Publications by authors named "Keiichiro Yokota"

21 Publications

  • Page 1 of 1

Successful Conversion Surgery for Advanced Gastric Cancer With Multiple Liver Metastases Following Ramucirumab Plus Paclitaxel Combination Treatment.

In Vivo 2021 Sep-Oct;35(5):2929-2935

Department of Surgery, Kochi Medical School, Kochi, Japan.

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.
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http://dx.doi.org/10.21873/invivo.12584DOI Listing
August 2021

A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma.

Neoplasia 2021 Sep 28;23(9):939-950. Epub 2021 Jul 28.

Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan; Institute for Biomedical Sciences Molecular Pathophysiology, Iwate Medical University, Yahaba, Iwate, Japan; Division of Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Iwate, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neo.2021.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340053PMC
September 2021

Anti-Glypican-1 Antibody-drug Conjugate as Potential Therapy Against Tumor Cells and Tumor Vasculature for Glypican-1-Positive Cholangiocarcinoma.

Mol Cancer Ther 2021 Sep 17;20(9):1713-1722. Epub 2021 Jun 17.

Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Japan.

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 ( < 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 and 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 G-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.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0015DOI Listing
September 2021

Serum zinc deficiency in patients after gastrectomy for gastric cancer.

Int J Clin Oncol 2021 Jun 30. Epub 2021 Jun 30.

Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.

Purpose: 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.

Methods: 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 < 80 μg/dL.

Results: The median zinc level of the 617 patients was 73 μg/dL (range, 31-144 μg/dL), and serum zinc deficiency was present in 68.6% of patients. Median age was significantly higher in the zinc low level group than in the normal group (69 vs. 66 years, P < 0.001). Albumin was significantly lower in the zinc low level group than in the normal group (3.9 vs. 4.2 g/dL, P < 0.001). C-reactive protein level was significantly higher in the zinc low level group than in the normal group (0.12 vs. 0.10 mg/dL, P = 0.014). The median serum zinc level was significantly lower in the patients who received chemotherapy after gastrectomy than in those who were not received chemotherapy (72 vs. 76 μg/dL, P < 0.001). Serum zinc levels showed a significant positive correlation with serum albumin (r = 0.505, P = 0.044). Multivariate analysis showed that serum albumin level was significantly associated with serum zinc level (β = 0.489, P < 0.001).

Conclusions: Serum zinc deficiency was found in 68.6% of postoperative patients who underwent gastrectomy for gastric cancer, which was highly correlated with serum albumin.
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http://dx.doi.org/10.1007/s10147-021-01978-wDOI Listing
June 2021

Spontaneous intra-abdominal hemorrhage of a well-differentiated, grade 3 gastric neuroendocrine tumor during drug-based treatment.

Clin J Gastroenterol 2021 Aug 11;14(4):1244-1249. Epub 2021 May 11.

Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.

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.
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http://dx.doi.org/10.1007/s12328-021-01433-3DOI Listing
August 2021

Cystic lymphangioma of the greater omentum treated by laparoscopic resection.

Clin J Gastroenterol 2021 Aug 29;14(4):1004-1007. Epub 2021 Mar 29.

Department of Surgery, Kochi Medical School, Oko-cho, Nankoku, Kochi, 783-8505, Japan.

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.
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http://dx.doi.org/10.1007/s12328-021-01404-8DOI Listing
August 2021

Enteral Vitamin B12 Supplementation Is Effective for Improving Anemia in Patients Who Underwent Total Gastrectomy.

Oncology 2021 18;99(4):225-233. Epub 2021 Feb 18.

Department of Surgery, Kochi Medical School, Nankoku, Japan.

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.
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http://dx.doi.org/10.1159/000513888DOI Listing
April 2021

Incidence and risk factors of osteoporotic status in outpatients who underwent gastrectomy for gastric cancer.

JGH Open 2020 Oct 23;4(5):903-908. Epub 2020 Apr 23.

Department of Surgery Kochi Medical School Nankoku Japan.

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 <70, with a dominance of females over males (66.7% 17.4%;  < 0.001). The median body weight, hemoglobin concentration, and serum alkaline phosphatase (ALP) level of the patients with osteoporosis was significantly lower than in those with a percentage of YAM ≥70 group (39.6 kg 53.1 kg,  < 0.001; 10.9 mg/dL 12.5 mg/dL, = 0.010; 210 U/L 251 U/L, = 0.002). Further analyses revealed a significant positive correlation between body weight and percentage of YAM (r = 0.441,  < 0.001). Despite the administration of bisphosphonates in these patients during this study, one acquired a bone fracture.

Conclusion: Osteoporosis was found in 14.8% of postoperative gastric cancer patients, with female gender, low body weight, and low ALP proposed as risk factors for osteoporosis and thus future bone fracture.
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http://dx.doi.org/10.1002/jgh3.12347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578282PMC
October 2020

Synchronous duodenal mucosa-associated lymphoid tissue lymphoma and gastric cancer.

Clin J Gastroenterol 2021 Feb 21;14(1):109-114. Epub 2020 Sep 21.

Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.

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.
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http://dx.doi.org/10.1007/s12328-020-01241-1DOI Listing
February 2021

Assessment of Systemic Inflammatory Response and Nutritional Markers in Patients With Trastuzumab-treated Unresectable Advanced Gastric Cancer.

In Vivo 2020 Sep-Oct;34(5):2851-2857

Department of Surgery, Kochi Medical School, Kochi, Japan.

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) <2.8 was significantly longer than that for those with NLR ≥2.8 (8.9 vs. 6.0 months; p=0.048). Although the median OS also tended to be longer for patients with NLR <2.8, the difference was not statistically significant. No significant differences in median OS and PFS were observed between patients with a prognostic nutrition index (PNI) <41.6 and those with PNI ≥41.6.

Conclusion: An NLR ≥2.8 is a predictor of poorer prognosis in patients receiving systemic treatment with trastuzumab and chemotherapy for unresectable advanced or recurrent gastric cancer.
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http://dx.doi.org/10.21873/invivo.12112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652530PMC
June 2021

Systemic inflammatory response and nutritional biomarkers as predictors of nivolumab efficacy for gastric cancer.

Surg Today 2020 Nov 15;50(11):1486-1495. Epub 2020 Jun 15.

Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.

Purpose: To investigate the usefulness of clinicopathological systemic inflammatory response and nutritional biomarkers for predicting the efficacy of nivolumab in patients with advanced gastric cancer.

Methods: 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.

Results: 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.

Conclusion: The irAE, NLR, PNI, and GPS may be useful predictive markers for nivolumab efficacy in patients with advanced gastric cancer.
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http://dx.doi.org/10.1007/s00595-020-02048-wDOI Listing
November 2020

Successful management of aortoesophageal fistula caused by esophageal cancer using thoracic endovascular aortic repair.

Clin J Gastroenterol 2020 Oct 24;13(5):678-682. Epub 2020 May 24.

Department of Surgery, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan.

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.
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http://dx.doi.org/10.1007/s12328-020-01132-5DOI Listing
October 2020

Correlation between indocyanine green visualization time in the gastric tube and postoperative endoscopic assessment of the anastomosis after esophageal surgery.

Surg Today 2020 Nov 22;50(11):1375-1382. Epub 2020 May 22.

Department of Surgery, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan.

Purpose: 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).

Methods: 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.

Results: 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.

Conclusion: Delay in the ICG visualization time of pulled-up GT was associated with ulcer formation on the anastomosis and AL after esophageal surgery.
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http://dx.doi.org/10.1007/s00595-020-02025-3DOI Listing
November 2020

Evaluation of Systemic Inflammatory Response and Nutritional Biomarkers as Predictive Factors in Patients with Recurrent Gastric Cancer.

Oncology 2020 17;98(7):452-459. Epub 2020 Mar 17.

Department of Surgery, Kochi Medical School, Kochi, Japan.

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.
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http://dx.doi.org/10.1159/000505973DOI Listing
July 2020

[Multidisciplinary Treatment for a Patient with Recurrent Gastric Cancer, Presenting 13 Years after the Radical Gastrectomy].

Gan To Kagaku Ryoho 2019 Dec;46(13):2087-2089

Dept. of Surgery, Kochi Medical School.

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.
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December 2019

Bowel obstruction associated with a feeding jejunostomy and its association to weight loss after thoracoscopic esophagectomy.

BMC Gastroenterol 2019 Jun 25;19(1):104. Epub 2019 Jun 25.

Department of Surgery, Kochi Medical School, Kohasu-Okocho, Nankoku, Kochi, 783-8505, Japan.

Background: Our aim was to clarify the incidence of bowel obstruction associated with a feeding jejunostomy (BOFJ) after thoracoscopic esophagectomy and its association to characteristics and postoperative change in body weight.

Methods: We reviewed 100 consecutive patients who underwent thoracoscopic esophagectomy with gastric tube reconstruction and placement of a jejunostomy feeding catheter for esophageal cancer. The incidence of BOFJ was evaluated and the change in body weight after surgery was compared between patients with and without BOFJ.

Results: BOFJ developed in 17 patients. Compared to patients without BOFJ, those with BOFJ had a higher preoperative body mass index (23.3 kg/m versus 20.9 kg/m, P = 0.022), and greater postoperative body weight loss rate: 3 month, decrease to 84.2% of initial body weight versus 89.3% (P = 0.002). Patients with BOFJ had shorter distance between the jejunostomy and midline (40 mm versus 48 mm, P = 0.011) compared to patients without BOFJ. On multivariate analysis, higher preoperative body mass index (odds ratio (OR) = 9.248; 95% confidence interval (CI) = 1.344-63.609; p = 0.024), higher postoperative weight loss at 3 months (OR = 8.490; 95% CI = 1.765-40.837, p = 0.008), and shorter distance between the jejunostomy and midline (OR = 8.160; 95% CI = 1.675-39.747, p = 0.009) were independently associated with BOFJ.

Conclusion: Patients of BOFJ had greater preoperative body mass, shorter distance between jejunostomy and midline, and greater postoperative weight loss.
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http://dx.doi.org/10.1186/s12876-019-1029-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593545PMC
June 2019

Intraoperative Neurological Monitoring During Neck Dissection for Esophageal Cancer With Aberrant Subclavian Artery.

Anticancer Res 2019 Jun;39(6):3203-3205

Department of Surgery, Kochi Medical School, Nankoku, Japan.

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.
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http://dx.doi.org/10.21873/anticanres.13459DOI Listing
June 2019

Early gastric cancer with multiple submucosal heterotopic gastric gland: A case report.

Mol Clin Oncol 2019 Jun 18;10(6):583-586. Epub 2019 Apr 18.

Department of Surgery, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.

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.
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http://dx.doi.org/10.3892/mco.2019.1846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488944PMC
June 2019

Scheduled Intravenous Acetaminophen for Postoperative Management of Patients Who Had Thoracoscopic Esophagectomy for Esophageal Cancer.

Anticancer Res 2019 Jan;39(1):467-470

Department of Surgery, Kochi Medical School, Kochi, Japan.

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.
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http://dx.doi.org/10.21873/anticanres.13135DOI Listing
January 2019

Factors influencing the number of retrieved lymph nodes after colorectal resection: a retrospective study from a single institute.

Int J Clin Exp Pathol 2018 1;11(3):1694-1700. Epub 2018 Mar 1.

Depatment of Surgery, Kochi Medical School, Kochi University Kochi, Japan.

Accurate diagnosis of lymph node (LN) metastasis is important to determine the staging and consequent treatment of resected colorectal cancer. Therefore, factors influencing the number of retrieved LNs were explored. This study included 400 patients that underwent surgical resection for Stage 0-III colorectal cancer from 2009 to 2014 in Kochi Medical School. In all cases, surgeons retrieved the LNs within the resected mesentery immediately after the operation without fixation. Age, gender, body mass index (BMI), American Association Anesthesiologist (ASA) scores, tumor locations, maximum tumor diameters, nodal status, and pathological tumor types were extracted as patient and tumor factors. The extent of LN dissection and surgical approaches (laparoscopic or laparotomy) were extracted as operative factors. Multivariate regression analysis was performed to identify independent predictive factors for LN number retrieved, after potential influential factors were explored by univariate analysis. As results, we found that the median number of retrieved LNs was 13, ranging from 1 to 50. Approximately 60% of the patients thus received an adequate examination (LN number of 12 or more). Multivariate analysis using the remaining factors of univariate analysis identified BMI, tumor diameter, nodal status, and extent of dissection as independent predictive factors for the number of retrieved LNs ( < 0.05). If any or all these factors are present, a vigorous search for LNs using additional measures, such as visual enhancement and fat dissolution method, should be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958128PMC
March 2018

Safety of laparoscopic surgery for colorectal cancer in patients over 80 years old: a propensity score matching study.

Surg Today 2017 Aug 27;47(8):951-958. Epub 2017 Jan 27.

Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.

Purposes: To establish the safety of laparoscopic-assisted colorectal resection for colorectal cancer in elderly patients aged ≥80 years.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1007/s00595-017-1470-5DOI Listing
August 2017
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