Feasibility and Safety of Super Energy-dense Oral Nutritional Supplementation in Postoperative Gastric Cancer Patients.

BACKGROUND/AIM: Ensuring that postoperative gastric cancer patients receive sufficient oral nutritional supplementation (ONS) to prevent body weight loss (BWL) is a serious challenge. The present pilot study evaluated the feasibility and safety of small, frequent sip feeds (SIP) with super energy-dense ONS (SED ONS; 4 kcal/ml) in postoperative gastric cancer patients. PATIENTS AND METHODS: Patients received 400 kcal/day of SED ONS in four, daily, 25 ml SIP for 12 weeks after gastrectomy. The primary outcome was the percentage of postoperative weight change. The expected mean weight change was 90% (10% standard deviation). A sample population of 14 patients, sufficient for a 95% confidence interval with a 10% margin of error, was enrolled. RESULTS: The mean weight change for patients receiving SIP with SED ONS was 93.8%. The mean SED ONS intake was 348 kcal/day. Thirteen patients consumed more than 200 kcal/day of SED ONS. One patient with a mean intake of 114 kcal/day had undergone total gastrectomy followed by adjuvant chemotherapy. CONCLUSION: Small, frequent SIP with SED ONS was found to be feasible and safe in postoperative gastric cancer patients. A multicenter randomized controlled trial is warranted to determine whether SIP with SED ONS is effective in preventing BWL.

Identifying Risk Factors of Complications following Total Gastrectomy for Gastric Cancer: Comparison between Splenectomy and Spleen-Preserving Surgery - A Supplementary Analysis of JCOG0110.

INTRODUCTION: Splenectomy for proximal gastric cancer was found to offer no survival benefit in a randomized trial clarifying the role of splenectomy (JCOG0110 study). Although many studies have explored risk factors for morbidities following total gastrectomy, none have assessed the risk factors for postoperative complications in spleen-preserving total gastrectomy. METHODS: Using data from 505 patients enrolled in a previous randomized trial, risk factors for postoperative complications were identified by multivariable logistic regression analysis. Then, the risk factors were assessed separately between splenectomy and spleen-preserving total gastrectomy. RESULTS: Postoperative complications were identified in 119 patients (23.6%) and were more common following splenectomy than following spleen-preserving surgery (30.7% and 16.1%, respectively, p < 0.01). Multivariable analysis revealed that age ≥65 years (p = 0.032), body mass index ≥25 (p = 0.003), and blood loss ≥350 (p = 0.019) were independent risk factors for postoperative complications in the entire cohort. Among them, only body mass index was a significant independent risk factor for complications in both spleen preservation (p = 0.047) and splenectomy groups (p = 0.017). CONCLUSION: Risk factors for postoperative complications were essentially the same between splenectomy and spleen preservation. Being overweight increased the risk of postoperative complications.

Impact of super energy-dense oral nutritional supplementation (SED ONS) on glycemic variability and food intake postoperatively in gastric cancer patients.

PURPOSE: Adherence to oral nutritional supplements (ONS) to prevent weight loss after gastrectomy is problematic. The present study evaluated the impact of super energy-dense ONS (SED ONS; 4 kcal/mL) on glycemic change and energy intake after gastrectomy. METHODS: Gastrectomy patients were placed on continuous glucose monitoring for a 3-day observation period after food intake had been stabilized postoperatively. In addition, they were given 0, 200, and 400 kcal/day of SED ONS on Days 1, 2, and 3, respectively. The primary outcome was the area under the curve < glucose 70 mg/dL (AUC < 70). The secondary outcomes were other indices of glucose fluctuation and the amount of food and SED ONS intake. RESULTS: Seventeen patients were enrolled. The AUC < 70 did not differ significantly with or without SED ONS over the observation period. SED ONS did not cause postprandial hypoglycemia and prevented nocturnal hypoglycemia. The mean dietary intake did not change significantly during the observation period, and the total energy intake increased significantly according to the amount of SED ONS provided. CONCLUSION: SED ONS after gastrectomy increased the total energy intake without dietary reduction and it did not result in hypoglycemia.

A case of late postoperative intra-abdominal hemorrhage developing 13 months after laparoscopic sleeve gastrectomy.

A 29-year-old male patient underwent laparoscopic sleeve gastrectomy (LSG) for morbid obesity and was discharged without any complications. Thirteen months later, he visited the emergency room with epigastric pain. A few hours before onset, he had had a larger-than-usual meal and vomited afterwards. Enhanced abdominal computed tomography revealed a hematoma 127 × 63 mm in diameter around the stomach. Angiography revealed no extravasation or pseudoaneurysm. Upper gastrointestinal endoscopy found no ulcers or abnormality of the stapler line scar from the LSG. The patient's vital signs were stable, and his hemoglobin had not fallen below the previous day's value. Conservative treatment was therefore chosen. The patient was discharged in stable condition after 11 days of hospitalization. However, the exact source of the hemorrhage was unable to be detected on the imaging findings. In view of his clinical course and the hematoma location, omental vessels were suspected of being the source of the hemorrhage.

Liver retraction using an L-shaped retractor during sleeve gastrectomy.

PURPOSE: The Nathanson liver retractor (NLR) and the snake liver retractor (SLR) are commonly used in bariatric surgery and their use is associated with some disadvantages. We developed an L-shaped liver retractor (LLR) and herein evaluated its efficacy and safety. METHODS: The present retrospective study enrolled patients undergoing sleeve gastrectomy in our department between June 2014 and December 2020. The patients were divided into three groups according to the liver retractor used (LLR, SLR or NLR) for a comparative analysis of the efficacy and safety of the devices. The procedural time (PT) of each retractor type, defined as the time from retractor insertion to liver fixation, was compared. RESULTS: In total, 140 patients successfully underwent laparoscopic sleeve gastrectomy. The LLR, SLR and NLR were used in 37, 91, and 12 of these patients, respectively. The PT for the LLR was the shortest. AST/ALT elevation was significantly more frequent in the NLR group than in the SLR group and tended to be less frequent in the LLR group in comparison to the NLR group (p = 0.09). The length of hospital stay in the NLR group was significantly longer in comparison to the LLR group. CONCLUSION: Our study suggested that the LLR was superior to the conventional liver retractors used in sleeve gastrectomy.

Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody.

Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.

Clinical predictors of gangrenous appendicitis: elevated total bilirubin level and computed tomography scan findings.

AIM: Patients with gangrenous appendicitis usually require emergency surgery. Preoperative diagnosis of gangrenous appendicitis is clinically important but not always straightforward. We undertook this study to identify preoperative predictors of gangrenous appendicitis. METHODS: This was a single-center case-control study. We identified 162 patients who underwent appendectomy between September 2011 and August 2014 after the diagnosis of acute appendicitis was established. We identified laboratory parameters and computed tomography (CT) scan findings predictive of histologically or surgically diagnosed gangrenous appendicitis by univariable and multivariable analyses. RESULTS: Of 146 study patients, gangrenous appendicitis was confirmed in 102. Univariable analysis showed that two laboratory factors (C-reactive protein []and total bilirubin [T-Bil]) and three CT scan findings were significant predictors for gangrenous appendicitis. Multivariable analysis showed that T-Bil and two CT scan findings (appendicolith and fat stranding around the appendix) were independent predictors. The combination of "T-Bil ≥ 1.0 mg/dL or appendicolith" was able to predict gangrenous appendicitis with a sensitivity of 90.5%, positive predictive value of 80.4%, and accuracy of 77.8%. The combination of "T-Bil ≥ 1.0 mg/dL or fat stranding around the appendix" was able to predict gangrenous appendicitis with a sensitivity of 98.9%, positive predictive value of 76.4%, and accuracy of 71.9%. CONCLUSION: These combinations of laboratory and CT scan findings could be valuable as predictors of gangrenous appendicitis.

A case of disseminated carcinomatosis of the bone marrow from gastric cancer developing rapidly after a gastrectomy.

BACKGROUND: Disseminated carcinomatosis of the bone marrow (DCBM) is often associated with disseminated intravascular coagulation (DIC) and a poor prognosis. Moreover, the timing of the diagnosis varies. We presented herein the first report of a case of DCBM from gastric cancer that developed rapidly after a gastrectomy. CASE PRESENTATION: A 42-year-old male patient was referred to us for gastric cancer. Preoperative laboratory tests were normal. Abdominal computed tomography (CT) revealed no obvious bone metastasis, and he underwent a laparoscopic distal gastrectomy. On postoperative day (POD) 1, laboratory data indicated severe thrombocytopenia. Postoperative bleeding requiring reoperation was found. Afterwards, he complained of lower back pain. His ALP and LDH gradually became elevated. On POD 8, DIC was diagnosed. CT and bone scintigraphy showed multiple, widespread bone metastases. Based on these findings, DCBM from gastric cancer was diagnosed. Systemic chemotherapy was started on POD 12. The DIC subsided during the first course, and he was discharged on POD 21. The patient died of tumor progression 7 months later. CONCLUSION: When thrombocytopenia is observed immediately after a gastrectomy for gastric cancer, the possibility of DCBM should be considered.

Intratumoral pseudoaneurysm within a liver metastasis of gastric cancer: a case report.

BACKGROUND: Intrahepatic artery pseudoaneurysms are mostly iatrogenic and result from hepatobiliary interventions. The incidence of intrahepatic artery pseudoaneurysms within liver tumors without prior intervention is extremely rare. We presented herein the first report of a case of an intratumoral pseudoaneurysm within a liver metastasis of gastric cancer without any prior intervention during chemotherapy. CASE PRESENTATION: A 59-year-old male patient underwent a distal gastrectomy and D2 lymph node dissection for gastric cancer. He was treated in the emergency room for right abdominal pain following the 4th cycle of nivolumab administration as second-line chemotherapy after adjuvant chemotherapy with S-1 and first-line chemotherapy for a liver metastasis of gastric cancer with ramucirumab plus paclitaxel. CT showed a 72-mm metastatic liver tumor containing a 9-mm pseudoaneurysm and fluid collection around the hepatic edge. Intrahepatic artery pseudoaneurysm within the metastatic liver tumor was diagnosed, with the surrounding fluid indicating potential, active bleeding. An emergency angiography confirmed the presence of a pseudoaneurysm in the intrahepatic artery, which was embolized using microcoils. The contributory causes of the intratumoral pseudoaneurysm were assumed to be the following: (1) tumor necrosis leading to encasement, erosion of the vessel wall, and subsequent arterial wall weakening; and (2) inhibition of vascular endothelial growth by ramucirumab resulting in a vessel wall breach and pseudoaneurysm formation. CONCLUSION: It is necessary to recognize that pseudoaneurysms can arise within a metastatic liver tumor during chemotherapy.

Right inferior phrenic artery pseudoaneurysm after a laparoscopic gastrectomy: a case report.

BACKGROUND: Ruptured pseudoaneurysms are a rare complication of gastrectomy, but when they do develop, they are often fatal. We presented herein the first report of a case of pseudoaneurysm arising from the right inferior phrenic artery (RIPA) after a laparoscopic gastrectomy. CASE PRESENTATION: A 61-year-old male patient underwent a laparoscopic distal gastrectomy and D1+ lymph node dissection with Roux-en-Y reconstruction for early gastric cancer. He was discharged on postoperative day (POD) 9 without any complications, such as anastomotic or pancreatic leakage. On POD 19, he was referred to the emergency room for upper abdominal pain. Enhanced abdominal computed tomography revealed a 60 × 70 mm hematoma, indicating intra-abdominal bleeding and a 10-mm pseudoaneurysm in the RIPA. Selective digital subtraction angiography confirmed the presence of a pseudoaneurysm in the RIPA, which was embolized using multiple microcoils. Thereafter, no clinical signs were observed, and the patient was discharged from the hospital 15 days after angiography without any recurrence of bleeding. We hypothesized that the cause of the pseudoaneurysm was mechanical vascular injury due to the thermal spread of the ultrasonically activated devices (USADs) during lymphatic node dissection. CONCLUSION: Given the thermal spread of USADs, safe and appropriate lymph node dissection based on precise anatomical knowledge is crucial to preventing postoperative pseudoaneurysms.

Elevation of Neutrophil-to-Lymphocyte Ratio before First-Line Chemotherapy Predicts a Poor Prognosis for Second-Line Chemotherapy in Gastric Cancer.

OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an indicator of cancer-related inflammation. The aim of our study was to examine the prognostic value of the NLR for patients with advanced gastric cancer receiving second-line chemotherapy. METHODS: The association of overall survival (OS) in second-line chemotherapy and the clinicopathological findings including NLR were analyzed retrospectively. The selection criteria were patients who received second-line chemotherapy between January 2010 and June 2015, had histologically confirmed gastric adenocarcinoma, and were followed up until death or for 180 days or longer. RESULTS: Eighty-six patients met the selection criteria. Multivariate analysis revealed that performance status 2, hemoglobin < 10 g/dL, and NLR before first-line chemotherapy ≥3 were adverse predictive markers. NLR before second-line chemotherapy was not associated with OS. A prognostic model was constructed dividing patients into three groups according to the number of adverse predictive factors: good (no factor), intermediate (one factor), and poor (more than two factors). The median OS for the good, intermediate, and poor groups was 14.3, 7.2, and 4.4 months, respectively (p < 0.001). CONCLUSIONS: Patients with advanced gastric cancer with performance status 2, hemoglobin < 10 g/dL, and NLR before first-line chemotherapy ≥3 are not likely to benefit from second-line chemotherapy.

Autopsied case of non-plaque-type dura mater graft-associated Creutzfeldt-Jakob disease presenting with extensive amyloid-ß deposition.

We present an autopsied case of non-plaque-type dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) with extensive amyloid-ß (Aß) deposition in the brain. A 39-year-old Japanese woman presented with memory disturbance and abnormal behavior. The patient had a history of craniotomy with dura matter-graft transplant for a head injury which occurred when she was 19 years old. Magnetic resonance imaging (MRI) showed hyperintensities in the cerebral cortex and striatum on diffusion-weighted images, particularly on the dura mater-grafted right side. Her clinical symptoms, including rapidly progressing cognitive impairment, myoclonus, and periodic sharp wave complexes on electroencephalogram, could not be distinguished from typical sporadic CJD cases. The patient died 11 months after symptom onset, and pathological investigations showed extensive spongiform degeneration with prion protein (PrP) deposition without Kuru plaques; these observations were essentially the same as those of typical sporadic CJD cases. Furthermore, Aß immunohistochemistry showed extensive diffuse staining in the cerebral neocortex, plaque-type deposition, positive staining in the pia mater, and cerebral amyloid angiopathy. Although the MRI findings suggested that the pathological involvement originated from the dura mater-grafted right side, the PrP and Aß depositions showed no apparent regionalization and laterality. Tau-pathology including neurofibrillary tangles was hardly identified. The proteins phosphorylated α-synuclein and phosphorylated transactivation response DNA-binding protein 43 kDa were not detected on immunostaining. Although this report describes only one case, various speculations were made based on detailed clinical and pathological observations in conjunction with previous reports of dCJD. In particular, this report provides significant insight into the characteristics and progression of dCJD pathology and its relationship with Aß pathology.

Bombyx mori ABC transporter C2 structures responsible for the receptor function of Bacillus thuringiensis Cry1Aa toxin.

Because Bombyx mori ABC transporter C2 (BmABCC2) has 1000-fold higher potential than B. mori cadherin-like protein as a receptor for Bacillus thuringiensis Cry1Aa toxin (Tanaka et al., 2013), the gate-opening ability of the latent pore under six extracellular loops (ECLs) of BmABCC2 was expected to be the reason for its higher potential (Heckel, 2012). In this study, cell swelling assays in Sf9 cells showed that BmABCC2 mutants lacking substrate-excreting activity retained receptor activity, indicating that the gate-opening activity of BmABCC2 is not responsible for Cry1Aa toxicity. The analysis of 29 BmABCC2 mutants demonstrated that 770DYWL773 of ECL 4 comprise a putative binding site to Cry1Aa. This suggests that specific toxicity of Cry1Aa toxin to a restricted range of lepidopteran insects is dependent on conservation and variation in the amino acid residues around 770DYWL773 of ECL 4 in the ABCC2.

Early Effects of Sleeve Gastrectomy on Obesity-Related Cytokines and Bile Acid Metabolism in Morbidly Obese Japanese Patients.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has wide-ranging positive effects on adipocytokine metabolism, bile acid profile, and chronic low-grade inflammation related to obesity. However, the early temporal changes in these markers following LSG have not been well investigated. This study aimed to evaluate the early effects of LSG on adipocytokines, bile acid profile, and inflammatory markers. METHODS: This was a nonrandomized prospective study examining morbidly obese Japanese patients undergoing LSG. Serial measurements of leptin, adiponectin, bile acids, fibroblast growth factor (FGF)-19, and inflammatory markers were performed preoperatively and 1 and 6 months after LSG. RESULTS: The study included ten patients (five females) with a mean age of 48.8 years and BMI 40.9 kg/m2. At baseline, 90% of the patients had T2DM, 70% had dyslipidemia, and 90% had hypertension. Patients lost 5.1 kg/m2 BMI at 1 month and 10.1 kg/m2 BMI at 6 months. The leptin levels sharply decreased, and FGF-19 increased significantly as early as 1 month postoperatively. Adiponectin levels showed an increasing trend at 1 month and a significant increase at 6 months. A significant decrease in high-sensitivity CRP and plasminogen activator inhibitor-1 was observed at 6 months. No significant changes were observed in interleukin (IL)-6, IL-8, tumor necrosis factor-α, serum amyloid A protein, or monocyte chemotactic protein-1 throughout the study. CONCLUSIONS: LSG improved the secretion of adipocytokines, increased FGF-19 secretion soon after surgery, and slowly ameliorated inflammation related to obesity through significant weight loss.

Cry toxin specificities of insect ABCC transporters closely related to lepidopteran ABCC2 transporters.

In this study, we examined insect and human ABCC transporters closely related to the lepidopteran ABC transporter C2 (ABCC2), a powerful receptor for the Bacillus thuringiensis Cry toxin, for their responses to various Cry toxins. ABCC2 and the lepidopteran ABC transporter C3 (ABCC3) conferred cultured cells with susceptibility to a lepidopteran-specific Cry1Aa toxin but not to lepidopteran-specific Cry1Ca and Cry1Da. One coleopteran ABCC transporter specifically responded to a coleopteran-specific Cry8Ca toxin. ABCC transporters from a dipteran insect and humans did not respond to any of the tested Cry toxins that are active to lepidopteran and coleopteran insects. These results yield important information for our understanding of insect specificity of Cry toxins and provide the first demonstration of a coleopteran ABCC transporter that serves as a Cry toxin receptor.

Randomized Comparison of Subcuticular Sutures Versus Staples for Skin Closure After Open Abdominal Surgery: a Multicenter Open-Label Randomized Controlled Trial.

BACKGROUND: The incisional surgical site infection (SSI) is an extremely common complication following open abdominal surgery and imposes a considerable treatment and cost burden. METHOD: We conducted a multicenter open-label randomized controlled trial at three Tokyo Metropolitan medical institutions. We enrolled adult patients who underwent either an elective or an emergency open laparotomy. Eligible patients were allocated preoperatively to undergo wound closure with either subcuticular sutures or staples. A central Web-based randomization tool was used to assign participants randomly by a permuted block sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to each group. The primary endpoint was the occurrence of a superficial SSI within 30 days after surgery in accordance with the Centers for Disease Control and Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 ( http://www.umin.ac.jp/ctr ). RESULTS: Between September 1, 2010 and August 31, 2015, 401 patients were enrolled and randomly assigned to either group. One hundred and ninety-nine patients were allocated to the subcuticular suture and 202 patients to the staple groups (hereafter the "suture" and "staple" group, respectively). Three hundred and ninety-nine were eligible for the primary endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201 staple patients. Overall, the rate of superficial SSIs did not differ significantly between the suture and staple groups. CONCLUSION: Subcuticular sutures did not increase the occurrence of superficial SSIs following open laparotomies mainly consisting of clean-contaminated surgical procedures. The applicability of the wound closure material and method is likely to depend on individual circumstances of the patient and surgical procedure.

Predictive factors for prognosis following unsedated percutaneous endoscopic gastrostomy in ALS patients.

INTRODUCTION: This study aimed to determine the prognostic factors and the values that predict survival after percutaneous endoscopic gastrostomy (PEG) tube placement in patients with amyotrophic lateral sclerosis (ALS). METHODS: We retrospectively analyzed the correlations for 97 consecutive patients with ALS between clinical parameters and survival following PEG tube placement using the log-rank test and Cox proportional-hazards models. RESULTS: The log-rank test showed that an arterial carbon dioxide pressure (PaCO2 ) of ≤ 40 mmHg (P = 0.0054), a forced vital capacity (FVC) of ≥ 38% of predicted (P = 0.0003), and bulbar-onset (P = 0.0121) were significantly associated with better post-PEG survival. Multivariate analysis showed that the FVC and PaCO2 were associated with better post-PEG survival (P = 0.0081 and P = 0.0265, respectively). CONCLUSIONS: PEG tube placement in ALS is recommended when FVC is ≥ 38% of predicted and when PaCO2 is normal. Muscle Nerve 54: 277-283, 2016.

Impact of visceral fat on laparoscopy-assisted distal gastrectomy.

BACKGROUND: Obesity is known to be a preoperative risk factor for gastric cancer surgery. However, the influence of obesity on laparoscopy-assisted distal gastrectomy (LADG) remains controversial. In the present study, we evaluated several obesity parameters and investigated the influence of obesity on the surgical outcomes of LADG for gastric cancer. MATERIALS AND METHODS: Between January 2010 and July 2011, 84 patients who underwent LADG for gastric cancer were enrolled. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured in cross-sectional CT scan using SlimVision(®) software. Patients were classified into two groups by the degree of BMI or VFA. Surgery time and blood loss were compared between each two groups. Predictive factors for perioperative complications were assessed by univariate and multivariate analyses. RESULTS: There were no significant differences in surgery time or blood loss between patients with high and low BMIs. In contrast, high VFA patients had significantly longer surgery times (p=0.0047) and higher estimated blood loss (p=0.0034) than low VFA patients. By univariate and multivariate analyses, only a high VFA significantly predicted perioperative complications (p=0.0162, p=0.0288). CONCLUSIONS: We suggest that VFA is more accurate than BMI in predicting surgery time, blood loss, and perioperative complications associated with LADG for gastric cancer. The visceral fat area could be efficiently assessed before laparoscopic surgery for gastric cancer in obese patients.