Search

Introduction: Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC. Methods: We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated. Results: The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence‐free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion. Conclusions: These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample‐based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study investigated novel tumor suppressor microRNAs (miRNAs) that decrease in plasma and predict chemosensitivity to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC) and revealed their usefulness as novel therapeutic agents. We selected four miRNA candidates (miR‐323, 345, 409, and 1254) based on the microRNA microarray comparing pre‐treatment plasma levels in ESCC patients with high and low histopathological responses to NAC and an NCBI database review. Among these miRNA candidates, miR‐1254 was more highly elevated in pre‐treatment plasma of ESCC patients with a high histopathological response than in those with a low histopathological response (P = 0.0021, area under the receiver‐operating characteristic curve 0.7621). High plasma miR‐1254 levels tended to correlate with the absence of venous invasion (P = 0.0710) and were an independent factor predicting a higher response to chemotherapy (P = 0.0022, odds ratio 7.86) and better prognosis (P = 0.0235, hazard ratio 0.23). Overexpressing miR‐1254 in ESCC cells significantly enhanced chemosensitivity to cisplatin through the transcriptional regulation of ABCC1 in vitro. Moreover, increased plasma miR‐1254 levels by subcutaneous injection significantly improved responses to cisplatin in mice. Plasma miR‐1254 might be a useful biomarker for predicting responses to NAC, and the restoration of plasma miR‐1254 levels might improve chemosensitivity in ESCC. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is the sixth leading cause of cancer‐related death worldwide. Recently, neoadjuvant chemotherapy (NAC) before curative surgery has become a standard treatment for clinical stage II or III EC patients. Some EC patients receive a complete response (CR) by NAC; thus, curative surgery may be unnecessary for such patients. MicroRNA levels in plasma have the potential to be a predictor of response to NAC. In the present study, we focused on miR‐192‐5p, which is highly expressed in EC tissue. The purpose was to investigate the correlations between levels of plasma miR‐192‐5p and the response to NAC. Furthermore, molecular functions of miR‐192‐5p associated with chemosensitivity were examined using EC cell lines. The levels of miR‐192‐5p in plasma before surgery were evaluated in 113 EC patients. Sixty‐nine patients received NAC. miR‐192‐5p levels in the CR group were significantly higher than in the other groups (p = 0.002). The downregulation of miR‐192‐5p in the EC cell line inhibited sensitivity to cisplatin, and the overexpression of miR‐192‐5p in the EC cell line promoted sensitivity to cisplatin. miR‐192‐5p regulated sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR‐192‐5p could be used as a predictor of response to chemotherapy and prognosis in EC patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tetraspanin has important functions in many cancers by aggregating with various proteins that interact with intracellular signaling proteins. The molecular function of Tetraspanin31 (TSPAN31), located in the 12q14 amplified region in various cancers, remains unclear in gastric cancer (GC). We tested whether TSPAN31 acts as a cancer‐promoting gene through its activation or overexpression in GC. We analyzed seven GC cell lines and 189 primary tumors, which were curatively resected in our hospital between 2011 and 2013. Overexpression of the TSPAN31 protein was frequently detected in three GC cell lines (42.9%) and 62 primary GC specimens (32.8%). Overexpression of TSPAN31 was significantly correlated with lymphatic invasion, venous invasion, more advanced pT and pN stages, and a higher recurrence rate. Moreover, TSPAN31 positivity was an independent factor predicting worse patient outcomes (p = 0.0283, hazard ratio 3.97). Ectopic overexpression of TSPAN31 facilitated cell proliferation of GC cells, and knockdown of TSPAN31 inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition of GC cells through the PI3K‐Akt pathway and increased cell apoptosis in a TP53 mutation‐independent manner. In vivo analysis also revealed knockdown of TSPAN31 suppressed tumor progression. In addition, knockdown of TSPAN31 improved chemosensitivity to cisplatin through the suppression of ABCC2. These findings suggest that TSPAN31 plays a crucial role in tumor‐malignant potential through overexpression, highlighting its utility as a prognostic factor and a potential therapeutic target in GC. [ABSTRACT FROM AUTHOR]

Introduction: Seprafilm® has been used to prevent postoperative adhesion. However, it is challenging to insert and apply Seprafilm during laparoscopic surgery because of its fragility and sticky nature caused by moisture. Some studies have reported how to apply Seprafilm into a surgical site during laparoscopic surgery; however, some required special equipment with additional costs, and some were technically difficult to use. Herein, we introduced our simple method for applying Seprafilm during laparoscopic surgery. Material and Surgical Technique: Seprafilm was cut into three equal rectangle‐shaped pieces and left to absorb moisture for a few minutes. All three pieces of Seprafilm were placed on the gauze, and the gauze was folded in half and grasped by forceps. The gauze with Seprafilm was inserted through a 12‐mm trocar and placed at the surgical site close to the target place. The gauze functioned as a working station and prevented Seprafilm from directly attaching to the surrounding tissue, which allowed the surgeons to handle it with ease. The gauze was used to press Seprafilm onto the target area and could be easily removed through a 12‐mm trocar. Through this method, Seprafilm was successfully applied in all cases and the average time of applying one sheet was 100 seconds. There was no small bowel obstruction within 30 days after surgery. Discussion: This method neither requires special training nor special equipment only used for Seprafilm. Moreover, it can be easily introduced to every surgeon for the application of Seprafilm during laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Background: A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages. Methods: Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors. Results: The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor. Conclusions: T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients. [ABSTRACT FROM AUTHOR]

The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty‐four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD‐L2 via interferon (IFN)‐related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD‐1 by downregulating the expression of PD‐L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD‐L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD‐L2 and binding ability to PD‐1 via IFN‐related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC. [ABSTRACT FROM AUTHOR]

Circular RNA is a novel endogenous non‐coding RNA that can serve as a biomarker because of its stable loop structure. We investigated and examined the utility of plasma circERBB2 as a prognostic biomarker in 70 patients with gastric cancer who underwent gastrectomy. We investigated by real‐time quantitative PCR the circERBB2 concentrations in the preoperative and postoperative plasma and the circERBB2 expression in the resected tumors. The relationships between circERBB2 concentration in plasma and the clinicopathological features and prognosis were analyzed. circERBB2 was detected in the preoperative plasma samples of 37 patients. The presence of circERBB2 in preoperative plasma (high group) was significantly correlated with lymph node metastasis (P =.035) and tended to be correlated with men (P =.069). Both relapse‐free and overall survival were significantly poor in the high group (P =.001 and P =.009, respectively). The Cox proportional‐hazard model revealed that the high group was an independent prognostic factor of relapse‐free survival (P =.038). Among 16 patients of the high group, 13 patients did not show circERBB2 in the postoperative plasma. The concentration of circERBB2 in plasma was significantly higher in patients with recurrent cancer than those recurrence‐free patients (P <.001). In 2 patients with recurrent cancer, plasma circERBB2 concentrations were increased, whereas, in 2 recurrence‐free patients, these concentrations hardly changed during the treatment progress. The circERBB2 concentrations in preoperative plasma samples can be considered as a noninvasive prognostic biomarker for gastric cancer. Furthermore, monitoring the postoperative plasma circERBB2 concentrations may be useful for detecting gastric cancer recurrences. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients. Glutathione S‐transferase Pi 1 (GSTP1) promoted tumor growth and cancer drug resistance in esophageal squamous cell carcinoma (ESCC) cell lines. GSTP1 protein expression in resected ESCC tissues with neoadjuvant chemotherapy was significantly associated with clinical downstaging and correlated with that in biopsy samples. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) has been reported in several cancers included colorectal cancer; however, it is not clear if there is an association between NLR and cancer-specific survival in colorectal cancer. And the optimal cut-off value is controversial. This study was designed to assess the prognostic value of preoperative NLR in colorectal cancer patients. Methods: Total 823 consecutive patients who underwent surgery for all stages of colorectal cancer in our hospital between January 2006 and December 2011 were included in the study. Preoperative NLR was calculated from their hospital records. Results: Using the receiver-operating characteristic curve, we found that the optimal preoperative NLR cut-off value that was strongly associated with cancer-specific survival was 2.1. Using this value, 505 patients were identified as having high NLR (≥2.1) and 397 patients were identified as having low NLR (<2.1). High NLR was associated with preoperative serum albumin values <4.0 g/dl ( p < 0.001), positive preoperative serum C-reactive protein (CRP; p < 0.001), preoperative carcinoembryonic antigen (CEA) values ≥5.0 ng/dl ( p = 0.003), and stage progression ( p = 0.002). Cox proportional hazard analyses identified preoperative high NLR as an independent poor prognostic factor ( p = 0.020, HR 1.66 (95 % CI: 1.08-2.63)). When comparing stage of disease, preoperative high-NLR patients with Stage III disease ( p = 0.024) and Stage IV disease ( p = 0.036) had significantly poorer prognoses. Conclusions: In this study, we have demonstrated that preoperative NLR ≥2.1 was a prognostic indicator for cancer-specific survival of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma ( HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC. [ABSTRACT FROM AUTHOR]

Asian J Endosc Surg. 2019; 12 (1): 111 - 3. 5 Karabay O, Gurbuz B, Zenger S, Balik E, Bugra D. Laparoscopic colon resection in patients with situs inversus totalis: Is it the same operation as in patients without situs inversus totalis? However, laparoscopic surgery for patients with situs inversus totalis requires careful consideration before and during surgery. Although several cases of laparoscopic surgery for patients with situs inversus totalis have been previously reported2-6, safe and secure laparoscopic surgery for patients with situs inversus totalis still remains challenging. [Extracted from the article]

The nickel-mediated [3+2] cycloaddition of 2-trifluoromethyl-1-alkenes with alkynes afforded fluorine-containing multi-substituted cyclopentadienes in a regioselective manner. This reaction involves the consecutive two CF bond cleavage of a trifluoromethyl or a pentafluoroethyl group through β-fluorine elimination. [ABSTRACT FROM AUTHOR]

Recent studies have shown that some members of the tripartite motif-containing protein ( TRIM) family, which is characterized by a conserved RING finger, B-box, and coiled-coil domains, function as important regulators for carcinogenesis. In this study, we tested whether TRIM44 (11p13) acts as a cancer-promoting gene through overexpression in gastric cancer. We analyzed seven gastric cancer cell lines and 112 primary tumors, which were curatively resected in our hospital between 2001 and 2003. Expression of the TRIM44 protein was detected in gastric cancer cell lines (2/7 cell lines; 29%) and primary tumor samples of gastric cancer (29/112 cases; 25%). Knockdown of TRIM44 expression using several specific si RNAs inhibited the proliferation, migration, and invasion of TRIM44-overexpressing cells. Overexpression of the TRIM44 protein was significantly correlated with an advanced type of macroscopic appearance, lymphatic invasion, and higher recurrence rate. TRIM44-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors ( P = 0.0038, log-rank test) in both intensity and proportion expression-dependent manner. TRIM44 positivity was independently associated with worse outcome in multivariate analysis ( P = 0.0233, hazard ratio 3.37 [1.18-9.64]). These findings suggest that TRIM44 plays a crucial role in tumor cell proliferation through its overexpression, and highlight its usefulness as a predictor and potential therapeutic target in gastric cancer. [ABSTRACT FROM AUTHOR]

The carbon–fluorine bond is known as one of the strongest chemical bonds. It is typically difficult to cleave, however, this cleavage can be achieved by a metal‐mediated approach involving oxidative addition. In their Communication on page 7564 ff., J. Ichikawa and co‐workers demonstrate a new method for CF bond cleavage that utilizes β‐fluorine elimination for a nickel‐mediated [3+2] cycloaddition. The cover image illustrates two different tools for processing wood—a metal saw (oxidative addition) and a chisel (β‐elimination)—as an analogy to the methods for metal‐mediated CF bond cleavage. [ABSTRACT FROM AUTHOR]

Die Kohlenstoff ‐ Fluor ‐ Bindung ist eine der stärksten chemischen Bindungen überhaupt und typischerweise schwer zu spalten. Eine Möglichkeit bieten metallvermittelte Ansätze unter Beteiligung einer oxidativen Addition. J. Ichikawa und Mitarbeiter präsentieren in ihrer Zuschrift auf S. 7694 ff. eine neue Methode zur C ‐ F ‐ Bindungsspaltung, die eine β ‐ Fluor ‐ Eliminierung für eine nickelvermittelte [3+2] ‐ Cycloaddition nutzt. Das Titelbild zeigt zwei Werkzeuge für die Holzbearbeitung – eine Metallsäge (oxidative Addition) und ein Stemmeisen (β ‐ Eliminierung) – in Analogie zu den Methoden der metallvermittelten C ‐ F ‐ Bindungsspaltung. [ABSTRACT FROM AUTHOR]