Lysyl Oxidase Regulates Epithelial Differentiation and Barrier Integrity in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is up-regulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown. METHODS: We investigated roles for LOX in the human esophageal epithelium using 3-dimensional organoid and air-liquid interface cultures stimulated with interleukin (IL)13 to recapitulate the EoE inflammatory milieu, followed by single-cell RNA sequencing, quantitative reverse-transcription polymerase chain reaction, Western blot, histology, and functional analyses of barrier integrity. RESULTS: Single-cell RNA sequencing analysis on patient-derived organoids revealed that LOX was induced by IL13 in differentiated cells. LOX-overexpressing organoids showed suppressed basal and up-regulated differentiation markers. In addition, LOX overexpression enhanced junctional protein genes and transepithelial electrical resistance. LOX overexpression restored the impaired differentiation and barrier function, including in the setting of IL13 stimulation. Transcriptome analyses on LOX-overexpressing organoids identified an enriched bone morphogenetic protein (BMP) signaling pathway compared with wild-type organoids. In particular, LOX overexpression increased BMP2 and decreased the BMP antagonist follistatin. Finally, we found that BMP2 treatment restored the balance of basal and differentiated cells. CONCLUSIONS: Our data support a model whereby LOX exhibits noncanonical roles as a signaling molecule important for epithelial homeostasis in the setting of inflammation via activation of the BMP pathway in the esophagus. The LOX/BMP axis may be integral in esophageal epithelial differentiation and a promising target for future therapies.

Lysyl oxidase regulates epithelial differentiation and barrier integrity in eosinophilic esophagitis.

Background & Aims: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is upregulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown. Methods: We investigated roles for LOX in the human esophageal epithelium using 3-dimensional organoid and air-liquid interface cultures stimulated with interleukin (IL)-13 to recapitulate the EoE inflammatory milieu, followed by single-cell RNA sequencing, quantitative reverse transcription-polymerase chain reaction, western blot, histology, and functional analyses of barrier integrity. Results: Single-cell RNA sequencing analysis on patient-derived organoids revealed that LOX was induced by IL-13 in differentiated cells. LOX-overexpressing organoids demonstrated suppressed basal and upregulated differentiation markers. Additionally, LOX overexpression enhanced junctional protein genes and transepithelial electrical resistance. LOX overexpression restored the impaired differentiation and barrier function, including in the setting of IL-13 stimulation. Transcriptome analyses on LOX-overexpressing organoids identified enriched bone morphogenetic protein (BMP) signaling pathway compared to wild type organoids. Particularly, LOX overexpression increased BMP2 and decreased BMP antagonist follistatin. Finally, we found that BMP2 treatment restored the balance of basal and differentiated cells. Conclusions: Our data support a model whereby LOX exhibits non-canonical roles as a signaling molecule important for epithelial homeostasis in the setting of inflammation via activation of BMP pathway in esophagus. The LOX/BMP axis may be integral in esophageal epithelial differentiation and a promising target for future therapies.

[A Case of cStage â £ Remnant Gastric Cancer after Proximal Gastrectomy with Double Tract Reconstruction Treated with Conversion Surgery].

Our patient was a man in his 70s who underwent proximal gastrectomy with double tract reconstruction in 2013. He was diagnosed with cStage Ⅳ unresectable remnant gastric cancer with paraaortic lymph node metastases in 2021. He was treated with 5 courses of S-1 plus oxaliplatin therapy. Computed tomography revealed that the lymph node metastases had decreased in size after treatment. We performed conversion surgery and achieved R0 resection. Furthermore, the elevated jejunum was preserved and total gastrectomy was possible without re-anastomosis. Postoperative adjuvant chemotherapy with S-1 was started and he remains alive without recurrence at 6 months postoperative.

[A Case of Recurrent Rectal Cancer with Acute Lower Extremity Arterial Occlusion during Treatment with Bevacizumab].

The patient was 40s male, who underwent laparoscopic low anterior resection for his upper rectal cancer with final pathology results of tub2, pT3(SS), no lymph metastasis and fStage Ⅱ. He was followed up without adjuvant chemotherapy. Half a year after surgery, tumor marker was elevated and CT scan revealed multiple liver metastases. He was treated with oxaliplatin, irinotecan, Leucovorin and 5-fluorouracil(FOLFOXIRI)plus bevacizumab because of RAS mutant type. In the third courses, he has pain in the lower extremities and was diagnosed with acute lower extremity arterial occlusion. Subsequently, chemotherapy was resumed with the exception of bevacizumab, in combination with DOAC, which resulted in tumor shrinkage and allowed resection of the liver metastases.

[A Case of Acute Circulatory Failure Due to Carbon Dioxide Embolization during Laparoscopic Hepatectomy].

A 78-year-old man who was diagnosed as having hepatocellular carcinoma(segment 4/8)underwent laparoscopic hepatectomy. About 5 hours after the start of the operation, SpO2 and systolic blood pressure suddenly dropped to 87% and 40 mmHg. EtCO2 level decreased to 8 mmHg and PaCO2 was 48.5 mmHg. Based on the discrepancy between the PaCO2 and EtCO2, the patient was diagnosed as having pneumoperitoneum-induced carbon dioxide embolism. The surgical procedure was immediately interrupted and the patient was hyperventilated with pure oxygen. After surgical interruption, general status was recovered to the normal condition. We carefully restarted the operation and completed it laparoscopically. The patient was discharged from the hospital on the 15th day without any postoperative complications. Carbon dioxide embolization is a serious life-threatening complication that requires careful monitoring.

[A Case of Long-Term Survival with Metachronous Hepatic and Pulmonary Metastases from Transverse Colon Cancer by Multidisciplinary Treatment].

A 64-year-old woman underwent right hemicolectomy for transverse colon cancer. Histopathological findings revealed T, type 2, 24×22 mm, tub2, pT2N1a(1/23)M0, and pStage Ⅲa. Postoperative adjuvant chemotherapy was not administered at the patient's request. One year after surgery, carcinoembryonic antigen(CEA)level was elevated, and Gd-EOB-DTPA- enhanced MRI revealed a nodule in segment 2 and 4/8 of the liver. Based on the diagnosis of hepatic metastasis, laparoscopic partial hepatectomy was performed. Three years after hepatectomy, CEA level was found to be elevated again, and chest CT showed a solitary pulmonary nodule in segment 7 of the right lung. With a diagnosis as pulmonary metastasis, FOLFIRI plus bevacizumab was performed. After 41 courses of FOLFIRI plus bevacizumab, the pulmonary nodule decreased in size, and no new lesions appeared. The chemotherapy was terminated at the patient's request. Six months later, the pulmonary nodule increased in size, and thoracoscopic partial pulmonary resection was performed. Hepatic and pulmonary resection specimens were histopathologically consistent as metastasis of colorectal cancer. The patient has been alive without recurrence for about 4 years after final surgery(pulmonary resection)without postoperative adjuvant chemotherapy. We report a case of long-term survival with metachronous hepatic and pulmonary metastases from transverse colon cancer by multidisciplinary treatment.

[A Case of the Rectal Cancer with Metastatic Skin Cancer after Inguinal Hernia Surgery].

A woman in her 90s underwent laparoscopic hernia repair for a recurrent left inguinal hernia with abdominal wall defect 2 years ago. She came to our department with a complaint of a mass in the hernia wound, which was suspected to be a skin cancer, and the pathology diagnosis was adenocarcinoma. A colonoscopy was performed and she was diagnosed with sigmoid rectal cancer with only skin metastasis and the operation was performed. Laparoscopic anterior resection of the rectum, excision of the skin tumor, mesh removal, and rectus abdominis skin grafting were performed, and these were radical surgery. Simultaneous cutaneous metastasis of rectal cancer is extremely rare, being part of the 2.0% of other sites, and is reported with some literature review.

[A Case of the Metastatic Colonic Carcinoma from an Endometrial Carcinoma].

A woman in her 80s, had undergone radical surgery for an endometrial carcinoma 9 years earlier, and her 5-year postoperative follow-up had been completed without recurrence. She consulted an orthopedic surgeon with a chief complaint of a mass in the left inguinal region, and was referred to surgery after MRI scan revealed lymph node metastases in the left inguinal and external iliac region and a sigmoid colon tumor. Due to postoperative adhesion of the uterine cancer, the colonoscope could not be inserted to the tumor, and no tissue diagnosis was made. CT and PET scans revealed a sigmoid colon tumor plus periungual lymph node metastasis, and it was determined that radical surgery was possible, and the patient underwent resection. Surgery was performed by laparoscopic resection of the sigmoid colon and lymphadenectomy, with R0 resection. The sigmoid colon tumor and lymph nodes were of the same histology as the 9-year-old endometrial carcinoma, leading to the diagnosis of colon and lymph node recurrence 9 years after endometrial carcinoma surgery.

CD73+ Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin ß4). Here, we investigated CD73+CD104+ cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. METHODS: We performed flow cytometry on esophageal biopsy samples from EoE and non-EoE patients to determine the quantity of CD73+CD104+ cells in the epithelium. Simulating the EoE milieu we stimulated primary patient-derived and immortalized cell line-derived esophageal organoids with interleukin (IL)4 and IL13 and analyzed by flow cytometry, immunohistochemistry, and quantitative reverse-transcription polymerase chain reaction. We performed single-cell RNA sequencing on primary organoids in the setting of IL13 stimulation and evaluated the CD73+CD104+ population. We performed fluorescent-activated cell sorting to purify CD73+CD104+ and CD73- CD104+ populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. RESULTS: EoE patients showed decreased epithelial CD73+CD104+ cell content. IL4 and IL13 stimulation depleted this population in 3-dimensional organoids with a recapitulation of basal cell hyperplasia as corroborated by single-cell RNA sequencing of the organoids, which suggests depletion of CD73+CD104+ cells. The CD73+CD104+ population had enhanced organoid formation compared with the CD73-CD104+ population. Similarly, knock-down of CD73 resulted in decreased organoid formation rate. Genetic and pharmacologic inhibition of STAT6 prevented T helper 2 cytokine-induced depletion of CD73+CD104+ cells. Lastly, omeprazole treatment prevented the effects of IL4 and IL13 on the CD73+CD104+ population. CONCLUSIONS: This study addressed the role of CD73+CD104+ cells in epithelial renewal and homeostasis in the context of EoE. The depletion of the CD73+CD104+ self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.

[Two Cases of Trousseau Syndrome during Chemotherapy].

Case 1 is a 56-year-old man. During postoperative adjuvant chemotherapy for pancreatic cancer, weakness in the right upper and lower limbs appeared, and a head CT scan was performed, but no abnormal findings were noted. Diffusion- weighted MRI scan of the head showed multiple cerebral infarcts, and a diagnosis of Trousseau syndrome was made. Case 2 is an 86-year-old man. During chemotherapy for postoperative recurrence of distal bile duct carcinoma, he developed weakness in the right upper and lower limbs, and a head MRI scan was performed. Diffusion-weighted MRI showed scattered high-signal areas, and a diagnosis of Trousseau syndrome was made. Trousseau syndrome is a condition in which stroke is caused by hypercoagulability associated with malignant tumor. The initial symptoms of cerebral infarction in patients with cancer are similar to those of chemotherapy-induced adverse events and brain metastases, and therefore, a head MRI scan is recommended even if there is no obvious abnormality on head CT scan.

[A Case of Wernicke Encephalopathy with Ileus by Small Intestinal Cancer].

The patient was a 74 year-old woman. She came to the hospital with the chief complaint of vomiting, difficulty walking, and disorientation. The MRI study showed increased FLAIR and DWI signals in the bilateral medial thalamus. Abdominal enhanced CT scan showed a 2.4 cm tumor in the jejunum. And ileus due to small intestinal tumor was observed. She diagnosed Wernicke's encephalopathy associated with gastrointestinal transit disorder. Vitamin B1 300 mg/day for 3 days was started, and eye movements and disorientation improved on the day following the start of administration. On the 10th day after admission, partial resection of the small intestine was performed for a small intestinal tumor. She was diagnosed as small intestinal cancer. She was transferred to the hospital on the 20th postoperative day.

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

ABSTRACT: Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach. ACE2 gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.

Peritumoral Lymphatic Vessels Associated with Resistance to Neoadjuvant Chemotherapy and Unfavorable Survival in Esophageal Cancer.

BACKGROUND: Peri- or intra-tumor lymphangiogenesis is induced in several types of cancer. However, the significance of peritumoral lymphatic vessels (LVs) in esophageal cancer (EC) remains to be clarified. METHODS: This study included 162 eligible EC patients with or without neoadjuvant chemotherapy (NAC). The numbers of non-tumoral and peritumoral LVs were counted in resected specimens based on podoplanin immunostaining. The association between peritumoral LV number and clinicopathologic parameters, including tumor heterogeneity as measured by positron emission tomography, NAC response, and patient survival were analyzed. RESULTS: In non-NAC patients, the number of peritumoral LVs was highest in the lamina propria mucosa (LPM), followed by non-tumoral LVs in the LPM, peritumoral LVs in the submucosa (SM), and non-tumoral LVs in the SM. The patients with a low number of peritumoral LVs in the LPM versus those with a high number constituted a larger fraction of the NAC patients (67.8% vs. 50.0%; P = 0.022) and had a poorer pathologic response to NAC (grades 0-1a: 68.8% vs. 47.2%; P = 0.035), as well as greater tumor heterogeneity and worse survival (5-year overall survival: 50.6% vs. 72.8%; P = 0.0097). The number of peritumoral LVs in the LPM was identified as an independent prognostic factor with the highest hazard ratio (HR) of overall survival (HR 2.06; P = 0.0049) in the multivariate analysis. CONCLUSION: For EC patients, peritumoral LVs in the LPM layer are associated with tumor heterogeneity, response to NAC, and unfavorable survival.

Modeling Epithelial Homeostasis and Reactive Epithelial Changes in Human and Murine Three-Dimensional Esophageal Organoids.

The homeostatic proliferation-differentiation gradient in the esophageal epithelium is perturbed under inflammatory disease conditions such as gastroesophageal reflux disease and eosinophilic esophagitis. Herein we describe the protocols for rapid generation (<14 days) and characterization of single-cell-derived, three-dimensional (3D) esophageal organoids from human subjects and mice with normal esophageal mucosa or inflammatory disease conditions. While 3D organoids recapitulate normal epithelial renewal, proliferation, and differentiation, non-cell autonomous reactive epithelial changes under inflammatory conditions are evaluated in the absence of the inflammatory milieu. Reactive epithelial changes are reconstituted upon exposure to exogenous recombinant cytokines. These changes are modulated pharmacologically or genetically ex vivo. Molecular, structural, and functional changes are characterized by morphology, flow cytometry, biochemistry, and gene expression analyses. Esophageal 3D organoids can be translated for the development of personalized medicine in assessment of individual cytokine sensitivity and molecularly targeted therapeutics in esophagitis patients © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Generation of esophageal organoids from biopsy or murine esophageal epithelial sheets Basic Protocol 2: Propagation and cryopreservation of esophageal organoids Basic Protocol 3: Harvesting of esophageal organoids for RNA isolation, immunohistochemistry, and evaluation of 3D architecture Basic Protocol 4: Modeling of reactive epithelium in esophageal organoids.

Effect of c-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: c-Met relies on CD44v6 for its activation and signaling in several cancer cell lines. However, the correlation of c-Met and CD44v6 expression and its biological significance in esophageal squamous cell carcinoma (ESCC) remains unknown. METHODS: Expression of c-Met and CD44v6 was examined by immunohistochemistry (IHC) in 147 ESCC specimens. We analyzed the impact of c-Met and CD44v6 expression on clinicopathological parameters, including chemoresistance or prognosis in ESCC. RESULTS: High expression of c-Met and CD44v6 in cancerous lesions was identified in 49.7% and 50.3% of all patients, respectively. The c-Met-high group comprised more advanced pT and pM stages than the c-Met-low group. In addition, more patients in the c-Met-high group received neoadjuvant chemotherapy (NACT) than the c-Met-low group (64.4% vs. 43.2%, P = 0.010). On the other hand, the CD44v6-high group was associated with more advanced pT/pN stages and a poorer clinical response to NACT (response rate 53.5% vs. 77.8%, P = 0.025) than the CD44v6-low group. Double-positive immunostaining of c-Met and CD44v6 was identified in 28.6% of all cases, and multivariate analysis of overall survival (OS) identified them (hazard ratio 1.79, 95% confidence interval 1.03-3.04, P = 0.038) as independent prognostic factors in addition to pN and pM stage. CONCLUSIONS: c-Met/CD44v6 were associated with tumor progression or chemoresistance. Double-positive expression of c-Met and CD44v6 negatively impacted patient prognosis in ESCC, implying that c-Met and CD44v6 are candidates for targeted therapy in ESCC.

Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells.

Background & Aims: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. Results: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.

Metastatic mixed acinar-endocrine carcinoma of the pancreas treated with a multidisciplinary approach: a case report.

BACKGROUND: Pancreatic neoplasms are usually characterized by ductal, acinar, or endocrine differentiation. Mixed exocrine and endocrine pancreatic tumours are extremely rare. Here, we report a case of pancreatic mixed acinar-endocrine carcinoma (MAEC) with multiple synchronous liver metastases that were treated with surgery and transcatheter arterial chemoembolization (TACE) that later recurred in the stomach. CASE PRESENTATION: A 45-year-old female with severe anaemia was referred to our hospital. Computed tomography (CT) demonstrated a hypervascular tumour, 17 cm in diameter, that was in the tail of the pancreas. In addition, there were multiple hypervascular tumours in the liver. She underwent a distal pancreatectomy with splenectomy after the liver metastases were treated with TACE. Pathology confirmed that the pancreatic tumour was MAEC. After 4.5 years, a follow-up CT showed a hypervascular tumour at the upper part of the stomach. Gastric endoscopy showed a big tumefactive lesion with surface irregularities, gastric erosion, and multiple dilated vessels in the fornix and greater curvature of the stomach. She underwent a proximal gastrectomy and survived 7 years and 2 months after the start of the treatment. CONCLUSIONS: This is the first report of a metastatic stomach tumour from pancreatic MAEC, which was successfully treated with a multidisciplinary approach. Additionally, we review the literature and discuss the treatment of MAEC.

[S-1 plus Cisplatin Combination Therapy for Gastric Cancer with Peritoneal Dissemination].

Peritoneal dissemination (PD) is the most common type of metastasis in advanced gastric cancer. The standard treatment of gastric cancer patients with PD is combination therapy with S-1 and cisplatin (SP therapy). Here, we describe the results of SP therapy for gastric cancer with PD. Sixteen gastric cancer patients with PD were treated with SP therapy as first-line chemotherapy. Second-look staging laparoscopy was performed for 10 patients who showed a good response to SP therapy. Gastrectomy was performed for 5 patients with P0CY0 and 1 case with P0CY1. The median survival time of all 16 patients was 571 days (19 months). The patients, who had surgery, had a significantly better survival time than the others (25 months vs 12.7 months). In conclusion, SP therapy is effective for gastric cancer with PD, and surgery for cases showing a good response to chemotherapy might improve the prognosis of patients with PD.

[Comparison of early clinical outcomes between laparoscopic total gastrectomy and open total gastrectomy for early-stage gastric cancer].

BACKGROUND/AIMS: Recently, laparoscopic distal gastrectomy has become one of the standard therapies for early gastric cancer. However, there are still some obstacles in performing laparoscopic total gastrectomy (LTG) as a standard therapy due to the difficulties in surgical techniques. We have performed LTG for patients with early gastric cancer in the upper portion of the stomach since 2010. In this study, we compared early clinical outcomes of LTG with those of open total gastrectomy (OTG) for patients with cT1N0 gastric cancer. METHODOLOGY: We reviewed 69 patients who had gastric cancer of cStage IA between January 2010 and December 2013. We performed a comparative study of short-term clinical outcomes, quantity of dissected lymph nodes, and in-hospital costs between patients undergoing LTG (n=34) and those undergoing OTG (n=35). RESULTS: The clinical characteristics of patients were well matched in the LTG and OTG groups. The median operating time was significantly longer for the LTG group (p<.0001). The estimated blood loss was significantly reduced in the LTG group (p< 0.0001). The postoperative morbidity rate was 14.7% in the LTG group and 14.2% in the OTG group with no significant difference. There were no differences in the total cost for hospital stay between the LTG and OTG groups. CONCLUSIONS: We were able to perform LTG safely and successfully for early gastric cancer in our institute. The total cost of the treatment was almost the same between LTG and OTG. We conclude that LTG is a potential alternative in the management of early gastric cancer.