Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

We report a rare case of long-term survival in a patient who received local therapy and salvage chemotherapy for recurrent metastases, along with a literature review. A 65-year-old male patient underwent subtotal gastrectomy for advanced gastric adenocarcinoma. Six months after gastrectomy, 2 metastatic intra-abdominal lymph node enlargements were detected, which were treated with radiotherapy. At 55 months after gastrectomy, an abdominal wall mass was detected, which was treated by surgical resection. The patient received 5-fluorouracil/leucovorin/irinotecan chemotherapy for 27 months before and after radiotherapy and docetaxel chemotherapy for 6 months after surgical resection of the abdominal wall metastasis. At the last visit, 7.8 years since the initial resection of the primary gastric cancer and 6.2 years since detection of the first metastases, the patient was disease-free and required no further chemotherapy. This case suggests that repeated local therapy offers potential for long-term survival in a carefully selected subset of patients with recurrent metastases.
Abdominal Wall ; Adenocarcinoma ; Aged ; Drug Therapy* ; Gastrectomy ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis* ; Radiotherapy ; Stomach Neoplasms*

PURPOSE: Gastric emptying may influence the quality of life of patients who undergo distal gastrectomy. Little is known, however, about gastric emptying after distal gastrectomy. The aim of our study was to investigate gastric emptying patterns after distal gastrectomy. METHODS: This gastric-emptying study investigated patients who underwent distal gastrectomy in the 6 months or more before May 2008 to July 2013 at Chungbuk National University Hospital with a study sample of 205 patients. We analyzed patterns of gastric emptying. RESULTS: Delayed gastric emptying was found in 109 of the 205 patients (53.2%). Food stasis was more frequent in a group with delayed gastric emptying. In multivariate analysis, risk factors for gastroparesis were laparoscopic operation (hazard ratio [HR], 2.731; P = 0.008) and duration of less than 24 months after distal gastrectomy (HR, 2.795; P = 0.001). Delayed gastric emptying tended to decrease with duration of the postoperative period. CONCLUSION: Delayed gastric emptying is common in distal gastrectomy, and is related to laparoscopic operation and duration of the postoperative period. Food stasis was more frequent in a group with delayed gastric emptying.
Chungcheongbuk-do ; Gastrectomy* ; Gastric Emptying* ; Gastroparesis ; Humans ; Multivariate Analysis ; Postoperative Period ; Quality of Life ; Risk Factors ; Stomach Neoplasms

PURPOSE: Gastric emptying may influence the quality of life of patients who undergo distal gastrectomy. Little is known, however, about gastric emptying after distal gastrectomy. The aim of our study was to investigate gastric emptying patterns after distal gastrectomy. METHODS: This gastric-emptying study investigated patients who underwent distal gastrectomy in the 6 months or more before May 2008 to July 2013 at Chungbuk National University Hospital with a study sample of 205 patients. We analyzed patterns of gastric emptying. RESULTS: Delayed gastric emptying was found in 109 of the 205 patients (53.2%). Food stasis was more frequent in a group with delayed gastric emptying. In multivariate analysis, risk factors for gastroparesis were laparoscopic operation (hazard ratio [HR], 2.731; P = 0.008) and duration of less than 24 months after distal gastrectomy (HR, 2.795; P = 0.001). Delayed gastric emptying tended to decrease with duration of the postoperative period. CONCLUSION: Delayed gastric emptying is common in distal gastrectomy, and is related to laparoscopic operation and duration of the postoperative period. Food stasis was more frequent in a group with delayed gastric emptying.
Chungcheongbuk-do ; Gastrectomy* ; Gastric Emptying* ; Gastroparesis ; Humans ; Multivariate Analysis ; Postoperative Period ; Quality of Life ; Risk Factors ; Stomach Neoplasms

BACKGROUND/AIMS: The relationship between halitosis and gastroesophageal reflux disease (GERD) remains controversial. The aim of this study was to investigate an association between subjective and objective halitosis and GERD. METHODS: The subjects were enrolled from participants who visited a health promotion center at Seoul National University Bundang Hospital. For diagnosis of halitosis, a questionnaire was requested, and volatile sulfur compounds (VSCs) were measured by Halimeter. Self-conscious halitosis was defined as halitosis perceived by himself or herself. Informed halitosis was defined as halitosis perceived by others. Objective halitosis was defined when mean VSCs values were > 100 parts per billion. GERD was defined based on a questionnaire and endoscopy, including erosive esophagitis and non-erosive reflux disease (NERD). RESULTS: A total of 54 subjects (male:female = 33:21) with mean age of 46.0 +/- 11.4 years were analyzed. The mean VSCs values were not significantly different between presence and absence of self-conscious halitosis (P = 0.322), but significantly different between presence and absence of informed halitosis (P = 0.021). Informed halitosis was associated with objective halitosis (P = 0.039). GERD, erosive esophagitis and NERD did not correlate with objective halitosis (P = 0.556, 0.206 and 0.902, respectively). In multivariable analysis, the relationship between objective halitosis and GERD symptoms including chest pain, heart burn, acid regurgitation, epigastric pain, hoarseness, globus sensation and coughing was not significant. Besides, GERD was not associated with self-conscious halitosis, informed halitosis and objective halitosis, respectively. CONCLUSIONS: GERD might not be associated with self-conscious, informed halitosis and objective halitosis indicated by Halimeter results. Informed halitosis could be correlated with objective halitosis determined by the Halimeter.
Burns ; Chest Pain ; Cough ; Diagnosis ; Endoscopy ; Esophagitis ; Gastroesophageal Reflux* ; Halitosis* ; Health Promotion ; Heart ; Hoarseness ; Surveys and Questionnaires* ; Sensation ; Seoul ; Sulfur Compounds

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of small- and medium-sized arteries in multiorgan systems. PAN may affect the gastrointestinal tract in 14%-65% of patients, but rarely involves the biliary tract and liver. We describe a patient without underlying disease who was diagnosed with PAN during resection of the gallbladder and liver.
Arteries ; Bile Ducts, Intrahepatic* ; Biliary Tract ; Dilatation* ; Gallbladder ; Gastrointestinal Tract ; Humans ; Liver ; Polyarteritis Nodosa* ; Vasculitis

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K+ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.
Apamin ; Glyburide ; Guanylate Cyclase ; Histamine ; Humans ; Muscle, Smooth* ; Nerve Block ; NG-Nitroarginine Methyl Ester ; Nitric Oxide* ; Ranitidine ; Receptors, Histamine H2 ; Relaxation* ; Tetraethylammonium