Minimally Invasive Pancreatic Enucleation With Main Pancreatic Duct Repair or Reconstruction

Pancreatic Neuroendocrine Tumor Clinical Trial

Official title:

Long-term Prognosis and Quality of Life in Minimally Invasive Pancreatic Enucleation With Main Pancreatic Duct Repair or Reconstruction: A Multicenter Prospective Single-Arm Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06024343
• Other study ID #: CSPAC-MEN-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: August 2023
• Source: Fudan University
• Contact: Xianjun Yu, MD, PhD
• Phone: +86-13801669875
• Email: yuxianjun[@]fudanpci.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the impact of concomitant main pancreatic duct repair or reconstruction during minimally invasive pancreatic tumor enucleation on long-term patient prognosis and quality of life.

Description:

Standard surgical procedures for benign or low-grade malignant pancreatic tumors is associated with increased risks of postoperative complications and long-term pancreatic functional impairment, while parenchyma-sparing pancreatectomy such as enucleation can reduce the incidence of complications and preserve healthy parenchyma, thereby preserve both endocrine and exocrine pancreatic function. It has been reported that pancreatic tumor enucleation is a safe and feasible approach in preserving normal physiological function in patients undergoing pancreatic surgery.

With the growing emphasis on routine screenings and the application of high-quality thin-slice imaging techniques, the detection rates of pancreatic tumors have witnessed a steady increase. Additionally, there is a notable trend towards younger patients being diagnosed with pancreatic tumors. Consequently, in conjunction with ensuring safe and thorough tumor resection while maximizing preservation of pancreatic function, there is a current clinical demand to further reduce surgical trauma.

Literature reviews and meta-analyses have demonstrated that minimally invasive enucleation procedures offer well-known advantages associated with minimally invasive approaches, such as shorter postoperative hospital stays and lower overall complication rates. While the occurrence rate of severe complications, such as postoperative hemorrhage, remains relatively low, the development of postoperative pancreatic fistula (POPF) continues to pose a challenging issue.

The distance between the tumor and the main pancreatic duct (MPD) is considered a crucial factor influencing the occurrence of POPF after enucleation. However, these data have been rarely described in previous studies, making it challenging to accurately assess their actual impact on the rate of POPF occurrence. Heeger et al. suggested that the risk of POPF increases with closer proximity of the tumor to the MPD. The incidence of POPF was higher in deep-seated tumors after pancreatic enucleation (distance to MPD <3 mm) compared to superficial tumors (>3 mm) (73.3% vs. 30.0%, P=0.002). Other studies have even limited this critical distance to 2mm. Some research has indicated that if the tumor invades or encases the MPD, enucleation surgery should be contraindicated, and standard resection should be preferred to avoid the risk of POPF postoperatively. However, a retrospective analysis by Strobel et al. on 166 cases of pancreatic tumor enucleation demonstrated that even tumors in close proximity to the MPD can be safely resected, although their study did not include cases with tumor encasement of the MPD. In 2021, Professor Liu Rong and colleagues introduced the concept of pancreatic duct surgery and outlined four main surgical approaches: MPD repair, pancreatic end-to-end anastomosis, local excision of branch-duct intraductal papillary mucinous neoplasms, and MPD replacement. However, detailed research data in this field are still lacking.

The safety and feasibility of minimally invasive pancreatic tumor enucleation procedures involving MPD repair or reconstruction, the control of POPF, and the long-term prognosis and quality of life of patients after MPD repair or reconstruction remain unclear. Therefore, this study aims to conduct a prospective, multicenter, single-arm clinical trial. The results of this study will serve as a valuable reference for clinical practice and promote the development and application of minimally invasive pancreatic tumor enucleation procedures.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 112
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and 70 years, regardless of gender.

2. Solitary benign or low-grade malignant tumor of the pancreas.

3. Patients evaluated according to guidelines indicating the need for surgery or strongly requesting surgery.

4. Feasibility of performing minimally invasive pancreatic tumor enucleation based on preoperative imaging evaluation.

5. Intraoperative procedure involving repair or reconstruction of the main pancreatic duct.

6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. Willingness to comply with the study's follow-up plan and other protocol requirements.

8. Voluntary participation and signed informed consent.

Exclusion Criteria:

1. Body mass index (BMI) > 35 kg/m2.

2. Individuals planning pregnancy, currently pregnant, or breastfeeding.

3. History of major abdominal surgery.

4. Concurrent presence of other malignant tumors.

5. Intraoperative frozen pathology or postoperative pathology indicating the tumor to be malignant, requiring curative resection instead.

6. Severe impairment of cardiac, hepatic, or renal function (e.g., NYHA class 3-4 heart failure, ALT and/or AST levels exceeding three times the upper limit of normal, creatinine levels exceeding the upper limit of normal).

7. Participation in other clinical trials simultaneously.

Withdrawal Criteria:

1. Significant changes in the participant's condition after enrollment that render the study protocol unsuitable or infeasible.

2. Occurrence of severe complications that impact the implementation of the study plan.

3. Identification of technical difficulties after enrollment, making the studied treatment protocol impossible to implement.

4. Emergent need for treatment due to other diseases confirmed after enrollment.

5. Deviation from the study protocol in the actual administration of treatment.

6. Voluntary withdrawal or discontinuation of any examinations, treatments, and monitoring required by the study at any stage, for personal reasons of the participant.

Related Conditions & MeSH terms

• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neoplasms
• Pancreatic Neuroendocrine Tumor
• Pancreatic Tumor, Benign
• Solid Pseudopapillary Tumor of the Pancreas

Intervention

Procedure:
• MPD Repair or Reconstruction
During laparoscopic or robotic pancreatic tumor enucleation, if the main pancreatic duct (MPD) is damaged due to its proximity or encasement by the tumor, MPD repair or reconstruction is performed.

Locations

Country	Name	City	State
China	Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (6)

Lead Sponsor	Collaborator
Fudan University	Chinese PLA General Hospital, Qilu Hospital of Shandong University, The Affiliated Hospital of Xuzhou Medical University, The Third Affiliated Hospital of Soochow University, Tongji Hospital

Country where clinical trial is conducted

China, 

References & Publications (14)

Bartolini I, Bencini L, Bernini M, Farsi M, Calistri M, Annecchiarico M, Moraldi L, Coratti A. Robotic enucleations of pancreatic benign or low-grade malignant tumors: preliminary results and comparison with robotic demolitive resections. Surg Endosc. 2019 Sep;33(9):2834-2842. doi: 10.1007/s00464-018-6576-3. Epub 2018 Nov 12. — View Citation

Brient C, Regenet N, Sulpice L, Brunaud L, Mucci-Hennekine S, Carrere N, Milin J, Ayav A, Pradere B, Hamy A, Bresler L, Meunier B, Mirallie E. Risk factors for postoperative pancreatic fistulization subsequent to enucleation. J Gastrointest Surg. 2012 Oct;16(10):1883-7. doi: 10.1007/s11605-012-1971-x. Epub 2012 Aug 8. — View Citation

Cauley CE, Pitt HA, Ziegler KM, Nakeeb A, Schmidt CM, Zyromski NJ, House MG, Lillemoe KD. Pancreatic enucleation: improved outcomes compared to resection. J Gastrointest Surg. 2012 Jul;16(7):1347-53. doi: 10.1007/s11605-012-1893-7. Epub 2012 Apr 24. — View Citation

Dalla Valle R, Cremaschi E, Lamecchi L, Guerini F, Rosso E, Iaria M. Open and minimally invasive pancreatic neoplasms enucleation: a systematic review. Surg Endosc. 2019 Oct;33(10):3192-3199. doi: 10.1007/s00464-019-06967-9. Epub 2019 Jul 30. — View Citation

Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao JC. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017 Oct 1;3(10):1335-1342. doi: 10.1001/jamaoncol.2017.0589. — View Citation

Ei S, Mihaljevic AL, Kulu Y, Kaiser J, Hinz U, Buchler MW, Hackert T. Enucleation for benign or borderline tumors of the pancreas: comparing open and minimally invasive surgery. HPB (Oxford). 2021 Jun;23(6):921-926. doi: 10.1016/j.hpb.2020.10.001. Epub 2020 Oct 18. — View Citation

Giuliani T, De Pastena M, Paiella S, Marchegiani G, Landoni L, Festini M, Ramera M, Marinelli V, Casetti L, Esposito A, Bassi C, Salvia R. Pancreatic Enucleation Patients Share the Same Quality of Life as the General Population at Long-Term Follow-Up: A Propensity Score-Matched Analysis. Ann Surg. 2023 Mar 1;277(3):e609-e616. doi: 10.1097/SLA.0000000000004911. Epub 2021 Apr 14. — View Citation

Guerra F, Giuliani G, Bencini L, Bianchi PP, Coratti A. Minimally invasive versus open pancreatic enucleation. Systematic review and meta-analysis of surgical outcomes. J Surg Oncol. 2018 Jun;117(7):1509-1516. doi: 10.1002/jso.25026. Epub 2018 Mar 25. — View Citation

Kromrey ML, Bulow R, Hubner J, Paperlein C, Lerch MM, Ittermann T, Volzke H, Mayerle J, Kuhn JP. Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut. 2018 Jan;67(1):138-145. doi: 10.1136/gutjnl-2016-313127. Epub 2017 Sep 6. — View Citation

Shukla PJ, Barreto SG, Shrikhande SV. Enucleation of pancreatic neoplasms (Br J Surg 2007; 94: 1254-1259). Br J Surg. 2008 Feb;95(2):261; author reply 261-2. doi: 10.1002/bjs.6148. No abstract available. — View Citation

Strobel O, Cherrez A, Hinz U, Mayer P, Kaiser J, Fritz S, Schneider L, Klauss M, Buchler MW, Hackert T. Risk of pancreatic fistula after enucleation of pancreatic tumours. Br J Surg. 2015 Sep;102(10):1258-66. doi: 10.1002/bjs.9843. Epub 2015 Jun 24. — View Citation

van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol. 2019 Nov;16(11):676-689. doi: 10.1038/s41575-019-0195-x. Epub 2019 Sep 16. — View Citation

Zhang RC, Zhou YC, Mou YP, Huang CJ, Jin WW, Yan JF, Wang YX, Liao Y. Laparoscopic versus open enucleation for pancreatic neoplasms: clinical outcomes and pancreatic function analysis. Surg Endosc. 2016 Jul;30(7):2657-65. doi: 10.1007/s00464-015-4538-6. Epub 2015 Oct 20. — View Citation

Zhou Y, Zhao M, Wu L, Ye F, Si X. Short- and long-term outcomes after enucleation of pancreatic tumors: An evidence-based assessment. Pancreatology. 2016 Nov-Dec;16(6):1092-1098. doi: 10.1016/j.pan.2016.07.006. Epub 2016 Jul 9. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Clinically Relevant Postoperative Pancreatic Fistula	Clinically Relevant Pancreatic Fistula including Grade B fistulas, which require treatment beyond simple drainage, as well as Grade C fistulas.	Within 90 days after surgery.
Secondary	Perioperative complication rate according to the Clavien-Dindo classification	Adverse events that occur during or after the surgery, reported according to the Clavien-Dindo classification.	Within 90 days after surgery.
Secondary	Postoperative pancreatic hemorrhage (PPH) rate	Postoperative pancreatic hemorrhage (PPH) rate within 90 days after surgery, reported according to the ISGPS definition.	Within 90 days after surgery.
Secondary	Delayed gastric emptying (DGE) rate	Delayed gastric emptying (DGE) rate within 90 days after surgery, reported according to the ISGPS definition.	Within 90 days after surgery.
Secondary	Reoperation rate	Reoperation rate within 90 days after surgery.	Within 90 days after surgery.
Secondary	Rate of pancreatic enzyme-dependent malabsorption	Postoperative pancreatic enzyme-dependent malabsorption rate.	Through study completion, an average of 3 year.
Secondary	Rate of new-onset diabetes	Postoperative new-onset diabetes rate.	Through study completion, an average of 3 year.
Secondary	Life quality satisfaction evaluated according to EORTC C30 scale	The patient's health-related quality of life after surgical intervention. It includes physical, emotional, and social aspects of a patient's well-being. This study evaluated quality of life using a telephone survey and the EORTC C30 scales.	Through study completion, an average of 3 year.
Secondary	R0 resection rate	R0 margin rate on postoperative pathological assessment.	From the date of surgery to 1 month after surgery.
Secondary	Recurrence-free survival (RFS)	The time of surgery to the time of tumor recurrence or death.	Through study completion, an average of 3 year.

External Links

•   In 2021, Professor Liu Rong and colleagues introduced the concept of pancreatic duct surgery for the first time and outlined four main surgical approaches.