High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings: A case report.

BACKGROUND: High-grade pancreatic intraepithelial neoplasia (PanIN) exhibits no mass and is not detected by any examination modalities. However, it can be diagnosed by pancreatic juice cytology from indirect findings. Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct (MPD) and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography (ERCP). We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range, but without caudal MPD dilatation on magnetic resonance cholangiopancreatography (MRCP). CASE SUMMARY: A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision, which revealed pancreatic cysts. MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation. Thus, course observation was performed. After 24 mo, MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst. We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination. We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN. Pancreatic parenchyma invasion was not observed, and curative resection was achieved. CONCLUSION: High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab.

INTRODUCTION: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. METHODS: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. RESULTS: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. CONCLUSION: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

Clinical features and images of malignant lymphoma localized in the pancreatic head to differentiate from pancreatic ductal adenocarcinoma: a case series study.

BACKGROUND: Pathological examination by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients' clinical features and imaging examinations. RESULTS: The median tumor size was larger in ML than in PDAC (45.8 [24-64] vs. 23.9 [8-44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0-3.5] vs. 7.1 [2.5-11.8] mm), both showing significant differences between these malignancies (both, P < 0.001). In the analysis of covariance, MLs showed a smaller caudal MPD per tumor size than PDACs, with a statistical difference (P = 0.042). Sensitivity and specificity using sIL-2R ≥ 658 U/mL plus CA19-9 < 37 U/mL for the differentiation of ML from PDAC were 80.0% and 95.6%, respectively. CONCLUSIONS: Diagnosing pancreatic ML using cytohistological examination through EUS-FNA can be difficult in some cases. Thus, ML should be suspected if a patient with a pancreatic tumor has a small MPD diameter per tumor size, high serum sIL-2R level, normal CA19-9 level. If the abovementioned features are present and still cannot be confirmed as PDAC, re-examination should be considered.

Metastatic pancreatic ductal adenocarcinoma followed by a fatal diffuse large B-cell lymphoma: A rare case report and literature review.

RATIONALE: Recently, the incidence of polyoncosis has been increasing due to advancements in treatment, such as antitumor therapy, which led to a prolonged survival. However, few patients with metastatic pancreatic ductal adenocarcinoma (PDAC) develop second tumors, which render a poor prognosis. We report a rare case of PDAC, which is metachronous with a fatal malignant lymphoma (ML). PATIENT CONCERNS: A 68-year-old woman who had been monitored due to liver cirrhosis secondary to hepatitis C virus infection presented with a 10-mm pancreatic head cancer with lung metastasis and had started an anticancer therapy with gemcitabine. Approximately 18 months after diagnosis, lymphadenopathies around the pancreas were noted, which eventually spread to the entire body over time. DIAGNOSIS: Diffuse large B-cell lymphoma was diagnosed using biopsies from cervical lymph nodes. INTERVENTIONS AND OUTCOMES: The patient started a gemcitabine + rituximab regimen; however, the patient died from cachexia-associated lymphoma progression, not PDAC. LESSONS: ML should be considered when intra-abdominal lymphadenopathies are detected in patients with pancreatic cancer, and ML should be differentiated from lymph node metastasis of pancreatic cancer.

A case of pancreatic adenosquamous carcinoma with direct invasion to the gastrointestinal tract through the retention cyst wall: A rare case report.

A 62-year-old man presented with a 7-cm cystic lesion with irregularly thickened cyst wall in contact with the pancreatic tail. The pancreatic tail was described as hypoechoic on endoscopic ultrasonography. The cyst subsequently increased rapidly to 13 cm, and surgery was performed. This revealed adenosquamous carcinoma in the pancreatic tail to have invaded the stomach and transverse colon along the cyst wall. The cyst was diagnosed as a retention cyst due to pancreatic tail tumor. Invasion of nearby organs by a pancreatic cancer via the retention cyst wall is very rare, but it is necessary to keep the potential for such progress in mind.

Long-standing diabetes mellitus increases concomitant pancreatic cancer risk in patients with intraductal papillary mucinous neoplasms.

BACKGROUND: When monitoring patients with an intraductal papillary mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed the risk factors for concomitant PDAC in IPMN. METHODS: In total, 547 patients with pancreatic cysts, including IPMNs inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance by imaging examination once or twice a year. RESULTS: Five IPMNs with high-grade dysplasia and one IPMN associated with invasive carcinoma were encountered. In comparison, 14 concomitant PDACs were encountered. The prognosis was very poor for concomitant PDACs. All 14 PDAC patients had IPMNs. In patients with IPMNs, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analyses (P < 0.001 and P < 0.01, respectively). Furthermore, patients with IPMNs and diabetes mellitus had a high frequency of concomitant PDACs (9.5%, 9/95) in a median 48-month surveillance period. CONCLUSIONS: When monitoring IPMNs, the development of not only IPMN-derived carcinomas but also concomitant PDACs should be considered. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

Effectiveness of Abdominal Ultrasonography for Improving the Prognosis of Pancreatic Cancer during Medical Checkup: A Single Center Retrospective Analysis.

Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 374 patients, 192 were men (51.3%), and the median age was 74 years (34−105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%, p < 0.01 and 42.2% vs. 9.4%, p < 0.001, respectively). The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be one of the useful modalities for promoting better prognosis of PCs.

Efficacy of a Traction Device for Endoscopic Submucosal Dissection Using a Scissor-Type Knife: A Randomized Controlled Trial.

INTRODUCTION: Although safe, colorectal endoscopic submucosal dissection (ESD) using a scissor-type knife has a slow resection speed. We aimed to evaluate the efficacy of a traction device to hasten the resection speed. METHODS: This multicenter randomized controlled trial was conducted at 3 Japanese institutions. Patients with a 20-50-mm superficial colorectal tumor were enrolled and randomly assigned to a conventional-ESD (C-ESD) group or a traction-assisted ESD (T-ESD) group. The primary outcome was the resection speed. RESULTS: The C-ESD and T-ESD groups comprised 49 and 48 patients, respectively. Although the mean resection speed was not significantly different in the entire cohort between the groups (23.7 vs 25.6 mm 2 /min, respectively; P = 0.43), it was significantly faster with T-ESD than with C-ESD at the cecum (32.4 vs 16.7 mm 2 /min, respectively; P = 0.02). The mean resection speed of tumors ≥30 mm tended to be faster by T-ESD than by C-ESD (34.6 vs 27.8 mm 2 /min, respectively; P = 0.054). The mean procedure time of T-ESD was significantly shorter than that of C-ESD (47.3 vs 62.3 minutes, respectively; P = 0.03). The en bloc (100% vs 100%), complete (98.0% vs 97.9%), and curative resection (93.9% vs 91.7%) rates were similar between the 2 groups. Perforation and delayed hemorrhage occurred in only 1 patient each in the T-ESD group. DISCUSSION: Although the resection rates were sufficiently high and adverse event rates were extremely low in both the groups, the use of a traction device for ESD in the proximal colon and for large lesions may increase the resection speed.

Advanced gallbladder cancer accompanied with cancer-associated dermatomyositis: A case report and literature review.

RATIONALE: Muscle weakness due to cancer-associated dermatomyositis (CADM) can be misdiagnosed as cancer cachexia and disuse atrophy. PATIENT CONCERNS: A 75-year-old female was admitted to our institute with muscle weakness, dysphagia, and suspected gallbladder cancer. Computed tomography and cytopathological examinations of the liver biopsy and fine-needle aspiration from swollen lymph nodes using endoscopic ultrasonography revealed cancer in the gallbladder body and metastasis to the lymph nodes around the abdominal aorta. We avoided the administration of anticancer drugs due to her poor general condition. DIAGNOSIS: Subsequently, we diagnosed her with muscle weakness and dysphagia as a result of CADM using species from muscle and skin biopsy. INTERVENTIONS AND OUTCOMES: Prednisolone therapy and anticancer agents partially improved the patient symptoms. LESSONS: CADM is reported to be associated with a high incidence of dysphagia, which may aid in the diagnosis of this disease.

The Deployment of a Newly Developed Proximal Release-Type Colonic Stent Is Feasible for Malignant Colorectal Obstruction near the Anal Verge: A Single-Center Preliminary Study.

INTRODUCTION: Colonic self-expandable metallic stents are widely used to treat malignant colorectal obstructions. Stent placement in lesions near the dentate line causes problems, including severe pain due to difficulty in positioning the stent accurately. Therefore, a proximal release-type stent was developed to overcome this issue, and this preliminary study aimed to investigate its efficacy and safety. PATIENTS AND METHODS: This research enrolled eight patients with malignant colorectal obstructions up to 10 cm from the anal verge who required placement of the newly developed proximal release-type colonic stent. The primary outcome was the clinical success rate, and the secondary outcomes were the technical success and adverse events rates. RESULTS: The technical and clinical success rates were 87.5% each, and the mean procedure time was 25.5 ± 22.0 min. The mean procedure time in the rectosigmoid colon was significantly longer than that in the rectum. Only one (12.5%) patient had stent migration, and neither anal pain nor tenesmus was observed. DISCUSSION: The stent was highly effective in treating lesions near the anal verge, and it might contribute to the expansion of indications for colorectal stents for lesions near the dentate line. However, the indications for rectosigmoid colon lesions should be cautiously considered.

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma.

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child-Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin-bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma.

INTRODUCTION: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. METHODS: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. RESULTS: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. CONCLUSION: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

Hematogenous metastasis to colon from gallbladder cancer.

Hematogenous metastasis to colon from gallbladder cancer is in rare situation and immunohistochemical staining is effective for differential diagnosis of the primary site of cancer.

A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). CASE PRESENTATION: We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. CONCLUSION: ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

Comparison of the Clinical Outcome of Ramucirumab for Unresectable Hepatocellular Carcinoma with That of Prior Tyrosine Kinase Inhibitor Therapy.

INTRODUCTION: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. METHODS: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. RESULTS: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. CONCLUSION: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.

Association of soluble T cell immunoglobulin domain and mucin-3 (sTIM-3) and mac-2 binding protein glycosylation isomer (M2BPGi) in patients with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver injury progress to cirrhosis or hepatocellular carcinoma (HCC). The aim of the present study was to determine whether circulating soluble TIM3 (sTIM3) is elevated in patients with AIH patients and whether sTIM-3 levels are associated with clinical parameters of AIH. METHODS: We enrolled 123 Japanese patients with AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 30 patients with primary biliary cholangitis (PBC) and healthy control subjects. Serum sTIM-3 concentrations were quantified by ELISA. RESULTS: Serum levels of sTIM-3 were significantly higher in AIH patients (median 4865 pg/ml; [interquartile range (IQR); 3122-7471]) compared to those in CHC (1026 pg/ml [IQR: 806-1283] p<0.001), PBC (2395 pg/ml [IQR: 2012-3422] p<0.001) or healthy controls (1285 pg/ml [IQR: 1098-1812] p<0.001). In AIH group, serum sTIM-3 were correlated with alanine aminotransferase (ALT), or total bilirubin (TB) and negatively correlated with serum levels of albumin (Alb). Serum levels of sTIM-3 were also strongly correlated with Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum sTIM-3 levels (2147±623pg/ml versus 1321±378pg/ml, p<0.001). CONCLUSIONS: Circulating sTIM-3 levels were elevated in AIH patients and are associated with AIH disease activity and AIH-related liver damage. These findings indicate that serum sTIM-3 correlated with disease status of AIH and could be useful biomarkers to detect autoimmune-mediated liver injury. Our data suggest a possible link between the TIM-3/GAL-9 pathway and AIH severity or phenotype, and further investigations of the TIM-3 pathway and AIH pathophysiology is warranted.

Mortality calculator as a possible prognostic predictor of overall survival after gastrectomy in elderly patients with gastric cancer.

BACKGROUND: The number of elderly patients with gastric cancer has been increasing. Most elderly patients have associated reduced physiologic functions that can sometimes become an obstacle to safe surgical treatment. The National Clinical Database Risk Calculator, which based on a large Japanese surgical database, provides predicted mortality and morbidity in each case as the surgical-related risks. The purpose of this study was to investigate the clinical significance of the risk for operative mortality (NRC-mortality), as calculated by the National Clinical Database Risk Calculator, during long-term follow-up after gastrectomy for elderly patients with gastric cancer. METHODS: We enrolled 73 patients aged ≥ 80 years and underwent gastrectomy at our institution. Their surgical risk was evaluated based on the NRC-mortality. Several clinicopathologic factors, including NRC-mortality, were selected and analyzed as the possible prognostic factors for elderly patients who have undergone gastrectomy for gastric cancer. Statistical analysis was performed using the log-rank test and Cox proportional hazard model. RESULTS: NRC-mortality ranged from 0.5 to 10.6%, and the median value was 1.7%. Dividing the patients according to mortality, the overall survival was significantly worse in the high mortality group (≥ 1.7%, n = 38) than in the low mortality group (< 1.7%, n = 35), whereas disease-specific survival was not different between the two groups. In the Cox proportional hazard model, multivariate analysis revealed NRC-mortality, performance status, and surgical procedure as the independent prognostic factors for overall survival. For disease-specific survival, the independent prognostic factors were performance status and pathological stage but not NRC-mortality. CONCLUSION: The NRC-mortality might be clinically useful for predicting both surgical mortality and overall survival after gastrectomy in elderly patients with gastric cancer.