Abbreviations:
IPMN (intraductal papillary mucinous neoplasia), MD (main duct), MPD (main pancreatic duct)In this issue of Gastrointestinal Endoscopy, Uehara et al
1
report on the predictive value of imaging and pancreatic juice cytologic analysis to diagnose malignant degeneration of main duct (MD) intraductal papillary mucinous neoplasia (IPMN).1
Although it might not be surprising that a positive result of cytologic analysis was identified as an independent predictor of malignancy, this series adds evidence to the association between the size of a mural nodule and the likelihood of malignant degeneration of MD-IPMN. Their results also indicate that main pancreatic duct (MPD) diameter as a predictive factor may have a more limited value.Within the spectrum of IPMN ranging from branch duct IMPN to mixed-type IPMN to MD-IPMN, the latter constitutes a unique clinicopathologic entity at the far end of the spectrum, with respect to both its appearance on imaging and its prognosis. The international consensus guidelines for the management of IPMN of the pancreas published in 2006 and revised in 2012 recommend resecting all MD-IPMNs with an MPD diameter of ≥10 mm on account of a high frequency of malignancy ranging from 60% to 92%.
2
, 3
, 4
This risk estimate is probably an overestimation of the actual risk because it is based mainly on surgical case series rather than on patients having undergone long-term follow-up. The consecutive cohort series of Uehara et al1
includes 32 patients with MD-IPMN resected at initial presentation, but also 26 patients who were not operated on at their initial presentation, with a median follow-up time of 79 months (15–135 months). MPD diameter, size of mural nodule, and outcome of cytologic analysis outcome differed significantly between benign and malignant cases. Only the latter 2 were independent predictors according to multivariate analysis. It is important to recognize that these estimations concern the whole group, not only those who underwent follow-up care.Although a recently updated guideline designates the presence of a mural nodule as a potential indicator for surgical resection, the size of the mural nodule is not considered.
4
Uehara et al1
show that when a patient has a mural nodule >10 mm, there is really no excuse not to offer surgery to a fit patient. Whether these results can also be interpreted the other way around—that is, that patients can be followed up “safely” until such time that the result of cytologic analysis is positive, or the mural nodule has grown to ≥10mm—is a whole different ball game. Although the risk in case of a mural nodule >10 mm is very high, as demonstrated by Uehara et al,1
this risk is obviously not dichotomous divided. Although the receiver operating curve suggests a steep risk increase from 10 mm onward, it must be noted that each point estimate has a confidence interval (not shown) dependent on the number of included patients and cases.In this series, pancreatic juice was obtained through cannulation of the pancreatic duct by means of endoscopic retrograde pancreatography. The optimal protocol in terms of both technique and timing needs to be defined. Given that collection of mucinous material through a catheter can be difficult, it might be helpful to optimize pancreatic juice collection by the use of secretin. In this series, that was done in selected cases but was not standard practice. It is not mentioned whether fluid quantities collected with secretin were higher and included a higher cytologic yield. Also, it remains unclear at which time point pancreatic juice was collected: on indication only or repetitively during regular surveillance. In the latter case, the burden and risk of repeated endoscopic retrograde pancreatography should be taken into consideration. If pancreatic juice is not collected during regular follow-up care, it raises the question of which preconditions must be met before obtaining samples for cytologic examination.
Let’s reconsider the objective when we care for patients with MD-IPMN. Although early detection of a malignancy is better than detecting cancer at a late(r) stage, the best management is to perform a preventive resection when the risk for malignant transformation is unacceptably high but no malignancy has yet developed. That patient, although subjected to the early and late adverse events of pancreatic surgery, does not risk dying of local cancer recurrence or a metastasis. Even when pathologic investigation of the resection specimens shows no malignancy, one cannot conclude that the surgery was redundant because the prophylactic resection might save the patient from the development of a malignancy at a later stage. From this viewpoint, the discussion about partial versus total pancreatectomy comes into play considering the development of technologies to better control post–total pancreatectomy diabetes, particularly in younger and fit patients.
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,6
Imagine you are the patient. You have this condition where the likelihood of having a malignancy is substantial, and there is this test with a sensitivity of ∼85%. You are of a certain age, and the longer this premalignant condition is present, the higher the likelihood that a malignancy develops. If this type of cancer is diagnosed at a more advanced stage or when you develop symptoms, the chances of survival are substantially lower. A pancreatic resection carries a certain risk for the development of short- and long-term adverse events. What do you decide?
Obviously, there is not a simple answer to this question. Many thoughts and considerations come into the equation. Importantly, to be able to make an informed decision the patient is much dependent on how and to what extent information is provided. These situations, therefore, are typically suited for “shared decision making.”
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Age, physical condition, comorbidities, and surgical risk must be weighed against the potential benefit and risks of the resection. In an elderly person, particularly one who is frail and has comorbidities, the risk-benefit ratio in relation to the expected remaining life years is potentially such that the sensible choice is not to operate. In a younger person, however, this is may be quite different because reliable longer-term follow-up data showing that surveillance is safe are lacking.How much time, effort, and risk do we permit ourselves and our patients before deciding that the benefits of a pancreatic resection outweigh the negatives? MD-IPMN is a very high-risk condition for harboring or developing cancer. We have a chance of doing a lot of good for these patients, particularly when the condition is diagnosed incidentally in a younger and fit patient. The bottom line is that we should not let the right opportunity pass by.
Disclosure
Dr Bruno is a consultant for, and the recipient of industry-initiated and investigator-initiated studies from, Boston Scientific, Cook Medical, and Pentax Medical and the recipient of support for investigator-initiated studies from Mylan, ChiRoStim, and 3M.
References
- Predictors of malignancy in main duct intraductal papillary mucinous neoplasm of the pancreas.Gastrointest Endosc. 2022; 95: 291-296
- International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.Pancreatology. 2006; 6: 17-32
- International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.Pancreatology. 2012; 12: 183-189
- Revisions of international consensus Fukuoka guidelines for the management of IPMN of the Pancreas.Pancreatology. 2017; 17: 738-753
- Is it time to expand the role of total pancreatectomy for IPMN?.Dig Surg. 2016; 33: 335-342
- Use of continuous glucose monitoring for evaluation of hypoglycemia pre- and post-operatively for patients undergoing total pancreatectomy with autologous islet cell transplant.Clin Transplant. 2021; 35: e14450
- Prophylactic total pancreatectomy in individuals at high risk of pancreatic ductal adenocarcinoma (PROPAN): systematic review and shared decision-making programme using decision tables.United European Gastroenterol J. 2020; 8: 865-877
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Published online: December 16, 2021
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- Predictors of malignancy in main duct intraductal papillary mucinous neoplasm of the pancreasGastrointestinal EndoscopyVol. 95Issue 2
- PreviewThe International Consensus Guidelines updated in 2017 recommended surgery to all main duct intraductal papillary mucinous neoplasms (MD-IPMNs) with the main pancreatic duct (MPD) of 10 mm or more and those with mural nodules regardless of size. The aim of the present study was to identify predictors of malignancy in MD-IPMN among preoperative factors including MPD and mural nodule size.
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