Neoplasms

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Cholangiocarcinoma

Carcinoma, Ductal

Carcinoma, Pancreatic Ductal

Bile Duct Neoplasms

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

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Gastrointestinal Diseases

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Endocrine System Diseases

Biliary Tract Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Pancreatic Cancer

Bile Duct Cancer

Patients who underwent pancreaticoduodenectomy for PDAC between 01/06/2010 and 31/05/2015

Patients who underwent pancreaticoduodenectomy for ampullary cancer between 01/06/2010 and 31/05/2015

Patients who underwent pancreaticoduodenectomy for distal extrahepatic cholangiocarcinoma between 01/06/2010 and 31/05/2015

Pancreaticoduodenectomy

Somaiah Aroori

Pancreatic head malignancies are aggressive cancers that are often inoperable when they are diagnosed. In the \~20% of patients who are diagnosed when the disease is still operable, surgery is the only treatment that can provide a chance of cure. Unfortunately, up to 75% of patients undergoing surgery will have the cancer come back (recur). One of the reasons for this is the challenge of removing the whole tumour with some surrounding non-cancerous tissue to ensure that every tumour cell has been removed. This is difficult because there are many structures very close to the pancreas (such as the blood vessels that supply the intestines) that cannot be removed. A recent review study of \>1700 patients who had a Whipple's operation (the cancer operation that is performed to remove the head of pancreas) and found that whilst the majority of patients had cancer recurrence in distant sites (like the liver) that would not be affected by how the operation was performed, 12% of patients had the cancer recur just at the site of where the operation had been; this is known as 'local' recurrence. This suggests that a small amount of cancer was not removed at the time of surgery in these patients. Very few studies have looked at the relationship between the Computerised Tomography (CT) scan before surgery and the histology results (information about the tumour after it has been examined under the microscope) and whether this can predict exactly where the tumour recurs. If investigators can find factors that predict which patients get local only recurrence, investigators may be able to offer improved surgical techniques or other therapies during or immediately after the operation to these patients, hopefully leading to improved cure rates.

This retrospective international study will look at these factors in patients who underwent a Whipple's operation for pancreatic cancer, bile duct cancer or ampullary cancer over a three year period between 2012 and 2015. Participating centres will provide data on pre-operative scans, complications around the time of surgery, any therapies (e.g. chemotherapy) that the patients had and if and where the cancer recurred. With this information, investigators hope to find ways to predict which patients will get local-only recurrence, so researchers can select them for future studies to see if additional treatments can improve the chance of cure from surgery for these patients.

Research window:

This retrospective observational cohort study will investigate the outcomes of patients who underwent pancreaticoduodenectomy at 30 hepatopancreaticobiliary (HPB) surgery centres in the UK and abroad between 01/06/2012 and 31/05/2015. These dates were chosen because:

* Most HPB units would expect to see 30-50 patients undergoing pancreaticoduodenectomy per annum. Based on the chief investigator's unit's prospectively maintained database of consecutive patients, 310 patients underwent pancreaticoduodenectomy during this window (benign and malignant). A five year research window would provide a large number of patients that is appropriate for subset analysis. This is especially important in distal cholangiocarcinoma, which is less commonly treated with pancreaticoduodenectomy compared to pancreatic and ampullary cancer. Even if all centres only provided 100 patients (20 per annum), this would provide a cohort of \~3000 patients. This number of cases will have greater resolution to detect small but significant statistical differences in studied variables.
* The amount of data available on patient records reduces with chronicity, in part due to a heavier reliance on paper rather than digital records. In addition, other reporting standards (e.g. TNM staging and histology reporting) change over time. 2010 was selected as a starting year as the 7th edition of the UICC TNM staging came into effect that year.
* An end date of June 2015 allows the study to collect full five-year follow up data on all patients to June 2020, thus providing a complete data set.

Data collection:

Data will be collected by each participating centre on a purpose-built REDCap database. REDCap is a well-established secure web-based data collection tool that is frequently used in medical research involving several centres. Advantages include:

* Real-time collection of data from all centres visible to the research team.
* Guaranteed anonymity of patients as only anonymised data will be collected.
* In-built data validation (e.g. set limits on expected ranges of values) to reduce poor quality/erroneous data collection.
* Easy download of data into a format suitable for processing on an appropriate statistical software package (e.g. SPSS).
* The ability to display or hide questions based on previous responses to tailor data collection to each record.

REDCap access is provided through University Hospitals Plymouth NHS Trust (UHPNT). Data is stored on the Microsoft Azure web-based cloud service. Servers are based in the EU and are GDPR compliant. REDCap access will be provided to all participating centres (one user log in per centre) for data collection.

Data collected falls into the following categories (examples given after each category are not exhaustive):

* Participant ID number (anonymised).
* Demographics: Age, sex, body mass index.
* Comorbidities: Diabetes, cardiovascular disease, respiratory disease, previous history of cancer.
* Pre-operative imaging: Dates, modalities, maximum tumour size, radiological TNM stage.
* Pre-operative biliary drainage: Approach, stent type.
* Neoadjuvant therapies: Type, duration.
* Pre-operative bilirubin.
* Surgery: Date, type, ASA grade, intraoperative procedures and findings.
* Post-operative complications: Types, date of occurrence, Clavien-Dindo grade, treatment, 30-day readmission, 90-day mortality and cause of death.
* Histology: Cancer type, differentiation, tumour size, pathological TNM stage, R status, involved margins and distance, total and involved number of resected lymph nodes, perineural, microvascular and named vessel invasion.
* Adjuvant therapies: Type, duration.
* Recurrence: Date of recurrence, site(s) of recurrence.
* Palliative therapies: Type, duration.
* Survival: Disease free survival (DFS) and overall survival (OS).

Screening of eligible patients:

Patients will be screened to ensure that they meet the inclusion and exclusion criteria (see below). Each unit will be responsible for screening patients for eligibility. All participating units have confirmed that they already have an existing list of consecutive patients who underwent PD during the research window. The clinical team at each participating unit will be responsible for maintaining a password-protected participant look up database that links the local patient hospital number to the anonymised participant ID number on REDCap.

Plymouth sub-study on sarcopenia and myosteatosis:

There is evidence that sarcopenia and myosteatosis may indicate a higher risk of postoperative complications, although its impact on DFS and OS is not yet established. Patients entered into the study from Plymouth will also have their pre-operative CT scan reviewed by a member of the research team trained in sarcopenia and myosteatosis estimation (an academic radiology trainee). The clinicians taking the measurements will be unaware of any outcomes or complications.

This is not being extended to other centres for the following reasons:

* Normal values of tissue attenuation are specific to local populations due to the variation in morphology of patients and the HU cut-offs in one country are not applicable to other countries. It would therefore not be possible to pool data on myosteatosis and sarcopenia from multiple countries.
* As the measurement relies on pre-operative CT imaging, and CT scanners and protocols vary between hospitals and change over time, it is difficult to retrospectively pool such data from multiple sites and maintain meaningful data. Using a single centre provides more robust data for analysis.
* The investigators will be using an inbuilt software package that is part of Plymouth's InSightWeb. This package may not be available in other centres.

As this reduces the number of patients in the cohort, Plymouth will extend its research window to 01/05/2006. This date was chosen as it is the beginning of their prospectively maintained database. This provides a pre-screened population of 365 patients who underwent PD at our unit, with a predicted 276 patients for analysis.

Recurrence After Whipple's (RAW) Study

An International Multi-centre Retrospective Cohort Study Investigating Patterns of Cancer Recurrence Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma, Ampullary Adenocarcinoma and Distal Bile Duct Cholangiocarcinoma

* The use of pre-operative endoscopic or percutaneous biliary stenting.
* Pre-operative systemic comorbidities.
* Pre-operative diagnosis of diabetes.
* Pre-operative radiological UICC Tumour Node Metastasis (TNM) staging.
* Named vessel involvement on pre-operative imaging.
* Sarcopenia or myosteatosis present on pre-operative imaging.\*
* The use of neoadjuvant chemotherapy/radiotherapy.
* Pre-operative serum bilirubin.
* Portal Vein (PV) / Superior Mesenteric Vein (SMV) resection.
* Hepatic Artery (HA) / Superior Mesenteric (SMA) / Coeliac Artery (CA) resection
* Need for peri-operative blood transfusion.
* Type of pancreatic anastomosis \[pancreatico-gastric (PG) vs. pancreatico-jejunal (PJ)\].
* Post-operative complications.
* The use and number of post-operative drains.
* Histological factors:
* The use of adjuvant chemotherapy.
* The use of palliative chemotherapy.

* Preoperative TNM staging.
* Named vessel involvement on preoperative imaging.
* The use of neoadjuvant chemotherapy/radiotherapy.
* PV/SMV resection.
* HA/SMA/CA resection.
* Histological factors
* The use of adjuvant chemotherapy.
* The use of palliative chemotherapy.

University of Plymouth

University Hospital Plymouth NHS Trust

Photodynamic therapy for neoadjuvant treatment of cholangiocarcinoma

Patients with cholangiocarcinoma undergo radical surgical resection

Patients with cholangiocarcinoma will undergo radical surgery after photodynamic therapy

Neoadjuvant PDT + radical surgery

Patients with cholangiocarcinoma will only receive radical surgery

Radical surgery

Yi Lv, MD,PHD

Rongfeng Wang, MD

Xiaogang Zang, MD

For patients with locally advanced cholangiocarcinoma with resectable margins, patients who meet the selection criteria are randomly divided into two groups A and B. Group A: neoadjuvant PDT therapy combined with radical surgery; Group B: radical surgery. This study aims to explore the clinical effectiveness and safety of neoadjuvant photodynamic therapy for cholangiocarcinoma, as well as its role in destroying local tumors and enhancing systemic inflammation.

The average 5-year survival rate of patients with cholangiocarcinoma is about 5-10%. Only 30%-40% of patients have the opportunity to obtain radical surgery. Surgical resection is limited by the extent of tumor spread along the bile duct branches and segments, and the degree of involvement of the portal vein and (or) hepatic artery branches. Complete resection with negative margins (R0) is the only possible radical treatment. Only 60%-78% of radical surgery for cholangiocarcinoma are considered to achieve true R0 resection, and the tumor-free margin is often very short. Even after R0 resection, the recurrence rate is as high as 50%-76%. Photodynamic therapy is a tumor specific ablation method with small side effects and repeated treatments will not produce drug resistance. It provides a new prospect for the treatment of cholangiocarcinoma. For the current patients with locally advanced cholangiocarcinoma, neoadjuvant photodynamic therapy is used to make them resectable. Demotion and subsequent resection may potentially improve their results. Similarly, patients with resectable margins can benefit from tumor downgrading by increasing their chances of undergoing R0 resection. In order to increase the negative rate of resection margins, and to ensure sufficient tumor-free margins of the bile duct stumps, the research is still blank. For patients with locally advanced cholangiocarcinoma with resectable margins, patients who meet the selection criteria are randomly divided into two groups A and B. Group A: neoadjuvant PDT therapy combined with radical surgery; Group B: radical surgery. This study aims to explore the clinical effectiveness and safety of neoadjuvant photodynamic therapy, as well as its role in destroying local tumors and enhancing systemic inflammation.This study plans to enroll 50 patients. It is planned to complete the enrollment operation within 2 years, and the follow-up observation will be continued for 5 years after the operation. All patients are expected to complete neoadjuvant PDT treatment and radical surgery within 2 years, survival period (5 years survival rate), R0 resection rate and local recurrence rate are the main observation indicators, and the bilirubin level, the number of intraoperative freezing, the length of the tumor-free margin of the tumor tissue, and the incidence of complications (biliary leakage, cholangitis, phototoxicity) are the secondary observation indicators.

Neoadjuvant PDT in the Treatment of Cholangiocarcinoma

A Prospective Randomized Controlled Study of Neoadjuvant PDT in the Treatment of Cholangiocarcinoma

Compare the incidence of positive margins of bile duct after surgical resection of cholangiocarcinoma between the two groups

Compare the local recurrence rate of cholangiocarcinoma between the two groups

Compare the 5-year survival time of the two groups

Compare the Bilirubin level of the two groups

Compare the incidence of bile leakage, cholangitis, phototoxicity and other complications between the two groups

Compare the length of the tumor-free margin of the two groups of cholangiocarcinoma tissues

First Affiliated Hospital Xi'an Jiaotong University

Neoplasm Metastasis

Lymphatic Metastasis

Neoplastic Processes

Intrahepatic Cholangiocarcinoma

Patients with ICC who had lymph node metastases at the time of primary tumor treatment with D2 dissection, in the first cohort.

Patients with ICC who did not have lymph node metastases at the time of primary tumor treatment with D2 dissection, in the first cohort.

Patients with ICC who had lymph node metastases at the time of primary tumor treatment with D2 dissection, in the second cohort.

Patients with ICC who did not have lymph node metastases at the time of primary tumor treatment with D2 dissection, in the second cohort.

A panel of exosomal miRNAs, whose expression levels are tested in serum or plasma samples collected prior to primary tumor resection, with reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR)

LyMIC (Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma)

Ajay Goel, PhD

Takayuki Noma, MD

Akinobu Taketomi, PhD

Kazuki Wakizaka, PhD

Masaki Mori, PhD

Takeo Toshima, PhD

Mitsuo Shimada, PhD

Yuma Wada, PhD

Yuji Morine, PhD

Tetsuya Ikemoto, PhD

Yu Saito, PhD

Lymph node metastasis (LNM) is a major prognostic factor in intrahepatic cholangiocarcinoma (ICC), and accurate preoperative prediction of the presence or absence of LNM has significant clinical implications in determining treatment strategy. Despite this, there are currently no reliable biomarkers established to detect LNM in ICC.

This study seeks to develop a liquid biopsy assay that can accurately detect LNM before treatment in ICC patients.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor of the liver arising from epithelial cells of the biliary tract, accounting for 10-15% of primary liver cancers, and the incidence of ICC has increased rapidly worldwide over the past decade. The long-term prognosis is dismal, with a 5-year overall survival (OS) as low as 25-30%. Many studies have highlighted lymph node metastasis as a strong predictor of poor prognosis in ICC patients, prompting efforts such as appropriate lymphadenectomy to accurately predict disease stage and reduce outcomes associated with LNM. Adequate lymphadenectomy in patients with suspected LNM is essential for achieving R0 resection and is a necessary component of complete cure and long-term survival. The routine use of highly invasive lymphadenectomy in all patients remains controversial, and lymphadenectomy rates for ICC range from 26.9% to 100% depending on the literature and are not universally adopted currently.

Currently, LNM is detected preoperatively by imaging, but imaging alone is not sufficient to diagnose LNM, as negative findings by imaging findings may have low sensitivity and may not rule out LNM. Other attempts have been made to develop predictive scoring systems based on Carbohydrate antigen 19-9 (CA 19-9) levels, location of the primary tumor, lymph node patterns on CT and MRI, and other clinical factors to predict LNM in ICC, but all these predictive systems rely heavily on judgment regarding lymph node size and tumor growth patterns are largely left to diagnostic imaging.

This study seeks to validate a panel of more accurate and non-invasive biomarkers (exo-miRNAs) in preoperative blood samples. Accurate preoperative detection of the presence of LNM would help provide clear criteria for ICC treatment decisions, such as the implementation of elective lymphadenectomy or the addition of chemotherapy.

Detecting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma (LyMIC)

An Exosome-based Liquid Biopsy Signature for Pre-operative Identification of Lymph Node Metastasis in Patients With Intrahepatic Cholangiocarcinoma

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data

True Positive Rate: the probability of a positive test result, conditioned on the individual truly being positive

True Negative Rate: the probability of a negative test result, conditioned on the individual truly being negative

A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Recurrence After Whipple's (RAW) Study	NCT04596865	Pancreatic Canc... Ampullary Cance... Bile Duct Cance... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Pancreatic Duct... Pancreatic Duct... Surgery Survivorship Recurrent Cance... Cancer Recurren... Cancer Recurren... Local Recurrenc...	Pancreaticoduod...	-	University Hospital Plymouth NHS Trust
Neoadjuvant PDT in the Treatment of Cholangiocarcinoma	NCT04824742	Cholangiocarcin...	Neoadjuvant PDT... Radical surgery	18 Years - 75 Years	First Affiliated Hospital Xi'an Jiaotong University
Detecting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma (LyMIC)	NCT06381648	Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin...	LyMIC (Lymph No...	18 Years -	City of Hope Medical Center

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