Is preoperative pancreatic juice cytology useful for determining therapeutic strategies for patients with intraductal papillary mucinous neoplasm of the pancreas?

BACKGROUND: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies. METHODS: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively. CONCLUSIONS: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery.

A case of hepatic anisakidosis caused by Anisakis pegreffii mimicking liver cancer.

Extra-gastrointestinal anisakidosis is rare. We herein report an Anisakis pegreffii infection in a patient with hepatic anisakidosis diagnosed based on its molecular identification. A 71-year-old male patient had a hepatic tumor presenting as a low-density area of 20 mm in diameter in segment 6 of the liver on abdominal ultrasonography, computed tomography, and magnetic resonance imaging. The surgically resected pathological specimen revealed a necrotizing eosinophilic granuloma containing nematode larvae, possibly an Anisakis larva. Molecular and phylogenetic analysis demonstrated Anisakis larvae belonging to A. pegreffii. The present results will help identify and characterize unknown Anisakis species in histological sections.

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm -Multicenter observational study in Japan.

BACKGROUND/OBJECTIVES: The detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. METHODS: This multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. RESULTS: Two-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). CONCLUSIONS: EUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.

Spontaneous regression in solid pseudopapillary neoplasm of pancreas.

A solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of spontaneous regression in SPN of the pancreas. A 48-years-old female was found to have a mass in the head of the pancreas on examination for her back pain and referred to our hospital in 20XX. Laboratory data showed no abnormalities in serum levels of pancreatic enzymes and tumor markers. A contrast CT scan of upper abdomen showed a slightly enhanced lesion (23 × 19 mm in diameter) without cystic component or fibrous capsule in the head of the pancreas. An MRI scan showed the mass as low-intensity in T1-WI and high-intensity in T2-WI. She admitted to our hospital for further examination of a pancreatic mass by EUS-FNA in 20XX + 4. EUS showed a slightly hypoechoic mass (30 × 19 mm in diameter) compared with the neighboring normal pancreas. Tumor margin was relatively clear and the internal echo image was homogenous. Histological findings revealed a solid and pseudopapillary proliferation of eosinophilic polygonal cells with oval nuclei. The tumor cells were positive for vimentin and CD10 in the cytoplasm and ß-catenin in the nuclei, which led to the diagnosis of SPN. We recommended this patient to undergo surgical resection, however, the patient chose follow-up examinations. Follow-up study after 1 year using MRI scan showed spontaneous regression, which was coincided with her menopause. These findings suggest that the natural regression of SPN may occur and female sex hormone changes may regulate the growth of SPN.

Comparison of 22-gauge standard and Franseen needles in EUS-guided tissue acquisition for diagnosing solid pancreatic lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: This large multicenter randomized controlled trial compared the diagnostic yields of 22-gauge standard and 22-gauge Franseen needles for EUS-guided tissue acquisition (EUS-TA) of solid pancreatic lesions. METHODS: Consecutive patients with solid pancreatic lesions were prospectively randomized to EUS-TA using standard or Franseen needles. Samples obtained with the first needle pass and with second and subsequent passes were evaluated separately. The primary endpoint was the rate of accuracy for diagnosis of malignancy. Other endpoints were technical success rate, sample cellularity, adverse events, diagnostic accuracy in patient subgroups, and the diagnostic accuracy and numbers of second and subsequent needle passes. RESULTS: Of 523 patients undergoing EUS-TA, 260 were randomized to using standard 22-gauge needles and 263 to 22-gauge Franseen needles. The technical success rate in each group was 99.6%, with similar adverse event rates in the standard (1.5%) and Franseen (.8%) needle groups. First-pass EUS-TA using the Franseen needle resulted in significantly greater diagnostic accuracy (84.0% vs 71.2%, P < .001) and sensitivity (82.4% vs 66.7%, P < .001) than first-pass EUS-TA using a standard needle and also resulted in superior diagnostic accuracy in patients requiring immunostaining. Second and subsequent EUS-TA using Franseen needles showed significantly greater accuracy (94.7% vs 90.0%, P = .049) and sensitivity (94.0% vs 88.6%, P = .047) and required fewer needle passes (1.81 vs 2.03, P = .008) than using standard needles. CONCLUSIONS: EUS-TA with the Franseen needle is superior to EUS-TA with a standard needle with respect to diagnostic accuracy per pass, particularly in patients who require immunostaining, and number of passes when using macroscopic on-site evaluation. (Clinical trial registration numbers: UMIN000030634 and jRCTs052180062.).

Concordance of human equilibrative nucleoside transporter-1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial.

BACKGROUND: Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. AIM: We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. METHODS: The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. RESULTS: The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p < .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody. CONCLUSION: The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut-off point and suggests that S-1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S-1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.

Malignant potential and specific characteristics of pure main duct type intraductal papillary mucinous neoplasm.

BACKGROUND: As the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN. METHODS: From 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN. RESULTS: The rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091). CONCLUSIONS: Measurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.

Pathological Features and Imaging Findings in Pancreatic Carcinoma In Situ.

OBJECTIVES: This study aimed to evaluate the pathological features and imaging findings of pancreatic carcinoma in situ (PCIS). METHODS: Twenty patients with PCIS were categorized as flat (F) (n = 6) and low papillary (LP) (n = 14) types. RESULTS: None of F type and 8 (57%) of 14 with LP type lesions showed intraductal infiltrations of the main pancreatic duct (MPD) greater than 10 mm. None of F type and 3 (21%) of 14 with LP type lesions showed skip lesions in the MPD. Magnetic resonance cholangiopancreatography showed irregular MPD stenoses in 5 (83%) of 6 with F and 13 (100%) of 13 with LP type lesions. Magnetic resonance cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 3.6 mm for F, and 11.6 mm for LP type lesions. Endoscopic retrograde cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 2.8 mm for F, and 14.3 mm for LP type lesions. Pancreatic cancer recurrences limited to the remnant pancreas occurred in 2 patients with LP type lesions. CONCLUSIONS: In LP type PCIS, intraductal infiltration of the MPD occurs frequently. There may be multiple lesions, and lesions may recur in the remnant pancreas. Long-term strict follow-up assessments should be implemented for LP type PCIS.

Utility of a 20G needle with a core trap in EUS-guided fine-needle biopsy for gastric submucosal tumors: A multicentric prospective trial.

BACKGROUND AND OBJECTIVES: Differential diagnosis to estimate the malignant potential of gastric submucosal tumor (g-SMT) is important for decision-making. This study evaluated the use of a 20G needle with a core trap for EUS-guided fine-needle biopsy (EUS-FNB) for g-SMT. METHODS: This multicentric prospective trial was registered in the University Hospital Medical Information Network (UMIN000021410). Consecutive patients with g-SMT who presented at one of the nine Japanese Referral Centers between June 2017 and November 2018 were enrolled. All patients underwent EUS-FNB using a 20G needle with a core trap. Samples obtained with the first-needle pass were used for central pathological review. EUS-FNB was evaluated in terms of (i) technical success rate, (ii) adequacy for histological evaluation, (iii) rate of complications, (iv) accuracy for histological diagnosis of gastrointestinal stromal tumor (GIST), and (v) concordance between GIST mitotic index determined by EUS-FNB and after tumor resection. RESULTS: The study included 52 patients. The technical success rate of EUS-FNB was 100%. The adequacy rate for histological evaluation was 90.4% (P < 0.001). There were no complications related to EUS-FNB. Of the 38/52 patients who underwent surgical resection, 36 were finally diagnosed with GIST. The sensitivity, specificity, and accuracy of EUS-FNB for the histological diagnosis of g-SMT were 80.6%, 100%, and 81.6%, respectively. The concordance rate between the mitotic index on EUS-FNB and that after analysis of the resected tumor was 89.7%. CONCLUSIONS: EUS-FNB using a 20G needle with a core trap is feasible, providing histological samples of sufficient quality for diagnosing g-SMT.

Surgical indication for intraductal papillary mucinous neoplasm without mural nodule ≥5 mm.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. METHODS: In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. CONCLUSIONS: This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.

Histological diagnosis and grading of pancreatic neuroendocrine tumor by endoscopic ultrasound-guided fine needle biopsy using a 25-gauge needle with a core trap: A multicenter prospective trial.

OBJECTIVES: Preoperative grading of pancreatic neuroendocrine tumors (PanNET) is challenging. The aim of this study was to prospectively evaluate the use of a 25-gauge needle with a core trap for diagnosis and grading of PanNET. METHODS: This multicenter prospective trial was registered with the University Hospital Medical Information Network (UMIN000021409). Consecutive patients with suspected PanNET between June 2016 and November 2017 were enrolled. All patients underwent endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a 25-gauge needle with a core trap. Samples obtained after the first needle pass were used for central pathological review. EUS-FNB was evaluated in terms of (i) technical success rate, (ii) adequacy for histological evaluation, (iii) complication rate during the procedure, and (iv) concordance between PanNET grading on EUS-FNB and that after analysis of the resected tumor. RESULTS: Fifty-two patients were enrolled. Of the 36/52 patients who underwent surgical resection, 31 were finally diagnosed with PanNET and were eligible for analysis. The technical success rate of EUS-FNB was 100%. The rate of adequacy for histological evaluation was 90.3%. There were no complications related to EUS-FNB. The concordance rate between PanNET grading on EUS-FNB and that after analysis of the resected tumor was 82.6% (95% confidence interval = 61.22-95.05, P = 0.579). CONCLUSIONS: EUS-FNB using a 25-gauge needle with a core trap is feasible, providing histological samples are of sufficient quality for diagnosis and grading of PanNET.

Recurrence patterns after surgical resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas; a multicenter, retrospective study of 1074 IPMN patients by the Japan Pancreas Society.

BACKGROUND: Although there are numerous reports focusing on surgical indication for intraductal papillary mucinous neoplasm (IPMN), the recurrence patterns following surgery are less widely reported. To ascertain optimal treatment and postoperative surveillance for IPMN patients, we analyzed patterns and risk factors for recurrence after surgery for IPMN. METHODS: This study is a retrospective, multi-institutional, observational study, including 1074 patients undergoing surgery for IPMN at 11 academic institutions. We analyzed the risk factors for recurrence after classifying postoperative recurrences into metachronous high-risk lesions (malignant progression of IPMN and/or metachronous pancreatic ductal adenocarcinoma) in the remnant pancreas and extra-pancreatic recurrence. RESULTS: Of 1074 patients undergoing surgery for IPMN, 155 patients (14.4%) developed postoperative recurrence. We found that 34.3% of 70 high-risk lesions in the remnant pancreas occurred over 5 years after surgery, and survival of 36 patients undergoing second operation for high-risk lesions was better than that of 34 patients who did not (P = 0.04). We found four independent risk factors for metachronous high-risk lesions in remnant pancreas: symptoms [P = 0.005, hazard ratio (HR) 1.988], location of pancreatic body/tail (P < 0.001, HR 3.876), main duct size ≥ 10 mm (P = 0.021, HR 1.900), and high-grade dysplasia/invasive intraductal papillary mucinous carcinoma (IPMC) (P < 0.001, HR 3.204). Although six patients (0.7%) with low- or high-grade dysplasia IPMN developed extra-pancreatic recurrence, invasive IPMC was the strongest risk factor for extra-pancreatic recurrence (P < 0.001, HR 39.667). CONCLUSION: We suggest that life-time continuous surveillance might be necessary for IPMN patients. Second surgery for metachronous high-risk lesions in remnant pancreas should be considered to improve survival.

New Model for Predicting Malignancy in Patients With Intraductal Papillary Mucinous Neoplasm.

OBJECTIVE: To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types. BACKGROUND: No predictive model for malignant IPMN has been widely applied in clinical practice. METHODS: The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma. RESULTS: Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725. CONCLUSION: This predictive model provides important information for physicians and patients in assessing an individual's risk for malignancy and may help to identify patients who need surgery.

Human equilibrative nucleoside transporter-1 expression is a predictor in patients with resected pancreatic cancer treated with adjuvant S-1 chemotherapy.

The high expression of human equilibrative nucleoside transporter-1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5-fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S-1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S-1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S-1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S-1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S-1 arm.

Residual Cancer Volume Predicts Clinical Outcome in Patients With Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemotherapy.

Background. The aim of this study was to assess the prognostic significance of residual cancer volume (RCV) in patients with esophageal squamous cell carcinoma (ESCC) who received esophagectomy after neoadjuvant chemotherapy. Methods. We measured RCV by using complete stepwise sections at 6- to 8-mm intervals obtained from 81 ESCC patients with clinical stages IB to III. RCV was defined as the summation of all products of residual cancer area and thickness, and its cutoff value was set by receiver operator characteristic curve analysis on 3-year disease-specific survival (DSS). The multivariate analyses were performed in comparison with histopathological factors including tumor regression grades according to the Japanese Classification of Esophageal Cancer (TRG-JPN) or reported by Becker et al (TRG-Becker). Results. The range of RCV was 0 to 49.3 cm3 (median = 1.4 cm3), and the cutoff value was set at 1.0 cm3 (sensitivity = 78%; specificity = 68%). In the Kaplan-Meier curve analysis with the log-rank test, RCV > 1.0 cm3 predicted poorer prognosis for relapse-free survival (RFS; 5-year RFS rate, 12% vs 47%; P < .001) and DSS (5-year DSS rate, 27% vs 61%; P < .001). The multivariate analyses by the Cox hazards model revealed that RCV > 1.0 cm3 was a factor predicting poor prognosis for RFS (P = .013; hazard ratios [HR] = 2.62) and DSS (P = .028; HR = 2.56) compared with histopathological factors including TRG-JPN; RFS (P = .014; HR = 3.03) and DSS (P = .045; HR = 2.71) compared with histopathological factors including TRG-Becker. Conclusions. The study suggested that determining RCV is a new method of predicting prognosis in ESCC patients after neoadjuvant chemotherapy.

Genomic analysis of pancreatic juice DNA assesses malignant risk of intraductal papillary mucinous neoplasm of pancreas.

Intraductal papillary mucinous neoplasm (IPMN) of pancreas has a high risk to develop into invasive cancer or co-occur with malignant lesion. Therefore, it is important to assess its malignant risk by less-invasive approach. Pancreatic juice cell-free DNA (PJD) would be an ideal material in this purpose, but genetic biomarkers for predicting malignant risk from PJD are not yet established. We here performed deep exome sequencing analysis of PJD from 39 IPMN patients with or without malignant lesion. Somatic alterations and copy number alterations (CNAs) detected in PJD were compared with the histologic grade of IPMN to evaluate their potential as a malignancy marker. Somatic mutations of KRAS, GNAS, TP53, and RNF43 were commonly detected in PJD of IPMNs, but no association with the histologic grades of IPMN was found. Instead, mutation burden was positively correlated with the histologic grade (r = 0.427, P = 0.015). We also observed frequent copy number deletions in 17p13 (TP53) and amplifications in 7q21 and 8q24 (MYC) in PJDs. The amplifications in 7q21 and 8q24 were positively correlated with the histologic grade and most prevalent in the cases of invasive carcinoma (P = 0.002 and 7/11; P = 0.011 and 6/11, respectively). We concluded that mutation burden and CNAs detected in PJD may have potential to assess the malignant progression risk of IPMNs.

A Consensus Study of the Grading and Typing of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: The grading and typing of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are challenging for pathologists. We aimed to clarify the points of consistency and disagreement in assessing the grades and types of IPMNs. METHODS: Digital slide images of 20 IPMNs were independently assessed by 10 Japanese pathologists, who then held a consensus meeting to discuss the points of disagreement and develop a consensus and recommendations. RESULTS: The average agreement rates for grade and type were 83.5% (range, 100%-40%) and 82.5% (range, 100%-50%) and the Fleiss' κ values were 0.567 and 0.636, respectively. CONCLUSIONS: The disagreement points and recommendations were as follows: destructed ductal walls with desquamated neoplastic epithelia or mucin lakes partially lined with neoplastic cells could be invasion; intraductal stromal invasion could be dismissed unless vascular or lymphatic invasion existed; elastica staining may help visualize ducts in colloidal nodules; high-grade can be distinguished from low/intermediate grade by marked nuclear disarrangements and complex architecture in the intestinal papillae; oncocytic papillae are characterized by eosinophilic cells with round disoriented nuclei; high-grade gastric papillae can be distinguished from pancreatobiliary papillae by relatively low but complex architecture; and the most dysplastic papillae should be used to assess type in mixed papillae types.