Analysis of Progression Time in Pancreatic Cancer including Carcinoma In Situ Based on Magnetic Resonance Cholangiopancreatography Findings

Abstract

Background: Pancreatic cancer (PC) exhibits extremely rapid growth; however, it remains largely unknown whether the early stages of PC also exhibit rapid growth speed equivalent to advanced PC. This study aimed to investigate the natural history of early PCs through retrospectively assessing pre-diagnostic images.

Methods: We examined the data of nine patients, including three patients with carcinoma in situ (CIS), who had undergone magnetic resonance cholangiopancreatography (MRCP) to detect solitary main pancreatic duct (MPD) stenosis >1 year before definitive PC diagnosis. We retrospectively analyzed the time to diagnosis and first-time tumor detection from the estimated time point of first-time MPD stenosis detection without tumor lesion.

Results: The median tumor size at diagnosis and the first-time tumor detection size were 14 and 7.5 mm, respectively. The median time to diagnosis and first-time tumor detection were 26 and 49 months, respectively.

Conclusions: No studies have investigated the PC history, especially that of early PCs, including CIS, based on the initial detection of MPD stenosis using MRCP. Assessment of a small number of patients showed that the time to progression can take several years in the early PC stages. Understanding this natural history is very important in the clinical setting.

Keywords: carcinoma in situ; computed tomography; early diagnosis; magnetic resonance cholangiopancreatography; natural history; pancreatic carcinoma.

Figure 1

Flow-chart detailing the patient selection process. Abbreviations: MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography.

Figure 2

Kaplan–Meier curves. (A): Time to diagnosis (the median time to diagnosis was 26 months), (B): time to first-time tumor detection (the median first-time tumor detection was 49 months after three patients with CIS were censored). Abbreviation: CIS, carcinoma in situ.

Figure 3

Carcinoma in situ (0 mm in size) diagnosed over a 23-month observation period (Case 1 in Supplementary Table S1). A 79-year-old man was referred to our hospital for further examination concerning pancreatic head cysts that had been observed during abdominal ultrasonography screening. MRCP showed MPD stenosis in the pancreatic head with slight distal MPD dilation, in addition to the detected cysts ((A): first-time MRCP). CE-CT (B) and EUS images also revealed MPD dilation (yellow arrow head), but not a tumor lesion around the MPD stenosis; however, severe distal pancreatic parenchymal atrophy was detected. Therefore, these lesions were initially diagnosed as branch duct IPMN, and careful follow-up examination was required. Subsequently, although no changes to the pancreatic cysts and MPD abnormality findings were observed on CT (green arrow head: MPD dilation, (C)) and MRCP (D), MPD stenosis, and distal MPD dilation were clearly observed on MRCP after 18 (E) and 21 months (F). However, no tumor lesions were detected on CT (G) or EUS images. Endoscopic retrograde cholangiopancreatography was performed as malignancy was suspected. Pancreatic juice cytology was not performed because of failure to cannulate into the MPD. Despite the lack of a definitive diagnosis, the lesion was resected after 23 months because of possible malignancy. The final diagnosis was high-grade PanIN of the MPD, which had only spread in the MPD in the pancreatic head (Tis N0 M0, stage 0, final tumor size: 0 mm (CIS), (H)), along with retention cysts in the pancreatic head. This patient was diagnosed at 23 months after the first MRCP (I). Abbreviations: CIS, carcinoma in situ; EUS, endoscopic ultrasound; CE, contrast-enhanced; CT, computed tomography; IPMN, intraductal papillary mucinous neoplasm; MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography; PanIN, pancreatic intraepithelial neoplasia.

Figure 4

A 3 mm lesion over a 50-month observation period (Case 4 in Supplementary Table S1). The case of a 73-year-old woman who had a history of idiopathic acute pancreatitis at 4 years prior is presented. No MPD abnormalities were observed on MRCP (A); however, solitary MPD and branch pancreatic duct dilation were evident in the pancreatic tail (yellow arrow head, first-time MRCP, (B)), although no tumor lesions were detected on CT (C). The MPD abnormality gradually progressed (D,E), and MPD stenosis was detected at the beginning of solitary MPD dilation after 47 months (green arrow head, (F)). No tumor lesion was observed on CT or EUS images. ERCP detected localized irregular stenosis with suspected malignancy by pancreatic juice cytology findings. In addition, a tiny lesion was detected on CT after 49 months (blue arrow head, (G)). Therefore, surgery was undertaken after 50 months for a suspected small PC. The final diagnosis was the presence of a 3 mm invasive PC in the pancreatic tail (T1 N0 M0, stage IA, final tumor size: 3 mm, (H)). This patient was diagnosed at 50 months after the first MRCP (I). Abbreviations: EUS, endoscopic ultrasound; CT, computed tomography; IPMN, intraductal papillary mucinous neoplasm; MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; PC, pancreatic cancer.

Figure 5

A 14 mm lesion over a 55-month observation period (Case 5 in Supplementary Table S1). The case of a 75-year-old woman who had experienced idiopathic acute pancreatitis 7 months prior is presented. MRCP findings revealed MPD stenosis in the pancreatic body accompanied by distal MPD dilation and multilocular cysts in the pancreatic head (first-time MRCP, (A)). CE-CT scan images failed to detect a tumor lesion, although partial parenchymal atrophy consistent with MPD stenosis was observed (yellow arrow head, (B)); therefore, MPD stenosis was treated as chronic pancreatitis despite the absence of pancreatic stones. MRCP performed 27 months later showed progression of distal MPD dilation (C), although no tumor lesion was observed on CE-CT scan images (green arrow head: partial parenchymal atrophy, (D)). Finally, CE-CT scan performed 54 months later indicated the presence of a tumor lesion (blue arrow head, (E)). In addition, MRCP detected further MPD dilation (F) and the patient was referred to our hospital. EUS scans performed 55 months later showed a 14 mm diameter tumor (pink arrow head, (G)). EUS-FNA was performed, and the pathological diagnosis was adenocarcinoma (final tumor size: 14 mm). Therefore, distal pancreatectomy was performed for PC post-NAC. The final diagnosis was the presence of a 12 mm invasive nodule in the pancreatic body (T1 N1 M0, stage IIB, (H)). This patient was diagnosed 55 months after the first MRCP (I). Abbreviations: EUS, endoscopic ultrasound; CE-CT; contrast-enhanced computed tomography; CT, computed tomography; FNA, fine needle aspiration; IPMN, intraductal papillary mucinous neoplasm; MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; NAC, neoadjuvant chemotherapy; PC, pancreatic cancer.

Figure 6

A 36 mm lesion over a 39-month observation period (Case 9 in Supplementary Table S1). A 49-year-old woman presented with idiopathic acute pancreatitis and underwent MRCP, which showed slight MPD stenosis accompanied by distal MPD dilation (first-time MRCP, (A)). CE-CT scans detected a partial MPD stenosis without tumor lesion or pancreatic stone (yellow arrow head, (B)), and the patient was diagnosed with chronic pancreatitis. Subsequently, a recurrent attack of pancreatitis occurred, and MPD stenosis and distal MPD dilation were clearly observed on MRCP and CT findings (C–E). An EUS scan performed after 16 months detected a 7 mm diameter tumor (green arrow head, (F)). However, EUS-FNA could not be performed because the endoscopist failed to recognize the tumor lesion. Therefore, ERCP was performed to determine a diagnosis of malignancy after 19 months. However, pancreatic juice cytology findings did not indicate malignancy. Subsequently, the tumor lesion was observed to have gradually progressed on EUS (blue arrow head, (G)) and CT (pink arrow head, (H)) images. This patient was referred to our hospital after 39 months following clear detection of the tumor (I). EUS-FNA was performed on the 36 mm diameter tumor (J), and the pathological diagnosis was adenocarcinoma (final tumor size, 36 mm). Therefore, distal pancreatectomy was performed for PC after NAC. The final diagnosis was the presence of a 30 mm invasive nodule in the pancreatic body (T3 N1 M0, stage IIB, (K)). This patient was diagnosed at 39 months after the first MRCP (L). Abbreviations: EUS, endoscopic ultrasound; CE-CT; contrast-enhanced computed tomography; CT, computed tomography; FNA, fine needle aspiration; IPMN, intraductal papillary mucinous neoplasm; MPD, main pancreatic duct; MRCP, magnetic resonance cholangiopancreatography; NAC, neoadjuvant chemotherapy; PC, pancreatic cancer.