Clinical features, therapeutic outcomes, and recovery period of long COVID.

To characterize the clinical features of long COVID, 286 patients who received care in our outpatient clinic for long COVID from May to December 2021 were surveyed. The recovery periods of each symptom and the key factors contributing to early recovery were statistically analysed. The median age of the patients was 35.8 years, with 137 men and 149 women. The median number of symptoms was 2.8. The most frequent symptoms were respiratory manifestations (52.1%), followed by fatigue (51.4%). Respiratory symptoms, fatigue, and headache/arthralgia were major complaints in the initial phase, whereas hair loss was a major complaint in the late phase, suggesting that the chief complaint of patients with long COVID may vary temporally. The best treatment outcome was observed for pulmonary symptoms, and hair loss had the worst outcome. COVID-19 severity, the number of manifestations, and the delay in starting treatment exerted a negative effect on the recovery period of long COVID. In addition, the smoking habit was an independent risk factor for slowing the recovery period from long COVID. This study provides insights into the clinical course of each manifestation and therapeutic options with a more certain future of long COVID to meet the unmet medical needs.

STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, as second-line therapy for chemotherapy-refractory patients with unresectable pancreatic cancer: An open label, phase I/IIa trial.

Background: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). Methods: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80-120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055). Findings: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events. Interpretation: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment. Funding: The present study was supported by the Japan Agency for Medical Research and Development (AMED).

Gastric Tube Ulcer that Could Be Saved by Early Conservative Treatment.

The patient was an 81-year-old man who had received subtotal esophagectomy for esophageal cancer reconstructed by a gastric tube via a posterior mediastinal route. He presented to our emergency room with a complaint of epigastric pain and a small amount of hematemesis. Thoracoabdominal computed tomography showed that the reconstructed gastric tube was filled fluid and had irregular wall thickening. We suspected upper gastrointestinal bleeding, and we started to treat with administration of proton pump inhibitors (PPIs) since the anemia was mild and his vitals were stable. However, his anemia was rapidly progressed to Hb 6.0 with a large amount of old blood melena. The emergency gastroscopy showed an A2 stage ulcer with active oozing at middle esophagus reconstructed by a gastric tube. Therefore, we applied thrombin spray to treat the bleeding. Fortunately, his recovery was progressing nicely with medical treatments for a week. In this study, we experienced a case in which early administration of PPIs might be a key player to prevent his medical condition worsened further.

Impact of qualitative endoscopic ultrasonography on fatty pancreas at a referral medical center.

BACKGROUND: Taking advantage of the current advances in diagnostic imaging modalities, including endoscopic ultrasonography (EUS), and due to the increased attention to ectopic fat accumulation in the pancreas following the rising trend of metabolic syndrome, we qualitatively assessed the clinical implication of pancreatic steatosis by EUS in this study. METHODS: The study included 243 patients that were divided into four groups. The correlation between the average echogenicity of the pancreas and that of the control organs and the key clinical data of all study patients were collectively analyzed. The cut-off point of the pancreas-control (PC) ratio in EUS and liver-control (LC) ratio on abdominal ultrasound were determined from the population distribution and the obtained median values. RESULTS: With the cut-off point of 1.30 for the PC ratio and 1.20 for the LC ratio, sex, the Brinkman index, habitual alcohol drinkers, and fatty pancreas were significant factors. The associations between each relevant factor in fatty pancreas, metabolic syndrome in the fatty liver group, and age in the pancreatic cancer group were all significant in the analysis. In addition, we investigated whether the PC ratio differed according to age and staging in pancreatic cancer patients. Interestingly, the PC ratio was lower in the advanced stage group than in the early-stage group. CONCLUSION: Our results suggest that, irrespective of the degree, ectopic fat infiltration in the pancreas could be a specific clinical phenotype of serious pancreatic diseases, including pancreatic cancer, especially in high-risk patients.

Characteristics and Endoscopic Classification of Ulcerative Lesions Affecting the Ileocecal Valve.

OBJECTIVES: The aim of this study was to propose an endoscopic classification system for ulcerative lesions on the ileocecal valve and investigate its relevance to the underlying etiology. METHODS: Among the 60,325 patients who underwent colonoscopy at our hospital from January 2006 to December 2018, patients with ulcerative lesions on the ileocecal valve were included. The following data were obtained using the hospital's medical records: sex, age, clinical diagnosis, laboratory data, and endoscopic and histological findings. Patients who have ulcerative colitis and who were not evaluated by histological examination were excluded. Ulcerative lesions on the ileocecal valve were classified into 3 groups according to their endoscopic appearance: small shallow ulcerative lesions without edematous change (group A), lateral spreading shallow ulcerative lesions with edematous change (group B), and deep deformed ulcerative lesions (group C). The association between this endoscopic classification and its clinical diagnosis, clinical course, and the interobserver reliability were evaluated. RESULTS: Of 72 patients who were eligible for analysis, 18 were assigned to group A, 9 to group B, and 45 to group C. Infectious enteritis was mainly assigned to group A (group A, 12; group B, none; and group C, 6; p < 0.0001), inflammatory bowel disease was mainly assigned to group C (group A, none; group B, 5; and group C, 35; p < 0.0001), and malignant tumor was assigned to group C only. Interobserver reliability was extremely high among the 3 examining doctors (kappa value 0.7-0.8). CONCLUSION: Endoscopic classification was divided into 3 groups for ulcerative lesions on the ileocecal valve, and this system could be beneficial for presuming their clinical diagnoses.

Endoscopic ultrasound-guided fine-needle biopsy histology with a 22-gauge Franseen needle and fine-needle aspiration liquid-based cytology with a conventional 25-gauge needle provide comparable diagnostic accuracy in solid pancreatic lesions.

BACKGROUND AND AIM: Fine-needle biopsy (FNB) needles obtain more core samples and support the shift from cytologic to histologic evaluation; however, recent studies have proposed a superior diagnostic potential for liquid-based cytology (LBC). This study compared the diagnostic ability of endoscopic ultrasound (EUS)-guided FNB histology with a 22-gauge Franseen needle (22G-FNB-H) and fine-needle aspiration (FNA) LBC with a conventional 25-gauge needle (25G-FNA-LBC). METHODS: We analyzed 46 patients who underwent both 22G-FNB-H and 25G-FNA-LBC in the same lesion during the same endoscopic procedure. This study evaluated the diagnostic ability of each needle, diagnostic concordance between needles, and incremental diagnostic effect of both needles compared to using each needle alone. RESULTS: The agreement rate for malignancy between both techniques was 93.5% (kappa value = 0.82). There was no significant difference in the diagnostic ability of both methods. 22G-FNB-H and 25G-FNA-LBC provided an incremental diagnostic accuracy in two (4.3%) cases and one (2.2%) case, respectively. CONCLUSION: Our study demonstrated that the diagnostic accuracy of 25G-FNA-LBC and 22G-FNA-H for solid pancreatic lesions were comparable. A conventional 25-gauge needle that punctures lesions with ease can be used in difficult cases and according to the skill of the endoscopist.

Best period to replace or change plastic stents with self-expandable metallic stents using multivariate competing risk regression analysis.

In endoscopic biliary drainage (EBD) for various benign and malignant biliary disorders, the appropriate timing to replace or change a plastic stent (PS) with a self-expandable metallic stent (SEMS) remains unclear. This study aimed to define the best period to replace or change a PS with a SEMS. Between January 1, 2012, and December 31, 2018, 1,887 consecutive EBD procedures, including 170 SEMS placements, were retrospectively identified. The period to recurrent biliary obstruction (PRBO) was estimated and compared between the malignant and benign groups and according to each disease using time to event analysis and competing risk analysis. Compared with the benign group, the malignant group had significantly shorter median PRBO with interquartile range (IQR) after PS placement [108 (39 - 270) vs. 613 (191 - 1,329) days, P < 0.001], even on multivariate analysis, with a subdistribution hazard ratio (SHR) of 3.58 (P < 0.001). The shortest PRBO distribution from the first quartile of the non-RBO period was seen in Mirizzi syndrome cases (25 days, P = 0.030, SHR = 3.32) in the benign group and in cases of pancreatic cancer (32 days, P = 0.041, SHR = 2.06); perihilar bile duct cancer (27 days, P = 0.006, SHR = 2.69); and ampullary cancer (22 days, P = 0.001, SHR = 3.78) in the malignant group. Our study supports that stent replacement for the benign group is feasible after 6 months, and the best period to replace or change a PS with a SEMS should be decided on the basis of the underlying disease to prevent RBO.

The Diverse Involvement of Cigarette Smoking in Pancreatic Cancer Development and Prognosis.

Despite extensive research in the pathogenesis, early detection, and therapeutic approaches of pancreatic ductal adenocarcinoma (PDAC), it remains a devastating and incurable disease. As the global incidence and prevalence of PDAC continue to rise, there is a pressing need to place strong emphasis on its prevention. Although it is widely recognized that cigarette smoking, a potentially modifiable risk factor, has been linked to PDAC development, its contribution to prognosis is still uncertain. Moreover, the mechanistic pathways of PDAC progression secondary to smoking are various and lack a summative narration. Herein, we update and summarize the direct and indirect roles cigarette smoking plays on PDAC development, review literature to conclude the impact cigarette smoking has on prognosis, and postulate a comprehensive mechanism for cigarette smoking-induced PDAC.

IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second-line therapeutic option in these patients. This study aimed to evaluate the long-term outcome(s) of combined UDCA and bezafibrate therapy in UDCA-refractory PBC patients and identify prognostic factors. METHODS: Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long-term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis. RESULTS: Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK-PBC-risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma-glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis-related symptoms or liver-related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis-related symptoms and liver-related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM < 240 mg/dL. Thus, normalization of IgM levels was a good surrogate predictor of long-term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow-up period. CONCLUSIONS: Our findings point to the beneficial effects of long-term UDCA plus bezafibrate combination therapy for UDCA-refractory PBC patients, and IgM response can be a useful predictive biomarker of long-term clinical outcomes.

Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis.

BACKGROUND: Sarcopenia and osteoporosis reduce life quality and worsen prognosis in patients with liver cirrhosis (LC). When these two complications coexist, a diagnosis of osteosarcopenia is made. We aimed to investigate the actual situations of sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture, and to clarify the relationship among these events in patients with LC. METHODS: We describe a cross-sectional study of 142 patients with LC. Sarcopenia was defined according to the Japan Society of Hepatology (JSH) criteria, Asian Working Group for Sarcopenia (AWGS) criteria, and European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The skeletal muscle mass index (SMI) and handgrip strength were assessed using bioelectrical impedance analysis and a digital grip strength dynamometer, respectively. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and vertebral fracture was evaluated using spinal lateral X-rays. The severity of LC was assessed using the Child-Pugh classification. RESULTS: Among the 142 patients, the prevalence of sarcopenia was 33.8% (48/142) according to the JSH and AWGS criteria and 28.2% (40/142) according to the EWGSOP2 criteria. The number of patients with osteoporosis, osteosarcopenia, and vertebral fracture was 49 (34.5%), 31 (21.8%), and 41 (28.9%), respectively. Multivariate analysis revealed a close association between sarcopenia and osteoporosis. Osteoporosis was independently associated with sarcopenia [odds ratio (OR) = 3.923, P = 0.010]. Conversely, sarcopenia was independently associated with osteoporosis (OR = 5.722, P < 0.001). Vertebral fracture occurred most frequently in patients with osteosarcopenia (19/31; 61.3%) and least frequently in those without both sarcopenia and osteoporosis (12/76; 15.8%). The SMI and handgrip strength values were significantly correlated with the BMD of the lumbar spine (r = 0.55 and 0.51, respectively; P < 0.001 for both), femoral neck, (r = 0.67 and 0.62, respectively; P < 0.001 for both), and total hip (r = 0.67 and 0.61, respectively; P < 0.001 for both). CONCLUSIONS: Sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture were highly prevalent and closely associated with one another in patients with LC. Specifically, patients with osteosarcopenia had the highest risk of vertebral fractures. Early diagnosis of these complications is essential for treatment intervention.

Characterisation of blood microbiota in patients with liver cirrhosis.

BACKGROUND AND AIMS: Bacterial infections arising in patients with liver cirrhosis are associated with life-threatening complications such as hepatic encephalopathy and spontaneous bacterial peritonitis in relation to bacterial translocation. To investigate the state of bacterial translocation, we surveyed the peripheral blood microbiota by 16S rRNA gene sequencing and analysed the blood microbial profiles. METHODS: Sixty-six patients with liver cirrhosis were enrolled in this study, whereas 14 healthy individuals were also analysed as controls. Total RNA was purified from the peripheral blood, and an approximately 430 base pair genomic locus which included the V3-V4 region of the 16s rRNA gene was amplified and assessed using bacterial pyrosequencing. RESULTS: At the genus level, a total of 183 operational taxonomic units were identified in cirrhotic patients, whereas 123 units in controls. Intergroup differences in gut microbiota were analysed by the linear discriminant analysis effect size, which showed that the abundance of Enterobacteriaceae was significantly higher in cirrhotics. On the contrary, the abundance of Akkermansia, Rikenellaceae and Erysipelotrichales were significantly lower in cirrhotics (relative abundance of Akkermansia in cirrhotics and controls: 0% and 0.2%, respectively; Rikenellaceae: 0.1% and 0.92%; Erysipelotrichales: 0.58% and 1.21%). CONCLUSION: The present study has demonstrated that various circulating bacteria are present in cirrhotic patients, and the diversity of such bacteria is consistent with the presence of dysbiosis in cirrhotics. Although the clinical significance of the findings remains to be clarified, the findings may potentially facilitate diagnostic and therapeutic attempts to comprehend and furthermore to manipulate bacterial infections in cirrhotic patients.

Recent Insights Into the Multiple Pathways Driving Non-alcoholic Steatohepatitis-Derived Hepatocellular Carcinoma.

The incidence of metabolic syndrome with fatty liver is spreading on a worldwide scale. Correspondingly, the number of patients with the hepatic phenotype of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and in its advanced states, non-alcoholic steatohepatitis (NASH), and the subsequent hepatocellular carcinoma (HCC) derived from NASH (NASH-HCC) is increasing remarkably. A large-scale epidemiological study revealed that obesity can be a risk factor of such cancers as HCC. Moreover, despite the ongoing trends of declining cancer incidence and mortality for most cancer types, HCC has experienced a markedly increased rate of both. Considering the differences in liver-related mortality among NAFLD patients, NASH, and NASH-HCC should be included in the objectives of initiatives to manage NAFLD patients and their progression to the advanced stages. Unfortunately, research has yet to make a crucial drug discovery for the effective treatment of NASH and NASH-HCC, although it is urgently needed. The latest widespread concept of the "multiple parallel hits hypothesis," whereby multiple factors contribute concurrently to disease pathogenesis has led to advances in the elucidation of hepatic and systemic molecular mechanisms driving NASH and the subsequent NASH-HCC progression; the results are not only extensive but promising for therapeutics. Here, we have summarized the myriad landmark discoveries of recent research into the pathogenic processes underlying NASH-HCC development and with the greatest possibility for a new generation of pharmaceutical products for interference and treatment.

The Clinical Potential of Oligonucleotide Therapeutics against Pancreatic Cancer.

Although many diagnostic and therapeutic modalities for pancreatic cancer have been proposed, an urgent need for improved therapeutic strategies remains. Oligonucleotide therapeutics, such as those based on antisense RNAs, small interfering RNA (siRNA), microRNA (miRNA), aptamers, and decoys, are promising agents against pancreatic cancer, because they can identify a specific mRNA fragment of a given sequence or protein, and interfere with gene expression as molecular-targeted agents. Within the past 25 years, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Several clinical and preclinical studies of oligonucleotides have been conducted for patients with pancreatic cancer. To support the discovery of effective diagnostic or therapeutic options using oligonucleotide-based strategies, in the absence of satisfactory therapies for long-term survival and the increasing trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients, with underlying preclinical and scientific data, and focus on the possibility of oligonucleotides for targeting pancreatic cancer in clinical implications.

Hemobilia Derived from Cystic Artery Pseudoaneurysm.

Cystic artery pseudoaneurysm (CAP) is a rare disease, with small number of previous reports related to CAP. Besides, it is frequently prone to critical condition due to arterial bleeding. Here, we presented a case of ruptured CAP with acute calculus cholecystitis and its subsequent successful management with temporary endoscopic biliary drainage for obstructive jaundice and embolization for the culprit artery without cholecystectomy. Since CAP is at high risk of bleeding, intravascular treatment, which is only one currently available therapeutic option, is urgently required in the clinical sites.

Chronic intestinal pseudo-obstruction with pneumatosis cystoides intestinalis in a patient with systemic sclerosis: A case report.

RATIONALE: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (PCI) are rare abdominal diseases and the pathological mechanisms have not been fully elucidated. Systemic sclerosis (SSc), which is characterized by the progressive sclerotic changes of skin and internal organs, is a refractory collagen disease and is frequently associated with digestive disorders including CIPO. PATIENT CONCERNS: A 68-year-old woman who has been well managed for SSc over the long term, who presented with abdominal fullness for the first time. DIAGNOSES: Abdominal X-ray and computed tomography (CT) images showed PCI with pneumoperitoneum findings. Based on the diagnosis of CIPO, we evaluated the intestinal peristalsis of the patient by using cine magnetic resonance imaging (MRI). INTERVENTIONS: Oral medications of 15 g/d of Daikenchuto, 750 mg/d of Metronidazole and Sodium Picosulfate were started for improving the bowel peristaltic movement and decreasing intestinal gas production. OUTCOMES: A great improvement of CIPO and PCI by multidrug therapy without any surgical treatments for such an unusual case. LESSONS: This case indicates that SSc can be accompanied with not only CIPO but also PCI as digestive disorders and that cine MRI, which is a definitely beneficial imaging modality, can intelligibly visualize the peristalsis of the intestines and lead to successful medical control by noninvasive treatment.

Pancreatic cancer screening in patients with presumed branch-duct intraductal papillary mucinous neoplasms.

Because delayed diagnosis is one of the causes of poor prognosis in pancreatic ductal adenocarcinoma (PDAC), early detection is a key for overall improvement of prognosis. Towards this end, periodic screening is recommended for individuals considered high-risk for PDAC. Advances in diagnostic imaging modalities have increased the frequency of incidental findings of pancreatic cysts, including the intraductal papillary mucinous neoplasm (IPMN) - a major risk factor of PDAC, having 1% annual prevalence of concomitance with IPMN. Proper retainment of patients with IPMN and regular follow-up by routine imaging examination will likely improve early detection and better prognosis of PDAC. Unfortunately, current guidelines only address management of PDAC derived from IPMN and overlook PDAC concomitant with IPMN. Screening of patients with IPMN, by endoscopic ultrasonography (currently the most reliable modality for detecting small PDAC), may facilitate early detection of both IPMN-derived and -concomitant PDAC. Prospective studies to evaluate the usefulness of endoscopic ultrasonography in screening of IPMN-concomitant PDAC will also help in determining the optimal surveillance strategy for more widespread applications.

Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma.

The only current curative treatment for patients with pancreatic ductal adenocarcinoma (PDA) is surgical resection, and certain patients still succumb to disease shortly after complete surgical resection. Wilms' tumor 1 (WT1) serves an oncogenic role in various types of tumors; therefore, in the present study, WT1 protein expression in patients with PDA was analyzed and the association with overall survival (OS) and disease-free survival (DFS) time in patients with PDA was assessed following surgical resection. A total of 50 consecutive patients with PDA who received surgical resection between January 2005 and December 2015 at the Jikei University Kashiwa Hospital (Kashiwa, Chiba, Japan) were enrolled. WT1 protein expression in PDA tissue was measured using immunohistochemical staining. Furthermore, laboratory parameters were measured within 2 weeks of surgery, and systemic inflammatory response markers were evaluated. WT1 protein expression was detected in the nucleus and cytoplasm of all PDA cells and in tumor vessels. WT1 exhibited weak staining in the nuclei of all PDA cells; however, the cytoplasmic expression of WT1 levels was classified into four groups: Negative (n=0), weak (n=19), moderate (n=23) and strong (n=8). In patients with PDA, it was demonstrated that the OS and DFS times of patients with weak cytoplasmic WT1 expression were significantly prolonged compared with those of patients with moderate-to-strong cytoplasmic WT1 expression, as determined by log-rank test (P=0.0005 and P=0.0001, respectively). Furthermore, an association between the density of WT1-expressing tumor vessels and worse OS/DFS times was detected. Multivariate analysis also indicated a significant association between the overexpression of WT1 in PDA tissue and worse OS/DFS times. To the best of our knowledge, the present study is the first to demonstrate that moderate-to-strong overexpression of WT1 in the cytoplasm of PDA cells is significantly associated with worse OS/DFS times. Therefore, overexpression of WT1 in the cytoplasm of PDA cells may impact the recurrence and prognosis of patients with PDA following surgical resection. The results further support the development of WT1-targeted therapies to prolong survival in all patients with PDA.

Mouse models for investigating the underlying mechanisms of nonalcoholic steatohepatitis-derived hepatocellular carcinoma.

As the incidence of hepatocellular carcinoma (HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.

An Appraisal of Current Guidelines for Managing Malignancy in Pancreatic Intraductal Papillary Mucinous Neoplasm.

Pancreatic intraductal papillary mucinous neoplasm was originally regarded as a benign mucinous cystic tumor but certainly has a marked malignant potential. With the array of high-resolution imaging modalities that are now available, more frequent incidental asymptomatic intraductal papillary mucinous neoplasm patients can be diagnosed. Until now, our clinicians have been managing intraductal papillary mucinous neoplasm patients by referring to the international consensus guidelines which have been revised twice or American Gastroenterological Association guidelines. The aim of this review is to reassess the current guidelines for the management of malignancy in intraductal papillary mucinous neoplasm. Furthermore, we specifically discuss the problems to be solved for establishing more refined guideline for the early detection, risk stratification and better management of pancreatic cancer in intraductal papillary mucinous neoplasm patients.