Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Maintenance steroid therapy is associated with decreased risk of malignancy and better prognosis of patients with autoimmune pancreatitis: A multicenter cohort study in Japan.

BACKGROUND/OBJECTIVES: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan. METHODS: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis. RESULTS: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex. CONCLUSIONS: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.

Intravenous injection of tumor extracellular vesicles suppresses tumor growth by reducing the regulatory T cell phenotype.

BACKGROUND: Colorectal cancer is a disease of unmet medical need. Although extracellular vesicles (EVs) have been implicated in anti-tumor responses, discrepancies were observed among studies. We analyzed the role of tumor-derived EVs (TEVs) in tumor progression in vivo by focusing on regulatory T (Treg) cells, which play essential roles in tumor development and progression. METHODS: A mouse model of colorectal cancer lung metastasis was generated using BALB/c mice by tail vein injection of the BALB/c colon adenocarcinoma cell line Colon-26. TEVs derived from Colon-26 and BALB/c lung squamous cell carcinoma ASB-XIV were retrieved from the culture media supernatants. A TEV equivalent to 10 µg protein was injected every other day for 2 weeks. RESULTS: Histology and immunohistochemistry studies revealed that lung tumors reduced in the Colon-26-EV group when compared to the phosphate-buffered saline (PBS) group. The population of CD4 + FoxP3 + cells in the lung was upregulated in the PBS group mice when compared to the healthy mice (P < 0.001), but was significantly downregulated in the Colon-26-EV group mice when compared to the PBS group mice (P < 0.01). Programmed cell death protein 1, glucocorticoid-induced TNFR-related protein, and CD69 expression in lung Treg cells were markedly upregulated in the PBS group when compared to the healthy mice, but downregulated in the Colon-26-EV group when compared to the PBS group. The changes in expression were dose-dependent for Colon-26-EVs. ASB-EVs also led to significantly downregulated Treg cell expression, although non-cancer line 3T3-derived EVs did not. CONCLUSION: Our study suggests that TEVs possess components for tumor suppression.

A Short-Term Model of Colitis-Associated Colorectal Cancer That Suggests Initial Tumor Development and the Characteristics of Cancer Stem Cells.

The mechanisms underlying the transition from colitis-associated inflammation to carcinogenesis and the cell origin of cancer formation are still unclear. The azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model reproduces human colitis-associated colorectal cancer. To elucidate the mechanisms of cancer development and dynamics of the linker threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr)-positive cells, we explored the early stages of colitis-associated colorectal cancer in AOM/DSS mice. The AOM/DSS mice were sacrificed at 4 to 6 weeks following AOM administration. To analyze the initial lesions, immunofluorescence staining for the following markers was performed: ß-catenin, Ki67, CDK4, Sox9, Bmi1, cyclin D1, and pSmad2/3L-Thr. Micro-neoplastic lesions were flat and unrecognizable, and the uni-cryptal ones were either open to the surfaces or hidden within the mucosae. These neoplastic cells overexpressed ß-catenin, Sox9, Ki67, and Cyclin D1 and had large basophilic nuclei in the immature atypical cells. In both the lesions, pSmad2/3L-Thr-positive cells were scattered and showed immunohistochemical co-localization with ß-catenin, CDK4, and Bmi1 but never with Ki67. More ß-catenin-positive neoplastic cells of both lesions were detected at the top compared to the base or center of the mucosae. We confirmed initial lesions in the colitis-associated colorectal cancer model mice and observed results that suggest that pSmad2/3L-Thr is a biomarker for tissue stem cells and cancer stem cells.

Cardiac 18F­FDG uptake and new­onset rectal cancer.

The present study aimed to investigate the factors affecting the cardiac uptake of 18F-fluorodeoxyglucose (18F-FDG) during 18F-FDG positron emission tomography (PET) for new-onset rectal cancer and new-onset colon cancer (ascending, transverse, descending, sigmoid colon cancer) and to examine the association between the cardiac uptake of 18F-FDG and prognosis. The participants were diagnosed with new-onset rectal cancer and new-onset colon cancer (ascending, transverse, descending, sigmoid cancer) at the Iga City General Hospital (Iga, Japan) between January 1, 2013, and March 31, 2018, and underwent an 18F-FDG PET scan for pretreatment staging. The relationship between cardiac maximum standard uptake value (SUVmax), the presence/absence of distant metastasis and prognosis was examined. A total of 26 patients (14 men and 12 women) aged 72.0±10 years with new-onset rectal cancer were selected for the study. No patients had multiple simultaneous cancers. The median cardiac SUVmax was 3.8 and 2.5 in patients with no distant metastasis and distant metastasis, respectively, revealing a statistically significant difference (P<0.01). The median tumor volume on PET-computed tomography (CT) images was 7,815 cm2 and was 66,248 cm2 in patients with no distant metastasis and distant metastasis, respectively, revealing a statistically significant difference (P<0.01). Echocardiography findings revealed no significant difference between patients with and without distant metastasis. The correlation coefficient between cardiac SUVmax and total tumor volume on PET/CT images (primary + lymph + distant metastases) was statistically significant (r=-0.42, P=0.03). Analysis of the association between the occurrence of distance metastasis and cardiac SUVmax as a continuous variable gave a statistically significant result [hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.09-0.98, P=0.045]. Receiver operating characteristic analysis showed a cardiac SUVmax of 2.6 with an area under the curve of 0.86 for determining the presence of distant metastasis (95% CI: 0.70-1.00). The median observation time was 56 months, and nine patients died during observation. Analysis of the association between the overall survival and cardiac SUVmax (cutoff: 2.6) showed 95% CI: 0.01-0.45 and HR: 0.06 (P<0.01); that between the overall survival and total tumor volume on PET images showed 95% CI: 1.00-1.00 and HR: 1.00 (P<0.01); and that between the overall survival and presence of distant metastasis showed 95% CI: 1.72-116.4 and HR: 14.1 (P<0.01). Furthermore, 25 patients (16 men and nine women) aged 71.4±14.2 years with new-onset colon cancer were selected for the study. Analysis of new-onset colon cancer revealed no statistically significance between the cardiac SUVmax and distant metastasis.

A case of type 2 autoimmune pancreatitis with spontaneous remission.

A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.

Establishment of a Novel Colitis-Associated Cancer Mouse Model Showing Flat Invasive Neoplasia.

BACKGROUND: Chronic inflammation, such as ulcerative colitis, increases the risk of developing colitis-associated cancers. Currently, mice administered with azoxymethane/dextran sodium sulfate are well-known models for colitis-associated cancers. Although human colitis-associated cancers are often flat lesions, most azoxymethane/dextran sodium sulfate mouse cancers are raised lesions. AIMS: To establish a novel mouse model for colitis-associated cancers and evaluate its characteristics. METHODS: A single dose of azoxymethane was intraperitoneally administered to CD4-dnTGFßRII mice, which are genetically modified mice that spontaneously develop inflammatory bowel disease at different doses and timings. The morphological and biological characteristics of cancers was assessed in these mice. RESULTS: Colorectal cancer developed with different proportions in each group. In particular, a high rate of cancer was observed at 10 and 20 weeks after administration in 12-week-old CD4-dnTGFßRII mice dosed at 15 mg/kg. Immunohistochemical staining of tumors was positive for ß-catenin, ki67, and Sox9 but not for p53. Grade of inflammation was significantly higher in mice with cancer than in those without cancer (p < 0.001). In CD4-dnTGFßRII/azoxymethane mice, adenocarcinomas with flat lesions were observed, with moderate-to-severe inflammation in the non-tumor area. In comparison, non-tumor areas of azoxymethane/dextran sodium sulfate mice had less inflammation than those of CD4-dnTGFßRII/azoxymethane mice, and most macroscopic characteristics of tumors were pedunculated or sessile lesions in azoxymethane/dextran sodium sulfate mice. CONCLUSIONS: Although feasibility and reproducibility of azoxymethane/CD4-dbTGFßRII appear to be disadvantages compared to the azoxymethane/dextran sodium sulfate model, this is the first report to demonstrate that the chronic inflammatory colitis model, CD4-dnTGFßRII also develops colitis-related colorectal cancer.

Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study.

OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: Based on a Japanese nationwide study.

BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULTS: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P < .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

Efficacy and safety of endoscopic stent placement for afferent loop obstruction using a short double-balloon endoscopy.

Background: Afferent loop obstruction (ALO) is a rare mechanical complication that occurs after gastrojejunostomy. Recently the use of double-balloon endoscopy (DBE) can be useful for benign and malignant ALO. Methods: We retrospectively identified 22 patients who underwent DBE for ALO from January 2009 to December 2020. We evaluated the efficacy and safety of short DBE treatment for ALO. Results: Short DBE was able to reach an obstructive site in the afferent limb in all patients (100%) and was able to reach the blind end in 14 patients (64%). The technical success rate was 100%, and the clinical success rate was 95%. Procedure-related adverse events occurred in two patients (9%). In the case of benign ALO, three of nine patients showed improvement in ALO with single stent placement. Two of nine patients improved after the replacement of the plastic stent (PS) two or three times. Four of nine patients continued with the replacement of PS. In the case of malignant ALO, the metallic stent was placed in 10 patients, and eight patients with metallic stents did not experience stent occlusion until they died. Reintervention was attempted in six patients (27%) with benign ALO but was not attempted in malignant ALO. Conclusions: Treatments for ALO using the short DBE was effective and relatively safe because the technical and clinical success rates were very high and there were relatively low complications. Consequently, short DBE could be the first-choice treatment for both benign and malignant ALO.

Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: A nationwide survey in Japan.

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. METHODS: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. RESULTS: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037). CONCLUSIONS: NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

Steroid therapy still plays a crucial role and could serve as a bridge to the next promising treatments in patients with IgG4-related sclerosing cholangitis: Results of a Japanese Nationwide Study.

OBJECTIVE: The acceptable duration of steroid therapy for patients with IgG4-sclerosing cholangitis (SC) has been under debate. Our aim is to clarify the feasible duration of steroid treatment. DESIGN: We retrospectively reviewed the data of patients with IgG4-SC and analyzed the following: biliary status during the steroid therapy, incidence of remission, relapse, relapse-free survival rate, and steroid-related complications (SRCs). RESULTS: Remission was achieved 99.5% (763/767) of patients who received steroid therapy, while remission rate dropped to 63.6% (78/129) of patients who didn't receive it. Relapse was noted in 19.7% (151/763) of the patients who received steroid. Besides, relapse rate went up 38.4% (30/78) of the counterpart. Normalization of the serum total bilirubin and serum alkaline phosphatase (ALP) levels were achieved at two weeks regardless of biliary drainage. Multivariate analysis identified younger onset, MST less than three years, immunosuppressant, and steroid cessation as independent risk factors for relapse. Steroid-free was achieved in the patients underwent MST only 3.4% over 54 months. SRCs were recorded in a total of 99 patients (12.9%) despite sufficient preemptive medications. Multivariate analysis identified history of malignancy and immunosuppressant as independent risk factors for SRCs. CONCLUSION: Steroid therapy should be continued for no less than three years to reduce the risk of relapse, with use of preemptive measures taken around five years. The biliary drainage might not be mandatory. Steroid as 1st line therapy could serve as a bridge to further promising treatments.

Nationwide epidemiological survey of immunoglobulin G4-related disease with malignancy in Japan.

BACKGROUND AND AIM: To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with malignancy, a nationwide epidemiological survey was conducted. METHODS: Immunoglobulin G4-related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4-RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire. RESULTS: The frequencies of autoimmune pancreatitis (AIP), IgG4-related sialadenitis, IgG4-related eye disease, IgG4-related kidney disease, and IgG4-related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4-RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4-RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4-related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4-RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4-RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4-RD diagnosis. CONCLUSIONS: The nationwide survey for IgG4-RD with malignancy in Japan showed that IgG4-RD may be related with malignant diseases.

Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Linker Threonine-phosphorylated Smad2/3 Is a Biomarker of Colorectal Neoplastic Stem-like Cells that Correlates With Carcinogenesis.

BACKGROUND/AIM: This study analysed threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr) expression and investigated whether pSmad2/3L-Thr is related to the transition from human colorectal adenoma (CRA) to carcinoma (CRC). MATERIALS AND METHODS: Immunofluorescent staining was performed forß-catenin, p53, CDK4, Ki67, Sox9, aldehyde dehydrogenase (ALDH) 1, and pSmad2/3L-Thr. RESULTS: We analysed specimens of diffuse p53-positive CRCs arising from p53-negative CRAs. Percentage of p53, nuclear ß-catenin, Ki67, CDK4, and pSmad2/3L-Thr-positive cells at the site of CRCs was significantly higher than that at the site of CRAs. At the site of normal colorectal mucosae, few epithelial cells were stained positively for pSmad2/3L-Thr. At the site of CRCs, pSmad2/3L-Thr-positive cells showed co-localization with p53, nuclear ß-catenin, and ALDH1. At any site, pSmad2/3L-Thr-positive cells showed co-localization with CDK4. CONCLUSION: pSmad2/3L-Thr correlates with human CRC carcinogenesis, and pSmad2/3L-Thr-positive cells show human colorectal stem cell-like and cancer stem cell characteristics.

A giant Brunner gland hamartoma successfully treated by endoscopic excision followed by transanal retrieval: A case report.

RATIONALE: Brunner gland hamartoma (BGH) is a rare tumor of the duodenum. Although BGH is a benign tumor, larger lesion with gastrointestinal symptoms requires tumor removal. We report a giant BGH, successfully treated by endoscopic excision followed by transanal retrieval. PATIENT CONCERNS: A 38-year-old woman complained of severe anemia, tarry stool, and vomiting. DIAGNOSES: Esophagogastroduodenoscopy (EGD) showed a pedunculated giant submucosal mass at the duodenal bulb. INTERVENTIONS: We attempted to remove it because the lesion seemed to be responsible for patient's anemia and vomiting. The lesion had clear but bulky stalk. We carefully cut the stalk using needle-knife and IT knife2. We tried to retrieve specimen, but the mass could not pass through the pyloric ring because of its size. Then we tried to obtain the specimen from anus. Polyethylene glycol solution was administered to accelerate rapid excretion. OUTCOMES: The mass was successfully removed and was histologically confirmed as a giant BGH, measuring 55 mm in size. LESSONS: Reports about endoscopic resection of giant BGH are rare. Moreover, our case is the first report of transanal retrieval of resected specimen using polyethylene glycol solution. Endoscopic resection of BGH is less-invasive but can be more challenging if the mass is large. Our case provides useful option for endoscopic treatment of giant BGH.

Pancreatic cancer in patients with autoimmune pancreatitis: A scoping review.

BACKGROUND: Chronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP). OBJECTIVE: The aim of our study was to identify and analyse all published cases of AIP and PDAC co-occurrence, focusing on the interval between the diagnoses and the cancer site within the pancreas. METHODS: Relevant studies were identified through automatic searches of the MEDLINE, EMBASE, Scopus, and Web of Science databases, and supplemented by manual checks of reference lists in all retrieved articles. Missing/unpublished data were obtained from the authors of relevant publications in the form of pre-prepared questionnaires. RESULTS: A total of 45 cases of PDAC in AIP patients were identified, of which 12 were excluded from the analysis due to suspicions of duplicity or lack of sufficient data. Thirty-one patients (94%) had type 1 AIP. Synchronous occurrence of PDAC and AIP was reported in 11 patients (33%), metachronous in 22 patients (67%). In the metachronous group, the median period between diagnoses was 66.5 months (2-186) and a majority of cancers (86%) occurred more than two years after AIP diagnosis. In most patients (70%), the cancer originated in the part of the pancreas affected by AIP. CONCLUSIONS: In the literature, there are reports on numerous cases of PDAC in AIP patients. PDAC is more frequent in AIP type 1 patients, typically metachronous in character, and generally found in the part of the pancreas affected by AIP.

Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort.

BACKGROUND: The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. AIMS: To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. METHODS: We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. RESULTS: AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. CONCLUSIONS: The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Serum free light chain assessment in type 1 autoimmune pancreatitis.

BACKGROUND: /Object: Some patients with type 1 autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease, have normal serum IgG4. The aim of this study is to investigate the diagnostic value of measuring serum free light chains (FLCs) in type 1 AIP. MATERIALS AND METHODS: Thirty-seven patients with type 1 AIP, and 21 healthy, 17 alcoholic chronic pancreatitis (ACP), 21 idiopathic chronic pancreatitis (ICP) and 20 pancreatic cancer (PC) patients were enrolled. Serum IgG4 and FLC concentrations were measured using sFLC Freelite assays on a nephelometric analyzer. RESULTS: Active AIP patients have significantly higher serum levels of κ (median 30.97 (12.3-227.0) mg/L) and λFLC (median 20.53 (12.36-102.7) mg/L)) than healthy controls (κFLC; median 12.5 (3.1-52.1) mg/L), λFLC: median 12.45 (5.4-39.5) mg/L) (p < 0.05) correlating with raised serum IgG4, and significantly higher summated FLCs (∑) (median 53.09 (25.0-218.0) mg/L) than ICP patients (median 26.77 (15.0-89.2) mg/L) and healthy controls (median 24.43 (8.5-91.6) mg/L) (p < 0.05). AIP patients (median 1.43 (0.84-3.24)) showed significantly higher κ/λ ratios than ACP (median 0.83 (0.42-1.18)), ICP (median 0.87 (0.47-2.16)), PC patients (median 0.90 (0.48-1.27)) and healthy controls (median 0.963 (0.51-1.32)). There was a correlation between increased κ and λ FLCs levels and the number of affected organs involved in IgG4 related disease. CONCLUSION: Patients with type 1 AIP have increased serum k and λ FLC concentrations, Σ FLC, and κ/λ ratios. These novel biomarkers may be useful in the diagnosis of type 1 AIP and in monitoring disease activity.

Development of Severe Acute Pancreatitis Following Uncovered Metallic Stent Placement: A Rare Case Report.

Self-expandable metallic stents (SEMSs) are widely used for malignant biliary stricture (MBS). Acute pancreatitis is an early complication following SEMS placement. In the present case, the patient developed severe acute pancreatitis after SEMS placement for MBS because of metastatic lymph nodes. Endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy and an endoscopic nasobiliary drainage tube placement were performed. After seven days, an uncovered SEMS was placed; however, severe acute pancreatitis occurred, and the SEMS was drawn out emergently. In SEMS placement for patients with MBS caused by non-pancreatic cancer, SEMS should be selected carefully while considering each patient's case.