Does Neoadjuvant Chemoradiotherapy Have an Additional Effect to Lateral Pelvic Lymph Node Dissection for Rectal Cancer?

Objectives: A total mesenteric excision (TME) with lateral pelvic lymph node dissection (LLND) is the standard treatment for advanced low rectal cancer in Japan. Recently, neoadjuvant (chemo)radiotherapy (n(C)RT) has been used with LLND to improve outcomes at multiple Japanese institutes. This study evaluates the benefits of adding nCRT to TME with LLND. Methods: Seventy-two consecutive patients who underwent TME and LLND with or without nCRT between 2006-2019 to treat advanced low rectal cancer were retrospectively reviewed. The clinicopathological data were compared and the risk factors for local recurrence were evaluated. Results: Fifty-seven patients (79.1%) underwent TME and LLND with nCRT, and 15 patients (20.9%) without nCRT. There was no significant difference in the clinicopathological characteristics except the clinical T stage. The occurrence of postoperative complications was statistically insignificant. The 5-year local recurrence rate of patients with nCRT was significantly lower than those without (4.0% versus 26.6%, in all patients, p=0.002). Multivariate analysis revealed that the absence of nCRT was an independent risk factor for local recurrences in patients who underwent TME with LLND (hazard ratio: 6.04, p=0.04). Conclusions: The administration of nCRT prevented local recurrences more effectively in patients with advanced low rectal cancer who underwent TME with LLND.

Pathophysiological Implications of Protein Lactylation in Pancreatic Epithelial Tumors.

Protein lactylation is a post-translational modification associated with glycolysis. Although recent evidence indicates that protein lactylation is involved in epigenetic gene regulation, its pathophysiological significance remains unclear, particularly in neoplasms. Herein, we investigated the potential involvement of protein lactylation in the molecular mechanisms underlying benign and malignant pancreatic epithelial tumors, as well as its role in the response of pancreatic cancer (PC) cells to gemcitabine. Increased lactylation was observed in the nuclei of intraductal papillary mucinous adenoma, non-invasive intraductal papillary mucinous carcinoma, and invasive carcinoma, in parallel to the upregulation of hypoxia-inducible factor-1α. This observation indicated that a hypoxia-associated increase in nuclear protein lactylation could be a biochemical hallmark in pancreatic epithelial tumors. The standard PC chemotherapy drug gemcitabine suppressed histone lactylation in vitro, suggesting that histone lactylation might be relevant to its mechanism of action. Taken together, our findings suggest that protein lactylation may be involved in the development of pancreatic epithelial tumors and could represent a potential therapeutic target for PC.

Risk factors for liver dysfunction and their clinical importance after gastric cancer surgery.

Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Impact of hypoglycemia after gastrectomy on Global Leader Initiative on Malnutrition-defined malnutrition: a retrospective study.

PURPOSE: The Global Leader Initiative on Malnutrition (GLIM) criteria were developed in 2018 as a global indicator of malnutrition, and the term 'malnutrition-sarcopenia syndrome' was established. Recently, it has been reported that fluctuations in blood glucose are related to sarcopenia. In this study, we investigated the effects of glucose fluctuations on malnutrition after gastrectomy using a continuous glucose monitoring (CGM) device. METHODS: We analyzed the data of 69 patients with gastric cancer (GC) who underwent curative gastrectomy between November 2017 and December 2020. CGM was performed over a 2-week period at 1 month and 1 year after surgery. The GLIM criteria included weight loss, the body mass index (BMI), and the psoas muscle mass index (PMI). RESULTS: One year after surgery, 25 and 35 patients had severe and moderate malnutrition, respectively. The time below range (TBR) (percent of time the glucose concentration was < 70 mg/dL) and nocturnal (00:00-06:00) TBR were significantly higher in the severe malnutrition group than in the other groups (TBR: normal/moderate 17.9% vs. severe 21.6%, P = 0.039, nocturnal TBR; normal/moderate 30.6% vs. severe 41.1%, P = 0.034). CONCLUSIONS: Post-gastrectomy hypoglycemia, including long nocturnal hypoglycemia, was higher in severely malnourished patients than in other patients even 1 year after surgery. Prevention of nocturnal hypoglycemia may be the key to improving malnutrition following gastrectomy.

Laparoscopic and open minor liver resection for hepatocellular carcinoma with clinically significant portal hypertension: a multicenter study using inverse probability weighting approach.

BACKGROUND: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH). METHODS: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed. RESULTS: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87). CONCLUSIONS: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival.

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial).

Background: Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods: This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results: Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions: This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration: UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.

Cancer Stem Cells of Hepatocellular Carcinoma Are Suppressed by the Voltage-gated Calcium Channel Inhibitor Amlodipine.

BACKGROUND/AIM: The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for hepatocellular carcinoma (HCC). The present investigation demonstrated the expression profiles of ion channels in CSCs of HCC. MATERIALS AND METHODS: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from HepG2 cells, a human HCC cell line, by fluorescence-activated cell sorting, and CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were investigated using microarray analysis. RESULTS: Among HepG2 cells, ALDH1A1 messenger RNA level was higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels, such as calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The cytotoxicity of the CACNG4 inhibitor amlodipine was higher at lower concentrations in CSCs than in non-CSCs, and markedly decreased the number of tumorspheres. The cell population among HepG2 cells that highly expressed ALDH1A1 was also significantly reduced by this inhibitor. CONCLUSION: CACNG4 plays a role in maintaining CSCs, and its inhibitor, amlodipine, could potentially be a targeted therapeutic agent against HCC.

Pleomorphic liposarcoma of the extremity with solitary huge liver metastasis at initial diagnosis treated with conversion surgery combined with adjuvant chemotherapy: a case report.

BACKGROUND: Pleomorphic liposarcoma is the rarest subtype of liposarcoma. Pleomorphic liposarcomas are generally unresponsive to chemotherapy and radiotherapy. Moreover, metastasis in the liver, as the first and sole site, from a primary extremity soft tissue sarcoma, including pleomorphic liposarcoma, is extremely rare. Information regarding the appropriate management of these lesions is limited. CASE PRESENTATION: A 50-year-old Japanese woman presented with a mass in the left thigh. Imaging examination revealed a soft tissue sarcoma on the left posterior thigh. The tumor was histologically diagnosed as pleomorphic liposarcoma. Computed tomography examination for assessment of metastases incidentally detected a huge liver mass. Wide excision of sarcoma was performed prior to chemotherapy. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant volume was insufficient. Therefore, we decided to administer anthracycline-based chemotheraphy to shrink the tumor. After seven courses of adriamycin-based chemotherapy, the liver tumor size was reduced from 211 mm × 106 mm × 180 mm to 105 mm × 66 mm × 90 mm. Finally, a right hemihepatectomy was performed. The patient was continuously monitored and was metastasis or local recurrence free within 5 months after liver surgery. CONCLUSION: Chemotherapy is effective in some cases for the treatment of unresectable liver metastases of pleomorphic liposarcoma, and complete resection is possible with conversion surgery. If the patient's general condition permits, anthracycline-based chemotherapy can be used for the treatment of stage 4 pleomorphic liposarcoma.

Preoperative oral antibiotic administration in patients undergoing curative resection with stoma creation for colorectal cancer: effectiveness in preventing surgical site infection and the possibility of peristomal candidiasis induced by enterobacterial alteration.

AIM: There are many reports that preoperative oral antibiotics (OAs) are effective in preventing surgical site infections (SSIs) in colorectal surgery. However, there is no consensus on the optimal dose of OAs. In this study, we investigated the efficacy of OAs in preventing SSIs and the possibility that OAs induce enterobacterial alteration in the intestinal tract. METHOD: We performed a retrospective cross-sectional analysis of 389 patients who underwent R0 resection and stoma creation for colorectal cancer in our department between 2009 and 2020. We focused on the incidence of peristomal candidiasis (PSC) as an indicator of enterobacterial alteration and used kanamycin (KM) and metronidazole (MNZ) as the OAs. A low-dose group received 1000 mg/day of both KM and MNZ, and a high-dose group received 2000 mg/day of both KM and MNZ. RESULTS: SSI occurred in 60 of the 389 cases (15.4%). Regardless of stoma type, SSI was significantly more common in the non-OA group, while PSC was significantly less common. When examined by OA dose, the incidence of SSI was not significantly different between the low-dose and high-dose groups. However, PSC was significantly more common in the high-dose group than in the non-OA and low-dose groups. Analysis of bacterial and fungal levels in stool samples showed that bacterial levels after OAs were significantly lower than before OAs, while fungal levels increased. CONCLUSION: OAs significantly reduce SSI in colorectal cancer surgery. However, excess OAs were significantly associated with the occurrence of PSC without contributing to further reduction in SSI.

A case of hepatic anisakidosis caused by Anisakis pegreffii mimicking liver cancer.

Extra-gastrointestinal anisakidosis is rare. We herein report an Anisakis pegreffii infection in a patient with hepatic anisakidosis diagnosed based on its molecular identification. A 71-year-old male patient had a hepatic tumor presenting as a low-density area of 20 mm in diameter in segment 6 of the liver on abdominal ultrasonography, computed tomography, and magnetic resonance imaging. The surgically resected pathological specimen revealed a necrotizing eosinophilic granuloma containing nematode larvae, possibly an Anisakis larva. Molecular and phylogenetic analysis demonstrated Anisakis larvae belonging to A. pegreffii. The present results will help identify and characterize unknown Anisakis species in histological sections.

Effect of laparoscopic liver resection on postoperative delirium in elderly patients with hepatocellular carcinoma.

BACKGROUND: Delirium is a multifactorial and heterogeneous syndrome that is defined as acutely altered consciousness. This retrospective multicenter study evaluated the impact of postoperative delirium after liver resection for hepatocellular carcinoma (HCC) in elderly patients. METHODS: Patients aged ≥75 years, who underwent curative liver resection for HCC at nine university hospitals from April 2010 to December 2017, were evaluated to compare short- and long-term outcomes between patients with and without delirium. Risk factors for delirium were determined using multivariate regression analysis. RESULTS: The rate of postoperative delirium was 14.2% (n = 80) in the study cohort of 562 patients. Multivariate analysis revealed smoking history, hypertension, sleeping pill consumption, and open liver resection as risk factors for postoperative delirium. The rate of other causes of death was significantly higher in the delirium group than in the no-delirium group although the rate of death at 1 year due to HCC or liver failure was similar between the two groups (p = .015). The 1-year mortality rates due to vascular diseases were 71.4% and 15.4% in the delirium and no-delirium groups, respectively (p = .022). The 1-, 3-, and 5-year survival rates after liver resection were 86.6%, 64.1%, and 36.5% in the delirium group and 91.3%, 71.2%, and 56.9% in the no-delirium group, respectively (p = .046). CONCLUSION: The multivariate analysis revealed the possible benefits of laparoscopic liver resection in reducing the rate of postoperative delirium after liver resection for HCC in elderly patients.

Postoperative liver dysfunction is associated with poor long-term outcomes in patients with colorectal cancer: a retrospective cohort study.

BACKGROUND: Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery. METHODS: We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I-IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction. RESULTS: Forty-eight (13.3%) colorectal cancer patients (Stages I-IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P < 0.001). Univariate and multivariate analyses using Cox's proportional hazards model revealed that postoperative liver dysfunction independently was a poor prognostic factor (P = 0.001, Hazard ratio 2.75, 95% CI: 1.54-4.73). CONCLUSIONS: Postoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction.

Predictors of the difficulty of transcervical subcarinal lymph node dissection for esophageal cancer.

BACKGROUND: Transmediastinal radical esophagectomy (TME) is a new minimally invasive approach without thoracotomy. However, the transcervical dissection of subcarinal lymph nodes (SCLN) is challenging. The shape or narrowness of the mediastinal space, particularly around the aortic arch to the tracheal bifurcation, may increase the difficulty of this procedure. The present study aimed to clarify predictors of the difficulty of transcervical SCLN dissection. METHODS: Patients who underwent TME between 2016 and 2019 were included (n = 126). Four indicators, the cervical angle, carina distance, aorta distance, and sternum distance, were defined as indicators of mediastinal narrowness by 3D-CT. The relationships between the difficulty of transcervical SCLN dissection and clinicopathological features, including the above indicators, were investigated. RESULTS: In a univariate analysis, the cervical angle (p = 0.023), aorta distance (p = 0.002), and middle thoracic tumor (p = 0.040) correlated with difficulty. The median cervical angle and aorta distance were 15° and 33 mm in difficult cases and 19° and 43 mm in easy cases, respectively. In a multivariate analysis, the short aorta distance (odds ratio: 7.96, p = 0.002) and middle thoracic tumor (odds ratio: 3.35, p = 0.042) were independent predictive factors. CONCLUSIONS: The cervical angle, aorta distance, and middle thoracic tumor may predict the difficulty of transcervical SCLN dissection. In difficult cases, a transhiatal approach should be combined for complete SCLN dissection.

Surgical Outcomes for Hepatocellular Carcinoma in Patients with Child-Pugh Class B: a Retrospective Multicenter Study.

BACKGROUNDS: Liver resection for hepatocellular carcinoma (HCC) in patients with Child-Pugh class (CPC) B increases the incidence of postoperative complication and in-hospital death and decreases the disease-free survival (DFS) and overall survival (OS) compared with those with CPC A. Conversely, some selected patients possibly gained benefits for liver resection. METHODS: Clinical records of 114 patients with CPC B who underwent liver resection for HCC were retrospectively reviewed. The risk of postoperative complications (Clavien-Dindo classification grade of ≥ II), postoperative recurrence, and death was analyzed. RESULTS: Postoperative complications occurred in 36 patients (31.6%), and 2 died within 90 days postoperatively due to the liver and respiratory failure, respectively. Multivariate analysis indicated that albumin-bilirubin (ALB) grade III and extended operation time were found as independent risk factors for postoperative complications. The DFS and OS rates at 3/5 years after liver resection were 30.8%/25.3% and 68.4%/48.9%, respectively. Multivariate analysis indicated that the extended blood loss, high α-fetoprotein (AFP) level (≥ 200 ng/mL), and Barcelona Clinic Liver Cancer stage C were found to be independent risk factors for postoperative recurrence. The high AFP level was also an independent prognostic factor for OS. Patients with high AFP levels had postoperative recurrence within 2 years and a higher number of extrahepatic recurrences than those with low AFP levels (< 200 ng/mL). CONCLUSION: For patients with HCC with CPC B who were scheduled for liver resection, ALBI grade III and high AFP level should be considered as unfavorable outcomes after liver resection.

Impact of the preoperative clinical N stage on the prognosis of patients with colon cancer.

AIM: Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. METHOD: This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. RESULTS: Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p = 0.04). CONCLUSION: Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

Short- and long-term outcomes of laparoscopic versus open repeat liver resection for hepatocellular carcinoma: A multicenter study.

OBJECTIVE: This multicenter study aimed to compare the short- and long-term outcomes of laparoscopic (LRLR) versus open repeat liver resection (ORLR) for recurrent hepatocellular carcinoma (HCC) using propensity score matching (PSM). Despite the expanding indications for laparoscopic liver resection, limited data regarding the outcomes of LRLR have previously been reported. METHODS: This study included patients who underwent repeat liver resection for recurrent HCC. Patients were divided into the LRLR and ORLR groups, and their short- and long-term outcomes were compared via PSM. RESULTS: There were 256 and 130 patients in the ORLR and LRLR groups, respectively. After PSM, 64 patients were included in each group. Intraoperative blood loss was significantly less in LRLR than in ORLR (56 vs 208 ml, P < .001). Postoperative complications of Clavien-Dindo IIIa or more were significantly less in LRLR than in ORLR (3.1% vs 15.6%, P = .030). The length of hospital stay was notably shorter in LRLR than in ORLR (9 vs 12 days, P < .001). Survival rates after repeat liver resection at 1, 3, and 5 years, respectively, were comparable at 93.4%, 81.9%, and 63.5% for ORLR and at 94.8%, 80.7%, and 67.3% for LRLR (P = .623). Subgroup analysis of patients who underwent wedge resection in repeat liver resection revealed that the postoperative complication rate was notably lower in LRLR than in ORLR (7.2% vs 21.8%, P = .030). CONCLUSION: LRLR for recurrent HCC is a viable option due to its better short-term outcomes and comparable long-term outcomes compared to ORLR.

Postoperative Nutrition Status of Patients With Esophago-gastric Junction Cancer With Gastric Tube or Esophago-gastric Reconstruction.

BACKGROUND/AIM: Postoperative nutritional management for esophago-gastric junction cancer (EGJC) has become increasingly important. This study compared the nutritional status of patients with EGJC who underwent gastric tube reconstruction versus esophago-gastric anastomosis. PATIENTS AND METHODS: Mediastinoscopic esophagectomy with gastric tube reconstruction was performed in 17 cases (group GT) and laparoscopic proximal gastrectomy with esophago-gastric anastomosis in 33 cases (group EG). The perioperative characteristics and nutritional status of the two groups in the 2 years postoperatively were compared. RESULTS: Group GT had a significantly higher level of serum total protein at 24 months postoperatively than did group EG. No other significant differences in postoperative nutritional status were observed between the groups. CONCLUSION: Gastric tube reconstruction for EGJC was not inferior to esophago-gastric anastomosis in terms of nutritional status. It is a candidate surgical procedure to avoid higher mediastinal anastomosis.

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy.

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.

miR­4730 suppresses the progression of liver cancer by targeting the high mobility group A1 pathway.

As liver cancer (LC) is the sixth most commonly diagnosed malignancy, it is necessary to elucidate the molecular mechanisms responsible for LC progression. MicroRNAs (miRNAs/miRs) play crucial roles in tumor progression by regulating target gene expression. The present study assessed miRNA­4730 expression and function in LC. The effects of miR­4730 overexpression were examined in LC cell lines, and the target genes of miR­4730 were evaluated using microarray analysis and TargetScan data. In addition, the association between miR­4730 expression in tissue samples and the prognosis of 70 patients with LC was evaluated. miR­4730 expression was suppressed in LC tissues and cell lines. miR­4730 overexpression suppressed cell proliferation and cell cycle progression and promoted apoptosis. High mobility group A1 (HMGA1) was revealed as the direct target of miR­4730 using luciferase reporter assay, and the inhibition of downstream integrin­linked kinase (ILK) expression and Akt or glycogen synthase kinase 3ß (GSK3ß) phosphorylation was confirmed. The lower expression of miR­4730 in tissue samples was significantly associated with a worse recurrence­free survival of patients with LC. On the whole, miR­4730 suppressed tumor progression by directly targeting HMGA1 and inhibiting the ILK/Akt/GSK3ß pathway. miR­4730 thus has potential for use as a prognostic marker and may prove to be a therapeutic target for miRNA­based therapies.