Symptoms and General Pathology

All Conditions

Jaundice

Hyperbilirubinemia

Skin Manifestations

10 Fr plastic stent (Percuflex Amsterdam® or C-flex pigtail® or Advanix® Biliary stent)

Uncovered metal stent (WallFlex® Biliary RX stent)

Stent

Jaihwan Kim, MD

Currently, routine preoperative biliary drainage (PBD) was not recommended. However, PBD is still necessary in case of patients with cholangitis or very high level of bilirubin or patients who are expected to receive delayed surgery.

The aim of this clinical trial is to demonstrate non-inferiority of uncovered self-expandable metal stent to plastic stent for PBD by endoscopic retrograde cholangiopancreatography in patients with periampullary cancer undergoing curative intent pancreaticoduodenectomy.

Jaundice is one of the most common symptoms in patients with periampullary cancers including pancreatic cancer, common bile duct (CBD) cancer, ampulla of Vater (AoV) cancer, and duodenal cancer. Traditionally, preoperative biliary drainage (PBD) was routinely performed in these cancers because it might favorably influence sepsis, endotoxemia, and intravascular coagulation. However, a recent randomized control study reported that routine PBD in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. Therefore, routine PBD was not recommended. However, PBD is still necessary in case of patients with cholangitis or very high level of bilirubin or patients who are expected to receive delayed surgery.

In these patients with necessity of PBD, a plastic stent (PS) has been used because it is good for temporary use with cheap prices. However, it is sometimes occluded before surgery or not enough for rapid decompressing jaundice mainly because of its short diameter. In this aspect, a self-expandable metal stent (SEMS) has strength compared to PS because it has a longer diameter which enables rapid decompression with a fewer events of occlusion. However, SEMS is much more expensive than PS and the exact length of stent is more critical.

Although there are still lack of evidence which compares the results between PS and SEMS, National Comprehensive Cancer Network (NCCN) guidelines recently recommended the use of a short SEMS for pancreatic adenocarcinoma patients with cholangitis or fever. However, we needed more concrete evidence about this principle.

Preoperative Biliary Drainage With Metal Versus Plastic Stents in Periampullary Cancer

A Randomized Controlled Trial for Preoperative Biliary Drainage With Metal Versus Plastic Stents in Patients With Periampullary Cancer

Between preoperative biliary drainage and surgery, reintervention (re-preoperative biliary drainage) would be checked and analyzed.

Until surgery, preoperative biliary drainage associated with complication would be checked and analyzed.

Amount of decrease of total bilirubin between preoperative biliary drainage and surgery would be checked.

Interval between preoperative biliary drainage and surgery would be checked.

Interval between surgery and discharge would be checked.

Boston Scientific Corporation

Seoul National University Hospital

All Drugs and Chemicals

Bilirubin

patients subjected to direct surgery (DS) within 1 week after randomization

patients managed by Preoperative Biliary Drainage followed by surgery after 4-6 weeks.

Endoscopic retrograde biliary drainage (ERBD) and stent placement was the first choice for PBD while ultrasound-guided percutaneous transhepatic biliary drainage (PTBD) was done if ERBD was not feasible. Biliary drainage was considered successful if the serum bilirubin level decreased by 50% or more within 2 weeks after the procedure. Patients with failed PBD were referred directly to surgery, while those with successful PBD were referred to surgery 4 to 6 weeks after first drainage procedure according to the latest guidelines

Preoperative Biliary Drainage (PBD)

The standard surgical procedure for operable tumors Whipple procedure with triple reconstruction, namely pancreatogastrostomy or pancreatojejunostomy,hepaticojejunostomy and gastrojejunostomy

Surgery

Mohamed M Elmessiry, MD,PhD

Eman A Mohamed, MD, PhD

The impact of preoperative biliary drainage (PBD) on morbidity and mortality associated with Pancreaticoduodenectomy (PD) in patients with peri-ampulary tumors is still controversial. The objective of this study is to evaluate the impact of PBD on surgical and oncologic outcomes after PD in jaundiced patients with operable peri-ampulary tumors.

150 consecutive jaundiced patients with suspected operable peri-ampullary tumors were randomized via concealed envelopes into 2 groups (each included 75 patients), group I managed by direct surgery while group II managed by PBD followed by surgery. Both groups were compared regarding perioperative mortality, morbidities, tumor recurrence and 2 years survival rates.

Preoperative Biliary Drainage in Patients With Operable Malignant Periampulary Tumors

"Impact of Preoperative Biliary Drainage on Surgical and Oncologic Outcomes After Pancreatico-Duodenectomy in Patients With Operable Malignant Periampulary Tumors. A Randomized Controlled Study"

Any complications related to surgery within 3 months including: postoperative bleeding, pancreatic fistula, Biliary leakage, Intra-abdominal infection, wound infection/ dehiscence

Local or systemic recurrence of the malignant tumor

% of patients survived without any evidence of tumor recurrence after 2 years follow up

% of patients survived with or without tumor recurrence after 2 years follow up

University of Alexandria

Ass. Professor

Neoplasms

Rare Diseases

Cholangiocarcinoma

Klatskin Tumor

Postoperative Complications

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Percutaneous transhepatic biliary drainage(PTBD) is performed under the guidance of ultrasound. The duration may be around four weeks to make the total bilirubin of patients lower than 85μmol/L.

Preoperative biliary drainage

Lijian Liang

Dong Chen, MD

Xiaoyu Yin, MD

This study is to investigate whether preoperative biliary drainage can reduce the postoperative morbidity in patients with hilar cholangiocarcinoma.

Preoperative biliary drainage(PBD) or not, is a Hot Spot issue in the management of Hilar cholangiocarcinoma. Surgeons from Japan tend to perform PTBD(Percutaneous Transhepatic Biliary Drainage) before a definite operation until the total bilirubin(TB) lower than 85μmol/L. For some patients needed to perform extended curative resection, PVE(Portal Vein Embolization) is performed and thus the duration of PBD may be around six weeks and the final TB is lower than 34μmol/L. Some tend to perform a definite curative operation in a short time after diagnosis. There is no RCT research on the effect of PBD for the resectable Hilar Cholangiocarcinoma patients to date.

Preoperative Biliary Drainage for Resectable Hilar Cholangiocarcinoma

Effect of Preoperative Biliary Drainage on Postoperative Complications in Resectable Patients With Hilar Cholangiocarcinoma(Klatskin Tumor)

Sun Yat-sen University

Liang Li-jian

Infections

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Communicable Diseases

Surgical Wound Infection

Pancreatic Cancer

Anti-Infective Agents

Anti-Bacterial Agents

Metronidazole

Cefazolin

Cefuroxime

Cefuroxime axetil

Antibiotics, Antitubercular

Gentamicins

Antiprotozoal Agents

Antiparasitic Agents

Prolonged prophylaxis: a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4 hours of surgery (perioperative prophylaxis) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily

Perioperative prophylaxis: a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4 hours of surgery.

1500mg IV cefuroxime thrice daily during five days.

500mg IV metronidazole thrice daily during five days.

Daphne HM Droogh, MD

J. Sven D. Mieog, MD PhD

Marc GH Besselink, Prof. Dr

Marc GH Besselink, Prof. Dr.

Jan H Wijsman, MD PhD

Koop Bosscha, MD

Misha DP Luyer, MD PhD

Daan J Lips, MD PhD

Frederik JH Hoogwater, MD PhD

Stefan AW Bouwense, MD PhD

Martijn Stommel, MD PhD

Bas Groot Koerkamp, Prof. Dr.

Hjalmar C van Santvoort, Prof. Dr

Hjalmar C van Santvoort, Prof. Dr.

The goal of this multicenter randomized controlled trial is to evaluate the additional value of pre-emptive antibiotic treatment on clinically relevant organ/space surgical site infections (OSIs) in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile. The main objectives it aims to answer are:

* To evaluate the effect of pre-emptive antibiotic prophylaxis on clinically relevant OSIs in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile
* To evaluate the effect of pre-emptive antibiotic prophylaxis on other postoperative outcomes (e.g. OSIs, superficial SSIs, POPF, PPH, major morbidity, ICU admission, readmission, length of hospital stay, and mortality).
* To evaluate concordance between perioperatively obtained bile cultures and postoperative cultures from infectious sites, and to evaluate antibiotic sensitivity patterns of the cultured microorganisms.

Participants will be randomized with a 1:1 allocation before surgery into the intervention or control group:

* Patients in the intervention group will receive perioperative prophylaxis (similar to the control group) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily.
* Patients in the control group will only receive perioperative prophylaxis (a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4h of surgery), which will be discontinued after surgery.

Rationale: The additional value of pre-emptive antibiotic treatment after pancreatoduodenectomy is undetermined as previous research reported conflicting results regarding infectious complications. Prolonged antibiotic prophylaxis (formally pre-emptive antibiotic treatment) after pancreatoduodenectomy might reduce the rate of surgical site infections in patients with a high risk for contaminated bile (predominantly patients with preoperative biliary drainage or an ampullary malignancy). Current national and international guidelines lack clear recommendations regarding pre-emptive antibiotic treatment leading to substantially varying antibiotic prophylactic regimes between institutes.

Objective: This trial evaluates the additional value of pre-emptive antibiotic treatment on clinically relevant organ/space surgical site infections (OSIs) in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile.

Study design: This multicenter, randomized controlled, superiority trial compares perioperative versus pre-emptive antibiotic treatment during five postoperative days after pancreatoduodenectomy in patients with a high risk for contaminated bile.

Study population: Adult patients undergoing pancreatoduodenectomy with a high risk for contaminated bile (patients with preoperative biliary drainage or an ampullary malignancy). Patients with a contraindication for the study antibiotics or a preoperative indication for antibiotics (e.g. cholangitis of preoperative abscesses) are excluded.

Intervention: Participants will be randomized to either perioperative prophylaxis (cefazolin, metronidazole and a single dose of 5-7mg/kg gentamicin, control arm) or additional cefuroxime and metronidazole for five postoperative days (experimental arm).

Main study endpoints: The primary endpoint are organ/space infections (OSIs) within 90 days after surgery requiring a therapeutic intervention. Secondary endpoints are OSIs, isolated OSIs, wound infections, postoperative pancreatic fistula, bile or enteric anastomotic leakage, post pancreatectomy hemorrhage, delayed gastric emptying, bacteremia, Clostridium difficile infection, major morbidity (Clavien-Dindo ≥III), reintervention, ICU admission, length of hospital stay, readmission, and in-hospital and 90-day mortality. Besides, switch of postoperative antibiotics, antibiotic sensitivity patterns and concordance between perioperative bile and postoperative surgical site cultures are analyzed.

Sample size: The sample size is calculated for superiority to achieve an OSI difference of 15% (40% vs 25%). With a 80% power (1-β) and a two-sided significance level (α) of 5.0%, a sample of 304 evaluable patients is required for superiority. Assuming a 3% non-resection rate due to metastatic disease and a 3% loss-of-follow-up rate, an expected number of 322 included patients are needed to reach the sample size of 304 evaluable patients to demonstrate superiority for the intervention.

Patients will be randomized with a 1:1 allocation before surgery into the intervention or control group:

* Patients in the intervention group will receive perioperative prophylaxis (similar to the control group) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily.
* Patients in the control group will only receive perioperative prophylaxis (a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4h of surgery), which will be discontinued after surgery.

Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)

Standard Versus Pre-emptive Antibiotic Treatment to Reduce the Rate of Infectious Outcomes After Whipple's Procedure (SPARROW): a Multicenter, Randomized Controlled Trial

Available upon request to the principal investigator

Study protocol:

* Control arm: Perioperative antibiotic prophylaxis (cefazolin, metronidazole and single-dose gentamicin).
* Intervention arm: Perioperative plus prolonged antibiotics (cefuroxime and metronidazole for five postoperative days).

Rate of Antibiotic sensitivity patterns in bile cultures and cultures from surgical sites

Defined as the similarity of microorganisms between perioperative bile cultures and postoperative cultures from infectious sites.

A clinically relevant OSI is defined by the following criteria:

* A deep surgical site infection involving any part of the abdomen (e.g. organs and/or spaces) other than the surgical incision within 90 days after surgery.
* AND Requires radiological, endoscopic or surgical intervention OR therapeutic antibiotics required for an episode of sepsis, defined as two or more SIRS criteria.
* AND Organisms isolated from an aseptically obtained culture.

An OSI is defined by the CDC definition:

o The infection appears to be related to the operative procedure and infection involves any part of the anatomy (e.g., organs or spaces) other than the incision opened or manipulated during the operative procedure, and at least one of the following is present:

1. Purulent drainage from a drain that is placed into the organ/space.
2. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space.
3. An abscess or other evidence of infection involving the organ/space on direct examination, during reoperation, or by histopathologic or radiologic examination.
4. Diagnosis of an organ/space SSI by a surgeon or attending physician."

Isolated OSI is defined as an OSI without concurrent anastomotic leakage (pancreatojejunostomy, hepaticojejunostomy or gastrojejunostomy). The concept of an isolated OSI is used to separately classify abdominal infections without concurrent anastomotic leakage.

A superficial surgical site infection after surgery which involves superficial or deep soft tissue (skin, muscle or fascia, but no intra-abdominal tissue), and at least one of the following criteria is present:

* Purulent drainage from the incision or subcutaneous tissue.
* Isolation of microorganisms from an aseptically obtained culture of fluid or tissue from the superficial incision of subcutaneous tissue.
* Superficial infections of the skin or subcutaneous tissue which is deliberately opened by a surgeon or attending physician OR at least one of the following signs are present: localizes pain, tenderness, swelling, heat or fever \>38 degrees).

Grade B or C postoperative pancreatic fistula (POPF) defined by the International Study Group of Pancreatic Surgery definition:

Grade A: Amylase \>3 times upper limit of the institutional normal serum amylase value

Grade B: Grade A + persistant drainage \>3 weeks, clinically relevant change in management of POPF, percutaneous or endoscopic drainage, angiographic procedures for bleeding, or signs of infection without organ failure.

Grade C: Grade A or B requiring reoperation, resulting in organ failure or death.

Grade A, B or C defined by the ISGLS definition:

Grade A: Bile leakage requiring no or little change in patients' clinical management.

Grade B: Bile leakage requiring a change in patients clinical management (eg, additional diagnostic or interventional procedures) but manageable without relaparotomy, or a Grade A bile leakage lasting for \>1 week.

Grade C: Bile leakage requiring relaparotomy

Grade A, B or C defined by the ISGPS definition:

Grade A: Early (\<24h after surgery), intra- or extraluminal, clinically mild.

Grade B: Early (\<24h after surgery), intra- or extraluminal and clinically severe OR later (\>24h after surgery), intra- or extraluminal and clincally mild.

Grade C: Late (\>24h after surgery), intra- or extraluminal and clinically severe.

Grade A, B or C defined by the ISGPS definition:

Grade A: Until day 4-7 or replacement of feeding tube \> 3 days after surgery

Grade B: Until day 8-14 or replacement of feeding tube \> 7 days after surgery

Grade C: \>day 14 or replacement of feeding tube \> 14 after surgery

Defined as a positive blood culture obtained during a septic period (defined as two or more SIRS criteria)

Defined by a positive fecal culture for Clostridium difficile

Major complications is defined by a Clavien-Dindo score of ≥III.

Clavien-Dindo classification of Surgical Complications:

Grade I: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions.

Grade II: Requiring pharmacological treatment with drugs other than such allowed for grade I complications.

Grade IIIa: Requiring surgical, endoscopic or radiological intervention not under general anesthesia Grade IIIb: Requiring surgical, endoscopic or radiological intervention under general anesthesia

Grade IVa: Life-threatening complication (including CNS complications)\* requiring IC/ICU-management with single organ dysfunction (including dialysis).

Grade IVb: Life-threatening complication (including CNS complications)\* requiring IC/ICU-management with multi organ dysfunction.

Grade V: Death of a patient

Reinterventions could be either radiological, surgical or endoscopic reinterventions

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative Biliary Drainage With Metal Versus Plastic Stents in Periampullary Cancer	NCT02787512	Jaundice Periampullary C...	Stent	20 Years -	Seoul National University Hospital
Preoperative Biliary Drainage in Patients With Operable Malignant Periampulary Tumors	NCT04289831	Periampullary C... Biliary Obstruc... Preoperative Bi...	Preoperative Bi... Surgery	18 Years - 70 Years	University of Alexandria
Preoperative Biliary Drainage for Resectable Hilar Cholangiocarcinoma	NCT00797121	Cholangiocarcin... Drainage Surgery	Preoperative bi...	18 Years - 75 Years	Sun Yat-sen University
Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)	NCT05784311	Pancreatic Canc...	Cefuroxime Metronidazole	18 Years - 90 Years	Leiden University Medical Center

Spots Global Cancer Trial Database for preoperative biliary drainage