Title: Outcome of patients with perihilar cholangiocarcinoma and previous biliary
instrumentation: An observational study
Version: 2 Date: 21 Dec 2023
Reviewer's report:
This is an interesting and thoughtful paper which addresses an important topic and management
conundrum.  However I do not think the issue of inherent selection bias has been adequately
addressed.  The authors put forth that patients who present to their institution with prior
transpapillary biliary drainage done at another institution ultimately do worse and have delays in
treatment.  The overarching question seems to be why certain patients presented with or without
prior procedures, and where those prior procedures were performed.  Were the patients that
were stented more jaundiced with higher bilirubins initially than those that were not?  In their
Introduction they state that ERCP if often next step with stent placement even without indication,
but it is unclear what they consider to be appropriate indications.  Do they advocate for a strict
preop Tbili cutoff (i.e. 13 for pancreaticoduodenectomies)?  In their indications for additional
drainage procedures they list need to decrease bilirubin for treatment as an indication in 50% of
their patients.  Would this not be a reasonable indication for stenting at an outside institution as
well?  As more than 50% of the patients who presented without instrumentation then went on to
require instrumentation, why it is unreasonable that for many patients the initial instrumentation
took place elsewhere?  How many of the patients that were instrumented at their institution went
on to develop complications afterwards?
In their Methods they describe situations where bilirubins remained elevated as ineffective
drainage procedures.  Is it possible that some of those patients were in liver failure even with
adequate drainage? And what time interval were they considering, as sometimes even after
adequate drainage bilirubins can take days to weeks to normalize.
The Discussion focuses on the inadequacy of endoscopic drainage in these patients, however a
number of patients, albeit a minority, underwent percutaneous drainage at outside institutions
prior to their evaluation at the authors' center.  Do this authors deem this acceptable, or no
because all devices crossed the papilla?  In theory an advantage to crossing the papilla is to
allow for internalization of drainage and prevent ongoing fluid losses and complications thereof.
Could the authors comment on this and how they manage patients with external drainage?
In their conclusion they state that patients with perihilar cholangiocarcinoma should be evaluated
at a specific cancer referral center before any intervention.  Patients may present to a cancer
center for consultation and potential treatment , but this does not mean they their initial
management was at a place incapable of treating biliary cancers, and does not mean that an
HPB surgeon was not initially involved in their care, unless the authors knew this information
but failed to state it.  Often the suspicion for a cholangiocarcinoma is not raised until the time
of ERCP when a malignant stricture as demonstrated, as, even on high quality cross-sectional
imaging, the diagnosis can remain unclear.
Title: Outcome of patients with perihilar cholangiocarcinoma and previous biliary
instrumentation: An observational study
Version: 2 Date: 21 Dec 2023
Reviewer's report:
This is an interesting and thoughtful paper which addresses an important topic and management
conundrum.  However I do not think the issue of inherent selection bias has been adequately
addressed.  The authors put forth that patients who present to their institution with prior
transpapillary biliary drainage done at another institution ultimately do worse and have delays in
treatment.  The overarching question seems to be why certain patients presented with or without
prior procedures, and where those prior procedures were performed.  Were the patients that
were stented more jaundiced with higher bilirubins initially than those that were not?  In their
Introduction they state that ERCP if often next step with stent placement even without indication,
but it is unclear what they consider to be appropriate indications.  Do they advocate for a strict
preop Tbili cutoff (i.e. 13 for pancreaticoduodenectomies)?  In their indications for additional
drainage procedures they list need to decrease bilirubin for treatment as an indication in 50% of
their patients.  Would this not be a reasonable indication for stenting at an outside institution as
well?  As more than 50% of the patients who presented without instrumentation then went on to
require instrumentation, why it is unreasonable that for many patients the initial instrumentation
took place elsewhere?  How many of the patients that were instrumented at their institution went
on to develop complications afterwards?
In their Methods they describe situations where bilirubins remained elevated as ineffective
drainage procedures.  Is it possible that some of those patients were in liver failure even with
adequate drainage? And what time interval were they considering, as sometimes even after
adequate drainage bilirubins can take days to weeks to normalize.
The Discussion focuses on the inadequacy of endoscopic drainage in these patients, however a
number of patients, albeit a minority, underwent percutaneous drainage at outside institutions
prior to their evaluation at the authors' center.  Do this authors deem this acceptable, or no
because all devices crossed the papilla?  In theory an advantage to crossing the papilla is to
allow for internalization of drainage and prevent ongoing fluid losses and complications thereof.
Could the authors comment on this and how they manage patients with external drainage?
In their conclusion they state that patients with perihilar cholangiocarcinoma should be evaluated
at a specific cancer referral center before any intervention.  Patients may present to a cancer
center for consultation and potential treatment , but this does not mean they their initial
management was at a place incapable of treating biliary cancers, and does not mean that an
HPB surgeon was not initially involved in their care, unless the authors knew this information
but failed to state it.  Often the suspicion for a cholangiocarcinoma is not raised until the time
of ERCP when a malignant stricture as demonstrated, as, even on high quality cross-sectional
imaging, the diagnosis can remain unclear.
Please review this paper.
user
Title: Outcome of patients with perihilar cholangiocarcinoma and previous biliary
instrumentation: An observational study
Version: 2 Date: 21 Dec 2023
Reviewer's report:
This is an interesting and thoughtful paper which addresses an important topic and management
conundrum.  However I do not think the issue of inherent selection bias has been adequately
addressed.  The authors put forth that patients who present to their institution with prior
transpapillary biliary drainage done at another institution ultimately do worse and have delays in
treatment.  The overarching question seems to be why certain patients presented with or without
prior procedures, and where those prior procedures were performed.  Were the patients that
were stented more jaundiced with higher bilirubins initially than those that were not?  In their
Introduction they state that ERCP if often next step with stent placement even without indication,
but it is unclear what they consider to be appropriate indications.  Do they advocate for a strict
preop Tbili cutoff (i.e. 13 for pancreaticoduodenectomies)?  In their indications for additional
drainage procedures they list need to decrease bilirubin for treatment as an indication in 50% of
their patients.  Would this not be a reasonable indication for stenting at an outside institution as
well?  As more than 50% of the patients who presented without instrumentation then went on to
require instrumentation, why it is unreasonable that for many patients the initial instrumentation
took place elsewhere?  How many of the patients that were instrumented at their institution went
on to develop complications afterwards?
In their Methods they describe situations where bilirubins remained elevated as ineffective
drainage procedures.  Is it possible that some of those patients were in liver failure even with
adequate drainage? And what time interval were they considering, as sometimes even after
adequate drainage bilirubins can take days to weeks to normalize.
The Discussion focuses on the inadequacy of endoscopic drainage in these patients, however a
number of patients, albeit a minority, underwent percutaneous drainage at outside institutions
prior to their evaluation at the authors' center.  Do this authors deem this acceptable, or no
because all devices crossed the papilla?  In theory an advantage to crossing the papilla is to
allow for internalization of drainage and prevent ongoing fluid losses and complications thereof.
Could the authors comment on this and how they manage patients with external drainage?
In their conclusion they state that patients with perihilar cholangiocarcinoma should be evaluated
at a specific cancer referral center before any intervention.  Patients may present to a cancer
center for consultation and potential treatment , but this does not mean they their initial
management was at a place incapable of treating biliary cancers, and does not mean that an
HPB surgeon was not initially involved in their care, unless the authors knew this information
but failed to state it.  Often the suspicion for a cholangiocarcinoma is not raised until the time
of ERCP when a malignant stricture as demonstrated, as, even on high quality cross-sectional
imaging, the diagnosis can remain unclear.
assistant