Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

Days of the week and 90-day mortality after esophagectomy: analysis of 33,980 patients from the National Clinical Database.

PURPOSE: The effect of the days of the week on the short-term outcomes after elective surgeries has been suggested; however, such data on esophagectomies remain limited. This study aimed to investigate the association between the day of the week and mortality rates after elective esophagectomy using a large-scale clinical database in Japan. METHODS: The data of elective esophagectomies, registered in the National Clinical Database in Japan, for esophageal cancer treatment between 2012 and 2017 were analyzed. We hypothesized that the later days of the week could have higher odds ratios of death after elective esophagectomy. With 22 relevant clinical variables and days of surgery, 90-day mortality was evaluated using hierarchical logistic regression modeling. RESULTS: Ninety-day mortality rates among 33,980 patients undergoing elective esophagectomy were 1.8% (range, 1.5-2.1%). Surgeries were largely concentrated on earlier days of the week, whereas esophagectomies performed on Fridays accounted for only 11.1% of all cases. Before risk adjustment, lower odds ratios of 90-day mortality were found on Tuesday and a tendency towards lower odds ratios on Thursday. In the hierarchical logistic regression model, 21 independent factors of 90-day mortality were identified. However, the adjusted odds ratios of 90-day mortality for Tuesday, Wednesday, Thursday, and Friday were 0.87, 1.09, 0.85, and 0.88, respectively, revealing no significant difference. CONCLUSION: The results imply that the variation in 90-day mortality rates after esophagectomy on different days of the week may be attributed to differing preoperative risk factors of the patient group rather than the disparity in medical care provided.

Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab.

BACKGROUND: In Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy. METHODS: The clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves. RESULTS: During January 2017-June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70 years; male, 77%). With a median follow-up period of 9.1 (range, 1.0-34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0-16.6) and 4.0 (95% CI, 2.6-5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR < 0.62 (hazard ratio, 0.39; 95% CI, 0.22-0.67; p = 0.001). CONCLUSIONS: Inflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR < 0.62, suggesting that CAR adequately reflects prognosis.

A descriptive comparison of postoperative outcomes between hybrid mediastino-thoracoscopic approach and conventional thoracoscopic esophagectomy for esophageal cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

What is the optimal range of glycemic control for non-diabetic patients undergoing gastroenterological surgery? A single-center randomized controlled trial using an artificial pancreas.

BACKGROUND: This study aimed to determine the optimal target range of perioperative glycemic control for gastroenterological surgery. A closed-loop-type artificial pancreas (AP) was used to diminish the negative impact of hypoglycemia and glycemic variability during tight glycemic control. METHODS: In this single-center randomized trial, non-diabetic patients were assigned to tight (80-110 mg/dL) or moderate glycemic control (110-140 mg/dL) groups between August 2017 and May 2021. AP was used from the intraoperative period until discharge from the intensive care unit. The primary endpoint was the serum interleukin (IL)-6 level on the third postoperative day (3POD), and the secondary endpoints included clinical outcomes. RESULTS: Recruitment was closed before reaching the planned number of patients due to slow enrollment. Tight glycemic control (n = 62) resulted in lower mean glucose levels than moderate glycemic control (n = 66) (121.3 ± 10.8 mg/dL vs. 133.5 ± 12.0 mg/dL, p < 0.001). Insulin was administered at a 65% higher rate for tight glycemic control, achieving appropriate glucose control more than 70% of the treatment time. No hypoglycemia occurred during the AP treatment. No significant difference was observed in serum IL-6 levels on 3POD (23.4 ± 31.1 vs. 32.1 ± 131.0 pg/mL, p = 0.64), morbidity rate, surgical mortality rate, or length of hospital stay between the two groups. CONCLUSIONS: Clinically relevant short-term results did not differ, implying that 80-110 and 110-140 mg/dL are permissible glycemic control ranges when using AP in non-diabetic patients undergoing gastroenterological surgery. (Registered in UMIN; UMIN000028036).

Near-infrared fluorescence imaging with indocyanine green to assess the blood supply of the reconstructed gastric conduit to reduce anastomotic leakage after esophagectomy: a literature review.

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.

Impact of the hospital volume and setting on postoperative complications of surgery for gastroenterological cancers in a regional area of Western Japan.

PURPOSE: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan. METHODS: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery. RESULTS: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes. CONCLUSION: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed.

[Long-Term Survival of an Adolescent and Young Adult Patient with Unresectable Advanced Gastric Cancer in Whom Multidisciplinary Treatment Was Effective].

We report the case of a long-term-surviving adolescent and young adult patient with unresectable advanced gastric cancer for whom multidisciplinary treatment was effective. A 29-year-old woman was referred to our hospital for further examination following a diagnosis of gastric cancer by a local physician. Esophagogastroduodenoscopy showed a deep ulcerated lesion in the lower third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. Abdominal contrast- enhanced computed tomography showed gastric wall thickening in the lower third of the stomach. The patient underwent distal gastrectomy with lymph node dissection, including resection of localized peritoneal metastases, followed by Roux-en- Y reconstruction. The pathological diagnosis was serosa-invading poorly differentiated adenocarcinoma with 1 lymph node metastasis measuring 6.0×5.5 cm in the posterior wall of the lower third of the stomach and negative immunohistochemical staining for human epidermal growth factor receptor 2. The patient received postoperative chemotherapy with S-1 and oxaliplatin. She developed bilateral ovarian metastases measuring 13.0 cm and 7.8 cm after 17 months. The patient presented with severe lower abdominal pain and underwent an emergency bilateral ovarian metastasectomy, which revealed torsion of the right ovarian tumor, which had twisted twice on its pedicle, and a left ovarian mass. After the operation, 41 courses of ramucirumab with nab-paclitaxel were administered as a second-line treatment, and she received systemic drug treatment. Sixty months after the gastrectomy, the patient developed left hydronephrosis due to peritoneal metastases and was treated with nivolumab after ureteral stent replacement. No effective treatment was proposed in cancer multigene panel testing, and she died 66 months after the initial treatment because of disease progression. Comprehensive multidisciplinary treatment, including surgical and local therapy for peritoneal dissemination based on drug therapy for unresectable advanced gastric cancer, may result in long-term survival. Further research and accumulation of such cases would lead to the development of novel treatments.

Analysis of the short-term outcomes after esophagectomy for esophageal cancer during the COVID-19 pandemic using data from a nationwide Japanese database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.

Current status of photodynamic technology for urothelial cancer.

5-Aminolevulinic acid is a new-generation photosensitizer with high tumor specificity. It has been used successfully in the diagnosis, treatment, and screening of urological cancers including bladder cancer; specifically, it has been used in photodynamic diagnosis to detect tumors by illuminating the lesion with a specific wavelength of light to produce fluorescence in the lesion after administration of 5-aminolevulinic acid, in photodynamic therapy, which induces tumor cell death via production of cytotoxic reactive oxygen species, and in photodynamic screening, in which porphyrin excretion in the blood and urine is used as a tumor biomarker after administration of 5-aminolevulinic acid. In addition to these applications in urological cancers, 5-aminolevulinic acid-based photodynamic technology is expected to be used as a novel strategy for a large number of cancer types because it is based on a property of cancer cells known as the Warburg effect, which is a basic biological property that is common across all cancers.

Impact of Gut Microbiota on the Pharmacokinetics of Glycyrrhizic Acid in Yokukansan, a Kampo Medicine.

Individual differences in gut microbiota can affect the pharmacokinetics of drugs. Yokukansan is a traditional Japanese kampo medicine used to treat peripheral symptoms of dementia and delirium. A study examining the pharmacokinetics of the components of yokukansan reported large individual differences in the pharmacokinetics of glycyrrhizic acid (GL). It is known that GL is metabolized by intestinal bacteria to glycyrrhetinic acid (GA), which is absorbed in the gastrointestinal tract. Thus, the gut microbiota may affect GL pharmacokinetics. We aimed to clarify the relationship between the gut microbiota composition and pharmacokinetics of GL in yokukansan. Mice were orally administered yokukansan, following the administration of various antibiotics, and the plasma concentration of GA and composition of gut microbiota were measured. The GA plasma concentration was low in mice treated with amoxicillin and vancomycin. The composition of gut microbiota revealed a different pattern from that of the control group. Mice with low plasma levels of GA had lower levels of the phylum Bacteroides and Firmicutes. Additionally, bacteria, such as those belonging to the genera Parabaceroides, Bacteroides, Ruminococcus and an unknown genus in families Lachnospiraceae and Ruminococcaceae, exerted positive correlations between the gene copies and plasma GA levels. These bacteria may contribute to the absorption of GA in the gastrointestinal tract, and multiple bacteria may be involved in GL pharmacokinetics. The pharmacokinetics of GL may be predicted by evaluating the composition of gut bacteria, rather than by evaluating the amount of a single bacterium.

Frequency and therapeutic strategy for patients with ovarian metastasis from gastric cancer.

PURPOSE: This study aimed to analyze the clinicopathological features and treatment outcomes of ovarian metastasis from gastric cancer. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Neutrophil-to-lymphocyte ratio and C-reactive protein-to-albumin ratio as prognostic factors for unresectable advanced or recurrent gastric cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: High CAR and NLR are associated with poor survival in patients with unresectable and recurrent gastric cancer.

Successful treatment of diabetic ketoacidosis secondary to fulminant type 1 diabetes mellitus using a closed-loop artificial pancreas in a pediatric patient.

Diabetic ketoacidosis (DKA) is a life-threatening complication of pediatric diabetes mellitus (DM). A bedside closed-loop artificial pancreas (AP) (STG-55; NIKKISO, Tokyo, Japan) maintains the blood glucose (BG) levels within the target range via automatic infusion of insulin and glucose. We report the application of the closed-loop AP to safely control the BG levels of a pediatric patient with DKA. A 12-year-old child with an unremarkable medical history presented with fever and restlessness. The patient was diagnosed with DKA secondary to fulminant type 1 DM and was treated with insulin infusion. He presented with Glasgow Coma Scale of E2V3M4. Arterial blood gas analysis revealed metabolic acidosis and BG levels of 489 mg/dL. His urine test was positive for ketones. Along with infusion therapy, automatic BG control using a closed-loop AP was initiated after ICU admission. This was adjusted to maintain BG levels within 100 mg/dL/6 h or less. After 24 h in the ICU, the patient regained consciousness and recovered from the metabolic acidosis. His general condition improved, and he was prescribed a diet treatment. The treatment was shifted to continuous insulin infusion, and he was transferred to the general ward, and was discharged on the 33rd day of hospitalization. The closed-loop AP prevented repetitive blood extractions, achieved prompt glycemic control, and prevented cerebral edema in a pediatric patient with DKA. This is the first report of successful treatment of DKA using a bedside closed-loop AP.

The impact of the quantitative assessment procedure for coronary artery bypass graft evaluations using high-resolution near-infrared fluorescence angiography.

PURPOSE: Near-infrared angiography (NIR) is used for on-site graft assessment during coronary artery bypass grafting. This study evaluated the results of a quantitative NIR assessment using a new high-resolution NIR device (h-NIR) for graft assessment. METHODS: Forty-three patients were enrolled in our study. Internal thoracic artery (ITA) grafts anastomosed to the left anterior descending artery and examined intraoperatively using h-NIR were included. The ITA grafts were divided into 2 groups for a comparative analysis: patent grafts (P group; n = 37) and failed grafts (F group; n = 6). The graft flow was evaluated by a "quantitative NIR assessment", and the fluorescence luminance intensity (FLI) was measured. Direct observation of the graft and anastomosis with h-NIR was also performed. RESULTS: The FLI was higher in the P group than in the F group. The receiver operating characteristic analysis revealed the following cut-off values for FLIs depending on imaging duration: 21.1% at 1 s, 35.5% at 2 s, 58.4% at 3 s, and 83.3% at 4 s. The sensitivity and specificity for detecting graft failure were 83.3% and 69.8-80.6%, respectively. Furthermore, h-NIR was also able to visualize arterial dissection in ITA grafts. CONCLUSIONS: A quantitative NIR assessment with an h-NIR device can improve the detectability of anastomotic stenosis, and h-NIR successfully detected arterial dissection of grafts.

Frequency and prognostic impact of cachexia during drug treatment for unresectable advanced gastric cancer patients.

PURPOSE: Patients with unresectable advanced metastatic gastric cancer have a poor prognosis. This study examined the incidence and prognostic impact of cachexia during systemic drug treatment in such patients. METHODS: We enrolled patients with unresectable advanced gastric cancer who were treated with chemotherapy at Kochi Medical School from 2007 to 2020. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m2 within the past 6 months. Associations between clinicopathological parameters, cancer cachexia, and the overall survival were analyzed. RESULTS: Cancer cachexia occurred in 55.2% of 134 enrolled patients 6 months after chemotherapy. The incidence of cancer cachexia in initial unresectable gastric cancer was significantly higher than that in patients with recurrent cancer after curative resection. The median overall survival was significantly lower in the patients with cancer cachexia than in those without cancer cachexia at 6 months after starting systemic chemotherapy (13.7 months vs. 21.6 months, P = 0.032). Cancer cachexia at 6 months of starting treatment and CRP > 0.14 were identified as significantly associated with poor outcomes in a multivariate analysis (hazard ratio [HR] 1.339, 95% confidence interval [CI] 1.160-2.085, P = 0.019; HR 1.885, 95% CI 1.124-3.161, P = 0.016); respectively). CONCLUSIONS: Cancer cachexia was frequently observed in unresectable advanced gastric cancer patients who received chemotherapy and was useful as a prognostic factor for the overall survival.

[Brain Metastasis Arising from Gastric Cancer during Long-Term Treatment Using Nivolumab].

Metastasis to the central nervous system from gastric cancer is exceedingly uncommon. We report a gastric cancer patient with cerebral metastasis during the period when durable response was obtained by systemic drug treatment using nivolumab. A 78-year-old male was referred to our hospital for further examination following diagnosis of gastric cancer by a local medical doctor. Esophagogastroduodenoscopy showed a slightly elevated lesion with central depressed area in the upper-third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. The patient underwent laparoscopic total gastrectomy with lymph nodes dissection followed by Roux-en-Y reconstruction, resulting in submucosal invasive carcinoma and no lymph node metastasis. The patient developed solitary splenic metastasis measuring 4.2 cm after 28 months later, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Subsequently, the patient was received S-1 plus oxaliplatin chemotherapy based on negative immunohistochemical staining of the resected specimens for human epidermal growth factor receptor 2. Four months after the splenectomy, the patient developed multiple liver metastases and was treated with ramucirumab plus paclitaxel. Because of disease progression, the patient was administered 3 mg/kg, iv, nivolumab every 2 weeks. After 4 courses of systemic treatment using nivolumab, abdominal computed tomography revealed marked shrinkage of the liver metastases. After 12 courses of nivolumab, the liver metastases had disappeared completely. The patient developed hypothyroidism, which could be controlled by thyroid hormone replacement treatment. The patient continues to receive nivolumab, and there is no evidence of disease recurrence in the 33 month period since starting nivolumab. However, he developed cerebral metastases after 69 months after surgery, complaining of articulation disorder. The patient underwent tumor resection by craniotomy followed by radiation therapy; however, he died 3 months after the operation. Although brain metastasis arising from gastric cancer is rare, future identification of risk factors and development of novel treatments are desired by further investigations and accumulation of these cases.

Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). BACKGROUND: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. METHODS: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. RESULTS: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. CONCLUSIONS: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.

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

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.

Evaluation of Perioperative Intestinal Motility Using a Newly Developed Real-Time Monitoring System During Surgery.

BACKGROUND: This study aimed to investigate perioperative intestinal motility using a novel bowel sound monitoring system in patients undergoing breast and neck surgery. MATERIALS AND METHODS: This study enrolled 52 patients who underwent surgery for breast cancer, thyroid tumor, and parathyroid tumor at Kochi Medical School from May 2019 to June 2020. Perioperative bowel sound counts (BSCs) were recorded using a newly developed real-time analysis system in the operating theater. Clinical information and BSC per minute (cpm) data during the preanesthetic, preoperative, operative, postoperative periods, and period in recovery room were obtained to compare between each period. The Mann-Whitney U and Pearson Chi-square tests were used in data analysis. RESULTS: The BSCs during the intraoperative period and postoperative period were significantly decreased compared to those during the preanesthetic period (0.07 cpm versus [vs.]. 1.4 cpm, P = 0.002 and 0.1 cpm vs. 1.4 cpm, P = 0.025, respectively). The preoperative BSC with a preanesthetic BSC < 1.4 was significantly lower than that with a preanesthetic BSC ≥ 1.4 (0.40 cpm vs. 1.78 cpm, P = 0.006). The preanesthetic, preoperative, and postoperative BSCs with an intraoperative BSC < 0.07 were significantly lower than those with an intraoperative BSC ≥ 0.07 (0.48 cpm vs. 2.83 cpm, P = 0.007; 0.40 cpm vs. 1.81 cpm, P = 0.008; and 0.07 cpm vs. 0.42 cpm, P = 0.006, respectively). CONCLUSION: The real-time bowel sound analysis system demonstrated an inhibitory effect associated with anesthetic and surgical stress on intestinal motility as the BSC sequentially.