Tumor Depth Prediction of Gastric Cancer With a T4 Score.

BACKGROUND/AIM: Peritoneal metastases are often found at surgery of pT4 gastric cancers, preventing R0 resection. In the event of successful R0 resection, distant metastases still occur in a sizeable proportion of patients. Estimation of the depth of invasion has a relatively low accuracy (57%-86%) compared with pathological findings. This study sought to develop a clinical score to distinguish between pathological stage T4 (pT4) and pT1-3 gastric cancer. PATIENTS AND METHODS: Reviewing the data of 2,771 patients who had undergone gastrectomy at our hospital from January 1996-December 2016, we assessed demographic factors plus tumor markers, diameter, location, histology, and macroscopic type according to the fifth edition (2019) of the WHO classification. Significant factors on multivariate analysis were used to develop a pT4 gastric cancer depth prediction score (T4 score). RESULTS: Multivariate analysis revealed that the clinical factors associated with pT4 disease were CA19-9 elevation, tumor diameter ≥50 mm, poorly cohesive type adenocarcinoma, mucinous adenocarcinoma, and WHO macroscopic types 2-4. The T4 score was obtained by weighing these factors according to the ß-coefficient. The optimum cutoff value of the T4 score was 4 points. A total of 79.4% of cases with a T4 score ≥4 points were stage pT4. A total of 93.9% of cases with a T4 score <4 points were stage pT1-3, with 91.1% sensitivity, 85.3% specificity, 79.4% positive predictive value, and 93.9% negative predictive value. CONCLUSION: T4 scoring can differentiate pT4 gastric cancer from pT1-3 gastric cancer.

Phase II study of neoadjuvant chemotherapy with S-1 plus oxaliplatin for gastric cancer clinical T4 or N2-3.

In Japan, the standard treatment for stage II or III gastric cancer is D2 gastrectomy followed by administration of S-1 for one year. However, patients with stage III disease have unsatisfactory survival rates. The purpose of this study was to evaluate the efficacy and safety of neoadjuvant chemotherapy consisting of S-1 and oxaliplatin for advanced gastric cancer. Patients with cT4 or cN2-3 gastric cancer were scheduled to receive two courses of chemotherapy (130 mg/m2 oxaliplatin on Day 1, 80 mg/m2 S-1 per day twice daily for 14 days) followed by surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were rates of completion of protocol treatment, pathological response, and adverse events; and 3-year overall survival, 5-year overall survival, and 5-year recurrence-free survival. Between May 2016 and March 2019, 30 patients were enrolled in the study, all of whom completed the protocol treatment. The R0 resection rate (primary endpoint) was 93.3% (95% confidence interval: 77.9-99.2). The pathological response rate was 63.3%. Grade 3-4 toxicities included anemia (3.3%), anorexia (6.7%), and fatigue (3.3%). Relative dose intensities were 91.2% and 94.2% for S-1 and oxaliplatin, respectively. Neoadjuvant S-1 and oxaliplatin is highly effective, achieving an acceptable R0 resection rate with relatively few severe toxicities and good compliance.Trial registration: Registry name: A prospective intervention study on the availability of preoperative SOX therapy for T4 or N2-3 gastric cancer. Trial ID: UMIN: UMIN000024656. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R00002836.

Rapid Flow Cytometry of Gastrointestinal Stromal Tumours Closely Matches the Modified Fletcher Classification.

AIM: We aimed to develop a rapid, simple procedure and an algorithm for quantitative analysis and classification of the metastatic risk of gastrointestinal stromal tumours (GIST) for clinical use. MATERIALS AND METHODS: Eighteen specimens from laparoscopic local gastrectomy were assessed by flow cytometry. We devised a new risk classification for GIST by combining flow cytometry parameters with tumour size and evaluated whether the combined parameters correlated with the modified Fletcher risk classification. RESULTS: We found a significant correlation between clinical prognostic factors (mitotic count and Ki-67 labelling index) and the flow cytometry parameters DNA ploidy, DNA index and S-phase fraction. The combined parameters established from tumour size and the flow cytometry parameters showed a high correlation with the modified Fletcher risk classification (p=0.0064). Flow cytometry had to be performed for approximately 10 minutes to determine the metastatic risk. CONCLUSION: Rapid flow cytometry parameters can classify risk without the need for histological analysis.

Leiomyosarcoma arising from the right ovarian vein.

Leiomyosarcomas (LMS) of the ovarian vein are extremely rare and have a poor prognosis. Only 10 cases have been reported since 1977. The patient is a 69-year-old woman presented with right abdominal pain. Computed tomography showed a regularly shaped tumor, 80 mm in diameter in the retroperitoneum, adjacent to the descending part of the duodenum. Intraoperatively, the right ovarian vein was found to run through the tumor and was, therefore, resected together with the tumor. Pathological examination revealed a LMS of the right ovarian vein. Nine months postoperatively, multiple lung metastases were detected and chemotherapy was initiated. Delayed diagnosis is associated with high mortality. It is important that the diagnosis of LMS should be made preoperatively when you have already diagnosed a tumor to better direct the surgical approach. Multimodal therapy may improve prognosis.

Preoperative high C-reactive protein level is associated with an increased likelihood for conversion from laparoscopic to open appendectomy in patients with acute appendicitis.

Background: Laparoscopic appendectomy (LA) has been increasingly adopted for its advantages over the open appendectomy, but there are possibilities of conversion from laparoscopic to open appendectomy (CA) if the patients had complicated appendicitis concurrently, or when the extent of inflammation prohibits successful procedure. In this retrospective study, we aimed to clarify the preoperative predictors for CA. Patients and methods: From January 2010 to April 2016, medical records of 93 consecutive patients who underwent LA for suspected appendicitis were reviewed retrospectively. Factors evaluated were age, gender, body mass index, C-reactive protein (CRP), white cell count, albumin, Neutrophil count, lymphocyte count, Neutrophil/lymphocyte ratio, preoperative CT imaging (abscess formation: yes/no, appendicolith: yes/no), operative factors (time to operation, amount of bleeding), length of hospital stay, period until oral intake after surgery, and period from initial symptoms to surgery. Results: CA occurred in nine patients (9.7%). The reason for conversion was severe dense adhesion in two cases, inadequate exposure of appendix in two cases, uncompleted appendectomy in two cases, perforated appendicitis in one case, gangrenous appendicitis in one case, and abscess formation in one case. Based on 93 patients evaluated by preoperative CT scan, significant factors in the final multivariate analysis associated with CA was CRP [odds ratio=1.13, 95% CI:1.00-1.28, p=0.04]. Conclusion: Identifying the potential factors for conversion preoperatively may assist the surgeons in making decisions concerning the management of patients with appendicitis and in the judicious use of LA.

[A Case of Synchronous Liver Metastasis of Ascending Colon Cancer with Pathological Complete Response to S-1/Oxaliplatin (SOX) and Bevacizumab].

A 77-year-old man was diagnosed with ascending colon cancer with synchronous liver metastasis. Per our policy we first only performed a right hemicolectomy (pSSN2H2M0, stage IV). We then planned S-1 and oxaliplatin (SOX) plus bevacizumab (Bmab) chemotherapy as a neoadjuvant for the resection of liver metastasis. After 4 courses, enhanced CT and EOB-MRI findings showed the liver tumor had significantly decreased in size with no side effects, and we performed a partial liver resection for the S7 lesion. Postoperatively, histopathological analysis revealed only a fibrotic lesion and no cancerous cells in the resected specimen, indicating that chemotherapy had downgraded the tumor to Grade 3. Adjuvant chemotherapy was not continued owing to the patient's refusal, but no recurrence was noted 18 months after the second operation. SOX plus Bmab chemotherapy is, therefore, effective in terms of its anti-tumor effects, tolerance, and accessibility. We believe SOX plus Bmab chemotherapy can be considered as an effective option for cases with synchronous liver metastasis of colon cancer as neoadjuvant chemotherapy for interval liver resection.

Comparison of clinical outcome of laparoscopic versus open appendectomy, single center experience.

INTRODUCTION: Laparoscopic appendectomy (LA) is now a treatment of choice in patients with appendicitis. This study compares the treatment outcomes of LA and open appendectomies (OA) in our department. PATIENTS AND METHODS: From January 2006 to April 2016 a total of 185 patients underwent appendectomy at our institution. We divided the patients into two groups; LA group (LAG) and OA group (OAG). Following parameters were analyzed: age, gender, preoperative clinicolaboratory characteristics, operative factors, interval appendectomy, length of hospital stay (LHS), and surgical site infections (SSI). RESULTS: There were 93 patients in LA G and 92 in OAG. According to the Univariate analysis, there were statistically significant differences among age (p = 0.037), LHS (p = 0.0001), duration till resuming oral intake (p = 0.016), blood loss (p = 0.038), SSI ratio (p = 0.044) and CRP level (p = 0.038) between the LAG and the OAG. According to the Multivariate analysis, blood loss (p = 0.038) and LHS (p = 0.023) were significantly different between both groups. CONCLUSION: LA was decreasing blood loss and LHS.

Detection of synthetic RGDS(PO3H2)PA peptide adsorption using a titanium surface plasmon resonance biosensor.

The purpose of this study was to measure the time-dependent chemical interaction between synthetic RGDS(PO(3)H(2))PA (P-RGD) peptide and titanium surfaces using a titanium surface plasmon resonance (SPR) biosensor and to determine the degree of peptide immobilization on the surfaces. An SPR instrument for 'single-spot' analysis was used for nanometer-scale detection of biomolecular adsorption using a He-Ne laser light according to Knoll's method. The oxidized titanium surface was etched when exposed to H(3)PO(4) solutions with a pH of 2.0 or below. The amount of P-RGD adsorbed at pH 1.9 was approximately 3.6 times as much as that at pH 3.0 (P < 0.05). P-RGD naturally adsorbed on the oxidized titanium surface as a consequence of the bonding and dissociation mechanism of the phosphate functional group. Furthermore, the control of pH played a very important role in the interaction between P-RGD and the surface. These findings show that pH control may promote progressive binding of biomolecules with the phosphate functional group to the titanium surface.

Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2.

Multiple roles have been already recognized for CCN2 in cartilage development and regeneration. However, the effects of CCN2 on bone regeneration remain to be elucidated. In this study, the utility of CCN2 on bone regeneration was examined in vitro and in vivo in combination with hydroxyapatite (HAp) as a scaffold. Human bone marrow stromal cells (hBMSCs) were isolated from human iliac bone marrow aspirates of healthy donors and expanded, and the effects of CCN2 on their proliferation and migration were examined in vitro. The proliferation of hBMSCs on a plastic or HAp plate was significantly enhanced by CCN2. Moreover, the migration of hBMSCs also dramatically increased by CCN2. Interestingly, a C-terminal signal modular fragment of CCN2 (CT-module) also enhanced the cell proliferation and migration as efficiently as the full-length CCN2. Next, in order to estimate the effect of CCN2 on the migration and survival of hBMSCs and bone formation inside the HAp scaffold in vivo, two experiments were performed. First, the porous HAp carrier was cultured with hBMSCs for a week, and the cell-scaffold hybrid was transplanted with or without CCN2 subcutaneously into immunocompromised mice. CCN2 accelerated the hBMSC-like cell migration and survival inside the porous HAp within 4 weeks after transplantation. Second, the porous HAp carrier with or without CCN2 was directly implanted into bone defects within a rabbit mandible, and bone regeneration inside was evaluated. As a result, CCN2 efficiently induced the cell invasion and bone formation inside the porous HAp scaffold. These findings suggest that CCN2 and its CT-module fragment could be useful for regeneration and reconstruction of large-scale bone defects.

Effect of polyphosphoric acid pre-treatment of titanium on attachment, proliferation, and differentiation of osteoblast-like cells (MC3T3-E1).

PURPOSE: To evaluate the effect of polyphosphoric acid (PPA) pre-treatment of titanium (Ti) on the initial attachment, proliferation, and differentiation of mouse osteoblast-like cells (MC3T3-E1). MATERIALS AND METHODS: Adsorption of PPA to Ti was achieved by immersing Ti disks (15 mm in diameter) into 0, 1, and 10 wt% PPA and 10 wt% orthophosphoric acid (OPA) for 24 h. On each pre-treated Ti disk, 5.0 x 10(4) MC3T3-E1 cells were seeded, and 1, 3, and 5 h later cell attachment was evaluated. Cell proliferation was also determined 1, 3, and 5 days after cell seed. Cell differentiation was evaluated 5, 10, and 15 days after cell seed using osteoblast marker gene expression. Total RNA was purified from each culture and Type-I collagen, alkaline phosphatase, and osteocalcin mRNA expression levels were measured by real-time reverse transcription polymerase chain reaction. RESULTS: Adsorption of PPA or OPA to Ti significantly accelerated initial cell attachment at every time point (P<0.0001). As with cell attachment, cell proliferation was also accelerated on the PPA-treated Ti disks in a dose-dependent manner at every time point (P<0.0001). However, OPA-treated Ti disks did not enhance the cell proliferation. Regarding osteoblastic differentiation, PPA-treated Ti significantly accelerated the Type-I collagen gene expression at 5 and 10 days after cell seed. Regarding alkaline phosphatase and osteocalcin gene expression, no significant difference was found among the different Ti surface conditions. CONCLUSION: The accelerated cell behavior following Ti pre-treatment with PPA is a promising new strategy to fabricate bioactive Ti implants.

NMR study on the adhesion efficacy of experimental phosphonic acid monomers.

Three experimental self-etching primers - consisting of N-methacryloyl-omega-aminoalkyl phosphonic acid (NMomegaP) with different methylene chain lengths and N-methacryloyl glycine (NMGly) - were formulated. The influence of methylene chain length in NMomegaP derivatives on the chemical nature of calcium salts was examined following their application to tooth components. Bond strengths of experimental self-etching primers created with these monomers to enamel and dentin were also investigated. Nuclear magnetic resonance spectroscopy showed that NMomegaPs decalcified tooth components with formation of calcium salts, which changed from calcium hydrogen phosphonate to calcium phosphonate with increase in methylene chain length within the NMomegaP structure. Disparity in calcium salt formation was related to increases in bond strength to enamel from 18 to 24 MPa. However, bond strength to dentin remained unchanged (22 MPa). The relative dependency of bond strength on monomer methylene chain length was probably attributable to the sites where these NMomegaP calcium salts had deposited on the bonding substrates.

Promotion of attachment of human bone marrow stromal cells by CCN2.

Cell attachment is a crucial step in tissue regeneration. In this study, human bone marrow stromal cells (hBMSCs) were isolated, and the effects of CCN2 on their attachment were examined. CCN2 significantly enhanced the hBMSC attachment, and this enhanced cell attachment was mainly regulated by the C-terminal module of CCN2. This enhancement was negated by the anti-integrin alpha(v)beta(3) antibody and p38 MAPK inhibitor, and phosphorylation of p38 MAPK was detected upon the enhanced cell attachment mediated by CCN2. We thus conclude that CCN2 enhances hBMSC attachment via integrin-p38 MAPK signal pathway. Enhanced hBMSC attachment on hydroxyapatite plates by CCN2 further indicated the utility of CCN2 in bone regeneration.

Chemical interaction of polyphosphoric acid with titanium and its effect on human bone marrow derived mesenchymal stem cell behavior.

The aim of this study was to evaluate the effect of treating titanium (Ti) with polyphosphoric acid on the attachment and proliferation of human bone marrow derived mesenchymal stem cells (hBMSCs). Cleaned Ti disks were immersed into three different concentrations of polyphosphoric acid solution (0.1, 1, and 10 wt %) and 10 wt % orthophosphoric acid solution for 24 h at 37 degrees C. Ti immersed in distilled water for 24 h at 37 degrees C served as control. The level of polyphosphoric acid that interacted with the Ti surface was determined by measuring the surface P/Ti ratio (atom%/atom%) using X-ray photoelectron spectroscopy. Degrees of cell attachment (1, 3, 5 h after cell seed) and proliferation (1, 3, 5, and 7 days after cell seed) on each treated Ti disk were evaluated by MTS assay. The mean surface P/Ti ratios increased in a polyphosphoric acid concentration dependent manner. A significantly higher cell attachment was found on Ti treated with polyphosphoric acid in contrast to untreated Ti (control) for all three culture periods. MTS assay also revealed that cell proliferation levels significantly increased following a polyphosphoric acid dose dependency. Ti surface treatment with orthophosphoric acid did not influence the cell attachment and proliferation. It was concluded that polyphosphoric acid treatment of Ti enhanced the attachment and proliferation of hBMSCs.

Cytocompatibility of a tissue conditioner containing vinyl ester as a plasticizer.

In the current study, we examined the cytocompatibility of eight vinyl esters as candidate plasticizers for producing phthalate- and ethanol-free tissue conditioners. We measured the estrogenic activity and cytotoxicity of vinyl esters in human fibroblasts and keratinocytes using an E-screen assay and a mitochondrial dye conversion assay, respectively. We also assessed the cytotoxicity of three prototype materials and commercially available tissue conditioners on human fibroblasts grown in collagen gels. Finally, we measured the effects of these materials on the expression of cytokines in three-dimensional cultures by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays. None of the tested vinyl esters had estrogenic activity. Vinyl octanoate and vinyl pivalate were the least cytotoxic of the eight tested vinyl esters. In the same vein, a prototype tissue conditioner containing vinyl octanoate had equivalent or weaker cytotoxicity and induction of cytokine expression than conventional materials.

Initial tissue response to a titanium implant coated with apatite at room temperature using a blast coating method.

We previously reported a blast coating method (BC method) as a new coating method of titanium (Ti) with apatite (AP) at room temperature. The BC method gives much stronger AP coating on the Ti surface compared with those obtained by other room temperature coating methods. However, no in vivo study has been made, so far, to evaluate the stability or the tissue response to the implant. As an initial step to evaluate the feasibility of the BC method, we evaluated the tissue response and stability of AP coated Ti implant prepared with the BC method (AP-BC implant) using rats as experimental animals. The AP coating adhered tightly to the Ti surface even after the implant procedure and throughout the experimental period up to six weeks post operation. AP-BC implant caused no inflammatory response, showed strong bone response and much better osteoconductivity compared with the pure Ti implant. The new bone formed on the surface of AP-BC implants was thinner compared with that formed on the surface of Ti implant. Therefore, the AP-BC implant has a good potential as an osteoconductive implant material.