This study analysed outcome after surgery in a large series of patients with malignant IPMT and was the first to propose direct comparison of survival in patients undergoing surgery for either malignant IPMT or ductal pancreatic adenocarcinomas. Complete clinical and pathological data were recorded for 73 patients from four French centres. To reduce interobserver variability, all the resected specimens were reviewed by one pathologist.
Male/female ratio (2/1), age, clinical manifestations, and tumour localisation were in accordance with previous reports.1,4,9,17–19
In contrast, the proportion of main pancreatic duct involvement, either alone or combined with branch duct lesions (89%), was higher than that previously published.9,20
This may be explained by the selection of malignant forms of IPMT (that is, in situ or invasive), which as recently demonstrated involve the main pancreatic duct more frequently than branch ducts.11,20,21
The median delay between first symptoms and diagnosis of malignant IPMT (nine months) is shorter than previously reported (12 to 43 months)4,9
; this result may reflect increased physician awareness, improvements in imaging methods and the selection in this study of malignant forms of IPMT.
The natural history of IPMT remains poorly defined. Most studies have reported an excellent prognosis in patients undergoing surgery for benign tumours.6,9,19,22
In contrast, a wide variability in five year survival rates has been reported (0% to 82%) in patients treated for malignant IPMT.1,4,8–10,14
In this study, the five year survival rate of 48% is in accordance with some previous surgical studies,10
except for two Japanese series that reported overall five year survival rates of 75% to 82%.8,9
Possible explanations for such discordance include: small numbers of patients studied, data selection from compiled series, lack of distinction between in situ and invasive carcinomas, exclusion of postoperative mortality, or unclear causes of deaths in some studies.8,9,19
In this study, the five year survival rate of patients undergoing surgery for in situ IPMT was excellent and mortality in such forms was only related to early or late surgical complications. As neither relapse nor cancer death was observed in this subgroup of patients, perioperative morbidity and mortality should be as low as possible. Resection in such patients should be adapted to tumour extension, however extensive resection has to be counterbalanced with long term complications such as brittle diabetes mellitus. Management in these patients requires careful decision making in reference centres with precise intraoperative evaluation including frozen section examination of pancreatic resection margins.
In contrast, patients with invasive IPMT had a high rate of cancer relapse and cancer deaths, in line with previous reports.6,10
Lymph node involvement remained the only predictive factor of death on multivariate analysis (OR 7.5). Some studies reported that tumour size (>6 cm), peripancreatic invasion, and lymph node involvement are of prognostic value.9,10,14
In this study, tumour size did not influence survival. The precise determination of size in malignant IPMT is often problematic because of the intrinsic cystic nature of these tumours, which are composed of numerous dilated ducts, while areas of solid (malignant) tumour components are difficult to individualise. While a high serum CA 19.9 concentration was found to predict poor prognosis in this study, as observed in pancreatic ductal adenocarcinoma, this factor was no longer significant on multivariate analysis.23
As lymph node involvement is of large prognostic importance, the question of extended surgical lymph node dissection, as proposed by Japanese authors,24
can be raised. This problem has never been formally resolved in patients with IPMT. It has been reported that extended lymph node dissection does not influence long term survival in patients with pancreatic ductal adenocarcinoma,25
but whether such strategies have an impact on survival in IPMT needs to be analysed in a prospective fashion. The prognosis in patients with IPMT is often considered more favourable than for ordinary pancreatic ductal adenocarcinoma,9,14,15
but a matched comparison between these two forms of pancreatic cancers has never been performed. To answer this question, we compared survival in patients who underwent surgical resection for invasive malignant IPMT or ductal adenocarcinoma according to age and TNM classification. In our series, the five year survival rate after resection for all stages of ductal adenocarcinoma was 21%, a rate similar to that previously reported.14,26–28
Overall survival rates were better in patients with IPMT compared with those treated for ductal adenocarcinomas of early stage (I), but this difference was no longer significant in the subgroups of patients with stage II or stage III tumours. The apparent better prognosis in malignant IPMT compared with ductal carcinomas may be partly attributable to the high prevalence of in situ or invasive stage I IPMT, which are earlier diagnosed because of symptoms resulting from ductal obstruction by mucus. However, when the tumour is locally advanced (peripancreatic extension or lymph node involvement), the prognosis is as poor as for ductal carcinomas. As there is no current evidence for efficacy of adjuvant therapy in pancreatic cancers, patients with locally advanced malignant IPMT should be included in the same protocols assessing adjuvant chemotherapy or radiotherapy regimens as patients with ductal adenocarcinoma.
In conclusion, lymph node involvement was the only prognostic survival factor in patients who underwent resection for malignant IPMT. Overall five year survival rate was 48% in patients with malignant IPMT after surgical resection, but a clear cut difference was observed according to the stage of disease. Prognosis is good in patients with in situ or stage I carcinoma, who should be treated with function preserving minimal pancreatectomy. In contrast, patients with locally advanced malignant IPMT (that is, stage II or III) had the same poor prognosis as patients with pancreatic ductal adenocarcinomas.