen not only has low antigenicity, but also has excellent hemostatic effect and cell attachment ability, so it is often used as a major component of hemostatic agents and artificial tissue substitutes. In addition, collagen provides an environment in which fibroblasts can be produced and induces wound healing by inactivating elastase and matrix metalloproteases (MMPs).
   * The investigators developed a novel flowable thrombin containing collagen hemostat matrix (T-C matrix) having flowable paste-like form. The T-C matrix consists of two connectable syringes, one of which contains collagen granules and thrombin, and the other contains calcium chloride (CaCl2) solution. Due to the flowable characteristic of the resultant matrix, T-C matrix can be easily applicable to irregular surface such as surgical site where anastomotic leakage is a concern. Currently, thrombin /coated L-3,4-dihydroxyphenylalanine (L-dopa DOPA) contained collagen patch (T-CD patch) are using on prevention of leakage and bleeding in pancreatic surgery. Although L-DOPA is known to contribute to adhesiveness which facilitates application of T-CD patch on wound sites, there are some controversial studies that L-DOPA have cytotoxicity and may induce inflammatory reaction with a high dose.
4. Methodology

   * The clinical study was designed to evaluate the effect of T-C matrix on the prevention of leakage in a pancreatectomy. The expected number of participants is 60.
   * This clinical study is a randomized prospective comparative study of the outcome according to the hemostat materials as a non-inferiority test, and the research hypothesis is as follows.

     √ Null Hypothesis: There is no difference in the incidence of POPF between patients who were applied TC matrix (CollaStat®, Dalim Tissen. Co., Ltd., Korea) and T-CD patch (CollaSeal®, Dalim Tissen Co. Ltd., Korea) after pancreatectomy.
   * In the case of evaluating the incidence of POPF after pancreatectomy, the results of previous studies of the 'leakage' ratio showed a leak prevention effect (θA) = 88% of the existing treatment method of CollaSeal® analog (Montorsi M et al. 2012). The new treatment effect (θT) is intended to demonstrate non-inferiority that does not exceed the non-inferiority limit (δ) compared to the existing treatment effect (θA). The non-inferiority limit (δ) was calculated by more than 75% of the existing treatment effect. The non-inferiority limit was calculated to be 0.22 based on the case where more than 75% of the 88% of the existing treatment method is confirmed, that is, the treatment success rate is more than 66%. It was decided that CollaStat® was non-inferior to CollaSeal® when the lower limit of the 95% CI for the difference between the two groups was greater than -0.22. If the allocation ratio between the two groups is 1: 1 and the first-class error α = 5% and the second-class error β = 20%, considering the dropout rate of 10%, 30 study groups and control groups each need 30 subjects.
   * The random assignment of this study is assigned according to the order of assignment in the planning stage of the study as a block randomization scheme with appropriate block size set.

Arm1 (intervention) : flowable thrombin containing collagen hemostat matrix Arm2 (Control) : thrombin coated L-dopa contained collagen patch

Effect of Thrombin-containing Collagen-based Hemostatic Matrix

Randomized Controlled Study to Evaluate the Effect of Thrombin-containing Collagen-based Hemostatic Matrix on Prevention of Pancreatic Fistula After Pancreatecomy

Pancreatic leakage is measured through the drainage tube before discharge and evaluated as biochemical leakage (BL), B, or C according to the definition of International Study Group for Pancreatic Fistula (ISGPS).

The length of hospital stay after surgery is observed.

The amount of blood transfusion performed during surgery should be described.

According to the Clavien-Dindo classification, the grade of complication including readmission should be described.

Asan Medical Center

Director

Hypoglycemic Agents

Hematinics

Insulin

Insulin, Globin Zinc

Liver Extracts

Total pancreatectomy with autologous islet cell transplantation

Pancreaticoduodenectomy (classic Whipple or pylorus-preserving)

Islet cells are isolated from patients healthy pancreatic tissue. Following total pancreatectomy, these autologous cells are injected into the portal vein, to implant in the liver and produce insulin.

Intraportal transplantation of isolated autologous pancreatic islets after total pancreatectomy

As a standard procedure, the tumor-affected region of the pancreatic head with surrounding tissue and lymph nodes is removed during surgery. Reconstruction is performed by pancreaticojejunostomy.

Barbara Ludwig, Prof. Dr.

Marius Distler, Prof. Dr.

The primary objective of this clinical trial is to evaluate whether primary total pancreatectomy with simultaneous islet autotransplantation compared with pancreatic head resection (alone) can reduce perioperative morbidity and time to initiation of adjuvant therapy in patients with a high-risk constellation for pancreatic fistulas.

Pancreatic Head Resection or Total Pancreatectomy With Islet Autotransplantation in Patients With Periampullary Cancer and High Risk Profile for the Development of Postoperative Pancreatic Fistula

Pancreatic Head Resection or Total Pancreatectomy With Islet Autotransplantation (IAtx) in Patients With Periampullary Cancer and High Risk Profile for the Development of Postoperative Pancreatic Fistula (POPF)

Time (days) between surgery and the date of certified fitness to begin adjuvant therapy, confirmed by an oncology consult, starting at day of discharge, than assessed at POD 90, POD 180, POD 365, 24 months

Postoperative day on which adjuvant therapy was started

Rate of peri-operative morbidity/mortality will be assessed acc. to Clavien-Dindo classification

Rate of (serious) adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0, 2017)

The QoL analyses will include QoL mean values, QoL response. EORTC QLQ C30 contains 30 questions28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much).

2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent).; assessed at POD 90, POD 180, POD 365, and 24 months after surgery

The QoL analyses will include QoL mean values, QoL response. EORTC QLQ PAN26 contains 30 questions regarding pain, nutrition, body fitness, sexuality, from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much).

28 questions regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, and body conditions from (1) to (4); 1 (not a bit), 2 (little), 3 (moderate), 4 (much); , assessed at POD 90, POD 180, POD 365, and 24 months after surgery

2 questions regarding state of health and Quality of life with a horizontal rating from 1 to 7; 1 (very bad), 7 (excellent).

Metabolic outcome will be determined on continuous monitoring of glucose (CGM) in plasma (mmol/L) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on the hormone glucagon in plasma at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on glycohemoglobin (HbA1c in %) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on serum C-peptide (nmol/L) as measure for functionality of pancreas at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on serum fructosamine (µmol/L) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on requirement of insulin (yes/no) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on number of hypoglycemic events (defined as value of blood glucose below 3.5 mmol/l) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Metabolic outcome will be determined on severity of hypoglycemic events (decrease of blood glucose level) at every visit: Screening, POD 1, POD 3, day of discharge, POD 90, POD 180, POD 365 and 24 months after intervention

Within 24 months after intervention, oncological outcome is evaluated, as measured by tumor markers CA 19-9, CEA

Within 24 months after intervention, oncological outcome is evaluated, as measured by recurrences of tumor shown in CT imaging

Within 24 months after intervention, oncological outcome is evaluated, as measured by metastases shown in CT imaging

KKS Dresden

German Cancer Research Center

Technische Universität Dresden

Pancreatitis

Postoperative care according to a best practice algorithm for postoperative care focussing on early detection and minimally invasive management of postoperative pancreatic fistula.

Postoperative care according to current usual practice.

Best practice algorithm for postoperative care

Jasmijn Smits, MD

Hjalmar C van Santvoort, MD, PhD

Koop Bosscha

Marc Besselink

Sebastiaan Festen

Geert Kazemier

Jennifer Schreinemakers

Daphne Roos

Ignace de Hingh

Mike Liem

Vincent de Meijer

Fennie Wit

Bert Bonsing

Ronald van Dam

Marion van der Kolk

Casper van Eijck

Erwin van der Harst

Hjalmar van Santvoort

Quintus Molenaar

Gijs Patijn

Quintus Molenaar, MD, PhD

This Nationwide stepped-wedge cluster randomized trial is designed to evaluate if the implementation of a best practice algorithm for postoperative care results in a decrease in incidence of major complications and death after pancreatic resection as compared to current practice.

Rationale

Pancreatic resection is a major abdominal operation with 50% chance of postoperative complications. A feared complication is severe pancreatic fistula, in which there is leakage of enzyme rich fluid into the abdominal cavity. Adequate complication management appears to be the most important factor in improving outcomes of patients undergoing pancreatic resection.

Objective

To investigate whether implementation of a best practice algorithm for postoperative care focusing on early detection and step-up management of postoperative pancreatic fistula results in a lower rate of major complications and death after pancreatic resection as compared to current practice

Study design

A nationwide stepped-wedge, cluster randomized, superiority trial. In this design all participating centers cross over from current practice to best practice according to the algorithm, but are randomized to determine the exact order. At the end of the trial, all centers will have implemented the best practice algorithm.

Study population

All centers performing pancreatic surgery in the Netherlands (i.e. the Dutch Pancreatic Cancer Group).

Intervention

Cluster level education on postoperative care according to a best practice algorithm, focusing on early detection and step-up management of postoperative pancreatic fistula. This algorithm is based on findings in Dutch observational cohort studies, systematic literature analyses, an inventory in current protocols on postoperative care and expert opinion. The proposed algorithm is validated in a multicenter cohort and consensus upon this algorithm is reached with pancreatic surgeons from all centers of the Dutch Pancreatic Cancer Group. The final algorithm was reviewed critically by the advisory committee of internationally respected experts in the field of pancreatology before implementation in this trial.

Comparison

Postoperative care according to current practice.

Endpoints

The primary outcome was measured in all patients undergoing pancreatic resection and is a composite of major complications (i.e. postpancreatectomy bleeding, new-onset organ failure and death). Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, number of patients receiving adjuvant chemotherapy, healthcare resource utilization and costs analysis. Follow-up will be 90 days after pancreatic resection.

POstopeRative Standardization of Care: THe Implementation of Best Practice After Pancreatic Resection

POstopeRative Standardization of Care: THe Implementation of Best Practice After Pancreatic Resection. a Nationwide Stepped-Wedge Cluster Randomized Trial

The datasets generated during and/or analysed during the current study are/will be available upon request from Hjalmar van Santvoort (h.van.santvoort@antoniusziekenhuis.nl)

The primary endpoint of this trial is a composite of the most severe complications associated to postoperative pancreatic fistula. This endpoint will be considered positive if one of the following complications occurs within 90 days after pancreatic resection: late postpancreatectomy bleeding, new-onset organ failure and/or death

Measured as rate of death at 90-day follow-up

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intravenous Human Albumin In Improving Pancreaticoduodenectomy Outcomes	NCT04418739	Pancreaticoduod... Pancreatic Fist... Delayed Gastric... Pancreatic Canc... Anastomotic Lea...	Human albumin	-	Universiti Kebangsaan Malaysia Medical Centre
Glycocalyx Levels in Patients Undergoing Pancreatectomy	NCT04058236	Endothelial Deg... Pancreatic Canc... Pancreatectomy Postoperative P...	human albumin 5... gelofusine.	18 Years - 75 Years	University of Malaya
Efficacy and Safety of TPIAT for Resectable Adenocarcinoma of the Pancreas Region at High Risk of Postoperative Fistula	NCT05116072	Adenocarcinoma ... Adenocarcinoma ... Ampullary Adeno...	total pancreate... intraportal isl...	18 Years -	University Hospital, Lille
Intravenous Human Albumin In Improving Pancreaticoduodenectomy Outcomes	NCT04418739	Pancreaticoduod... Pancreatic Fist... Delayed Gastric... Pancreatic Canc... Anastomotic Lea...	Human albumin	-	Universiti Kebangsaan Malaysia Medical Centre
Effect of Thrombin-containing Collagen-based Hemostatic Matrix	NCT04357483	Pancreatic Tumo...	flowable thromb... thrombin coated...	20 Years - 80 Years	Asan Medical Center
Pancreatic Head Resection or Total Pancreatectomy With Islet Autotransplantation in Patients With Periampullary Cancer and High Risk Profile for the Development of Postoperative Pancreatic Fistula	NCT05843877	Periampullary C... Postoperative P...	Intraportal tra... Pancreaticoduod...	18 Years -	Technische Universität Dresden
Glycocalyx Levels in Patients Undergoing Pancreatectomy	NCT04058236	Endothelial Deg... Pancreatic Canc... Pancreatectomy Postoperative P...	human albumin 5... gelofusine.	18 Years - 75 Years	University of Malaya
POstopeRative Standardization of Care: THe Implementation of Best Practice After Pancreatic Resection	NCT03400280	Pancreatic Dise... Pancreatic Neop... Pancreatic Canc... Pancreatitis	Best practice a...	-	St. Antonius Hospital
POstopeRative Standardization of Care: THe Implementation of Best Practice After Pancreatic Resection	NCT03400280	Pancreatic Dise... Pancreatic Neop... Pancreatic Canc... Pancreatitis	Best practice a...	-	St. Antonius Hospital
Efficacy and Safety of TPIAT for Resectable Adenocarcinoma of the Pancreas Region at High Risk of Postoperative Fistula	NCT05116072	Adenocarcinoma ... Adenocarcinoma ... Ampullary Adeno...	total pancreate... intraportal isl...	18 Years -	University Hospital, Lille

Spots Global Cancer Trial Database for postoperative pancreatic fistula