Intracholecystic papillary neoplasm associated with invasive carcinoma of the remnant gallbladder after subtotal cholecystectomy: a case report.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a rare tumor and a relatively new concept. Therefore, the natural history and imaging characteristics of ICPN have not yet been fully documented. Moreover, cases who underwent curative resection for remnant gallbladder cancer, including ICPN with associated invasive carcinoma, have been rarely reported. We report a resected case of ICPN of the remnant gallbladder with associated invasive carcinoma for which we could observe a temporal change in imaging findings until malignant transformation. CASE PRESENTATION: A 79-year-old female patient with a surgical history of subtotal cholecystectomy for acute cholecystitis was an ambulatory patient of our institution because of postoperative surveillance for colon cancer. Ultrasonography and computed tomography incidentally detected a small nodule in the cystic remnant gallbladder. The nodule had increased in size 3 months later; thus, additional investigations were performed. Magnetic resonance imaging revealed a 10-mm enhanced nodule without evidence of extraluminal invasion. Diffusion-weighted magnetic resonance imaging revealed restricted diffusion of the lesion, and positron emission tomography revealed marked accumulation in the lesion. The lesion was diagnosed as suspicious for a malignant remnant gallbladder tumor. Therefore, remnant cholecystectomy with gallbladder bed resection was performed. Because preoperative endoscopic retrograde cholangiography revealed a relatively long intact cystic duct, extrahepatic bile duct resection was planned to be omitted. Intraoperatively, the hepatic and duodenal side bile duct where the cystic duct diverged was taped. Using these tapes, which permitted pulling the bile duct, the cystic duct located behind the bile duct could be safely exposed. The lesion was pathologically diagnosed as biliary morphologic ICPN with associated invasive carcinoma. CONCLUSIONS: Because remnant cholecystectomy is an uncommon procedure and technically difficult, accurate preoperative investigation and surgical planning are important to prevent bile duct injury and omit extrahepatic bile duct resection. In the present case, intracystic change could be detected incidentally at an early stage because of previous remnant gallbladder producing (reconstituting) subtotal cholecystectomy and surveillance for other disease. This case suggests the existence of ICPN that can progress to invasive carcinoma during a short period.

Prognostic implications of the coexisting precursor lesion types in invasive gallbladder cancer.

Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P < 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.

Concomitant Intraductal Papillary Mucinous Neoplasm in Pancreatic Ductal Adenocarcinoma Is an Independent Predictive Factor for the Occurrence of New Cancer in the Remnant Pancreas.

OBJECTIVE: To determine the factors predicting the subsequent development of pancreatic ductal adenocarcinoma in remnant pancreas (PDAC-RP) after partial pancreatectomy for PDAC. SUMMARY BACKGROUND DATA: PDAC-RP after partial pancreatectomy for PDAC is currently not so rare because of improved prognosis of PDAC patients due to recent advances in surgical techniques and adjuvant therapy. However, the predictive factors related to PDAC-RP remain unknown. METHODS: We retrospectively reviewed the clinicopathological data of a consecutive series of 379 patients with PDAC treated by partial pancreatectomy between 1992 and 2015; 14 patients (3.69%) had PDAC-RP. Clinicopathological variables were compared between PDAC-RP and non-PDAC-RP. RESULTS: In univariate analysis, concomitant intraductal papillary mucinous neoplasm (IPMN) (P = 0.0005), cancer location (body/tail) (P = 0.0060), and lower T factor in UICC (P = 0.0039) were correlated with PDAC-RP development. Multivariate analysis revealed concomitant IPMN (P = 0.0135) to be an independent predictive factor for PDAC-RP. PDAC concomitant with IPMN had higher cumulative incidence of PDAC-RP (47.5%/10 yrs) than PDAC without IPMN (9.96%/10 yrs) (P = 0.0071). Moreover, the density of pancreatic intraepithelial neoplasia lesions in the background pancreas of cases of PDAC concomitant with IPMN (1.86/cm) was higher than that of cases of PDAC without IPMN (0.91/cm) (P = 0.0007). CONCLUSIONS: Concomitant IPMN in PDAC is an independent predictive factor for the development of new PDAC in remnant pancreas. Cancer susceptibility of remnant pancreas after resection for PDAC concomitant with IPMN is probably due to an increased density of pancreatic intraepithelial neoplasia lesions.

Paracecal hernia due to membranous adhesion of the omentum to the right paracolic gutter.

BACKGROUND: Paracecal hernias, also known as pericecal hernias, are an exceptionally rare type of internal hernia. We report a unique case of paracecal hernia due to membranous adhesion of the omentum to the right paracolic gutter. CASE PRESENTATION: An 86-year-old female was admitted to our hospital with vomiting and abdominal pain. Laboratory findings showed a slightly elevated C-reactive protein level. Computed tomography scan showed dilated loops of the small intestine in the right paracolic gutter with medial displacement of the cecum and ascending colon. Internal hernia around the cecum due to postoperative adhesion after appendectomy was suspected, and she underwent emergency laparotomy. Intraoperative findings revealed the adhesion between the omentum and right paracolic gutter forming a cavity with the small intestine incarcerated. No abnormal adhesion in the ileocecal region was seen. We transected the omental adhesion from the orifice to the far end of the cavity near the hepatic flexure of the colon to release strangulation and to prevent recurrence. The patient was discharged on postoperative day 14 without complications. CONCLUSIONS: Paracecal hernias have a type of membranous adhesion of the omentum to the right paracolic gutter. Surgeons should be aware of this paracecal hernia type, when they encounter the internal hernia.

Superparamagnetic iron-oxide-enhanced diffusion-weighted magnetic resonance imaging for the diagnosis of intrapancreatic accessory spleen.

PURPOSE: To evaluate the diagnostic performance of superparamagnetic iron-oxide (SPIO)-enhanced diffusion-weighted image (DWI) for distinguishing an intrapancreatic accessory spleen from pancreatic tumors. MATERIALS AND METHODS: Twenty-six cases of intrapancreatic accessory spleen and nine cases of pancreatic tail tumors [neuroendocrine tumor (n = 8) and pancreatic adenocarcinoma (n = 1)] were analyzed. Two blind reviewers retrospectively reviewed the SPIO-enhanced magnetic resonance imaging (MRI) scans. The lesion visibility grades were compared and the diagnostic performance of SPIO-enhanced DWI was compared to those of SPIO-enhanced T2WI and T2*WI with the use of a receiver operating characteristic (ROC) analysis. RESULTS: The grade of lesion visibility was the highest on DWI [mean ± standard deviation (SD): 2.8 ± 0.3] followed by T2WI (2.3 ± 0.7, p < 0.001) and T2*WI (2.1 ± 0.7, p < 0.0001). Reviewers 1 and 2 correctly characterized the presence or absence of SPIO uptake in 34 of 35 cases (97.1%) on DWI, 24 (68.6%) and 25 (71.4%) cases on T2WI, respectively, and 16 (45.7%) and 17 (48.6%) cases on T2*WI. The area under the ROC curve (AUC) of DWI was 0.974 and 0.989 for reviewers 1 and 2, respectively. For Reviewer 1, the AUC of DWI was significantly higher than that of T2*WI (0.756, p < 0.01), although it was not significantly different from that of T2WI (0.868, p = 0.0857). For Reviewer 2, the AUC of DWI was significantly higher than those of T2WI (0.846, p < 0.05) and T2*WI (0.803, p < 0.01). CONCLUSION: The diagnostic performance of SPIO-enhanced DWI was better than those of SPIO-enhanced T2*WI and T2WI for the diagnosis of intrapancreatic accessory spleen.

Imaging features of undifferentiated carcinoma of the pancreas.

INTRODUCTION: The purpose of this retrospective study was to evaluate imaging features of undifferentiated carcinoma of the pancreas. METHODS: The study group included eight patients with surgically resected undifferentiated carcinoma of the pancreas. Multidetector-row computed tomography (MDCT, n = 8) and magnetic resonance imaging (MRI, n = 6) findings were retrospectively reviewed. RESULTS: On MDCT, all eight cases were hypovascular with upstream main pancreatic duct (MPD) dilatation, and only 1 showed exophytic growth. Five cases (62.5%) showed necrosis/cystic change, and calcification was observed in two cases (25%). Calcification reflected tumour osteoid components. On MRI, haemorrhage and hemosiderin were observed in 4 of 6 (66.7%) cases. In addition, tumour thrombus in the splenic vein (n = 1) and intraductal tumour growth in the MPD (n = 2) were pathologically identified, although imaging studies only revealed 1 of these latter cases. CONCLUSION: Undifferentiated carcinoma of the pancreas may present as a tumour with haemorrhagic necrosis. Coexistence of calcification, intraductal tumour growth in the MPD and tumour thrombus may support the imaging diagnosis of this entity.

Differential Diagnosis of Pancreatic Epidermoid Cyst Without a Solid Component (Residual Splenic Tissue) vs. Mucinous Cystic Neoplasm.

PURPOSE: The purpose of this study was to clarify whether there are differences in imaging findings between pancreatic epidermoid cyst (EDC) without a solid component (residual splenic tissue) and mucinous cystic neoplasm (MCN). MATERIALS AND METHODS: The study group consisted of histologically proven EDC (eight cases) and MCN (20 cases). CT and MRI findings were compared on the following imaging findings: the shape of the cystic lesions and the presence or absence of septum, calcification, and high-intensity fluid on T1- and diffusion-weighted images (b factor = 1000). The degree of contact with the pancreatic tail was compared between the EDCs and six of the MCNs at the edge of the pancreatic tail. RESULTS: The EDCs were round (n = 3) or oval (n = 5), while the MCNs consisted of three round, five oval, six pear-like, and six multilobulated lesions (P < 0.05). Septum was present in 4 of 8 (50%) EDCs and 19 of 20 (95%) MCNs (P < 0.05). The presence of calcification (2 of 8 [25%] EDCs vs. 8 of 20 [40%] MCNs), high-intensity fluid on T1-weighted images (2 of 7 [29%] EDCs vs. 5 of 20 [25%] MCNs), and high-intensity fluid on diffusion-weighted images (5 of 7 [71%] EDCs vs. 5 of 20 [25%] MCNs) were not significantly different. The degree of contact with the pancreatic parenchyma was similar between the two types of lesions. CONCLUSION: Although the imaging findings for EDC without a solid component and MCN overlap, a pear-like or multilobulated shape may favor a diagnosis of MCN.

Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix.

Although recent studies revealed that adipose tissue accelerates pancreatic tumor progression with excessive extracellular matrix, key players for desmoplasia in the adipose microenvironment remains unknown. Here, we investigated the roles of adipose tissue-derived stromal cells (ASCs) in desmoplastic lesions and tumor progression by in vitro and in vivo experiments. In a three-dimensional (3-D) organotypic fat invasion model using visceral fat from CAG-EGFP mice, GFP-positive fibroblastic cells infiltrated toward cancer cells. When tumor cells were inoculated into transplanted visceral fat pads in vivo, tumor weights and stromal components were enhanced compared to subcutaneous and orthotopic tumor cells inoculated without fat pads. Expression of αSMA in established human ASCs was lower compared to cancer associated fibroblasts, and the 3-D collagen matrices produced by ASCs cultured in cancer cell-conditioned medium changed from loose to dense structures that affected the motility of cancer cells. Microarray analyses revealed upregulation of S100A4 in ASCs, while S100A4-positive stromal cells were observed at extrapancreatic invasion sites of human pancreatic cancer. The present findings indicate that ASCs are recruited to extrapancreatic invasion sites and produce dense collagen matrices that lead to enhanced tumor progression. Both inhibition of ASCs recruitment and activation could lead to a novel antistromal therapy.

Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas: Metachronous multifocal lesion or local recurrence?

BACKGROUND: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. METHODS: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes-KRAS, TP53, CDKN2A, and SMAD4-associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. RESULTS: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. CONCLUSION: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence.

Intrapancreatic recurrence of intraductal tubulopapillary neoplasm (ITPN) 16 years after the initial surgery for noninvasive ITPN: a case report.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) is a rare pancreatic intraductal neoplasm. It is characterized by a tubulopapillary growth pattern, entirely high-grade atypical cells, minimal cytoplasmic mucin, and no obvious luminal mucin secretion. Most of its biological nature remains unclear. CASE PRESENTATION: We herein report a case of intrapancreatic recurrence of ITPN in the remnant pancreas of a patient who underwent pancreatoduodenectomy 16 years previously for a noninvasive intraductal pancreatic head tumor. We reexamined the primary tumor and compared it with the most recently resected specimen. Histologically, the primary tumor showed a tubulopapillary growth of high-grade atypical cells with scanty cytoplasmic mucin, which was similar to the recently resected specimen except for the invasive area. Immunohistochemically, the neoplastic cells in both specimens showed focal staining of MUC1 and positivity for MUC6 but negativity for MUC2, MUC5AC, CDX2, and trypsin. Molecular analysis revealed no KRAS/GNAS/BRAF/PIK3CA mutations in either of the specimens. CONCLUSIONS: These findings of the original tumor and recently resected tumor were compatible with the features of ITPN. Thus, recurrence is possible even for a primary noninvasive ITPN, and long-term surveillance is recommended.

"Pancreatic Mucoepidermoid Carcinoma" Is not a Pancreatic Counterpart of CRTC1/3-MAML2 Fusion Gene-related Mucoepidermoid Carcinoma of the Salivary Gland, and May More Appropriately be Termed Pancreatic Adenosquamous Carcinoma With Mucoepidermoid Carcinoma-like Features.

"Mucoepidermoid carcinoma (MEC)" has been accepted as a synonym for pancreatic adenosquamous carcinoma (ASC). Pancreatic ASC can show salivary gland-type MEC-like morphology. CRTC1/3-MAML2 fusion gene is a characteristic molecular feature of MEC of the salivary gland. We conducted this study to clarify whether the pancreatic ASC with salivary gland-type MEC-like morphology (Pan-MEC) is a pancreatic counterpart of salivary gland-type MEC (Sal-MEC). We retrospectively analyzed 37 pancreatic ASCs including 16 Pan-MECs and 21 tumors without MEC-like features (ASC-NOS [not otherwise specified]), and we investigated (1) clinicopathologic features, (2) the presence of CRTC1/3-MAML2 fusion gene by reverse transcription polymerase chain reaction, (3) the presence of rearrangement of MAML2 gene by fluorescence in situ hybridization, and (4) mucin core proteins by immunohistochemistry. We also compared 16 Pan-MECs with 20 Sal-MECs by immunohistochemistry for mucin core protein. There were no significant differences of any clinicopathologic characteristics and survival analysis between the Pan-MECs and ASCs-NOS. Of note, the pancreatic ASCs (including Pan-MEC and ASC-NOS) were significantly more aggressive than conventional pancreatic ductal adenocarcinoma. In addition, all Pan-MECs were histologically high-grade. CRTC1/3-MAML2 fusion gene and MAML2 gene rearrangement were not detected in any ASCs including Pan-MECs. There were significant differences of MUC5AC and MUC6 between the Pan-MECs and Sal-MECs, but no significant differences of mucin core protein between the Pan-MECs and pancreatic ASCs-NOS. Pan-MEC is histologically and biologically high-grade and unrelated to CRTC1/3-MAML2 fusion gene, unlike Sal-MEC which is related to CRTC1/3-MAML2 fusion gene. Pan-MEC is not a pancreatic counterpart of CRTC1/3-MAML2 fusion gene-related Sal-MEC.

Role of SpyGlass-DStm in the preoperative assessment of pancreatic intraductal papillary mucinous neoplasm involving the main pancreatic duct.

BACKGROUND/OBJECTIVES: It is often difficult to determine an adequate resection line during pancreatectomy for intraductal papillary mucinous neoplasm involving the main pancreatic duct during partial pancreatectomy. The aim of this study was to evaluate the usefulness of improved peroral pancreatoscopy using SpyGlass-DStm in the preoperative assessment of intraductal papillary mucinous neoplasm involving the main pancreatic duct. METHODS: We collected and retrospectively analyzed clinicopathological data from seven consecutive patients who underwent preoperative assessment of intraductal papillary mucinous neoplasm involving the main duct using SpyGlass-DStm. RESULTS: Good imaging quality of the intraductal protruding lesion was obtained in all seven patients, and only one adverse event was noted wherein a patient had mild pancreatitis. Six patients underwent pancreatectomy. In one patient, masked-type concomitant pancreatic ductal adenocarcinoma and low-length dysplastic lesion was found near the surgical margin, which was not detected by preoperative imaging modalities including SpyGlass-DStm. The sensitivity of targeting biopsy during SpyGlass-DStm to diagnose high-grade dysplasia was 0%. CONCLUSIONS: SpyGlass-DStm can be safely performed in patients with intraductal papillary mucinous neoplasm involving the main duct, and has excellent visualization of the target lesion. However, challenges include poor diagnostic ability of targeting biopsy, and, therefore, intraoperative frozen section is still needed to obtain negative surgical margins.

'Microcystic pattern' should be recognised as part of the morphological spectrum of solid-pseudopapillary neoplasm of the pancreas.

AIM: Solid pseudopapillary neoplasm (SPN) is an uncommon pancreatic tumour characterised by solid and pseudopapillary growth patterns. We have observed SPNs can show a microcystic pattern (microcystic SPN), which has been poorly described and may be confused with microcystic neoplasms. We conducted the present study to clarify the clinicopathological and immunohistochemical features of microcystic SPNs. METHODS AND RESULTS: We examined a consecutive series of 44 SPNs and 10 serous cystadenomas (SCAs), and classified them into 13 microcystic SPNs (29.5%) and 31 conventional SPNs (70.5%). Clinicopathological analysis, immunohistochemical staining and mucin histochemistry were performed. Clear cell change, hyalinised stroma and haemorrhage were observed significantly more frequently in the microcystic SPNs compared to the conventional SPNs. Immunohistochemically, the microcystic SPNs showed significantly lower frequencies of CD10 (0%) and CD56 expression (62%) compared to the conventional SPNs (87%; P < 0.001, 90%; P < 0.0085, respectively). There were no significant differences in other clinicopathological and immunohistochemical features between the two groups (i.e. the nuclear expression of ß-catenin, E-cadherin, progesterone receptor (PgR), lack of forkhead box (Fox)L2 and occasional oestrogen receptor (ER), AE1/AE3 expression). Microcystic SCAs lack such a characteristic immunophenotype. The myxoid stroma of microcystic SPNs contained hyaluronan revealed by Alcian blue stain with hyaluronidase digestion. CONCLUSION: We thus conclude that the microcystic pattern should be recognised as a part of the morphological spectrum of SPNs. Our findings may contribute to the correct diagnosis of the pancreatic neoplasms with the microcystic pattern. In addition, we speculate that stromal change caused by an accumulation of hyaluronan may contribute to the microcystic pattern of SPN.

Surveillance of patients with intraductal papillary mucinous neoplasm with and without pancreatectomy with special reference to the incidence of concomitant pancreatic ductal adenocarcinoma.

BACKGROUND: The presence of an intraductal papillary mucinous neoplasm is important in the detection of concomitant pancreatic ductal adenocarcinoma. The aim of this study was to elucidate the incidence and timing of development of concomitant pancreatic ductal adenocarcinoma in patients with and without pancreatectomy for intraductal papillary mucinous neoplasm. METHODS: We reviewed retrospectively the surveillance data for 22 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm (pancreatic ductal adenocarcinoma-resection group), 180 who underwent pancreatectomy for intraductal papillary mucinous neoplasm (intraductal papillary mucinous neoplasm-resection group), and 263 whose intraductal papillary mucinous neoplasms were left untreated (nonresection group). The incidence and timing of the development of a concomitant pancreatic ductal adenocarcinoma during the surveillance of patients with and without partial pancreatectomy for intraductal papillary mucinous neoplasm were investigated using the Kaplan-Meier method. RESULTS: During a median surveillance period of 40 months (range 6-262 months), 5 patients in the pancreatic ductal adenocarcinoma-resection group, 6 in the intraductal papillary mucinous neoplasm-resection group, and 8 in the nonresection group developed concomitant pancreatic ductal adenocarcinoma. The estimated 5-year (17%) and 10-year (56%) cumulative incidences of secondary pancreatic ductal adenocarcinoma in the pancreatic ductal adenocarcinoma-resection group were significantly greater than those in the other two groups (P < .01). Conversely, the difference in the estimated cumulative incidence of concomitant pancreatic ductal adenocarcinoma between the intraductal papillary mucinous neoplasm-resection and nonresection groups was not significant (5-year, 5.0% vs 2.2%; 10-year, 5.0% vs 8.7%; P = .87). CONCLUSION: Long-term (≥5-year) surveillance in patients with intraductal papillary mucinous neoplasm is necessary and important because of the potential for development of concomitant pancreatic ductal adenocarcinoma. Those with a history of resection of concomitant pancreatic ductal adenocarcinoma at the time of the initial operation are at quite high risk for the development of secondary pancreatic ductal adenocarcinoma.

Mucinous nonneoplastic cyst of the pancreas: CT and MRI appearances.

PURPOSE: The purpose of this retrospective study was to evaluate imaging features of mucinous nonneoplastic cyst (MNNC) of the pancreas. MATERIALS AND METHODS: Three (0.9%) patients with MNNC of the pancreas were found in 335 surgically resected pancreatic cystic lesions. Three MDCT and two MRI/MRCP studies were retrospectively reviewed. RESULTS: Three cases of MNNC were found in the pancreatic neck, body, and tail, respectively. All the three cases were multilocular without communication with the main pancreatic duct (MPD), although upstream MPD dilatation was seen in two of the three cases. The signal intensity of the cyst fluid was low on T1-weighted, high on T2-weighted, and low on diffusion-weighted images. Cyst wall was thin in two cases, and the remaining case with obstructive pancreatitis showed visible cyst wall enhancement. CONCLUSION: Imaging findings of MNNC of the pancreas were nonspecific without communication with the MPD. Cyst wall is typically thin without visible enhancement.

Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. BACKGROUND: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. METHODS: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. RESULTS: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95% of the samples. CONCLUSIONS: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression.

Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection.

BACKGROUND: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC. METHODS: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated. RESULTS: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC. CONCLUSIONS: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens.

GNAS and KRAS mutational analyses of intraductal papillary neoplasms of the pancreas and bile duct developing in the same individual: A case report.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas and intraductal papillary neoplasm of the bile duct (IPNB) are considered as counterparts of each other, and it is suggested that these two entities have similar molecular alteration pathways. However, the occurrence of IPMN of the pancreas and IPNB in the same patient is rare. We report a surgical case of a 69-year-old woman who developed invasive IPMN of the pancreas and underwent pancreatectomy, 6 months after hepatic resection of invasive IPNB. Molecular analysis revealed GNAS/KRAS mutation in both invasive IPMN of the pancreas and IPNB. This is believed to be the first case report investigating GNAS/KRAS mutational status in both IPMN of the pancreas and IPNB developing in the same patient, and these two entities may show similar molecular alternations.

Efficacy of laparoscopic resection in elderly patients with colorectal cancer.

PURPOSE: The perioperative outcomes of laparoscopic colorectal surgery in elderly patients were compared with those of open surgery in elderly patients and those of laparoscopic surgery in nonelderly patients to evaluate the feasibility and efficacy of laparoscopic surgery in elderly patients with colorectal cancer. METHODS: The data of the patients who underwent surgical resection for colorectal cancer between January 2007 and September 2012 were retrospectively collected. The clinical backgrounds and outcomes of elderly patients (≥ 70 years of age) who underwent laparoscopic surgery (EL group) were compared with those of elderly patients who underwent open surgery (EO group) and those of nonelderly patients (< 70 years of age) who underwent laparoscopic surgery (NL group). RESULTS: Compared with the EO group, the EL group showed significantly less blood loss (15 versus 100 ml), fewer postoperative complications (10.7 versus 36.7 %), earlier resumption of an oral diet (4 versus 5 days) and shorter postoperative hospital stays (16 versus 28 days). A case-matched analysis showed similar results. All perioperative outcomes were equivalent between the EL and NL groups. CONCLUSIONS: Laparoscopic colorectal surgery in elderly patients with cancer was not only superior to open surgery in elderly patients, but also equivalent to laparoscopic surgery in nonelderly patients in terms of the postoperative outcomes.