Durvalumab after chemoradiotherapy in non-small cell lung cancer with EGFR mutation: A real-world study (HOT2101).

Durvalumab has been administered to patients with unresectable stage III non-small cell lung cancer (NSCLC). However, it remains unclear whether durvalumab benefits these patients with epidermal growth factor receptor (EGFR) mutation. We conducted a retrospective, multicenter study of patients with EGFR mutation who received chemoradiotherapy (CRT) between June 2018 and March 2021. We assessed patient characteristics, efficacy of durvalumab, and durvalumab safety before and after targeted therapy. We collected data on a total of 673 patients, of whom 401 (59.6%) underwent EGFR mutation testing. Fifty-one patients were EGFR positive and 311 were EGFR negative. In the EGFR-positive group, there were higher proportions of females, never-smokers, and patients with adenocarcinoma histology. Of the 51 patients in the positive group and 311 in the negative group who received CRT, 45 (88.2%) and 247 (79.4%) received durvalumab, with median progression-free survival of 23.0 and 24.2 months in the positive and negative groups, respectively (hazard ratio 1.03; 95% confidence interval: 0.64-1.67). The main adverse event was pneumonitis (positive group: 62.2%; 4.4% grade 3; negative group: 62.3%; 6.9% grade 3). No treatment-related deaths were observed. Of the 45 patients in the positive group who received durvalumab, 14 (31.1%) received targeted therapy after durvalumab at the data cutoff. One patient discontinued targeted therapy after developing pneumonitis. In patients with unresectable stage III NSCLC with EGFR mutation, durvalumab after CRT is potentially safe and effective. This may be a suitable treatment sequence for these patients.

Formation of the brain by stem cell divisions of large neuroblasts in Oikopleura dioica, a simple chordate.

Stem cell division contributes to the generation of various cell types during animal development, especially a diverse pool of neural cells in the nervous system. One example is reiterated unequal stem cell divisions, in which a large stem cell undergoes a series of oriented unequal divisions to produce a chain of small daughter cells that differentiate. We show that reiterated unequal stem cell divisions are involved in the formation of the brain in simple chordate appendicularians (larvaceans). Two large neuroblasts in the anterior and middle of the brain-forming region of hatched larvae were observed. They produced at least 30 neural cells out of 96 total brain cells before completion of brain formation at 10 hours after fertilization by reiterated unequal stem cell divisions. The daughter cells of the anterior neuroblast were postmitotic, and the number was at least 19. The neuroblast produced small daughter neural cells posteriorly every 20 min. The neural cells first moved toward the dorsal side, turned in the anterior direction, aligned in a single line according to their birth order, and showed collective movement to accumulate in the anterior part of the brain. The anterior neuroblast originated from the right-anterior blastomeres of the eight-cell embryos and the right a222 blastomere of the 64-cell embryo. The posterior neuroblast also showed reiterated unequal stem cell divisions, and generated at least 11 neural cells. Sequential unequal stem cell divisions without stem cell growth have been observed in protostomes, such as insects and annelids. The results provide the first examples of this kind of stem cell division during brain formation in non-vertebrate deuterostomes.

Activation of Strigolactone Biosynthesis by the DWARF14-LIKE/KARRIKIN-INSENSITIVE2 Pathway in Mycorrhizal Angiosperms, but Not in Arabidopsis, a Non-mycorrhizal Plant.

Strigolactones (SLs) are a class of plant hormones that regulate many aspects of plant growth and development. SLs also improve symbiosis with arbuscular mycorrhizal fungi (AMF) in the rhizosphere. Recent studies have shown that the DWARF14-LIKE (D14L)/KARRIKIN-INSENSITIVE2 (KAI2) family, paralogs of the SL receptor D14, are required for AMF colonization in several flowering plants, including rice. In this study, we found that (-)-GR5, a 2'S-configured enantiomer of a synthetic SL analog (+)-GR5, significantly activated SL biosynthesis in rice roots via D14L. This result is consistent with a recent report, showing that the D14L pathway positively regulates SL biosynthesis in rice. In fact, the SL levels tended to be lower in the roots of the d14l mutant under both inorganic nutrient-deficient and -sufficient conditions. We also show that the increase in SL levels by (-)-GR5 was observed in other mycorrhizal plant species. In contrast, the KAI2 pathway did not upregulate the SL level and the expression of SL biosynthetic genes in Arabidopsis, a non-mycorrhizal plant. We also examined whether the KAI2 pathway enhances SL biosynthesis in the liverwort Marchantia paleacea, where SL functions as a rhizosphere signaling molecule for AMF. However, the SL level and SL biosynthetic genes were not positively regulated by the KAI2 pathway. These results imply that the activation of SL biosynthesis by the D14L/KAI2 pathway has been evolutionarily acquired after the divergence of bryophytes to efficiently promote symbiosis with AMF, although we cannot exclude the possibility that liverworts have specifically lost this regulatory system.

Mechanical Properties of a 3 Dimensional-Printed Transparent Flexible Resin Used for Vascular Model Simulation Compared with Those of Porcine Arteries.

PURPOSE: To develop a vascular intervention simulation model that replicates the characteristics of a human patient and to compare the mechanical properties of a 3-dimensional (3D)-printed transparent flexible resin with those of porcine arteries using the elastic modulus (E) and kinetic friction coefficient (µk). MATERIALS AND METHODS: Resin plates were created from a transparent flexible resin using a 3D printer. Porcine artery plates were prepared by excising the aorta. E values and the adhesive strengths of the resin and arterial surfaces toward a polyethylene plate, were measured with a tensile-compressive mechanical tester. Resin transparency was measured using an ultraviolet-visible light spectrometer. The µk value of the resin plate surface after applying silicone spray for 1-5 seconds and that of the artery were measured using a translational friction tester. RESULTS: E values differed significantly between the arteries and resin plates at each curing time (0.20 MPa ± 0.04 vs 8.53 MPa ± 2.37 for a curing time of 1 minute; P < .05). The resin was stiffer than the arteries, regardless of the curing times. The visible light transmittance and adhesive strength of the resin decreased as the curing time increased. The adhesive strength of the artery was the lowest. The µk value of the silicone-coated resin surface created by applying silicone for 2-3 seconds (thickness of the silicone layer, 1.6-2.0 µm) was comparable with that of the artery, indicating that the coating imparted a similar slippage to the resin as to the living artery. CONCLUSIONS: A transparent flexible resin is useful for creating a transparent and slippery vascular model for vascular intervention simulation.

Clinical outcomes and predictors of technical failure of endoscopic transpapillary gallbladder drainage in acute cholecystitis.

BACKGROUND AND AIMS: Endoscopic transpapillary gallbladder drainage (ETGBD) has been performed as an alternative therapy against cholecystectomy in patients with acute cholecystitis. To date, few studies have reported the safety, efficacy, and factors affecting ETGBD. We evaluated the clinical outcomes and predictors of technical failure of ETGBD. METHODS: Patients with acute cholecystitis who underwent ETGBD were retrospectively reviewed, and consecutive patients were included in the study. The technical success rate, clinical success rate, adverse events, and the predictors associated with the technical failure of ETGBD were investigated. RESULTS: A total of 242 patients were enrolled in the study. The technical success rate of ETGBD and clinical success rate of technically successful ETGBD cases were 87% and 93%, respectively. We experienced cystic duct injury in 24 patients as an ETGBD-related adverse event, and pancreatitis in 12 patients as an endoscopic retrograde cholangiopancreatography-related adverse event. Multivariate analysis indicated that cystic duct injury was the independent predictor associated with the technical failure of ETGBD (odds ratio, 11; 95% confidence interval, 3.9-29; p < 0.001). CONCLUSIONS: ETGBD was a safe and effective treatment method for acute cholecystitis with acceptable adverse events. There was no predictor based on the information from patient characteristics; however, cystic duct injury was associated with the technical failure of ETGBD.

Current status of first-line treatment with pembrolizumab for non-small-cell lung cancer with high PD-L1 expression.

It is not clear whether pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) should be selected for patients with advanced non-small-cell lung cancer (NSCLC) exhibiting high PD-L1 expression (tumor proportion score ≥ 50%). We performed a retrospective, multicenter study of 300 patients with NSCLC exhibiting high PD-L1 expression who received MONO or COMB as first-line treatment between December 2018 and January 2020. We reviewed the medical records of all consecutive patients with no driver mutations, and assessed the patient characteristics, therapeutic regimens, treatment periods, and adverse events. In total, 166 (55%; median age: 74 years) and 134 (45%; median age: 68 years) patients received MONO and COMB, respectively. Patients were younger and had better performance status (0-1) in the COMB group (p < 0.01). With a median follow-up time of 10.6 (range: 0.1-20.6) months, the median progression-free survival was 7.1 months with MONO and 13.1 months with COMB. The objective response rate was 42.2% with MONO and 67.9% with COMB. With respect to treatment discontinuation, 36 out of 166 (21.7%) and 28 out of 134 (20.1%) patients discontinued MONO and COMB, respectively. In conclusion, COMB may be a promising option for first-line treatment for NSCLC with high PD-L1 expression and good performance status.

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in Japan.

BACKGROUND AND AIMS: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted ERCP has been reported as useful in patients with surgically altered anatomy, most studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy. METHODS: This multicenter, retrospective study was conducted at 8 tertiary referral care centers in Japan. The data of patients who underwent ERCP-related procedures using short SBE between September 2011 and August 2019 at each facility were analyzed. RESULTS: Overall, 1318 patients were included in this analysis. The enteroscopy (reaching the target site), cannulation, and total procedural success rates were 87.9% (95% confidence interval [CI], 86.1%-89.6%), 87.0% (95% CI, 84.9%-88.8%), and 74.9% (95% CI, 72.5%-77.2%), respectively. Adverse events occurred in 7.7% of patients (95% CI, 6.4%-9.3%). Multiple logistic regression analysis indicated that age (≥75 years), Roux-en-Y reconstruction, pancreatic indication, and malignancy were factors affecting the total procedural failure. CONCLUSIONS: This large-scale study proved that short SBE-assisted ERCP in patients with surgically altered anatomy was effective. Moreover, it clarified factors affecting procedure results. Proficiency with alternative treatment techniques is required in difficult cases. (Clinical trial registration number: UMIN00004045.).

Evaluation of intercellular lipid lamellae in the stratum corneum by polarized microscopy.

BACKGROUND: Intercellular lipids contain a lamellar structure that glows in polarized images. It could be expected that the intercellular lipid content be estimated from the luminance values calculated from polarized images of stratum corneum strips. Therefore, we attempted to develop a method for simple and rapid evaluation of the intercellular lipid content through a procedure. Herein, we demonstrated a relationship between the luminance value and the amount of ceramides, one of the main components of intercellular lipids. MATERIALS AND METHODS: The stratum corneum was collected from the forearm using slides with a pure rubber-based adhesive, which did not produce unnecessary luminescence under polarizing conditions. Images were analyzed using luminance indices. The positive secondary ion peak images were obtained using the time of flight-secondary ion mass spectrometry; the polarized and brightfield images were obtained using a polarized microscope. The ceramide and protein amount was measured by high-performance liquid chromatography and bicinchoninic acid protein assay after microscope imaging. Images and quantitative values were used to construct evaluation models based on a convolutional neural network (CNN). RESULTS: There was a correlation between the highlighted areas of the polarized image to overlap with the area where ceramide-derived peak was detected. Evaluation of the CNN-based model of the polarized images predicted the amount of ceramides per unit of stratum corneum. CONCLUSION: The method proposed in the study enabled a large number of specimens to provide a simple, rapid, and efficient evaluation of the intercellular lipid content.

Incidence and management of cystic duct perforation during endoscopic transpapillary gallbladder drainage for acute cholecystitis.

BACKGROUND AND AIM: Evidence regarding the incidence and clinical outcome of cystic duct perforation (CDP) during endoscopic transpapillary gallbladder drainage (ETGBD) is inadequate. The present study aimed to evaluate the incidence and management of CDP during ETGBD. METHODS: Between March 2011 and December 2019, 249 patients underwent initial ETGBD for acute cholecystitis. The incidence of CDP was retrospectively examined and the outcomes between the CDP and non-CDP groups were compared. RESULTS: CDP during ETGBD occurred in 23 (9.2%) of 249 patients (caused by guidewire in 15 and cannula in 8). ETGBD was successful in 10 patients following CDP. In 13 patients who failed ETGBD, 11 underwent bile duct drainage during the same session; nine patients underwent gallbladder decompression by other methods, such as percutaneous drainage. Clinical resolution for acute cholecystitis was achieved in 20 patients, and no bile peritonitis was noted. ETGBD technical success rates (45.3% vs. 91.2%, p < 0.001), ETGBD procedure times (66.5 vs. 54.8 min, p = 0.041), and hospitalization periods (24.5 vs. 18.7 days, p = 0.028) were significantly inferior in the CDP group (n = 23) compared with the non-CDP group (n = 216). There were no differences in clinical success and adverse events other than CDP between both groups. CONCLUSIONS: Cystic duct perforation reduced the ETGBD technical success rate. However, even in patients with cystic duct perforation, an improvement of acute cholecystitis was achieved by subsequent successful ETGBD or additional procedures, such as percutaneous drainage.

Treatment outcomes of stereotactic body radiation therapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinomas.

AIM: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/ß ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.

Mouth opening is mediated by separation of dorsal and ventral daughter cells of the lip precursor cells in the larvacean, Oikopleura dioica.

Mouth formation involves the processes of mouth opening, formation of the oral cavity, and the development of associated sensory organs. In deuterostomes, the surface ectoderm and the anterior part of the archenteron are reconfigured and reconnected to make a mouth opening. This study of the larval development of the larvacean, Oikopleura dioica, investigates the cellular organization of the oral region, the developmental processes of the mouth, and the formation of associated sensory cells. O. dioica is a simple chordate whose larvae are transparent and have a small number of constituent cells. It completes organ morphogenesis in 7 h, between hatching 3 h after fertilization and the juvenile stage at 10 h, when it attains adult form and starts to feed. It has two types of mechanosensory cell embedded in the oral epithelium, which is a single layer of cells. There are twenty coronal sensory cells in the circumoral nerve ring and two dorsal sensory organ cells. Two bilateral lip precursor cells (LPCs), facing the anterior surface, divide dorsoventrally and make a wedge-shaped cleft between the two daughter cells named the dorsal lip cell (DLC) and the ventral lip cell (VLC). Eventually, the DLC and VLC become detached and separated into dorsal and ventral lips, triggering mouth opening. This is an intriguing example of cell division itself contributing to morphogenesis. The boundary between the ectoderm and endoderm is present between the lip cells and coronal sensory cells. All oral sensory cells, including dorsal sensory organ cells, were of endodermal origin and were not derived from the ectodermal placode. These observations on mouth formation provide a cellular basis for further studies at a molecular level, in this simple chordate.

Pancreatic duct guidewire placement for biliary cannulation as a risk factor for stone residue after endoscopic transpapillary stone removal.

BACKGROUND: Recent improvements in stone extraction implements and apparatus have lessened the complexity of the endoscopic bile duct stone treatment. However, despite confirmation of complete removal, cases of residual stones have been reported, which can result in recurrent biliary symptoms, cholangitis, and pancreatitis and considerably increase cost given the need for repeat imaging and/or procedures. To date, risk factors for residual bile duct stones following endoscopic retrograde cholangiopancreatography (ERCP) extraction have not been thoroughly evaluated. This study retrospectively investigated the incidence and risk factors of residual bile duct stones following extraction via ERCP. METHODS: We retrospectively reviewed all ERCP cases that underwent endoscopic bile duct stone extraction between April 2014 and March 2019. A total of 505 patients were enrolled and evaluated for the incidence and risk factors of residual bile duct stones after ERCP. RESULTS: The rate of residual stones was 4.8% (24/505). Residual stones were detected by computed tomography (12/24) or magnetic resonance cholangiopancreatography (12/24). In univariate analyses, a large number of stones (P = 0.01), long procedure time (P = 0.005), and performance of the pancreatic duct guidewire placement method (P-GW) for selective bile duct cannulation (P = 0.01) were the factors involved in residual stones. In multiple logistic regression analysis, performing P-GW was retained as the only independent factor of residual stones (adjusted odds ratio, 3.44; 95% CI, 1.19-9.88; P = 0.02). CONCLUSIONS: When removing bile duct stones with a pancreatic guidewire in place, paying attention to residual stones is necessary.

Percutaneous insertion of hepatic fiducial true-spherical markers for real-time adaptive radiotherapy.

Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating.Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed.Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver (n = 4) or intrahepatic vessels (n = 5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered.Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.

An allelic series at the KARRIKIN INSENSITIVE 2 locus of Arabidopsis thaliana decouples ligand hydrolysis and receptor degradation from downstream signalling.

Karrikins are butenolide compounds present in post-fire environments that can stimulate seed germination in many species, including Arabidopsis thaliana. Plants also produce endogenous butenolide compounds that serve as hormones, namely strigolactones (SLs). The receptor for karrikins (KARRIKIN INSENSITIVE 2; KAI2) and the receptor for SLs (DWARF14; D14) are homologous proteins that share many similarities. The mode of action of D14 as a dual enzyme receptor protein is well established, but the nature of KAI2-dependent signalling and its function as a receptor are not fully understood. To expand our knowledge of how KAI2 operates, we screened ethyl methanesulphonate (EMS)-mutagenized populations of A. thaliana for mutants with kai2-like phenotypes and isolated 13 new kai2 alleles. Among these alleles, kai2-10 encoded a D184N protein variant that was stable in planta. Differential scanning fluorimetry assays indicated that the KAI2 D184N protein could interact normally with bioactive ligands. We developed a KAI2-active version of the fluorescent strigolactone analogue Yoshimulactone Green to show that KAI2 D184N exhibits normal rates of ligand hydrolysis. KAI2 D184N degraded in response to treatment with exogenous ligands, suggesting that receptor degradation is a consequence of ligand binding and hydrolysis, but is insufficient for signalling activity. Remarkably, KAI2 D184N degradation was hypersensitive to karrikins, but showed a normal response to strigolactone analogues, implying that these butenolides may interact differently with KAI2. These results demonstrate that the enzymatic and signalling functions of KAI2 can be decoupled, and provide important insights into the mechanistic events that underpin butenolide signalling in plants.

Dengue Virus Type 1 Infection in Traveler Returning from Tanzania to Japan, 2019.

The largest outbreak of dengue fever in Tanzania is ongoing. Dengue virus type 1 was diagnosed in a traveler who returned from Tanzania to Japan. In phylogenetic analysis, the detected strain was close to the Singapore 2015 strain, providing a valuable clue for investigating the dengue outbreak in Tanzania.

Diagnostic Ability of Endoscopic Bile Cytology Using a Newly Designed Biliary Scraper for Biliary Strictures.

BACKGROUND: A new device with metallic wires for scrape cytology was developed. AIMS: To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures. METHODS: A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively. RESULTS: The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group. CONCLUSION: Scrape bile cytology for biliary strictures may be superior to conventional cytology.

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

A case of Ménétrier's disease seemingly caused by hilar cholangiocarcinoma.

A 54-year-old man presented to our department with abdominal discomfort and anorexia and was diagnosed as having Ménétrier's disease (MD) with hilar cholangiocarcinoma. Based on his clinical examination, there was no evidence of Helicobacter pylori or cytomegalovirus (CMV) infection. Although we administered proton pump inhibitor and high-calorie enteral nutrition, hypoproteinemia did not improve, and the refractory protein-losing enteropathy persisted. However, interestingly, MD improved immediately after resection of the hilar cholangiocarcinoma. Generally, the etiology of MD is unknown, but H. pylori and CMV infections have been implicated. To our knowledge, there has been no previous report indicating that a malignant tumor could be involved in the etiology of MD. Thus, we report an extremely rare case of MD which is seemingly caused by malignancy.