Pathological complete response of hepatocellular carcinoma confirmed by conversion hepatectomy following atezolizumab plus bevacizumab therapy: a case report and literature review.

The combination regimen of atezolizumab plus bevacizumab (Atezo/Bev) is currently used as first-line treatment in patients with unresectable hepatocellular carcinoma. Herein, we report a rare case of curative hepatic resection performed as conversion surgery in a patient with intermediate-stage hepatocellular carcinoma following preoperative Atezo/Bev therapy. After five treatment cycles of Atezo/Bev therapy, followed by four cycles of atezolizumab monotherapy, the tumor marker levels decreased to baseline levels and 22 small daughter nodules disappeared, leaving only the primary tumor. Therefore, we performed resection of the primary tumor as conversion surgery, and postoperative histopathology confirmed complete tumor necrosis. No cancer recurrence has been observed until the 5-month postoperative follow-up, and the patient remains drug free. Consistent with the findings in this case, a review of previously reported cases revealed that in cases of successful conversion surgery, neoadjuvant Atezo/Bev therapy was associated with intra-tumoral bleeding, immune-related adverse events, and normalization of the tumor marker levels.

Advanced Endoscopy for Benign Esophageal Disease: A Review Focused on Non-Erosive Reflux Disease and Eosinophilic Esophagitis.

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.

The Risk of Bleeding in Small/Straight Esophageal Varices with Red Color Sign on Endoscopy: A Retrospective Analysis from the Natural Course.

Red color sign-positive (RC-positive) esophageal varices present a high bleeding risk, necessitating prophylactic treatment. Among RC-positive esophageal varices, those classified morphologically as small straight varices (Form level 1: F1) are difficult to treat. Moreover, the appropriate time for therapeutic intervention remains undefined. This study assessed the bleeding risk in RC-positive F1 esophageal varices. After extracting 541 cases of F1 esophageal varices diagnosed during 1 January 2012−29 February 2020, 76 cases of RC-positive F1 esophageal varices were divided into two groups in terms of treatment intervention at diagnosis: 49 cases with (treatment group) and 27 cases without (follow-up group). We assessed the bleeding rates, bleeding-associated factors, and early-bleeding-associated factors. The treatment group's bleeding rate was 10% (5/49). The follow-up group's bleeding rate was 78% (21/24). The subsequent bleeding rate was low in the treatment group (p < 0.001). The median period of sustained absence of bleeding was longer in the treatment group than in the follow-up group (1156 [274−1582] days vs. 105 [1−336] days; p < 0.001). In the follow-up group, a significant number of bleedings had varices that included a hematocystic spot (HCS) as RC or combined with RC (p = 0.017). Early bleeding occurred often in varices that included HCS or combined with RC (p = 0.024). Red wale marking (RWM) only was not a factor of early bleeding (p = 0.012). In conclusion, RC-positive varices should be treated even as F1 varices. Patients with RWM only show the possibility of not accepting early treatment intervention. A fast response is crucially important in HCS cases because of its associated bleeding and early bleeding.

Efficacy of Pseudo-Ceramide-Containing Steroid Lamellar Cream in Patients with Mild to Moderate Atopic Dermatitis: A Randomized, Double-Blind Study.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure. METHODS: We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms. RESULTS: The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small- and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the double-blind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p < 0.01) and significant decrease in transepidermal water loss (p < 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group. CONCLUSION: The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.

Making Hematochezia of Unknown Origin Known: A Retrospective Analysis.

INTRODUCTION: Hematochezia is observed frequently in daily practice. However, natural hemostasis often prevents identification of the bleeding source during observations. This study was conducted to clarify risk factors related to rebleeding in hematochezia patients without an identified cause of bleeding. METHODS: We analyzed patients who were admitted to Dokkyo Medical University Hospital during April 1, 2009, through March 31, 2015, with the chief complaint of hematochezia. Main outcome measures included the rebleeding rate and the period until rebleeding in hematochezia patients without an identified bleeding source. RESULTS: We selected 159 patients for analyses. Rebleeding was observed in 46 (28.9%) of 159 patients. The median period until first rebleeding was 166 days (2-3,046 days). Univariate analysis indicated that risk factors for rebleeding were male gender (p = 0.029), higher age (p = 0.023), antithrombotic medicines (p = 0.047), lower hemoglobin on admission (p = 0.024), and the presence of diverticula (p = 0.002). Multivariate analysis indicated the presence of diverticula (p = 0.023) and male gender (p = 0.043) as rebleeding risk factors. DISCUSSION/CONCLUSION: In patients with hematochezia of unknown origin, risk factors for rebleeding indicated in this study, especially the presence of diverticula and male gender, should be given particular attention by physicians.

Measuring optimal ultrasound speed using endoscopic ultrasound in patients with chronic pancreatitis, including early stage.

OBJECTIVES: Ultrasound speed (USS) correction improves image quality by estimating the optimal USS correcting the deviation from a predetermined USS. This study assessed USS differences between chronic pancreatitis (CP), early CP (ECP), and normal pancreas when using endoscopic ultrasound (EUS). The usefulness of measuring optimal USS was evaluated for patients with CP, including early stage patients. METHODS: This study enrolled 116 consecutive patients for whom USS was measured using an EUS system. The USS correction principle is generation of a B-mode image by changing the USS in all ranges while correcting the delay in the received data. Final diagnoses were made according to the Japanese diagnostic criteria for CP in 2019. They were classified as CP, ECP, or normal. We compared USS applied for these three groups. RESULTS: The medians and ranges of USS values for patients in the normal, ECP, and CP groups were 1506.0 (1407-1600) m/s, 1580.0 (1520-1630) m/s, and 1574.0 (1537-1610) m/s, respectively. The USS values of the ECP and CP groups were significantly higher than those of the normal group (P < 0.001). Analyses of the receiver operating characteristic curve in the normal pancreas, ECP, and CP revealed the area as 0.957, with specificity and sensitivity of 95.9% and 87.5%, respectively, using the USS of 1535 m/s as a cut-off. CONCLUSION: Measurement of USS might be particularly useful for distinguishing between normal and ECP imaging.

Salvage Endoscopic Submucosal Dissection for Local Recurrence of Superficial Esophageal Squamous Cell Cancer after Photodynamic Therapy.

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

Efficacy of Heparinoid Cream Containing Pseudo-Ceramide for Remission of Atopic Dermatitis.

PURPOSE: Atopic dermatitis (AD) is characterized by chronic inflammation, which frequently recurs, is exacerbated, and enters remission. A maintenance remission period is important for AD patients. We developed a formulation for use during AD remission, containing heparinoid and pseudo-ceramide that forms a lamellar structure. We evaluated the allergen permeability and examined the formulation's efficacy in maintaining remission in patients with AD. MATERIALS AND METHODS: Seventeen AD patients applied a cream containing 0.3% heparinoid and pseudo-ceramide (test cream group, n = 10), or a general cream containing 0.3% heparinoid (control cream group, n = 7) to their arm for four weeks after inducing remission with the application of a steroid cream for two weeks. RESULTS: The lamellar structure of the test cream was confirmed with small- and wide-angle x-ray scattering analysis and observation by transmission electron microscopy. The test cream inhibited the penetration of V8 protease significantly compared to the control cream in vitro. According to AD severity score by dermatologists, the effects remission maintenance of the test cream group were comparable to those of the control cream group. However, the test cream group had a significantly increased skin hydration value compared to the control cream group. A significant decrease in transepidermal water loss, an indicator of skin barrier function, was shown in the test cream group compared to the control cream group. CONCLUSION: The cream with lamellar structures containing heparinoid and pseudo-ceramides may inhibit allergen penetration. Moreover, skin properties improved during the remission period; thus, the formulation we developed was suitable for use during the AD remission period.

Analysis of Endoscopic Evaluation Reliability for Ulcerative Colitis in Histological Remission.

The Mayo endoscopic subscore (MES) is a major endoscopic scoring system used to assign a status of mucosal inflammation and disease activity to patients with ulcerative colitis (UC). Using interobserver reliability (IOR), this study clarified the difficulties for endoscopic observers imposed by MES parameters used for the endoscopic evaluation of UC in histological remission. First, 42 endoscopists of four observer groups examined each MES parameter, which were evaluated from endoscopically obtained images of 100 cases as Grade 0 or 1 of the Nancy histological index of histopathological inflammation. Then, IOR was assessed using multiple κ statistics for each finding of MES. The results showed that IOR among all the observers was slight or fair for all the parameters, indicating a low IOR. The experts of the UC practice group had "moderate" or higher IOR for seven of the nine parameters, whereas "slight" or "fair" results were found for all parameters by the trainee group. The IOR for each MES parameter was calculated separately for the observer groups. All the groups showed "slight" or "fair" for "Erythema" and "Decreased vascular pattern". Large differences between the endoscopists were found in the IOR for the MES parameters in UC in histological remission. Even among UC practice experts, the IOR was low for "Erythema" and "Decreased vascular pattern".

Whole circumferential endoscopic submucosal dissection of superficial adenocarcinoma in long-segment Barrett's esophagus: A case report.

BACKGROUND: Esophageal adenocarcinoma (EAC) derived from long-segment Barrett's esophagus (LSBE) is extremely rare in Asia. LSBE-related EAC is often difficult to diagnose in the horizontal extent. If the tumor has spread throughout the LSBE, whole circumferential endoscopic submucosal dissection (ESD) should be performed, which is difficult to complete safely. Additionally, whole circumferential ESD can bring refractory postoperative stenosis. We hereby report a case of EAC involving the whole circumference of the LSBE, achieving complete endoscopic removal without complications. CASE SUMMARY: An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy. We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE (C 3.5, M 4.0) using narrow-band imaging magnification endoscopy (NBI-M). We achieved circumferential en bloc resection of the lesion safely with special ESD techniques. Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE, and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin. To prevent post-ESD stenosis, we performed endoscopic local injection of steroids, followed by oral administration of steroids. There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD. In summary, we experienced a rare case of LSBE-related EAC. The horizontal tumor extent was accurately diagnosed by NBI-M. Additionally, we achieve whole circumferential ESD safely without postoperative refractory stenosis. CONCLUSION: NBI-M, ESD, and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis.

Recent Advances in Endosonography-Elastography: Literature Review.

Ultrasonographic elastography is a modality used to visualize the elastic properties of tissues. Technological advances in ultrasound equipment have supported the evaluation of elastography (EG) in endosonography (EUS). Currently, the usefulness of not only EUS-strain elastography (EUS-SE) but also EUS-shear wave elastography (EUS-SWE) has been reported. We reviewed the literature on the usefulness of EUS-EG for various diseases such as chronic pancreatitis, pancreatic solid lesion, autoimmune pancreatitis, lymph node, and gastrointestinal and subepithelial lesions. The importance of this new diagnostic parameter, "tissue elasticity" in clinical practice might be applied not only to the diagnosis of liver fibrosis but also to the elucidation of the pathogeneses of various gastrointestinal diseases, including pancreatic diseases, and to the evaluation of therapeutic effects. The most important feature of EUS-EG is that it is a non-invasive modality. This is an advantage not found in EUS-guided fine needle aspiration (EUS-FNA), which has made remarkable progress in the field of diagnostics in recent years. Further development of artificial intelligence (AI) is expected to improve the diagnostic performance of EUS-EG. Future research on EUS-EG is anticipated.

Association of long-term endoscopic biliary stent placement with choledocholithiasis: a literature review.

Endoscopic stone removal is currently the first-line procedure for the treatment of common bile duct stones. Advances in equipment and treatment techniques have expanded the scope of application of endoscopic treatment to include stones that have previously been difficult to remove endoscopically, such as stacked stones and large stones. For the treatment of common bile duct stones in elderly patients in particular, long-term placement of a biliary stent is increasingly being selected. Although periodic stent replacement is required, some reports have stated that biliary stenting is useful in terms of treatment-associated invasiveness and the incidence of accidental complications. To date, various opinions have been presented on whether the treatment of bile duct stones should aim for complete removal of stones or adopt the biliary stenting approach. Findings in previous reports suggest that both the approach for complete stone removal and the long-term stenting approach are associated with advantages and disadvantages. In this study, we reviewed previous reports on the significance of placing a stent and implementing careful monitoring rather than stone removal in patients with bile duct stones.

Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by Tacrolimus: A Case Report.

Immune checkpoint inhibitors (ICIs) increase T-cell activity and antitumor immune response. However, they also have immune-related adverse effects that can affect the gastrointestinal (GI) tract. A 62-year-old male patient who had undergone right lung upper lobectomy for adenocarcinoma of the lung received chemotherapy with pemetrexed sodium hydrate, carboplatin, and pembrolizumab to prevent postoperative recurrence of liver metastasis. However, the patient experienced severe diarrhea four months after the start of chemotherapy. Although a corticosteroid and two biological preparations were administered to alleviate the diarrhea, no improvement was observed. Eventually, remission was achieved when tacrolimus was administered. Treatment with corticosteroids is recommended for patients with GI adverse effects of ICIs. Rapid introduction of infliximab is necessary for refractory patients. Nevertheless, for refractory cases such as that of our patient, for whom even this regimen is inefficacious, tacrolimus might be recommended to induce remission as with cases of ulcerative colitis.

Factors Affecting Technical Difficulty in Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Surgically Altered Anatomy.

Success rates of balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) for patients with a reconstructed intestinal tract after surgical procedures are unsatisfactory. We retrospectively investigated the factors associated with unsuccessful BE-ERCP. Ninety-one patients who had a reconstructed intestinal tract after gastrectomy or choledochojejunostomy were enrolled. Age, sex, operative method, malignancy, endoscope type, endoscopist's skill, emergency procedure, and time required to reach the papilla/anastomosis were examined. The primary endpoints were the factors associated with unsuccessful BE-ERCP selective cannulation, while the secondary endpoints were the rate of reaching the papilla/anastomosis, causes of failure to reach the papilla/anastomosis, cannulation success rate, procedure success rate, and rate of adverse events. Younger age (odds ratio, 0.832; 95% CI, 0.706-0.982; p = 0.001) and Roux-en-Y partial gastrectomy (odds ratio, 54.9; 95% CI, 1.09-2763; p = 0.045) were associated with unsuccessful BE- ERCP. The rate of reaching the papilla/anastomosis was 92.3%, the success rate of biliary duct cannulation was 90.5%, procedure success rate was 78.0%, and the rate of adverse events was 5.6%. In conclusion, Roux-en-Y partial gastrectomy and younger age were associated with unsuccessful BE-ERCP. If BE-ERCP is extremely difficult to perform in such patients after Roux-en-Y partial gastrectomy, alternative procedures should be considered early.

Interobserver Reliability of the Endoscopic Ultrasound Criteria for the Diagnosis of Early Chronic Pancreatitis: Comparison between the 2009 and 2019 Japanese Diagnostic Criteria.

In 2009, diagnostic criteria for early chronic pancreatitis (DCECP2009) were proposed by the Japan Pancreas Society. This study aimed to evaluate the interobserver reliability (IOR) of endoscopic ultrasound (EUS) criteria for diagnosis of early chronic pancreatitis (ECP) between DCECP2009 and 2019 diagnostic criteria for ECP (DCECP2019) to assess the validity of the revision from the perspective of EUS findings. Among patients who underwent a detailed observation of the pancreas by EUS at our institution between January 2018 and March 2019, EUS images of 97 patients were extracted. Images were reviewed by 12 gastrointestinal endoscopy experts (eight pancreatologists, group A and four nonpancreatologists, group B). The overall kappa (K)-values for the IOR of the DCECP2009 EUS criteria were 0.424 and 0.563:0.231 for groups A:B, whereas the overall K-values for the DCECP2019 criteria were 0.618, and 0.733:0.442 for groups A:B. Regarding changes in the final diagnosis of ECP based on clinical features and EUS findings, 20 cases were definite ECP, 53 were probable ECP, and 24 were normal according to DCECP2009. In contrast, seven were definite ECP, 19 were probable ECP, and 71 were normal according to DECEP2019. IOR of DCECP2019 was higher than that of DCECP2009, which indicates an improvement in precision.

Development of biliary stent applying the antibacterial activity of silver: A literature review.

BACKGROUND: Endoscopic transpapillary stenting is commonly performed in patients with obstructive jaundice caused by a biliary stricture. Although the plastic stent (PS) is widely used for biliary drainage because of the low-cost and easy procedure, patency is short after placement in the bile duct because of the small diameter. Dysfunction of PS is primarily caused by biliary sludge that forms as a result of bacterial adhesion and subsequent biofilm formation on the inner surface of the stent. It is well known that silver ions have excellent antibacterial activity against a wide range of microorganisms. OBJECTIVE: This review provides an overview and perspective of the significance of silver-coated biliary stents. METHODS: We collected literature regarding silver-coated biliary stents, reviewed the current research/development status and discussed their possible usefulness. RESULTS: To date, several in vivo/vitro studies evaluated the patency of silver-blended or silver-coated biliary stents. These studies suggested that the silver coating on a PS was likely to prolong the patency period. CONCLUSION: The development of biliary stents using silver is expected to prolong stent patency and prevent frequent stent replacement.

Feasibility and Safety of Transjugular Liver Biopsy for Japanese Patients with Chronic Liver Diseases.

BACKGROUND AND STUDY AIM: Transjugular liver biopsy (TJLB) can be used in patients who are ineligible for percutaneous liver biopsy (PLB) with acute and chronic hepatic disease. This study aimed to evaluate the usefulness and safety of TJLB in patients who were not indicated for PLB. METHODS: Between July 2014 and February 2019, a total of 134 patients underwent liver biopsies at our institution. Among these, PLB was performed in 110 patients and TJLB in 24 patients. A retrospective comparison of clinical results in these patients was then performed. The primary endpoints of this study were the utility and safety of TJLB in patients who were not indicated for PLB. RESULTS: The procedural success rate was 100% in both groups. The clinical response rate and the effective tissue sampling rate were 100% in the TJLB group and 97% in the PLB group (p = 0.55). There was no difference in the number of portal fields examined retrospectively between the two groups. No serious adverse events were observed in either group. CONCLUSIONS: It is suggested that TJLB is useful because it can be safely performed in patients with poor general condition who are not indicated for PLB.

Gastric Dieulafoy's lesion with subepithelial lesion-like morphology.

Most cases of Dieulafoy's lesion, a rare cause of upper gastrointestinal bleeding, occur in the upper gastric corpus, usually with no edematous bulging or fold convergence around the mucosal defect. This report describes a case of Dieulafoy's lesion with subepithelial lesion (SEL)-like morphology. Endoscopic treatment by hemoclipping was difficult. Because of repeated bleeding, abdominal dynamic contrast computed tomography (CT) was conducted. Results showed a large caliber, tortuous artery branching directly from the celiac artery and feeding into the gastric wall of the gastric fundus. Rupture of this vessel in the submucosa was thought to be responsible for the SEL-like morphology. All findings indicated endoscopic treatment from the gastric mucosal side was too difficult. Therefore, we treated the lesion using interventional radiology (IR) technique of vascular embolization. If an SEL-like Dieulafoy's lesion cannot be treated by endoscopic hemostasis, then IR might be necessary to treat the vascular anomaly.

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

AIM: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS: All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6 mm) and hyperbilirubinemia (≥2.0 mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. CONCLUSIONS: Treatment with SOF/VEL for 12 weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.