Impact of physiologically shaped pancreatic stent for chronic pancreatitis.

Endoscopic pancreatic stenting is used to prevent main pancreatic duct obstruction and relieve painful symptoms of chronic pancreatitis. However, the stent typically needs to be exchanged and the rate of adverse events is high. Few studies have evaluated the effect of stent shape on those outcomes. We evaluated the adverse events, stent patency, and total medical cost within 90 days of patients who received an 8.5 French (Fr) physiologically shaped pancreatic stent by comparing these features with those associated with a conventional straight-type stent for ≥ 90 days. The total stent-related adverse event rate was significantly lower for the physiologically shaped pancreatic stent (physiologically shaped, 6.7% [2/30]; straight-type, 50.6% [44/87]; P < 0.001). Stent occlusion was significantly less frequent (P < 0.001) and the total medical costs were significantly lower (P = 0.002) for the physiologically shaped stent. The stent-related adverse event rate was significantly higher for the 10 Fr straight type stent than for the 8.5 Fr physiologically shaped stent (10 Fr, straight-type vs. 8.5 Fr, physiologically shaped: 36.1% [13/36] vs. 6.7% [2/30]; P = 0.007). In conclusion, a physiologically shaped pancreatic stent was superior to a straight-type stent in terms of the patency rate and medical costs.

Early Detection of High-grade Biliary Intraepithelial Neoplasia (BilIN-3) in the Cystic Duct Visualized by SpyGlass DS Cholangioscopy.

An 84-year-old man was admitted with epigastralgia. Computed tomography showed contrast-enhanced wall thickness in the cystic duct. An endoscopic examination revealed short irregular stricture in the cystic duct, and per-oral cholangioscopy revealed a reddish papillary tumor at the stricture site. Surgical resection revealed high-grade biliary intraepithelial neoplasia (BilIN) at the stricture site of the cystic duct. To our knowledge, this is the first case of a solitary high-grade BilIN epithelium in the cystic duct detected by per-oral cholangioscopy.

Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer.

Patients with ulcerative colitis or colonic Crohn's disease have a significantly increased risk of developing colorectal cancer. Bovine lactoferrin (bLF) reportedly inhibited the development of colon cancer in rats and mice, and in a placebo controlled trial, ingestion of bLF inhibited the growth of intestinal polyps. In addition, in a case study, a patient with Crohn's disease was reported to have remained in remission for over 7 years while ingesting 1 g of bLF daily. Thus, bLF has an inhibitory effect on colon carcinogenesis, and it may also promote remission of Crohn's disease. The purpose of this study was to investigate the effects of bLF in a mouse model of colorectal cancer related to irritable bowel disease (IBD). The mice were divided into 4 groups: (i) no treatment; (ii) treated with bLF only; (iii) treated with azoxymethane plus dextran sulfate sodium (AOM + DSS); and (iv) treated with AOM + DSS + bLF. AOM was used to initiate intestinal cancer, and DSS was used to induce IBD-like inflammation in the intestine of the C57BL/6 mice. At the end of the study, the mice treated with AOM + DSS + bLF had a better fecal score, fewer lesions in the colon, and less weight loss than the mice treated with AOM + DSS without bLF. However, there were no statistically significant differences between the two groups with respect to tumor burden.

Iron deposition in autopsied liver specimens from older patients receiving intravenous iron infusion.

BACKGROUND: Vitamins and minerals are routinely administered by total parenteral nutrition (TPN). However, in Japan, adjustments in iron dosage are difficult because blended mineral preparations are often used. It is therefore unclear whether the iron content is appropriate in cases of long-term TPN. The aim of the study was to assess the influence of iron administration by long-term TPN on iron deposition in post-mortem liver samples isolated from older deceased patients. METHODS: Liver tissues were collected from post-mortem autopsies of 187 patients over a period of 15 years. Samples were stained with Prussian blue and histologically evaluated from Grade 0-V by at least three different observers. Specimens with positive and negative iron staining were compared, and positive samples were grouped according to the level and distribution of the staining. Post-mortem blood obtained from the subclavian vein during autopsy was also analysed. Samples were collected for the measurement of unsaturated serum iron, serum iron, albumin, prealbumin, hepcidin, and IL-6 concentrations. RESULTS: Iron accumulation in the liver was significantly higher in male patients (p = 0.005) with a history of surgery (p = 0.044) or central vein administration of iron (p<0.001). Additionally, the duration of TPN in the iron-positive group was significantly longer than in the iron-negative group (p = 0.038). Serum analysis revealed that unsaturated serum iron was significantly higher in the iron-negative group and that ferritin and serum iron were significantly higher in the iron-positive group. No other statistically significant differences were observed between the two groups. CONCLUSIONS: Chronic intravenous administration of iron was associated with iron deposition in the liver, even when given the minimum recommended dosage. In long-term TPN patients, the iron dose should therefore be carefully considered.

Laterally Spreading Adenocarcinoma Involving the Lower Bile Duct and Duodenum Expressing Heterogeneous Immunohistochemical Phenotypes.

A 70-year-old man was admitted to our hospital due to elevated levels of hepatobiliary and pancreatic enzymes. Computed tomography showed contrast-enhanced mucosal hypertrophy from the duodenal papilla to the distal bile duct. Endoscopic examinations revealed a laterally spreading granular tumor and ampullary swelling. After surgical resection, an examination revealed well-differentiated adenocarcinoma of the ampulla with tubular adenoma spreading from the distal common bile duct to the second part of the duodenum showing both bile duct and duodenal phenotypes. To our knowledge, this is the first case of a tumor spreading from the bile duct to the duodenum that exhibited multiple phenotypes.

[Effects of drug treatment on the surviral-time in patients with dementia].

AIM: The effect of polypharmacy on the surviral-time in patients with dementia has never been fully elucidated. METHODS: A retrospective study was conducted in a hospital in Aichi, Japan, by reviewing the medical charts and autopsy reports. Patients were hospitalized and neuropathologically diagnosed with dementia. The data on medication was collected from the prescribed drugs taking right before the admission. Patients were divided into two groups according to the number of prescribed drugs: ≥ 5 drugs (polypharmacy) vs. ≤ 4 drugs (non-polypharmacy). "Drugs to be prescribed with special caution" were defined in accordance with the guidelines for medical treatment and its safety in the elderly (2015). RESULTS: Seventy-six patients were eligible, and 39.5% of patients had polypharmacy. The Kaplan-Meier method showed that the polypharmacy group tended to have a shorter survival-time than the non-polypharmacy group (p=0.067). A Cox proportional hazard model showed that the polypharmacy group tended to have a higher risk for a reduced survival-time than the non-polypharmacy group, and this tendency was more prominent after adjusting for sex and age at admission (adjusted hazard ratio, 1.631; 95% confidence interval, 0.991-2.683; p=0.054). "Drugs to be prescribed with special caution", including hypnotic-sedative drugs, antianxiety drugs, antipsychotics, and benzodiazepines, were not found to be risk factors for a reduced survival-time. CONCLUSIONS: The present study showed that polypharmacy in terminal patients with dementia tended to carry a risk for reducing their remaining lifespan. The results warrant further additional study.

Clinical practice guidelines for IgG4-related sclerosing cholangitis.

IgG4-related sclerosing cholangitis (IgG4-SC) is a distinct type of cholangitis frequently associated with autoimmune pancreatitis and currently recognized as a biliary manifestation of IgG4-related disease. Although clinical diagnostic criteria of IgG4-SC were established in 2012, differential diagnosis from primary sclerosing cholangitis and cholangiocarcinoma is sometimes difficult. Furthermore, no practical guidelines for IgG4-SC are available. Because the evidence level of most articles retrieved through searching the PubMed, Cochrane Library, and Igaku Chuo Zasshi databases was below C based on the systematic review evaluation system of clinical practice guidelines MINDS 2014, we developed consensus guidelines using the modified Delphi approach. Three committees (a guideline creating committee, an expert panelist committee for rating statements according to the modified Delphi method, and an evaluating committee) were organized. Eighteen clinical questions (CQs) with clinical statements were developed regarding diagnosis (14 CQs) and treatment (4 CQs). Recommendation levels for clinical statements were set using the modified Delphi approach. The guidelines explain methods for accurate diagnosis, and safe and appropriate treatment of IgG4-SC.

Management of Pancreatolithiasis: A Nationwide Survey in Japan.

OBJECTIVES: The aim of this study was to assess prevailing treatment of pancreatolithiasis in Japan. METHODS: We surveyed clinical data from 1834 patients (1479 men and 355 women) at 125 hospitals. RESULTS: Extracorporeal shock-wave lithotripsy (ESWL) was performed alone in 103 patients (5.6%), ESWL plus an endoscopic procedure in 446 (24.3%), endoscopic treatment alone in 261 (14.2%), and surgery in 167 (9.1%). Other treatments were given to 358 (19.5%), whereas 499 (27.2%) received no treatment. Symptoms were relieved in 85.7% after ESWL, 80.8% after endoscopic treatment alone, and 92.8% after surgery. Early complication rates within 3 months after ESWL, endoscopic treatment alone, and surgery were 8%, 4.5%, and 27.1%, respectively. Late complications after ESWL, endoscopic procedures alone, and surgery were 1.7%, 2.5%, and 8.2%, respectively. Symptom relief but also early and late complications were greater after surgery than after ESWL and endoscopic treatment. Among 417 patients undergoing ESWL, 61 (14.6%) required surgery, as did 32 (16%) of 200 patients treated endoscopically. Surgery was required less frequently following initial operative treatment (11/164 patients [6.7%]). Nonsurgical initial treatments were chosen more frequently. CONCLUSIONS: First-line treatment of pancreatolithiasis should be ESWL with or without endoscopy because of minimal invasiveness and fewer complications.

Diagnosis of autoimmune pancreatitis by EUS-guided FNA using a 22-gauge needle: a prospective multicenter study.

BACKGROUND AND AIMS: Histopathologic examination is critical for diagnosing autoimmune pancreatitis (AIP). However, specimens obtained using EUS-guided FNA (EUS-FNA) are not recommended for histopathologic diagnosis because of inadequate sample size volume. We evaluated EUS-FNA efficacy for AIP diagnosis using a 22G needle. METHODS: Seventy-eight patients exhibiting the imaging characteristics indicative of AIP in the pancreatic parenchyma and pancreatic duct underwent EUS-FNA with a 22G needle at 12 institutions between February 2013 and March 2014. Samples were evaluated for tissue sampling conditions, CD38- and IgG4-positive plasma cell counts, storiform fibrosis (SF), and obliterative phlebitis (OP). RESULTS: Tissue specimens containing >10, 5 to 10, and 1 to 4 high-power fields (HPFs) were obtained from 29 (37.2%), 18 (23.1%), and 15 (19.2%) of 78 patients, respectively. The mean ± standard deviation (SD) CD38- and IgG4-positive plasma cell counts were 23.2 ± 18.8/HPF and 5.1 ± 6.7/HPF, respectively. SF was detected in 49 of 78 patients (62.8%) and OP in 38 of 78 patients (48.7%). According to the International Consensus Diagnostic Criteria (ICDC), histopathologic levels corresponded to level 1 in 32, level 2 in 13, and unclassifiable in 17 patients. Hence, 45 of 78 patients (57.7%) could be diagnosed with lymphoplasmacytic sclerosing pancreatitis according to ICDC. CONCLUSIONS: Pancreatic tissues with at least 1 HPF were obtained by EUS-FNA from approximately 80% of patients, and nearly 60% of patients were diagnosed with ICDC level 2 or higher. Our findings indicate that EUS-FNA with a 22G needle may be useful for the histopathologic diagnosis of AIP. (Clinical trial registration number: UMIN000010097.).

Clinical features of acute obstructive suppurative pancreatic ductitis: A retrospective review of 20 cases.

BACKGROUND AND AIMS: The clinical features of acute obstructive suppurative pancreatic ductitis (AOSPD) have not been elucidated. We aimed to clarify the clinical features of AOSPD. METHODS: We retrospectively reviewed the clinical features of 20 patients with AOSPD at two tertiary referral centers between 1993 and 2012. We compared 17 AOSPD patients with chronic pancreatitis (CP) and 42 patients with acute-on-CP in terms of clinical characteristics, presentation, and laboratory and imaging findings. RESULTS: The etiology of AOSPD involved CP in 17 (85%) patients, pancreatic ductal adenocarcinoma in 2 (10%), and intraductal papillary mucinous neoplasm in 1 (5%). Endoscopic pancreatic drainage was effective in 19 (95%) patients. Body temperature was significantly higher in AOSPD with CP than acute-on-CP patients (median: 38.2 vs 36.9 °C; P < 0.001). Serum amylase levels at onset were significantly lower (median: 133 vs 364.5 U/L; P = 0.009), and C-reactive protein was significantly higher (median: 9.42 vs 1.06 mg/dL; P < 0.001) in AOSPD with CP patients. Enlargement of the pancreatic parenchyma (18 vs 93%; P < 0.001) and stranding of the surrounding fat (12 vs 93%; P < 0.001) on computed tomography were observed less frequently in patients with AOSPD with CP patients. The diameter of the main pancreatic duct was significantly greater in AOSPD with CP than acute-on-CP patients (median: 7 vs 5 mm; P = 0.006). CONCLUSIONS: The major etiology of AOSPD involved CP, and endoscopic pancreatic drainage was effective. The clinical features differ between AOSPD with CP and acute-on-CP.

Predictive factors for positive diagnosis of malignant biliary strictures by transpapillary brush cytology and forceps biopsy.

OBJECTIVE: The diagnostic yields of endoscopic transpapillary brush cytology and forceps biopsies for malignant biliary strictures (MBS) remain unclear and predictive factors for diagnosis have not been established. We aimed to clarify the diagnostic yields of both methods and the predictive factors METHODS: We reviewed 241 patients with biliary strictures who underwent transpapillary brush cytology (n = 202) or forceps biopsy (n= 208) between 2004 and 2014 at a single academic center. RESULTS: The sensitivity of forceps biopsy for MBS was significantly higher than that of brush cytology [60.6% (97/160) vs 36.1% (57/158), P < 0.01). The sensitivity of forceps biopsy was significantly higher in diagnosing bile duct cancer than pancreatic cancer [78.8% (52/66) vs 42.4% (28/66), P < 0.01). Multivariate analysis revealed that serum total bilirubin (TB) level (T-Bil) ≥ 4 mg/dL [odds ratio (OR) 2.506, 95% confidence interval (CI): 1.139-5.495, P = 0.022) was an independent predictor for positive diagnosis by brush cytology, while bile duct cancer (OR 4.926, 95% CI 2.183-11.111, P < 0.001), stricture length ≥ 30 mm (OR 2.941, 95% CI 1.119-7.752, P = 0.029) and TB ≥ 4 mg/dL (OR 2.252, 95% CI 1.052-4.831, P = 0.037) were significant indicators of a positive diagnosis by forceps biopsy. CONCLUSIONS: Endoscopic transpapillary forceps biopsy shows higher sensitivity than that of brush cytology for MBS. Bile duct cancer, stricture length ≥ 30 mm and TB ≥ 4 mg/dL are good indicators of forceps biopsy.

Chemopreventive effect of resveratrol and apocynin on pancreatic carcinogenesis via modulation of nuclear phosphorylated GSK3ß and ERK1/2.

Despite progress in clinical cancer medicine in multiple fields, the prognosis of pancreatic cancer has remained dismal. Recently, chemopreventive strategies using phytochemicals have gained considerable attention as an alternative in the management of cancer. The present study aimed to evaluate the chemopreventive effects of resveratrol (RV) and apocynin (AC) in N-Nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamster. RV- and AC-treated hamsters showed significant reduction in the incidence of pancreatic cancer with a decrease in Ki-67 labeling index in dysplastic lesions. RV and AC suppressed cell proliferation of human and hamster pancreatic cancer cells by inhibiting the G1 phase of the cell cycle with cyclin D1 downregulation and inactivation of AKT-GSK3ß and ERK1/2 signaling. Further, decreased levels of GSK3ß(Ser9) and ERK1/2 phosphorylation and cyclin D1 expression in the nuclear fraction were observed in cells treated with RV or AC. Nuclear expression of phosphorylated GSK3ß(Ser9) was also decreased in dysplastic lesions and adenocarcinomas of hamsters treated with RV or AC in vivo. These results suggest that RV and AC reduce phosphorylated GSK3ß(Ser9) and ERK1/2 in the nucleus, resulting in inhibition of the AKT-GSK3ß and ERK1/2 signaling pathways and cell cycle arrest in vitro and in vivo. Taken together, the present study indicates that RV and AC have potential as chemopreventive agents for pancreatic cancer.

Japanese Clinical Guidelines for Endoscopic Treatment of Pancreatolithiasis.

OBJECTIVES: In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required. METHODS: Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. RESULTS: The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. CONCLUSIONS: After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed.

Photodynamic Therapy using Talaporfin Sodium for the Recurrence of Cholangiocarcinoma after Surgical Resection.

We herein report the case of a 72-year-old man who underwent photodynamic therapy (PDT) with talaporfin sodium for recurrent cholangiocarcinoma after surgical resection. Endoscopic retrograde cholangiography (ERC) showed severe stenosis with an irregular surface measuring approximately 1 cm in length from the anastomotic site, and a recurrent nodular lesion was observed at the anastomotic site of the right anterior intrahepatic bile duct on gastrointestinal endoscopy. ERC after PDT revealed a dramatic improvement in the bile duct stenosis, and the nodular lesion had disappeared. No adverse events from the PDT were detected. PDT using talaporfin sodium may be a safe alternative treatment for cholangiocarcinoma.

Correlation between long-term outcome and steroid therapy in type 1 autoimmune pancreatitis: relapse, malignancy and side effect of steroid.

OBJECTIVES: Autoimmune pancreatitis (AIP) responds well to corticosteroid therapy (CST), and CST is essential to induce remission. However, the correlation between long-term outcome and CST has not been evaluated. We aimed to clarify the correlation between long-term outcome of AIP and CST. MATERIAL AND METHODS: We retrospectively evaluated relapse, risk of malignancy and side effects of CST by focusing on the correlation with CST in 84 patients with type 1 AIP. RESULTS: The incidence of relapse was 23.8%. The frequency of relapse after CST administration was significantly lower in patients taking CST for >6 months than in those who did not (22% versus 67%; p = 0.036). The incidence of malignancy was 10.7%. The standardized incidence ratio of malignancy was 2.14 [95% confidence interval 0.74-3.54]. There were no significant correlations between development of malignancy and CST. The incidences of total and serious side effects due to CST were 75% and 19.1%, respectively. Relapse was the only significant independent predictive risk factor for serious side effects in a multivariate analysis (odds ratio 4.065; 95% confidence interval 1.125-14.706; p = 0.032). The cumulative dose of corticosteroid was significantly higher in patients with serious side effects than in those without (12,645 mg versus 7322 mg; p = 0.041). CONCLUSIONS: CST reduces relapse of AIP. However, CST causes serious side effects, particularly in relapsing patients. Alternative maintenance therapy to prevent relapse is needed.

Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma.

Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome.

Safety and benefits of self-expandable metallic stents with chemotherapy for malignant gastric outlet obstruction.

BACKGROUND AND AIM: The influence of chemotherapy on placement of self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (MGOO) has not been evaluated extensively. We investigated the influence of chemotherapy on the clinical outcomes of SEMS placement for MGOO. METHODS: A total of 152 cancer patients with MGOO from a university hospital and affiliate hospitals were included. The patients were classified according to chemotherapy status and evaluated for palliative efficacy and safety of SEMS placement. RESULTS: Technical success rate, time to oral intake, and parameters indicating improvement of physical condition did not differ between the with- and without-chemotherapy groups after stent placement. Re-intervention and stent migration were significantly more frequent in the with-chemotherapy group than in the without-chemotherapy group after stent placement (re-intervention, 32.4% vs 7.8%, P = 0.0005; stent migration, 13.5% vs 1.7%, P = 0.0097). The frequency of adverse events did not differ between the with- and without-chemotherapy groups. Although chemotherapy after stent placement was an independent predictive factor for shortening the stent patency period (hazard ratio [HR], 3.10; P = 0.0264), the use of additional stents facilitated uneventful recovery and further prolonged survival time (HR, 0.60; P = 0.0132). CONCLUSIONS: Various cancer patients with MGOO can undergo SEMS placement safely regardless of chemotherapy, and concurrent chemotherapy after stent placement can prolong survival time, although re-intervention and stent migration may be increased.

Comparison study of immunohistochemical staining for the diagnosis of type 1 autoimmune pancreatitis.

BACKGROUND: Various methods to evaluate immunohistochemical staining (IHC) for the diagnosis of type 1 autoimmune pancreatitis (AIP) have been proposed. Our goal was to determine the most useful IHC method for the diagnosis of AIP. METHODS: Specimens of AIP (18 patients), chronic pancreatitis (CP, 24 patients), and pancreatic ductal adenocarcinoma (PDA, 45 patients) were evaluated with IHC for immunoglobulin G (IgG), IgG1, IgG4, and CD138 (syndecan-1). The number of IHC-positive cells was counted in 3, 5, and 10 different high-power fields (HPFs) by selecting fields with the most numerous positive cells (hotspot) or by randomly selecting fields in the affected areas (random). We evaluated the mean number of IgG4-positive plasma cells (IgG4+)/HPF (mean IgG4+), the number of fields with >10 and >50 IgG4+ (NOF >10 and NOF >50 IgG4+), the ratio of IgG4+/IgG+, IgG4+/IgG1+, and IgG4+/CD138+. RESULTS: Analysis with receiver operator characteristic curves revealed that accurate and practical parameters in 3 HPFs were mean IgG4+ with the hotspot method (sensitivity, 88.9; specificity, 92.8 %), mean IgG4+ with the random method (100, 95.7 %), and NOF >10 IgG4+ with the random method (94.4, 97.1 %). These results were as accurate as results from 5 HPFs to 10 HPFs. The combination of mean IgG4+ and IgG4+/IgG+ did not provide more accurate diagnosis for AIP than a single criterion itself. CONCLUSIONS: Mean IgG4+ or NOF >10 IgG4+ with the random method in 3 HPFs was a useful and simple diagnostic method for AIP. The combined criteria of mean IgG4+ and IgG4+/IgG+ might not be required for accurate diagnosis of AIP.

Locus/chromosome aberrations in intraductal papillary mucinous neoplasms analyzed by fluorescence in situ hybridization.

Locus and chromosome abnormalities have not been well clarified in intraductal papillary mucinous neoplasms (IPMNs). The aim of this study was to retrospectively examine these abnormalities using fluorescence in situ hybridization. IPMNs (n=28) were histopathologically classified into noninvasive IPMN (n=17) and IPMN with an associated invasive carcinoma (invasive IPMN, n=11) groups. Noninvasive IPMNs possessed non-neoplastic and noninvasive spots in their tissues, and invasive IPMN cases possessed non-neoplastic, noninvasive, and invasive spots. Non-neoplastic (n=28), noninvasive (n=28), and invasive (n=11) spots were then analyzed for aneuploidy of chromosomes 3, 6, 7, 8, 17, and 18 and deletions of p16 and p53 loci. Polysomy 6 and p16 deletion were significantly more frequent in noninvasive than in non-neoplastic spots. Polysomy 7, polysomy 18, p16 deletion, and p53 deletion were significantly more frequent in invasive than in noninvasive spots. Detection of polysomy 7 and p53 deletion gave a high diagnostic accuracy for invasive IPMN (sensitivity, 90.9%; specificity, 94.1%; and accuracy, 92.5%). Our study suggests that: (1) polysomy 6 and p16 deletion may contribute to adenomatous change of IPMN; (2) polysomy 7, polysomy 18, p16 deletion, and p53 deletion play roles in malignant transformation of noninvasive IPMN; and (3) polysomy 7 and p53 deletion may be excellent diagnostic markers for invasive IPMN.