An increase in the number of predictive factors augments the likelihood of malignancy in branch duct intraductal papillary mucinous neoplasm of the pancreas

doi:10.1016/j.surg.2011.07.009

Surgery

Volume 151, Issue 1, January 2012, Pages 76-83

https://doi.org/10.1016/j.surg.2011.07.009 Get rights and content

Background

International consensus guidelines for the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas provide several factors that can be used to predict which IPMNs will become malignant.The sensitivity of each factor’s predictive accuracy, however, is relatively low, making it difficult to determine the appropriate treatment in individual cases. The aim of this study was to investigate whether increasing the number of predictive factors might augment the sensitivity of the established guidelines to detect malignant IPMNs.

Methods

The medical records of 138 patients with IPMNs resected at our institution were reviewed. Possible malignant predictors were analyzed by univariate and multivariate analysis, and the effects of the number of factors and the predictive score of the pathologic results were examined. The cutoff points for the number of predictors to discriminate between malignant and nonmalignant IPMNs were established by constructing receiver operating characteristic curves.

Results

A predictive analysis could not be carried out for the main duct IPMNs because of the high prevalence of malignancy and the small number of significant predictors associated with them. For malignant branch duct IPMNs, however, we identified 4 predictive factors that helped determine the correct diagnosis as follows: (1) the presence of a cyst ≥30 mm in diameter; (2) the presence of mural nodules; (3) a history of acute pancreatitis; and (4) atypical results of pancreatic juice cytology. An increase in the number of these factors significantly affected the sensitivity to predict malignancy. The area under the curve for the number of predictors for malignant branch duct IPMNs was 0.856, and the sensitivity and specificity were 96% and 71%, respectively, when the cutoff point was set at 2. The predictive scoring system also showed the same values of sensitivity and specificity for the number of factors.

Conclusion

Patients with branch duct IPMNs who have 2 or more of the 4 predictive factors described above should undergo standard pancreatectomy with lymph node dissection, whereas patients who present with 0 or 1 predictive factor can be treated by minimal pancreatectomy without nodal dissection or by careful observation without resection. All patients with main duct IPMNs, therefore, should be treated with resection as suspected malignancies.

Section snippets

Patients and methods

The medical records of 161 patients who underwent pancreatectomy for IPMN in the Department of Surgery and Oncology at Kyushu University Hospital between January 1990 and August 2010 were reviewed retrospectively. A total of 14 patients with synchronous distinct pancreatic ductal carcinomas and 9 without detailed pathology results were excluded; therefore, data from 138 patients were available. Among these patients, data from 126 who had undergone pancreatectomy between January 1990 and June

Results

Of the 138 patients whose data were included in the current study, 39 were diagnosed with main duct IPMNs and 99 with branch duct IPMNs. Of the 138 patients’ pathology reports, 24 showed cancer lesions in the main duct type patients (62%) and 22 documented cancer lesions in the branch duct type patients (22%). The diagnosis of main duct IPMN itself proved to be a significant independent predictive factor for malignancy by the univariate (P < .01) and multivariate (95% confidence interval [CI],

Discussion

Our present study analyzing the relationship between the number of predictive factors for malignant IPMNs and pathology results demonstrated the following findings: (1) a predictive analysis could not be carried out for main duct IPMNs because of the high prevalence of malignancy and the small number of significant predictors; (2) a total of 4 predictive factors for malignant IPMNs, including the presence of a cyst ≥30 mm, the presence of mural nodules, a history of acute pancreatitis, and the

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Cited by (53)

International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas
2024, Pancreatology
This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new “evidence-based guidelines” is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, “stop surveillance” or “continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma”, for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.
Predictors of malignancy in main duct intraductal papillary mucinous neoplasm of the pancreas
2022, Gastrointestinal Endoscopy
Citation Excerpt :
In 1994, we reported that malignancy of IPMNs could be demonstrated by cytologic examination of pancreatic juice sampled at ERP, when it was called a mucin-producing tumor of the pancreas.20 Although sensitivities for malignancy of pancreatic juice cytology in MD-IPMN varied among studies,12,21,22 positive cytology has been reported to be a predictor of malignancy in IPMN involving the MPD23-25 and in analyses without separating BD-IPMN from MD-IPMN.26,27 In particular, Yamaguchi et al28 reported a high sensitivity of 80% for malignancy in the cytology of MD-IPMNs by collecting materials directly using peroral pancreatoscopy, which was a procedure similar to ours that had been published,29 and a low sensitivity of 42% in BD-IPMNs using a catheter alone.
The 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.
Twenty-six benign MD-IPMNs (7 resected and 19 nonresected) and 32 malignant MD-IPMNs (31 resected and 1 nonresected) were included in the study. MRCP, CT, EUS, and cytology were performed using pancreatic juice collected by endoscopic retrograde pancrestography (ERP). Resected IPMNs were classified as benign or malignant by histologic examination and nonresected MD-IPMNs by imaging, cytology, and observation. Cutoff values of candidate parameters were determined by receiver operating characteristic curves. Univariate and multivariate analyses by regression model were performed.
MPD and mural nodule size and cytology results differed significantly between benign and malignant groups. Cutoff values of MPD and mural nodule sizes were 15 mm and 10 mm with areas under the curve of .66 and .86, respectively. Mural nodules of 10 mm or more (odds ratio, 8.32; 95% confidence interval, 1.13-61.2; P = .038) and positive cytology (odds ratio, 42.5; 95% confidence interval, 4.10-439; P = .002) were shown to be independent predictors of malignancy by multivariate analysis. When MD-IPMNs with either predictor were diagnosed to be malignant, sensitivities, specificities, and overall accuracy for malignancy were 94%, 85%, and 90%, respectively.
Mural nodules of 10 mm or more and positive cytology were independent predictors of malignancy in MD-IPMN.
Assessment of Malignancy Potential in Intraductal Papillary Mucinous Neoplasms of the Pancreas on MDCT
2021, Academic Radiology
Citation Excerpt :
The type and quantity of ICG WFs and HRS had unequal weights and were not cumulative in the prediction of the risk for malignancy or invasiveness in IPMN (26). If multiple risk factors were present, the sensitivity to detect malignant IPMNs increased (26,27). Our study found that the age of patients with malignant IPMNs was older than that of patients with benign IPMNs, suggesting that IPMNs may be slow-growing precancerous lesions.
To assess the malignancy potential of intraduct papillary mucinous neoplasms (IPMNs) on multidetector-row computerized tomography according to the 2012 International Consensus Guidelines (ICG).
This study retrospectively collected IPMNs confirmed by surgery from 2016 to 2019. The imaging findings of IPMNs were analyzed. IPMNs were classified as malignancy in the presence of high-grade dysplasia or invasive carcinoma and began in the presence of low- and intermediate-grade dysplasia.
A total of 207 patients (mean age: 63.7 ± 7.9 years) were included, and the prevalence of malignancy was 28.0% (58 of 207). According to the 2012 ICG, the imaging findings of IPMNs were divided into worrisome features (WFs) and high-risk stigmata (HRS). The malignancy of IPMN with only one WF was relatively low (1.4%, 3 of 207). In multivariate regression analyses, the independent factors of IPMNs were enhanced mural nodule ≥5 mm (odds ratio [OR] = 19.5, 95% confidence interval [CI] 6.8–55.4), abrupt change in the main pancreatic duct caliber with distal pancreatic atrophy (OR = 4.6, 95%CI 1.67–12.71), and thickened enhanced cyst walls (OR = 2.9, 95%CI 1.1–8.2). When the presence of more than two WFs or HRS (score ≥ 3) was regarded as indicating the malignancy potential of IPMNs on multidetector-row computerized tomography, the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were 89.7%, 75.8%, 79.7%, 59.1%, and 95.0%, respectively.
According to the ICG in 2012, patients with IPMNs with only one WF have a low risk for malignancy, and the presence of at least two WFs or any HRS (score ≥3) suggests malignant IPMNs.
Surgical indication for intraductal papillary mucinous neoplasm without mural nodule ≥5 mm
2021, Surgery (United States)
In intraductal papillary mucinous neoplasm, a mural nodule ≥5 mm is an important predictor of malignancy. Surgical indication is less clear in cases of intraductal papillary mucinous neoplasm without mural nodule ≥5 mm. This is a retrospective study evaluating predictors of high-grade dysplasia or invasive intraductal papillary mucinous carcinoma for intraductal papillary mucinous neoplasm without mural nodule ≥5 mm.
Among consecutive patients who underwent surgery for intraductal papillary mucinous neoplasm between 1999 and 2018, 174 had intraductal papillary mucinous neoplasm with mural nodule ≥5 mm (mural nodule[+] ≥5 mm group). The remaining 155 patients had intraductal papillary mucinous neoplasm but did not have mural nodule ≥5 mm: 24 patients with mural nodule <5 mm (mural nodule[+] <5 mm group) and 131 patients without mural nodule (mural nodule[–] group). We investigated predictors of high-grade dysplasia or invasive intraductal papillary mucinous neoplasm in cases of intraductal papillary mucinous neoplasm without mural nodule ≥5 mm.
The frequency of high-grade dysplasia invasive intraductal papillary mucinous neoplasm was significantly higher in the mural nodule(+) ≥5 mm group (87.4%) than in the mural nodule(+) <5 mm group (37.5%, P < .001) and mural nodule(–) group (45.0%, P < .001). However, frequency was not significantly different between mural nodule(+) <5 mm and mural nodule(–) groups (P = .494). Multivariate analysis showed three independent predictors of high-grade dysplasia invasive intraductal papillary mucinous carcinoma in intraductal papillary mucinous neoplasm without mural nodule ≥5 mm: branch cyst ≥40 mm (P = .038, odds ratio 3.704; 95% confidence interval, 1.075−12.821), positive cytology of pancreatic juice (P = .039, odds ratio 16.792; 95% confidence interval, 1.152−244.744), and carcinoembryonic antigen in pancreatic juice ≥30 mg/mL (P < .001, odds ratio 14.925; 95% confidence interval, 4.525−50.0).
For cases of intraductal papillary mucinous neoplasm without mural nodule ≥5 mm, large cysts, positive cytology of the pancreatic juice, and high levels of carcinoembryonic antigen in pancreatic juice may be useful to determine surgical indication, although further studies are needed to confirm these results.
Risk of malignancy in small pancreatic cysts decreases over time
2020, Pancreatology
Pancreatic cysts <15 mm without worrisome features have practically no risk of malignancy at the time of diagnosis but this can change over time. Optimal duration of follow-up is a matter of debate. We evaluated predictors of malignancy and attempted to identify a time to safely discontinue surveillance.
Bi-centric study utilizing prospectively collected databases of patients with pancreatic cysts measuring <15 mm and without worrisome features who underwent surveillance at the Massachusetts General Hospital (1988–2017) and at the University of Verona Hospital Trust (2000–2016). The risk of malignant transformation was assessed using the Kaplan-Meier method and parametric survival models, and predictors of malignancy were evaluated using Cox regression.
806 patients were identified. Median follow-up was 58 months (6–347). Over time, 58 (7.2%) cysts were resected and of those, 11 had high grade dysplasia (HGD) or invasive cancer. Three additional patients had unresectable cancer for a total rate of malignancy of 1.7%. Predictors of development of malignancy included an increase in size ≥2.5 mm/year (HR = 29.54, 95% CI: 9.39–92.91, P < 0.001) and the development of worrisome features (HR = 9.17, 95% CI: 2.99–28.10, P = 0.001). Comparison of parametric survival models suggested that the risk of malignancy decreased after three years of surveillance and was lower than 0.2% after five years.
Pancreatic cysts <15 mm at the time of diagnosis have a very low risk of malignant transformation. Our findings indicate the risk decreases over time. Size increase of ≥2.5 mm/year is the strongest predictor of malignancy.
Risk of advanced lesions in patients with branch-duct IPMN and relative indications for surgery according to European evidence-based guidelines
2019, Digestive and Liver Disease
Citation Excerpt :
Relative indications included a grow-rate ≥5 mm/year, serum Ca 19.9 ≥ 37 U/ml, MPD dilation between 5 and 9.9 mm, cyst size ≥40 mm, new onset of diabetes mellitus, acute pancreatitis and contrast-enhancing mural nodule <5 mm. This approach considering the number of features has already been suggested by some authors [5,6]; however, the inclusion of the comorbidities in the algorithm is novel. Although the risk of malignancy persists in long-term follow-up [7], the low progression of BD-IPMN [8,9] may justify a conservative approach in older patients or those with significant comorbidities.
European evidence-based guidelines proposed surgery for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) based on the presence of 1–2 relative indications, depending on the comorbidity burden.
To assess the accuracy of the guidelines in patients with relative indications in a surgical cohort of demonstrated BD-IPMNs.
This report describes a multi-centre, observational, retrospective study. All consecutive patients with relative indications and histologically confirmed BD-IPMN were included. The main outcome was risk of invasive carcinoma in patients with relative indications.
Ninety-one patients with BD-IPMN underwent surgery because of absolute (n = 21), relative (n = 60), or no formal indications (n = 10). In total, there were 60 patients (mean age: 66 ± 9, 50% male) with one (n = 35, 58.3%) or ≥2 relative indications (n = 25, 41.7%). The global advanced lesion and invasive carcinoma rates were 40% and 13.3%, respectively. No risk factor was associated with high-grade dysplasia or invasive carcinoma. Patients with one indication had a lower risk of invasive carcinoma than did those with ≥2 relative indications (5.7% vs. 24%, respectively, p = 0.048); however, the advanced lesion rates were comparable (37.1% vs. 44%, p = 0.593).
Invasive carcinoma is considerably more frequent in patients with two or more relative indications. The surgical strategy in these selected cases should be decided on an individual basis.

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Original CommunicationAn increase in the number of predictive factors augments the likelihood of malignancy in branch duct intraductal papillary mucinous neoplasm of the pancreas

Background

Methods

Results

Conclusion

Section snippets

Patients and methods

Results

Discussion

Pancreatology

Gastroenterology

Mod Pathol

Pancreatology

Surgery

Controversies in the management of pancreatic IPMN

Nat Rev Gastroenterol Hepatol

Intraductal papillary mucinous tumors of the pancreas: imaging studies and treatment strategies

Ann Surg

Clinicopathological features and treatment of intraductal papillary mucinous tumour of the pancreas

Br J Surg

Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas

Br J Surg

Main-duct intraductal papillary mucinous neoplasms of the pancreas. Clinical predictors of malignancy and long-term survival following resection

Ann Surg

Intraductal papillary mucinous neoplasms: predictors of malignant and invasive pathology

Ann Surg

Original Communication
An increase in the number of predictive factors augments the likelihood of malignancy in branch duct intraductal papillary mucinous neoplasm of the pancreas