Novel physiological analysis using blood flow velocity for colonic polyps: Pilot study.

Real-time visualization of red blood cell flow inside subepithelial microvessels is performed with magnifying endoscopy. However, microvascular blood flow velocity in the colorectum has not been investigated. Here, we aimed to evaluate the blood flow velocity of microvessels of colonic polyps and to compare it with that of surrounding mucosa. We examined 50 lesions, including 30 adenomas (ADs) and 20 hyperplastic polyps (HPs). Blood flow velocities of lesions and their surrounding mucosa were evaluated using magnifying blue laser imaging (BLI) prior to endoscopic resection. Calculation of mean blood flow velocities was based on mean movement distance of one tagged red blood cell using split video images of magnifying BLI. Mean microvascular blood flow velocity was significantly lower in ADs (1.65±0.66 mm/sec; range 0.46-2.90) than in HPs (2.83±1.10 mm/sec; 1.07-4.50) or the surrounding mucosa (3.73±1.11 mm/sec; 1.80-6.20; P <0.001). The blood flow velocity rate compared with the surrounding mucosa was significantly lower in ADs (0.41±0.16; 0.10-0.82) than in HPs (0.89±0.25; 0.46-1.51; P <0.001). We found that mean microvascular blood flow velocity was significantly lower in ADs than in HPs and the surrounding non-neoplastic mucosa. These findings indicate that a novel dynamic approach with microvascular blood flow velocity using magnifying endoscopy may be useful in assessing physiological differences between ADs and HPs.

Residual Recurrence of a Small Intestinal Capillary Hemangioma with Obscure Gastrointestinal Bleeding Treated by Double-Balloon Endoscopy: A Case Report and Literature Review.

An 86-year-old man presented with anemia. He underwent abdominal contrast-enhanced computed tomography, gastroscopy, and colonoscopy without any bleeding detected. Small bowel capsule endoscopy (SBCE) revealed a reddish polypoid lesion with blood oozing into the jejunum. Antegrade double-balloon endoscopy (DBE) revealed a 5 mm sized protrusion into the jejunum. Endoscopic mucosal resection (EMR) was difficult; the lesion was snared and resected before energization. Clips prevented further bleeding and the lesion's position was marked with a tattoo. Histopathological examination of the lesion led to a diagnosis of capillary hemangioma. After 11 months, the patient was again anemic. A reddish polypoid lesion oozing blood near the tattoo was found by SBCE. Another antegrade DBE showed a 7 mm sized protrusion near the tattoo. The lesion was successfully treated by EMR. Histopathological examination revealed the residual recurrence of a small intestinal capillary hemangioma. The patient recovered from anemia after the EMR. Two months later, SBCE showed no findings around the tattoo. Hemangiomas account for 7-10% of benign small intestinal tumors; most are cavernous hemangiomas, and capillary hemangiomas are rare. We report a rare case of a recurring small intestinal capillary hemangioma detected by SBCE and treated using DBE. We also review the literature.

Small Intestinal Arteriovenous Malformation Treated by Double-balloon Endoscopy: A Case Report.

A 42-year-old man was referred to our hospital because of anemia. The patient underwent gastroscopy and colonoscopy, but no bleeding site was detected. Abdominal contrast-enhanced computed tomography (CT) showed vascular dilatation along the wall of the small intestine. Small bowel capsule endoscopy and antegrade double-balloon endoscopy (DBE) were performed, and the patient was diagnosed with a small intestinal arteriovenous malformation (AVM). The AVM was clipped using DBE. After clipping, abdominal contrast-enhanced CT and small bowel angiography revealed the disappearance of the AVM. DBE may be a viable therapeutic option, helping avoid surgery and its associated risks.

Enterolith Treated with a Combination of Double-Balloon Endoscopy and Cola Dissolution Therapy.

A 71-year-old woman with rheumatoid arthritis who had been taking NSAIDs for many years consulted our hospital for abdominal pain. She was diagnosed with a small bowel obstruction due to an enterolith according to an abdominal CT scan that showed dilation from the enterolith in the small intestine on the oral side. It was considered that the intestinal stone was formed due to stagnation of intestinal contents and had gradually increased in size, resulting in an intestinal obstruction. We performed antegrade double-balloon endoscopy (DBE) to observe and remove the enterolith. We used forceps and a snare to fracture the enterolith. During this attempt, we found a seed in the center of the enterolith. Since the intestinal stone was very hard, cola dissolution therapy was administered from an ileus tube for 1 week. The following week, DBE was performed again, and it was found that the stone had further softened, making attempts at fracture easier. Finally, the enterolith was almost completely fractured. Intestinal stenosis, probably due to ulcers caused by NSAIDs, was found. Small bowel obstruction with an enterolith is rare. In this case, it was considered that the seed could not pass through the stenotic region of the small intestine and the intestinal contents had gradually built up around it. It has been suggested that DBE may be a therapeutic option in cases of an enterolith. Further, cola dissolution therapy has been shown to be useful in treating an enterolith, with the possible explanation that cola undergoes an acid-base reaction with the enterolith. In summary, we report, for the first time, treatment of an enterolith with a combination of DBE and cola dissolution therapy, thereby avoiding surgery and its risks.

Postoperative Complications Following Pharyngolaryngectomy With Total Esophagectomy: Comparison Between Cervical and Anterior Mediastinal Tracheostomy.

OBJECTIVES: Pharyngolaryngectomy with total esophagectomy (PLTE) is associated with high morbidity and mortality rates. Cervical tracheostomy (CT) is the first choice of tracheostomy, whereas anterior mediastinal tracheostomy (AMT) is sometimes required due to tumor extension or insufficient blood supply to the tracheal tip. However, the differences in the outcomes between CT and AMT after PLTE remain unclear. METHODS: We retrospectively reviewed 67 patients who underwent PLTE and compared the clinical features and postoperative complications between patients with CT and AMT. The characteristics and the outcomes were compared between the groups stratified by the causes of AMT. RESULTS: Of the 67 patients, 42 (62.7%) patients underwent PLTE with CT (CT group), whereas 25 (37.3%) underwent PLTE with AMT (AMT group). The AMT group included more cervicothoracic esophageal cancers and had showed an advanced T stage compared to the CT group (P < .01 and .01, respectively). The incidences of pneumonia and surgical site infection (SSI) were more frequent in the AMT group than in the CT group (P = .03 and .01, respectively). Surgery-related mortality was only observed in the AMT group. In the AMT group, 17 (68.0%) and 8 (32.0%) patients underwent AMT because of tumor extension and insufficient supply to the tracheal tip. The latter cases underwent transthoracic esophagectomy more frequently than former cases (P = .03). CONCLUSION: AMT after PLTE had more postoperative complications and mortality than CT. In cases that may need AMT, a transhiatal approach is preferable over transthoracic esophagectomy to avoid fatal complications when oncologically permissive.

Differential diagnosis of ulcerative colitis with increased diarrhea; collagenous colitis or irritable bowel syndrome? A case report.

A 50-year-old man with a 20-year history of left-sided ulcerative colitis (UC) presented to our hospital with sudden onset of watery diarrhea. To this point, he had been treated with mesalazine 2.0 g/day for UC and had maintained remission. We considered that the UC had worsened. We immediately performed surveillance colonoscopy, which revealed a normal mucous membrane. The results of blood laboratory examinations were normal. Histopathology of colonic biopsies revealed new-onset collagenous colitis (CC), with a thickened subepithelial collagen band (SECB) and inactive UC. We herein report the importance of random colonic biopsies to diagnose CC even when the endoscopic appearance of the colon is normal in patients with inflammatory bowel disease with worsened diarrhea.

Linked color imaging improves visibility of colorectal serrated lesion by high color contrast to surrounding mucosa.

OBJECTIVES: This study aimed to objectively evaluate the efficacy of linked color imaging (LCI) in diagnosing colorectal serrated lesions by utilizing visibility scores and color differences. METHODS: We examined 89 serrated lesions, including 36 hyperplastic polyps (HPs), 47 sessile serrated lesions (SSLs), and six traditional serrated adenomas (TSAs). Visibility changes were scored by six endoscopists as follows: 4, excellent; 3, good; 2, fair; and 1, poor. Furthermore, images obtained by white-light imaging (WLI) or LCI were assessed using the CIELAB color space in the lesion and adjacent mucosa. We calculated the mean color values (L*, a*, and b*) measured at five regions of interest of the sample lesion and surrounding mucosa and derived the color difference (ΔE*). RESULTS: The visibility scores of both HPs and SSLs in LCI were significantly higher than that in WLI (HPs, 3.67/2.89, P < 0.001; SSLs, 3.07/2.36, P < 0.001). Furthermore, SSLs showed a significantly higher L* value and significantly lower a* and b* values in LCI than the adjacent mucosae (L*, 61.76/58.23, P = 0.016; a*, 14.91/17.58, P = 0.019; b*, 20.42/24.21, P = 0.007), while WLI produced no significant difference in any color value. A similar trend was apparent in HPs. In all serrated groups, LCI revealed significantly greater ΔE* values between the lesion and adjacent mucosa than WLI (HPs, 11.54/6.12; SSLs, 13.43/7.67; TSAs, 35.00/22.48). CONCLUSION: Linked color imaging showed higher color contrast between serrated lesions and the surrounding mucosae compared with WLI, indicating improved visibility of colorectal serrated lesion using LCI.

Sessile serrated lesions: Clinicopathological characteristics, endoscopic diagnosis, and management.

The 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System (5th edition) introduced the term "sessile serrated lesion" (SSL) to replace the term "sessile serrated adenoma/polyp" (SSA/P). SSLs are early precursor lesions in the serrated neoplasia pathway that result in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potential. The 2019 WHO classification noted that dysplasia arising in an SSL most likely is an advanced polyp, regardless of the morphologic grade of the dysplasia. Detecting SSLs with or without dysplasia is critical; however, detection of SSLs is challenging, and their identification by endoscopists and pathologists is inconsistent. Furthermore, indications for their endoscopic treatment have not been established. Moreover, SSLs are considered to contribute to the development of post-colonoscopy colorectal cancers. Herein, the clinicopathological and endoscopic characteristics of SSLs, including features determined using white light and image-enhanced endoscopy, therapeutic indications, therapeutic methods, and surveillance are reviewed based on the literature. This information may lead to more intensive research to improve detection, diagnosis, and rates of complete resection of these lesions and reduce post-colonoscopy colorectal cancer rates.

CV2/CRMP5-antibody-related Paraneoplastic Neurologic Syndrome Associated with Gastrointestinal Stromal Tumor.

Paraneoplastic neurological syndrome (PNS) is a heterogeneous group of neurological disorders caused by immune-mediated inflammatory mechanisms. We herein report a 77-year-old man with CV2/CRMP5-antibody-related PNS associated with a gastrointestinal stromal tumor (GIST). He was admitted for forgetfulness and delusional behavior. His neurological symptoms were subacute, and a whole-body examination revealed a gastric GIST. Serology showed CV2/collapsin response mediator protein (CRMP)-5 antibodies. Partial gastrectomy was performed for the GIST, and the neurological symptoms and serum CV2/CRMP5 antibodies disappeared. No relapse has occurred since the surgery. PNS should be considered in patients with subacute neurological disorders.

Rare case of advanced rectal cancer with multiple liver and bone metastases presenting with McKittrick-Wheelock syndrome.

McKittrick-Wheelock syndrome (MWS) is a rare entity that has been described as electrolyte and fluid depletion secondary to secretory diarrhea caused by a large villous tumor in the colon or rectum. Most tumors associated with MWS are large but benign villous adenomas. Advanced cancers are seldom reported. We report a rare case of advanced rectal cancer with multiple liver and bone metastases presenting with MWS. A 59-year-old man was admitted to our hospital with a more than 3-year history of chronic mucous diarrhea. Laboratory data revealed hyponatremia, hypokalemia, hypochloremia, and renal failure. Based on the findings on colonoscopy, computed tomography, and magnetic resonance imaging, he was diagnosed with advanced rectal cancer with liver and bone metastases, and MWS. Following intravenous fluid treatment, abdominoperineal resection of the rectum with lymph node dissection was performed. The surgically resected specimen was a circumferential villous tumor measuring 110 × 80 mm. Histological examination of the resected specimens revealed signet ring cell carcinoma with villous adenoma and metastasis in regional lymph nodes. The renal dysfunction and electrolyte abnormalities that were present before surgery improved. Two courses of capecitabine were administered as adjuvant chemotherapy after the surgery. However, approximately 2 months after surgery, he died of poor general condition due to progression of the liver metastases.

A Comparative Study of Early Mucosal Healing Following Hot Polypectomy and Cold Polypectomy.

BACKGROUND Cold polypectomy (CP) and hot polypectomy (HP) are both accepted methods for polypectomy. In recent years, the use of CP has increased for reasons of safety. However, there have been few investigations of conditions at follow-up early after resection. This prospective study from a single center aimed to compare colonic mucosal healing at 1 week following HP vs CP of benign colonic polyps <10 mm in diameter. MATERIAL AND METHODS Six patients with a total of 52 lesions under 10 mm in size were randomized to either the HP group (n=25) or CP group (n=27) using information in opaque envelopes. One week after endoscopic treatment, the site of treatment was evaluated using colonoscopy. We assessed the mean tumor size, ulcer diameter, exposed blood vessels, residual lesion, and complications. RESULTS Mean tumor size did not differ between the 2 groups (CP vs HP: 5.41 mm vs 5.68 mm). The CP group had a smaller ulcer base diameter (2.70 mm vs 4.84 mm; P<0.05) and fewer exposed blood vessels than the HP group (3.7% vs 36.0%; P<0.05). One residual lesion was found in the CP group. No patients experienced delayed perforation or post-polypectomy bleeding. CONCLUSIONS Our study findings showed that at 1-week follow-up, cold polypectomy resulted in improved colonic mucosal healing, with a smaller ulcer diameter and fewer blood vessels, when compared with hot polypectomy.

Plasmablastic Lymphoma of the Small Intestine in an HIV- and EBV-negative Patient.

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder that is strongly associated with immunodeficiency, most often with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection, and that mainly occurs in the oral cavity. Although some clinical features can lead to a diagnosis, PBL in an extraoral site is difficult to suspect clinically in a patient who is HIV negative. The small intestine as a site of PBL has also been described very rarely. We herein present a rare case of PBL of the small intestine in an 85-year-old HIV- and EBV-negative male.

Long-term relapse-free treatment with endoscopic submucosal dissection combined with magnifying narrow-band imaging for a pregnant patient with flat-type condyloma acuminatum: a case report.

Condyloma acuminatum, in the form of genital warts, usually results from an infection by human papillomavirus, one of the most common causes of sexually transmitted diseases. It develops after an incubation period of 3 weeks to 8 months after infection; flat lesions are significantly rare. Condyloma acuminatum is prevalent in the genitals, particularly in the anus of immunodeficient patients. This also occurs in women during menstrual period and pregnancy. Although a common treatment option for rectal and anal lesions, surgical resection is highly invasive and results in a high rate of recurrence. Recently, endoscopic submucosal dissection has been performed for anorectal lesions, but data on its long-term follow-up are not available. We report the case of an immunocompromised patient due to pregnancy who remained recurrence-free 27 months after en-bloc resection by endoscopic submucosal dissection, with adequate visualisation of the flat lesion's safety margin, combined with magnifying narrow-band imaging.

Usefulness of the Japan narrow-band imaging expert team classification system for the diagnosis of sessile serrated lesion with dysplasia/carcinoma.

BACKGROUND: Sessile serrated lesion (SSL) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSL can be difficult to diagnose with conventional endoscopy, because most SSLs with dysplasia/carcinoma have subtle mucosal features. Many studies have indicated that narrow-band imaging (NBI) observations of colorectal polyps are very useful, accurate predictors of histology. We aimed to verify the usefulness of the Japan NBI Expert Team (JNET) classification system for the diagnosis of SSLs with dysplasia/carcinoma. METHODS: We examined 709 endoscopically or surgically resected lesions that were pathologically diagnosed as SSL, including 647 with no dysplasia, 37 with low-grade dysplasia, 15 with high-grade dysplasia, and 10 with submucosal invasive carcinoma. We retrospectively evaluated their clinicopathologic characteristics and conventional endoscopic and magnifying NBI endoscopic findings using the JNET system. RESULTS: Cases in all groups were more frequently located in the proximal colon. Submucosal invasive carcinomas were significantly larger than no dysplasia and low-grade dysplasia lesions. Almost all studied lesions (96.3%) were covered with a mucus cap. Five hundred and eighty (81.8%) lesions exhibited dark spots inside the crypts, which are NBI findings' characteristic of SSL. As for the JNET classification of magnifying NBI endoscopic findings, all 709 lesions showed Type 1. Six hundred and eighteen (95.5%) SSLs with no dysplasia lesions exhibited Type 1 only, whereas 52 (83.9%) SSLs with dysplasia/carcinoma had a combination of Type 1 and Type 2A, 2B, or 3, corresponding to SSL and dysplasia/carcinoma, respectively. The JNET classification had high sensitivity (83.9%), specificity (95.5%), and overall diagnostic accuracy (94.5%) for diagnosing SSLs with dysplasia/carcinoma. CONCLUSIONS: Use of magnifying NBI endoscopy with the JNET classification might be useful for diagnosing SSLs with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSLs with dysplasia/carcinoma.

Digestive Reconstruction After Pharyngolaryngectomy with Total Esophagectomy.

BACKGROUND: Pharyngolaryngectomy with total esophagectomy (PLTE) is often indicated for patients with synchronous head and neck cancer and thoracic esophageal cancer or those with head and neck cancer extending to the upper mediastinum. A long conduit is required for the reconstruction, and the blood flow at the tip of the conduit is not always sufficient. Thus, reconstructive surgery after PLTE remains challenging, and optimal reconstruction methods have not been elucidated to date. METHODS: This analysis investigated 65 patients who underwent PLTE. The short-term outcomes among the procedures were compared to explore the optimal digestive reconstruction methods. RESULTS: We used a simple gastric conduit for 7 patients, a gastric conduit with microvascular anastomosis (MVA) for 10 patients, an elongated gastric conduit with an MVA for 20 patients, a gastric conduit combined with a free jejunum transfer (FJT) for 25 patients, and other procedures for 3 patients. Postoperatively, 17 (26.2%) of the patients experienced severe complications, classified as Clavien-Dindo grade 3b or higher, including graft failure for 3 patients (6.2%). Anastomotic leakage was found in six patients (9.2%), and all leakages occurred at the pharyngogastric anastomosis. The reoperation rate was 15.4% (n = 10), and three patients (4.6%) died of massive bleeding from major vessels. The patients who underwent simple gastric conduit more frequently had graft failure (P = 0.04), anastomotic leakage (P < 0.01), and reoperation (P = 0.04) than the patients treated with the other reconstructive methods. CONCLUSION: Additional procedures such as MVA, gastric tube elongation, and FJT contribute to improving the outcomes of reconstruction after PLTE.

[Liver injury caused by exposure to silica and 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123):a case report].

This case report presents two males with drug-induced liver injury acquired from working at a glass factory dealing with silica and 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). Within one month of work, both patients presented with fever, icterus with liver dysfunction, and eosinophilia. Case 1 had experienced recurrence of symptoms twice while working and showed positive results for the drug-induced lymphocyte stimulation test (DLST). Meanwhile, case 2 was diagnosed by liver biopsy and clinical course but was negative for DLST. Hazard of exposure to non-crystalline silica is low, but drug-induced liver injury after exposure to HCFC-123 has been reported. Allergic liver injury is also caused by chemical substances;however, the insight into whether this injury is caused by exposure to silica or HCFC-123 remains unclear. Further studies are required to examine the influence of silica and HCFC-123 on drug-induced liver injury among glass-factory employees.

Predictive Factors for Completion of TPF Induction Chemotherapy in Patients With Locally Advanced Head and Neck Cancer.

BACKGROUND: Induction therapy with docetaxel, cisplatin and fluorouracil (TPF) is a treatment option for locally advanced head and neck cancer (LAHNC), but it is not known which patients are appropriate for TPF. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with LAHNC who underwent induction TPF, and evaluated factors predictive of the completion of TPF treatment (defined as ≥3 cycles administered). RESULTS: Of the total 93 enrolled patients, 73 (78.5%) achieved therapy completion. In a multivariate analysis, hypolaryngeal/ laryngeal primary tumor site was a negative predictive factor (hazard ratio(HR)=0.32, 95% confidence interval(CI)=0.11-0.96, p=0.041) and body mass index ≥22 kg/m2 was a positive predictive factor (hazard ratio=3.51, 95% confidence intervaI=1.04-11.83, p=0.043) of TPF completion. CONCLUSION: For patients with LAHNC, oropharyngeal primary tumor site and high body mass index can be used to predict TPF completion and may contribute to decisions on the indications for TPF in terms of safety and tolerability.

Incidence and risk factors of interstitial lung disease of patients with head and neck cancer treated with cetuximab.

BACKGROUND: Interstitial lung disease (ILD) is known as a potentially severe adverse event associated with epidermal growth factor receptor (EGFR)-targeted therapy. The incidence and risk factors of ILD in patients with head and neck squamous cancer (HNSCC) treated with cetuximab, an anti-EGFR monoclonal antibody, have not been established. METHODS: We retrospectively reviewed patients with HNSCC who received cetuximab from December 2012 to December 2016 at our institute and evaluated the incidence and risk factors of ILD. RESULTS: Of the 201 patients with HNSCC, ILD was observed in 9 patients (4.5%), 8 of whom had grade 3 or higher. High Krebs von den Lungen-6 (KL-6) and ≥50 pack-years of smoking were significantly predictive of associated with ILD (P = 0.00011 and 0.05, respectively). CONCLUSION: The incidence of ILD in patients with HNSCC treated with cetuximab was <5%, but most of the ILD cases were severe. High KL-6 and smoking histories might be predictive for ILD among patients with HNSCC.

Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis.

Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2. In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.

Formation of p62-positive inclusion body is associated with macrophage polarization in non-alcoholic fatty liver disease.

AIM: Hepatic inclusion composed of autophagy-specific substrate p62 is one of the histological features of non-alcoholic fatty liver disease (NAFLD) and can be a precursor to hepatic carcinogenesis. The expression of p62 was enhanced by not only autophagic dysfunction but also oxidative stress and inflammation. M1/M2 phenotypic balance of macrophages plays a pivotal role in the progression of NAFLD. We evaluated the correlation between macrophage polarization and the formation of p62 aggregation in NAFLD. METHODS: Liver biopsy specimens from NAFLD patients were analyzed by immunohistochemical staining for M1 macrophage marker CD11c, M2 macrophage marker CD163, and p62/SQSTM1 (p62). The histological severity of NAFLD is assessed by a NAFLD activity score (NAS). The number of autophagic vesicles in hepatocytes was visualized and counted by using transmission electron microscopy. RESULTS: The aggregation of p62 was undetectable in control, whereas hepatocytes with p62 aggregation were observed in approximately 88% of NAFLD specimens. The number of hepatocytes with p62 aggregation was positively correlated with the number of autophagic vesicles, serum alanine aminotransferase, NAS, fibrosis, and the number of CD11c-positive cells, but not CD163-positive cells. Assembly of CD11c-positive cells was observed around hepatocytes with p62 aggregation. The ratio of CD11c/CD163-positive macrophages was significantly associated with the formation of p62 aggregation. CONCLUSIONS: These findings indicate that chronic inflammation by M1-polarization of macrophages contributes to the disease progression from simple steatosis to non-alcoholic steatohepatitis in concert with autophagic dysfunction.