Search

Despite the widespread use of laparoscopic surgery, intracorporeal anastomosis remains a complicated procedure that often prolongs the operation time. This study aimed to investigate the efficacy of a novel staple line reinforcement (SLR) during laparoscopic gastrectomy for gastric cancer.The study included 30 patients who underwent laparoscopic gastrectomy for gastric cancer at the Kochi Medical School between November 2021 and May 2022. A review of these patients was conducted, and perioperative outcomes were compared according to the use of SLR.The reconstruction time using SLR was significantly shorter compared to when SLR was not used (20.5 min vs. 32.0 min, p=0.048). The incidence of hemostasis during anastomosis was significantly lower in the SLR group than in the non-SLR group (0 vs. 3 times, p=0.041). There were no significant differences in the operating time and estimated blood loss after surgery between the two groups. Furthermore, there were no significant differences in postoperative complications or nutritional status between the two groups.The usefulness of SLR in reducing the time for intracorporeal reconstruction and archiving the best interaction between device and tissue during laparoscopic gastrectomy for gastric cancer, was herein demonstrated.

Supplementary Data

Table S2

Figure S1

This study aimed to analyze the clinicopathological features and treatment outcomes of ovarian metastasis from gastric cancer.This study included 155 female patients with unresectable advanced or recurrent gastric cancer at the Kochi Medical School between January 2007 and December 2021. A review of patients with ovarian metastasis was conducted, and their clinicopathological information and survival outcomes were compared with respect to ovarian metastasis.Fifteen patients were diagnosed with ovarian metastasis from gastric cancer with a median age of 54 years (range: 30-87 years) and an incidence of 9.7%. The median age of patients who developed ovarian metastasis was significantly lower those without ovarian metastasis (54 years vs. 71 years, P = 0.014). The median survival time (MST) for 15 patients with unresectable advanced gastric cancer who developed ovarian metastasis was 21.4 months (range: 0.2-41.4 months). The MST for 15 patients who underwent surgical resection and systemic drug treatment including chemotherapy to ovarian metastasis was significantly higher than those who received systemic drug treatment alone (28.1 months vs. 10.0 months; P = 0.021).Ovarian metastasis was found in 9.7% of female patients with unresectable advanced or recurrent gastric cancer and in younger patients than in those without ovarian metastasis. Multidisciplinary treatment, including surgical resection and systemic drug treatment for ovarian metastasis from gastric cancer, may benefit selected patients.

This study evaluated the prognostic value of C-reactive protein–to–albumin (CAR) and neutrophil-to-lymphocyte ratios (NLR) in conjunction with host-related factors in patients with unresectable advanced or recurrent gastric cancer. A total of 411 patients with unresectable advanced gastric cancer were treated at Kochi Medical School between 2007 and 2019. Associations between clinicopathological parameters and systemic inflammatory and nutritional markers, including CAR and NLR, with overall survival were analyzed retrospectively. The optimal cut-off values of predicted median survival time were 0.096 (sensitivity, 74.9%; specificity, 42.5%) for CAR and 3.47 (sensitivity, 64.1%; specificity, 57.5%) for NLR, based on the results of receiver operating characteristic analysis. A weak significant positive correlation was identified between CAR and NLR (r = 0.388, P

Highlights • The authors developed a humanized anti-glypican-1 (GPC1) monoclonal antibody (clone T2) and produced an antibody-drug conjugate (ADC) linked to monomethyl auristatin E (MMAE). The ADC potently inhibited the growth of GPC1-positive pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma in vitro and in vivo, and exhibited bystander killing activity. Humanized GPC1-ADC(MMAE) was effective against BxPC-3-Luc#2 pancreatic cancer liver metastases in mice. Humanized GPC1-ADC(MMAE) may provide a promising therapeutic strategy for GPC1-positive tumors., An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Humanized anti-GPC1 antibody (clone T2) was developed and conjugated with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linkers (humanized GPC1-ADC[MMAE]). Humanized GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC and ESCC cell lines via inducing cycle arrest in the G2/M phase and apoptosis in vitro. The binding activity of humanized GPC1-ADC(MMAE) with GPC1 was comparable with that of the unconjugated anti-GPC1 antibody. The humanized GPC1-ADC(MMAE) was effective in GPC1-positive BxPC-3 subcutaneously xenografted mice but not in GPC1-negative BxPC-3-GPC1-KO xenografted mice. To assess the bystander killing activity of the humanized GPC1-ADC(MMAE), a mixture of GPC1-positive BxPC-3 and GPC1-negative BxPC-3-GPC1-KO-Luc cells were subcutaneously inoculated, and a heterogenous GPC1-expressing tumor model was developed. The humanized GPC1-ADC(MMAE) inhibited the tumor growth and decreased the luciferase signal, measured with an in vivo imaging system (IVIS), which suggests that the suppression of the BxPC-3-GPC1-KO-Luc population. The humanized GPC1-ADC(MMAE) also inhibited the established liver metastases of BxPC-3 cells and significantly improved the overall survival of the mice. It exhibited a potent antitumor effect on the GPC1-positive PDAC and ESCC patient-derived xenograft (PDX) models. Our preclinical data demonstrate that GPC1 is a promising therapeutic target for ADC.

Purpose Despite the widespread use of laparoscopic surgery, intracorporeal anastomosis remains a complicated procedure. This study aimed to investigate the efficacy of novel staple line reinforcement (SLR) during laparoscopic gastrectomy for gastric cancer. Methods This study included 30 patients who underwent laparoscopic gastrectomy for gastric cancer at Kochi Medical School between November 2021 and May 2022. A review of these patients was conducted, and perioperative outcomes were compared according to the use of SLR. Results The reconstruction time using SLR was significantly shorter than that for when SLR was not used (20.5 min vs. 32.0 min, P = 0.048). The incidence of hemostasis during anastomosis was significantly lower in the SLR group than in the non-SLR group (0 vs. 3 times, P = 0.041). There were no significant differences in the operating time and estimated blood loss after surgery between the two groups. Furthermore, there were no significant differences in postoperative complications or nutritional status between the two groups. Conclusions The results demonstrated the usefulness of SLR, which could reduce the time for intracorporeal reconstruction during laparoscopic gastrectomy for gastric cancer.

Zinc is an essential dietary component for humans and the second most prevalent trace element; however, serum zinc levels after gastrectomy have not been fully elucidated. This study aimed to evaluate the correlation between clinicopathologic features and serum zinc levels in patients who underwent gastrectomy for gastric cancer. The study enrolled 617 patients who underwent gastrectomy for gastric cancer at the Kochi Medical School. Clinical data were obtained to investigate associations between clinicopathological features, including nutritional indicators and serum zinc levels. Serum zinc deficiency was defined as serum zinc level

Cholangiocarcinoma is a highly malignant cancer. Many patients need systemic chemotherapy to prevent tumor development and recurrence; however, their prognosis is poor due to the lack of effective therapy. Therefore, a new treatment option is urgently required. We recently identified glypican-1 (GPC1) as a novel cancer antigen of esophageal squamous cell carcinoma. We also demonstrated the efficacy and safety of GPC1-targeted ADC (GPC1–ADC) conjugating anti-GPC1 mAb possessing high internalization activity with monomethyl auristatin F (MMAF), which is a potent tubulin polymerizing inhibitor. In this study, we confirmed that GPC1 was highly expressed in cholangiocarcinoma cells and tissues. IHC analysis of 49 extrahepatic cholangiocarcinoma patient tumor specimens revealed high expression of GPC1 in 47% of patients. These patients demonstrated significantly poorer prognosis compared with the low-expression group in terms of disease-free survival and overall survival (P < 0.05). GPC1 was also expressed in tumor vessels of cholangiocarcinoma, but not on the vessels of nontumor tissues. MMAF-conjugated GPC1–ADC showed potent tumor growth inhibition against GPC1-positive cholangiocarcinoma cells in vitro and in vivo. In a GPC1 knockout xenograft model, GPC1–ADC partially inhibited tumor growth. Vascular endothelial cells in tumor tissues of GPC1-negative xenograft mice expressed GPC1 and were arrested in the G2–M phase of cell cycle by GPC1–ADC. GPC1–ADC exhibits direct as well as indirect antitumor effects via inhibition of tumor angiogenesis. Our preclinical data highlight GPC1–ADC as a promising therapy for GPC1-positive cholangiocarcinoma.

The purpose of this study was to compare the results of the hybrid mediastino-thoracoscopic approach with that of the conventional thoracoscopic approach and to identify the advantages and disadvantages of the hybrid approach.We retrospectively analyzed 172 patients who underwent thoracoscopic esophagectomy for esophageal cancer from July 2009 to June 2021, excluding salvage surgery. In the mediastinoscopic approach, the lymph nodes were dissected from a small incision in the left aspect of the neck to the aortic arch with supine double-lung ventilation. Thereafter, the middle-to-lower mediastinum and right superior mediastinum were dissected thoracoscopically in the prone position. The patients' demographics, surgical outcomes, postoperative complications, and postoperative recurrence patterns were compared between 51 patients in the hybrid approach and 121 patients in the conventional approach.The hybrid group had more elderly patients (71 years vs. 67 years; P = 0.010), more cardiovascular disease (33.3% vs. 16.7%; P = 0.021), lower rates of preoperative chemotherapy (49.0% vs. 69.4%; P = 0.015), and shorter right lung collapse time (196 min vs. 264 min; P 0.001). Postoperative hoarseness was not different between the two groups (31.4% vs. 27.3%; P = 0.584), and there was a significant difference in the sternal-vertebral distance at the level of the sternal notch (41 mm in the hybrid group vs. 48 mm in the conventional group; P = 0.029). The sternal-vertebral distance of less than 45 mm was an independent risk factor for postoperative hoarseness in the logistic analysis (odds ratio 3.636, 95% confidence interval 1.054-12.546; P = 0.041).The hybrid mediastino-thoracoscopic approach could be safely adapted to elderly or cardiopulmonary diseased patients; however, short sternal-vertebral distance might be a risk factor of postoperative recurrent laryngeal nerve palsy.

This study aimed to analyze the clinicopathologic features and treatment outcomes of central nervous system (CNS) metastasis from gastric cancer.A total of 419 patients diagnosed with unresectable advanced or recurrent gastric cancer at Kochi Medical School between January 2007 and December 2021 were evaluated. Data of patients were reviewed, and clinicopathological information and survival outcomes of those with CNS metastases were compared to patients without CNS metastases.In total, 12/419 (2.9%) patients (median age: 66.5 years [range, 41-82 years]) were diagnosed with CNS metastasis from gastric cancer. Eleven had diffuse-type gastric cancer which was significantly more common than in those without CNS metastasis (91% vs. 61%, p = .034). Human epidermal growth factor receptor 2 status was positive in one of the 12 patients. The median survival time was significantly lower for patients with CNS metastasis than for those without CNS metastasis (1.8 months vs. 11.4 months, p.001). The median survival time for patients who underwent surgical resection, radiation, or chemotherapy for CNS metastasis was significantly higher than those who received only best supportive care (3.5 months vs. .6 months; p = .007).CNS metastasis was found in 2.9% (12/419) of patients with unresectable advanced or recurrent gastric cancer. Diffuse-type histology was a risk factor for CNS metastasis. Multidisciplinary treatment, including surgical resection, radiation treatment, or chemotherapy, for CNS metastasis from gastric cancer may benefit selected patients.

Introduction: Although it was reported that serum zinc levels were lower in patients with various malignancies, serum zinc levels of patients with gastric cancer was not well documented. Objectives: This study aimed to evaluate the association between clinicopathologic features and serum zinc levels in preoperative patients with gastric cancer. Methods: The study enrolled 83 patients scheduled for gastric cancer surgery at the Kochi Medical School. Clinical data were obtained to investigate associations between clinicopathological features, including nutritional indicators and serum zinc levels. Serum zinc deficiency was defined as serum zinc level < 80 μg/dL. Results: The median zinc level of the 83 patients was 73 μg/dL (range, 20–152 μg/dL), and serum zinc deficiency was present in 66.3% of patients. Albumin was significantly lower in the zinc low level group than in the normal group (3.9 g/dL vs. 4.4 g/dL, P < 0.001), and the median serum zinc level was significantly lower in the albumin < 4.1 g/dL group than in the albumin ≥ 4.1 g/dL group (69 μg/dL vs. 82 μg/dL, P < 0.001). Lymphocyte count was significantly lower in the zinc low level group than in the normal group (1500 vs. 1810 years, P = 0.041). The median serum zinc level was significantly lower in the age ≥ 74 group than in the age < 74 (71 μg/dL vs. 76 μg/dL, P = 0.002). Serum zinc levels showed a significant positive correlation with serum albumin (r = 0.637, P = 0.009). Discussion/Conclusion: Serum zinc deficiency was found in 66.3% of preoperative patients with gastric cancer, which was highly correlated with serum albumin.

Grade 3, well-differentiated, gastric neuroendocrine tumors (NET G3) are extremely rare. Herein, we report the case of a 64-year-old man with a grade 3 neuroendocrine tumor of the stomach who experienced intra-abdominal bleeding during the course of drug treatment. The patient was referred to our hospital for examination of a gastric tumor that was initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy revealed an elevated lesion with a central ulcer in the upper body of the stomach, and biopsy specimens confirmed the pathological diagnosis of NET G3. Abdominal contrast-enhanced computed tomography (CT) showed a 25-cm, well-defined mass lesion showing heterogeneous enhancement in the liver. A clinical diagnosis of NET G3 with multiple liver metastases was given, after which everolimus was administered in combination with a somatostatin analogue. However, the patient developed sudden-onset epigastric abdominal pain and general fatigue 2 months later, and emergency abdominal contrast-enhanced CT confirmed the presence of intra-abdominal hemorrhage. Following blood transfusion, the patient's symptoms and general condition improved. Although the patient was treated with streptozocin, abdominal CT indicated progression of the liver metastases. Unfortunately, despite receiving best supportive care, the patient died 8 months after the initial of the treatment. To the best of our knowledge, this is the first case of a patient who developed spontaneous hemoperitoneum during drug treatment for a NET G3 to be reported in the English literature. It is essential that additional data be obtained to determine the optimal treatment for this disease.

Background: This study aimed to investigate the efficacy of enteral supplementation of vitamin B12 for vitamin B12 deficiency in patients who underwent total gastrectomy for gastric cancer. Methods: The study enrolled 133 patients who underwent total gastrectomy for gastric cancer at Kochi Medical School. Clinical data were obtained to investigate associations between vitamin B12 supplementation and vitamin B12 levels. Vitamin B12 deficiency was defined as serum vitamin B12 less than 200 pg/mL. Baseline characteristics and changes in hematological variables, including vitamin B12 levels, were examined. Results: Vitamin B12 deficiency was present in 71.4% of the 133 patients. Vitamin B12 levels at 3, 6, and 12 months after enteral supplementation were 306 pg/mL, 294 pg/mL, and 367 pg/mL, respectively, which were all significantly higher than those before supplementation (p < 0.001 for all comparisons). The median red blood cell count at 3, 6, and 12 months after enteral supplementation were 380 × 104/mm3, 394 × 104/mm3, and 395 × 104/mm3, respectively, which were all significantly higher than those before supplementation (p = 0.020, p = 0.001, and p = 0.003, respectively). Vitamin B12 levels at 3, 6, and 12 months after supplementation were significantly higher in patients supplemented enterally than those supplemented parenterally (p < 0.001 for all comparisons). Conclusions: Vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.

To investigate the usefulness of clinicopathological systemic inflammatory response and nutritional biomarkers for predicting the efficacy of nivolumab in patients with advanced gastric cancer. The subjects of this study were 29 patients who received nivolumab treatment for advanced gastric cancer at the Kochi Medical School between 2017 and 2019. Clinicopathological information, including systemic inflammatory response data, were obtained to investigate the associations between baseline cancer-related prognostic variables and survival outcomes. Immune-related adverse events (irAEs) of any grade were identified in 34.5% (10/29) of the patients. The median progression-free survival of patients with irAEs was significantly greater than that of patients without irAEs (5.8 months vs. 1.2 months, respectively; P = 0.028). The neutrophil to lymphocyte ratio (NLR) after 4 weeks of treatment in the complete response (CR) or partial response (PR) group was significantly lower than that in the stable disease (SD) or progression disease (PD) group (2.2 vs. 2.9, respectively; P = 0.044). The prognostic nutrition index (PNI) before treatment in the CR or PR group was significantly higher than that in the SD or PD group (37.1 vs. 32.1, respectively; P = 0.011). The PNI 8 weeks after treatment and the Glasgow prognostic score (GPS) before treatment were significantly associated with a poor outcome. The irAE, NLR, PNI, and GPS may be useful predictive markers for nivolumab efficacy in patients with advanced gastric cancer.

Aortoesophageal fistula (AEF) is a highly life-threatening condition, even when treated promptly. However, little is known about the treatment for AEF in patients with advanced esophageal cancer. We report the case of a 69-year-old man diagnosed with esophageal squamous cell carcinoma (ESCC) that was admitted to our hospital for ESCC treatment. On diagnosis of unresectable ESCC invading the thoracic aorta, chemotherapy was administered. The response to treatment after two courses was evaluated as stable disease. We performed radiation therapy followed by bypass operation for esophageal stenosis. After radiation therapy, AEF was detected. His condition improved after hemostasis using thoracic endovascular aortic repair (TEVAR). He was discharged from our care after treatment with antibiotics; he died due to cancer progression 7 months after TEVAR. AEF with ESCC is a lethal condition that may occur during cancer treatment; however, TEVAR might help improve the patient's condition.

To evaluate the correlation between blood supply speed in the gastric tube (GT), assessed by the intraoperative indocyanine green (ICG) fluorescence method, and postoperative endoscopic assessment (PEA) of the anastomosis or anastomotic leakage (AL). The subjects of this retrospective analysis were 66 consecutive patients who underwent GT reconstruction using ICG fluorescence during esophageal surgery. We measured the ICG visualization time, from ICG injection to visualization at the top of the GT. We performed PEA on 54 patients and classified ulcer formation as involving less than or more than half of the circumference. PEA revealed that nine patients (16.7%) had an anastomotic ulcer involving more than half of the circumference and ten (15.4%) had AL. The ICG visualization time in these patients was significantly delayed compared with that in those with less than half of the circumference involved by ulcer formation (37 s vs. 27 s; P = 0.015) and without AL (36 s vs. 28 s; P = 0.045). Multivariate analysis revealed that delay in the ICG visualization time (> 36 s) of the pulled-up GT (odds ratio, 6.098; 95% confidence interval, 1.125–33.024; P = 0.036) was an independent risk factor associated with AL. Delay in the ICG visualization time of pulled-up GT was associated with ulcer formation on the anastomosis and AL after esophageal surgery.

Background and Aim Disorders in bone metabolism have long been recognized as typical sequelae of gastrectomy; however, the pathogenesis has not been fully elucidated, resulting in a variation of reported incidence. This study aimed to evaluate current bone health by measuring bone mineral density (BMD) in patients treated by gastrectomy for gastric cancer, with a focus on incidence and risk factors of osteoporosis. Methods The study enrolled 81 patients who underwent gastrectomy for gastric cancer at Kochi Medical School. BMD of the lumbar spine was measured by dual‐energy X‐ray mineral absorptiometry, with the results expressed as a percentage of the young adult mean (YAM). Clinical data were also obtained to investigate associations with BMD. Results Of the 81 study patients, 12 (14.8%) were deemed to have osteoporosis, defined by a percentage of YAM, We found osteoporosis in 14.8% of outpatients receiving periodic follow‐up physical examinations after gastrectomy for gastric cancer, and identified low BMD as a clear indicator of increased bone fragility and risk for fracture in these patients. In these patients, female gender, low body weight, low hemoglobin, and low ALP were potential risk factors for osteoporosis.

Aim: To determine whether markers of systemic inflammatory response and nutrition are a predictor of treatment response in patients with trastuzumab-treated unresectable advanced gastric cancer. Patients and Methods: Twenty-one patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2013 to 2020 were enrolled. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. Results: The median overall survival (OS) and progression-free survival (PFS) for the whole cohort were 24.5 (range=1.9-88.4) months and 7.0 (range=2.0-23.4) months, respectively. The objective response rate and disease control rate were 52.4% and 81.0%, respectively. The median PFS for patients with a neutrophil to lymphocyte ratio (NLR)

Mesenteric lymph node metastasis of gastric cancer is extremely rare. We report the case of a patient with advanced gastric cancer having lymph node metastasis in the transverse mesocolon who underwent gastrectomy with lymph node dissection followed by chemotherapy. A 74-year-old male complaining of tarry stool was referred to our hospital for further examination following a diagnosis of gastric cancer by a local medical doctor. Esophagogastroduodenoscopy revealed an irregular and ulcerated lesion in the lower third of the stomach, and analyses of biopsy specimens revealed adenocarcinoma. Abdominal computed tomography revealed abdominal wall thickening in the lower third of the stomach, with enlarged lymph nodes in the perigastric area and the left side area of the middle colic artery. With a clinical diagnosis of gastric cancer, the patient underwent distal gastrectomy with lymph node dissection followed by Billroth Ⅰ reconstruction. During surgery, the enlarged lymph node along with the middle colic artery in the transverse mesocolon was dissected. The gross appearance of the resected specimen shows a large and ulcerated tumor measuring 6.0×5.5 cm in the lesser curvature side of the lower third of the stomach. The pathological examination of the resected specimen showed solid-type poorly-differentiated adenocarcinoma with lymph nodes metastases, which was detected in the perigastric area and transverse mesocolon. The final diagnosis according to the Japanese classification of gastric carcinoma by the Japanese Gastric Cancer Association was L, Less-Post-Ant, Type 2, 6.0×5.5 cm, T3(SS), N2(5/19), M1(LYM), P0, H0, CY0, por1, Ly0, V1a, Stage Ⅳ, R0. Subsequently, the patient received S-1 plus oxaliplatin chemotherapy; however, he developed para-aortic lymph node metastases 18 months after surgery. Therefore, the patient was treated with ramucirumab plus nab-paclitaxel and was alive 20 months after the operation. Although mesocolonic lymph node metastasis of gastric cancer is rare, future identification of risk factors and the development of novel treatments should be achieved through further investigations and the accumulation of 3 cases.

Background: Anisakiasis-related gastric eosinophilic granuloma is rare. Case Report: Herein, we report a patient with anisakiasis-related gastric eosinophilic granuloma who was treated with laparoscopic and endoscopic cooperative surgery (LECS). A 59-year-old woman was presented to our hospital for further examination of a gastric lesion that was initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy showed a submucosal tumor-like lesion in the lower body of the stomach. Endoscopic ultrasonography showed a heterogeneous hypoechoic submucosal mass lesion in the submucosal layer measuring 10 mm, without evidence of deep involvement. Under a clinical diagnosis of gastrointestinal stromal tumor, the patient underwent LECS. Gross appearance of the resected specimen revealed a 1.5×1.0 cm submucosal tumor-like lesion. Microscopic examination revealed necrosed insects consistent with the characteristics of gastric anisakiasis, around which prominent eosinophilic infiltration and granulomas were observed. This prompted a diagnosis of gastric eosinophilic granuloma related to anisakiasis. Conclusion: To the best of our knowledge, this is the second case of gastric eosinophilic granuloma related to anisakiasis resected by LECS in the English medical literature. LECS might be a useful procedure for minimally invasive therapeutic diagnosis.

The blood supply of the right gastroepiploic artery after esophagectomy with gastric tube reconstruction is essential for avoiding anastomotic leakage. Near-infrared fluorescence (NIRF) imaging with indocyanine green is widely used to assess the blood supply because it can visualize it in real-time during navigation surgery. However, there is no established protocol for this modality. One reason for this lack of protocol is that NIRF provides subjective information. This study aimed to evaluate NIRF quantification. We conducted a literature review of risk factors for anastomotic leakage after esophagectomy, NIRF procedures, NIRF quantification, and new methods to compensate for NIRF limitations. Major methods for the quantification of NIRF include measuring the blood flow speed, visualization time, and fluorescence intensity. The cutoff value for the blood flow speed is 2.07 cm/s, and that for the visualization time is 30-90 s. Although the time-intensity curve provided patterns of change in the blood flow, it did not show an association with anastomotic leakage. However, to compensate for the limitations of NIRF, new devices have been reported that can assess tissue oxygenation perfusion, organ hemoglobin concentration, and microcirculation.

This study evaluated the prognostic value of C-reactive protein-to-albumin (CAR) and neutrophil-to-lymphocyte ratios (NLR) in conjunction with host-related factors in patients with unresectable advanced or recurrent gastric cancer.A total of 411 patients with unresectable advanced gastric cancer were treated at Kochi Medical School between 2007 and 2019. Associations between clinicopathological parameters and systemic inflammatory and nutritional markers, including CAR and NLR, with overall survival were analyzed retrospectively.The optimal cut-off values of predicted median survival time were 0.096 (sensitivity, 74.9%; specificity, 42.5%) for CAR and 3.47 (sensitivity, 64.1%; specificity, 57.5%) for NLR, based on the results of receiver operating characteristic analysis. A weak significant positive correlation was identified between CAR and NLR (r = 0.388, P 0.001). The median survival time was significantly higher in patients with intestinal-type than those with diffuse-type histology (18.3 months vs. 9.5 months; P = 0.001), CAR 0.096 than those with CAR ≥ 0.096 (14.8 months vs. 9.9 months; P 0.029), and those with NLR 3.47 than NLR ≥ 3.47 (14.7 months vs. 8.8 months; P 0.001). Multivariate survival analysis revealed that diffuse-type histology (hazard ratio (HR) 1.865; 95% confidence interval (CI) 1.397-2.490; P 0.001)), 1 or more performance status (HR 11.510; 95% CI 7.941-16.683; P 0.001), and NLR ≥ 3.47 (HR 1.341; 95% CI 1.174-1.769; P = 0.023) were significantly associated with independent predictors of worse prognosis.High CAR and NLR are associated with poor survival in patients with unresectable and recurrent gastric cancer.

Aim To present the case of a patient with unresectable gastric cancer showing a remarkable effect by second-line drug treatment with ramucirumab plus paclitaxel and conversion surgery. Case report A 68-year-old woman who was diagnosed with gastric cancer was referred to us. Esophagogastroduodenoscopy showed an ulcerated lesion with an irregular nodulated border in the lower third of the stomach, and histology of biopsied specimens indicated a poorly differentiated adenocarcinoma. Enhanced computed tomography revealed extensive invasion of the liver, and the patients was treated using S-1 plus oxaliplatin as first-line chemotherapy. Because she developed liver metastases, the treatment regimen was changed to ramucirumab plus paclitaxel as the second-line treatment. After four cycles of weekly paclitaxel with ramucirumab treatment, the liver metastases had completely disappeared. Because no other metastatic lesions in other organs were detected, we performed total gastrectomy with D2 lymphadenectomy. The macroscopic findings of the surgically resected specimen revealed an ulcerated lesion with an irregularly modulated lesion measuring 9.5×4.5 cm. Pathological analysis demonstrated a poorly differentiated adenocarcinoma in the stomach, with invasion to the liver through the serosal layer, and seven lymph node metastases. The postoperative course was unremarkable, and she received ramucirumab in combination with paclitaxel treatment. However, liver metastasis appeared at 4 months after the operation, for which she was treated with irinotecan. Although the patient continued to receive irinotecan chemotherapy for 10 months, her general condition gradually deteriorated, and she was started on best supportive care 13 months after conversion surgery. Conclusion Conversion surgery may prolong survival not only through first-line but also second-line treatments in selected patients with unresectable advanced gastric cancer; however, assessments of additional cases and further studies are required to establish this treatment strategy.

We report a rare case of cystic lymphangioma of the greater omentum, which was treated by laparoscopic resection. A 61-year-old man was referred to our hospital for the treatment of a perigastric cystic lesion. Esophagogastroduodenoscopy revealed neither a mucosal lesion nor a submucosal tumor in the stomach. Abdominal contrast-enhanced computed tomography imaging showed a cystic lesion in the ventral side of the lower part of the stomach and no mass lesions in the liver. The patient underwent laparoscopic resection of the cystic lesion. The intraoperative observation confirmed that a well-defined cystic lesion was present wrapped in the greater omentum and located predominantly in the right side. Although the cystic lesion was located directly beside the right gastroepiploic artery and vein, excision of the cystic lesion along with the cuff of the omentum was performed without sacrificing the vessels. Macroscopic examination of the resected specimen showed an ovoid, cystic mass measuring 7.5 × 4.3 cm within the omentum. The pathological diagnosis was “cystic lymphangioma without malignant signs.” Following surgery, the patient remained symptom-free without evidence of recurrence for 6 months. The laparoscopic approach, being minimally invasive, can be considered the most feasible approach for the resection of an abdominal cystic lymphangioma.

This study aimed to investigate the efficacy of enteral supplementation of vitamin B12 for vitamin B12 deficiency in patients who underwent total gastrectomy for gastric cancer.The study enrolled 133 patients who underwent total gastrectomy for gastric cancer at Kochi Medical School. Clinical data were obtained to investigate associations between vitamin B12 supplementation and vitamin B12 levels. Vitamin B12 deficiency was defined as serum vitamin B12 less than 200 pg/mL. Baseline characteristics and changes in hematological variables, including vitamin B12 levels, were examined.Vitamin B12 deficiency was present in 71.4% of the 133 patients. Vitamin B12 levels at 3, 6, and 12 months after enteral supplementation were 306 pg/mL, 294 pg/mL, and 367 pg/mL, respectively, which were all significantly higher than those before supplementation (p0.001 for all comparisons). The median red blood cell count at 3, 6, and 12 months after enteral supplementation were 380 × 104/mm3, 394 × 104/mm3, and 395 × 104/mm3, respectively, which were all significantly higher than those before supplementation (p = 0.020, p = 0.001, and p = 0.003, respectively). Vitamin B12 levels at 3, 6, and 12 months after supplementation were significantly higher in patients supplemented enterally than those supplemented parenterally (p0.001 for all comparisons).Vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.

Duodenal mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare tumor. Herein, we report multidisciplinary treatment of a patient with synchronous development of primary MALT lymphoma of the duodenum and gastric cancer. A 70-year-old woman was referred to our hospital for examination of a gastric cancer initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy showed an elevated lesion with a central ulcer in the lower body of the stomach, and a partially whitish aggregated lesion in the descending portion of the duodenum. Histopathological examination of biopsy specimens from the gastric lesion showed moderately differentiated adenocarcinoma, and duodenal specimens showed low-grade MALT lymphoma composed of atypical lymphoid cells with a lymphoepithelial lesion. The patient underwent distal gastrectomy with regional lymph node dissection for the gastric cancer. Histological examination showed muscularis propria invading adenocarcinoma with two lymph node metastases. After operation, four courses of systemic rituximab treatment were administered for the MALT lymphoma, followed by adjuvant S-1 (tegafur/gimeracil/oteracil) chemotherapy for the gastric cancer. In the 4 months after operation, the patient was well with no evidence of recurrence. To the best of our knowledge, this is the second reported case of synchronous gastric adenocarcinoma and duodenal MALT lymphoma in the English literature.

A 72-year-old woman was referred to our hospital for further examination of para-aortic lymph node swelling and elevated carbohydrate antigen 19-9 levels. Thirteen years ago, she had undergone distal gastrectomy for gastric cancer, and the final diagnosis was T4N1M0, Stage ⅢA. Abdominal contrast-enhanced computed tomography(CT)showed an enlarged para-aortic lymph node measuring 25 mm. Endoscopic ultrasound-guided fine-needle aspiration was performed, and biopsy specimens showed poorly differentiated adenocarcinoma. Under the clinical diagnosis of gastric cancer recurrence, the patient received chemotherapy with cisplatin plus S-1. After 5 cycles of systemic treatment, abdominal CT revealed a marked shrinkage of the para-aortic lymph node metastasis, with an 84% decrease. At 15 months after treatment, we switched to S-1 monotherapy because of general fatigue and the patient's preference. However, 22 months after the treatment, the patient was treated with ramucirumab due to the progression of para-aortic lymph node metastasis. After 33 months, the patient developed metastasis in the left ovary, measuring 11.0×8.5 cm. Because there was no evidence of further metastatic lesions in any other organs, she underwent left oophorectomy. After 37 months, the patient developed metastasis in the left cerebellum, measuring 3.2×2.5 cm, accompanied with headache and nausea. The patient underwent metastasectomy of the left cerebellum as palliative treatment. Simultaneous physical examination revealed a painful nodular elevated lesion in the subcutaneous tissue of the posterior neck region, measuring 18×15 cm. Pathological examination of the biopsy specimen showed infiltration of poorly differentiated adenocarcinoma cells into the subcutaneous mass. The patient received radiation therapy; however, she died due to septic shock with hydronephrosis 39 months after starting chemotherapy. Although late recurrence of gastric cancer is rare, identification of risk factors and the development of novel treatments should be achieved through further studies and accumulation of data from such cases.

Background: The present study sought to evaluate host-related factors as predictors in patients receiving chemotherapy for recurrent advanced gastric cancer. Methods: Sixty-three patients were enrolled in the study and received chemotherapy for recurrent gastric cancer at the Kochi Medical School from 2008 to 2015. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. Results: The median survival time was significantly higher for patients with a Glasgow prognostic score (GPS) of 0 compared to a GPS of 1 or 2 (18.2 vs. 7.1 months; p = 0.006), and for patients in the normal range for carbohydrate antigen-125 (CA125) compared to higher levels (17.9 vs. 4.1 months; p = 0.003). There was no significant influence on overall survival by age, gender, disease status, metastatic site, time to recurrence, carcinoembryonic antigen level, CA19–9 level, prognostic nutrition index, or neutrophil to lymphocyte ratio according to the results of the univariate log-rank tests. Multivariate survival analysis identified a GPS of 1 or 2 (hazard ratio, 3.520; 95% confidence interval, 1.343–9.227; p = 0.010) and a high CA125 level (hazard ratio, 3.135; 95% confidence interval, 1.276–7.697; p = 0.013) as significant independent predictors associated with a poorer prognosis in the studied group of cancer patients. Conclusions: A GPS of 1 or 2 and a high level of CA125 are independent predictors of a poorer prognosis in patients receiving chemotherapy for recurrent gastric cancer.

We report a case of esophageal cancer with a non-recurrent inferior laryngeal nerve associated with aberrant right subclavian artery that was treated by neck dissection using intraoperative neurological monitoring followed by thoracoscopic esophagectomy. A 76-year-old man had dysphagia. Endoscopy revealed thoracic esophageal cancer, and computed tomography revealed the presence of an aberrant right subclavian artery between the esophagus and vertebrae. We performed neck dissection followed by thoracoscopic esophagectomy. During the neck dissection, we confirmed a non-recurrent inferior laryngeal nerve through intraoperative neurological monitoring. No postoperative complications were observed, and the patient was discharged 19 days after surgery. We recommend using intraoperative neurological monitoring to avoid injury to the non-recurrent inferior laryngeal nerve associated with the aberrant right subclavian artery.

Cholangiocarcinoma (CCA) is one of highly malignant cancers. Systemic chemotherapy is used in many patients, however, there are few chemotherapy options, and their prognosis are poor. Therefore, it is necessary to develop new treatments. We have identified glypican-1 (GPC1) as a novel cancer antigen and reported that enhanced expression of GPC1 in esophageal squamous cell carcinoma and pancreatic cancer is significantly associated with poorer prognosis (Hara, Naka, et al. Br J Cancer. 2016, Nishigaki, Naka, et al. Br J Cancer. 2020). GPC1 is a heparan sulfate proteoglycan that is linked to the cell surface by a glycosylphosphatidylinositol anchor and promotes tumor growth, metastasis, and invasion by acting as a coreceptor, enhancing various signaling pathways. We recently identified that the expression of GPC1 was increased in cholangiocarcinoma. The present study aimed to develop a new therapy for cholangiocarcinoma using an antibody-drug conjugate (ADC) targeting glypican-1 (GPC1). Expression of GPC1 was evaluated in resected cholangiocarcinoma specimens and cell lines. GPC1 knockout cell was established from GPC1-positive cholangiocarcinoma cell line. The antitumor effect of monomethyl auristatin F conjugated GPC1-ADC was investigated in vitro and in vivo. GPC1 was highly expressed in cholangiocarcinoma cells and tissues. Immunohistochemical analysis of 49 extrahepatic cholangiocarcinoma patients revealed that 23 patients (47%) were high expression of GPC1, 24 patients (49%) were low expression of GPC1 and 2 patients (4%) were GPC1 negative. High-expression group demonstrated significantly poorer prognosis compared with the low-expression group in terms of disease-free survival and overall survival (p < 0.05). GPC1 was also expressed in tumor vessels of cholangiocarcinoma, but not on the vessels of nontumor tissues. Monomethyl auristatin F-conjugated GPC1-ADC significantly inhibited tumor growth against GPC1-positive cholangiocarcinoma cells in vitro and in vivo. In a GPC1 knockout xenograft model, GPC1-ADC partially inhibited tumor growth. Vascular endothelial cells in tumor tissues of GPC1-negative xenograft mice expressed GPC1 and were arrested in the G2/M phase of cell cycle by GPC1-ADC. In the present study, GPC1-ADC inhibits tumor growth and tumor angiogenesis for glypican-1 positive cholangiocarcinoma. Our preclinical data demonstrated GPC1-ADC as a promising strategy for GPC1-positive cholangiocarcinoma. Citation Format: Keiichiro Yokota, Satoshi Serada, Shigehiro Tsujii, Ichiro Murakami, Kazuhiro Hanazaki, Tetsuji Naka. Antibody-drug conjugate targeting glypican-1 inhibits tumor growth and tumor angiogenesis for glypican-1 positive cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1315.

To establish the safety of laparoscopic-assisted colorectal resection for colorectal cancer in elderly patients aged ≥80 years. Data were obtained from a chart review of patients who underwent colorectal cancer resection between 2009 and 2014 in Kochi Medical School. The effect of patient age on the extent of lymph node dissection and operative safety was assessed by comparing the short-term results of elderly patients with those of younger patients after propensity score matching. Of a total of 506 patients with colorectal cancer, 398 underwent laparoscopic surgery and 23% of these patients were aged ≥80 years old. The elderly patients tended to have poorer general condition and larger tumors, although no significant differences were found in tumor invasion, lymph node metastasis, or synchronous distant metastasis between the groups. After adjustment for preoperative factors, we noted that the elderly patients tended to undergo less aggressive surgical resection (P = 0.01). Further analysis after including surgical factors for propensity score matching revealed a similar rate of complications in the two groups (24 vs. 25%, respectively; P = 0.85), and similar postoperative death rates and length of postoperative hospital stay. The findings of the present study demonstrate that laparoscopic surgery for colorectal cancer should not be avoided based on simply the age of the patient.

A case of early gastric cancer involving multiple submucosal gastric glands that was treated by distal gastrectomy was described in the present case report. An 85-year-old man was referred to our hospital for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed an irregular, nodular, elevated lesion on the posterior wall of the middle third of the stomach, and biopsy specimens indicated well-differentiated tubular adenocarcinoma. Submucosal tumor (SMT)-like lesions were detected in the area adjacent to the nodular lesion, in the anterior wall side of the middle third of the stomach. Abdominal contrast-enhanced computed tomography showed cystic lesions in the middle part of the stomach, and no mass lesions in the liver. The patient underwent distal gastrectomy with regional lymphadenectomy. Macroscopic examination of the resected specimen showed an SMT-like lesion measuring 2.8×2.6 cm in contact with a superficial, depressed lesion measuring 1.7×0.9 mm in the middle third of the stomach, and another SMT-like lesion measuring 1.5×1.4 cm in diameter, which was also in the middle third of the stomach. The pathological diagnosis was well-differentiated tubular adenocarcinoma invading the gastric submucosal layer without lymph node metastasis, but with nearby submucosal heterotopic gastric gland (SHGG) detected. Following surgery, the patient remained symptom-free without evidence of recurrence for 3 months. The finding of SHGG remains a rare entity, and further studies are warranted to clarify the association between these submucosal lesions and the development of cancer.

Background/aim The aim of this study was to assess the effects of scheduled intravenous acetaminophen for postoperative management of patients who underwent thoracoscopic esophagectomy for esophageal cancer. Patients and methods The records of 56 consecutive patients who underwent thoracoscopic esophagectomy in the prone position for esophageal cancer were reviewed. For postoperative pain control, twenty-eight patients underwent the scheduled intravenous acetaminophen (SIVA group), whereas the other 28 were managed with intravenous flurbiprofen (Control group). The perioperative outcomes of the two groups were compared. Results The incidence of pneumonia and the total numerical rating scale of postoperative pain level were significantly lower in the SIVA group than in the Control group (3.6% vs. 25.0%; p=0.022, 40 vs. 93; p=0.027). Patients' fever on the third day after surgery in the SIVA group was significantly lower than in the Control group (36.9°C vs. 37.2°C; p=0.029). However, the incidence of anastomotic leakage, laryngeal nerve palsy, the changes of postoperative C-reactive protein level, and the duration of hospital stay were not different between the two groups. Conclusion Scheduled intravenous acetaminophen after thoracoscopic esophagectomy in patients with esophageal cancer was a useful strategy in reducing the incidence of postoperative pneumonia.

Cholangiocarcinoma is one of the most highly malignant cancers. Many patients need systemic chemotherapy for tumor development and recurrence, but their prognosis is poor. Therefore new treatment options are urgently required. We confirmed that the expression of glypican-1 (GPC1) was enhanced in cholangiocarcinoma. GPC1 is a cell surface membrane protein and has been reported as a poor prognostic factor in pancreatic cancer. In this study, we aimed to develop a new therapy for cholangiocarcinoma by the antibody-drug conjugate (ADC) targeting GPC1. By immunohistochemical analysis, enhanced expression of GPC1 was observed in clinical specimens of cholangiocarcinoma. KKU-055 and KKU-100 cells, which are cell lines of cholangiocarcinoma, had high expression of GPC1. In the KKU-055 xenograft model when we administered fluorescently-labeled GPC1 antibody to mice, it accumulated in tumor tissue. We developed a new anti-GPC1 monoclonal antibody (mAb) with highly internalizing activity. The anti-GPC1 mAb was conjugated with the cytotoxic agent monomethyl auristatin F (MMAF). GPC1-ADC showed potent antitumor effect toward KKU-055 and KKU-100 cells compared with the control ADC. In the KKU-055 xenograft model, GPC1-ADC had significant and potent tumor growth inhibition in a dose-dependent manner. In summary, our newly-developed GPC1-ADC showed significant tumor growth inhibition against GPC1-positive cholangiocarcinoma cell lines. Our preclinical data demonstrated that targeting GPC1 by ADC is a promising therapy for GPC1-positive cholangiocarcinoma. Citation Format: Keiichiro Yokota, Satoshi Serada, Shigehiro Tsujii, Kosuke Hiramatsu, Tsutomu Namikawa, Ichiro Murakami, Kazuhiro Hanazaki, Tetsuji Naka. Antibody-drug conjugate targeting glypican-1 shows tumor growth inhibition in cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4833.