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.

Ultra-structural evaluation of an anodic oxidated titanium dental implant.

Anodic oxidation is used for the surface treatment of commercial implants to improve their functional properties for clinical success. Here we conducted ultrastructural and chemical investigations into the micro- and nanostructure of the anodic oxide film of a titanium implant. The anodic oxidized layer of a Ti6Al4V alloy implant was examined ultrastructurally by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). They were also analyzed using energy dispersive X-ray spectrometry (EDS) and X-ray photoelectron spectroscopy (XPS). The TEM revealed that the oxide layer of the Ti6Al4V implant prepared through anodic oxidation was separated into two layers. Al and V were not present on the top surface of the anodic oxide. This can be attributed to the biocompatibility of the anodic oxidized Ti6Al4V alloy implant, because the release of harmful metal ions such as Al and V can be suppressed by the biocompatibility.

Effect of low-shrinking composite on the bonding effectiveness of two adhesives in occlusal Class-I cavities.

The purpose of this study was to evaluate if a low-shrinking composite can improve the bonding effectiveness of adhesives in highly constrained conditions. A low-shrinking composite ('els-extra low shrinkage', Saremco) was bonded in standardized occlusal Class-I cavities using a three-step ('cmf', Saremco) and a two-step etch-and-rinse adhesive ('XP Bond', Dentsply). Both adhesives were also combined with a conventional composite ('Z100', 3M ESPE). Half of the restored cavities were exposed to 20,000 thermo-cycles. 3-way ANOVA revealed a significant effect for the factors 'adhesive' and 'composite' (both p<0.0001), but not for 'thermo-cycling' (p=0.994). Significantly higher bond strengths were recorded for the low-shrinking composite than for the control composite, using either of the adhesives. The low-shrinking composite in combination with the three-step etch-and-rinse adhesive performed best in the high C-factor Class-I cavity. The two-step etch-and-rinse adhesive suffered strongly from polymerization-shrinkage stress, which could be partially restored by using the low-shrinking composite.

Real time assessment of surface interactions with a titanium passivation layer by surface plasmon resonance.

Due to the high corrosion resistance and strength to density ratio titanium is widely used in industry, and also in a gamut of medical applications. Here we report for the first time on our development of a titanium passivation layer sensor that makes use of surface plasmon resonance (SPR). The deposited titanium metal layer on the sensor was passivated in air, similarly to titanium medical devices. Our "Ti-SPR sensor" enables analysis of biomolecule interactions with the passivated surface of titanium in real time. As a proof of concept, corrosion of a titanium passivation layer exposed to acid was monitored in real time. The Ti-SPR sensor can also accurately measure the time-dependence of protein adsorption onto the titanium passivation layer at sub-nanogram per square millimeter accuracy. Besides such SPR analyses, SPR imaging (SPRI) enables real time assessment of chemical surface processes that occur simultaneously at "multiple independent spots" on the Ti-SPR sensor, such as acid corrosion or adhesion of cells. Our Ti-SPR sensor will therefore be very useful to study titanium corrosion phenomena and biomolecular titanium-surface interactions with application in a broad range of industrial and biomedical fields.

Effect of functional monomers in all-in-one adhesive systems on formation of enamel/dentin acid-base resistant zone.

This study aimed at evaluating the effect of functional monomers in all-in-one adhesive systems on formation of acid-base resistant zone (ABRZ) in enamel and dentin. Experimental adhesive systems containing one of three functional monomers; MDP, 3D-SR and 4-META were applied to enamel or dentin surface and light-cured. A universal resin composite was then placed. The specimens were subjected to a demineralizing solution (pH 4.5) and 5% NaClO for acid-base challenge and then observed by SEM. The ABRZ was clearly observed in both enamel and dentin interfaces. However, enamel ABRZ was thinner than dentin ABRZ in all adhesives. Morphology of the ABRZ was different between enamel and dentin, and also among the adhesives. Funnel-shaped erosion was observed only in the enamel specimen with the 4-META adhesive. The formation of enamel/dentin ABRZ was confirmed in all adhesives, but the morphology was influenced by the functional monomers.

Hydrolytic stability of one-step self-etching adhesives bonded to dentin.

PURPOSE: To evaluate the hydrolytic stability of three one-step self-etching adhesives (1-SEAs) bonded to dentin through bond strength testing and ultra-morphological interfacial analysis before and after long-term thermocycling. MATERIALS AND METHODS: Eighteen flattened mid-coronal dentin surfaces of extracted human molars were subjected to bonding treatment using three 1-SEAs (Clearfil S3 Bond, Kuraray (S3), G-Bond, GC (GB), Absolute, Dentsply-Sankin (AB)), after which the bonded surfaces were built up with composite. After storage overnight at 37°C, the specimens were sectioned into slabs and further trimmed into an hourglass shape with an interface area of approximately 1 mm2. The specimens were left untouched (control) or were thermocycled for 100,000 cycles. The microtensile bond strength (µTBS) was measured and the ultrastructure of the adhesive/dentin interface characterized using transmission electron microscopy (TEM). RESULTS: Long-term thermocycling significantly decreased the µTBS of all one-step adhesives tested (p < 0.05, one way ANOVA and Games-Howell test). TEM revealed a similar interfacial ultrastructure before and after thermocycling for S3. For GB, many voids were observed at the interface after 100,000 thermocycles. Regarding AB, collagen fibrils could no longer be clearly observed upon staining, while the adjacent unaffected dentin was rich in voids. CONCLUSION: The bond strength and ultramorphological data demonstrated that the bond of 1-SEAs to dentin degrades with time, although the degree of degradation is obviously material dependent.

Nanolayering of phosphoric acid ester monomer on enamel and dentin.

Following the "adhesion-decalcification" concept, specific functional monomers possess the capacity to primary chemically interact with hydroxyapatite (HAp). Such ionic bonding with synthetic HAp has been demonstrated for 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP), manifest as self-assembled "nanolayering". In continuation of that basic research this study aimed to explore whether nanolayering also occurs on enamel and dentin when a 10-MDP primer is applied following a common clinical application protocol. Therefore, the interaction of an experimental 10-MDP primer and a control, commercially available, 10-MDP-based primer (Clearfil SE Bond primer (C-SE), Kuraray) with enamel and dentin was characterized by X-ray diffraction (XRD), complemented with transmission electron microscopy interfacial ultrastructural data upon their reaction with enamel and dentin. In addition, XRD was used to study the effect of the concentration of 10-MDP on nanolayering on dentin. Finally, the stability of the nanolayers was determined by measuring the bond strength to enamel and dentin when a photoinitiator was added to the experimental primer or when interfacial polymerization depended solely on the photoinitiator supplied with the subsequently applied adhesive resin. XRD confirmed nanolayering on enamel and dentin, which was significantly greater on dentin than on enamel, and also when the surface was actively rubbed with the primer. Nanolayering was also proportional to the concentration of 10-MDP in the primer. Finally, the experimental primer needed the photoinitiator to obtain a tensile bond strength to dentin comparable with that of the control C-SE primer (which also contains a photoinitiator), but not when bonded to enamel. It is concluded that self-assembled nanolayering occurs on enamel and dentin, even when following a clinically used application protocol. The lower bonding effectiveness of mild self-etch adhesives to enamel should be ascribed in part to a lower chemical reactivity (nanolayering) with enamel HAp.

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.

Degree of immobilization of synthetic RGDS(PO(3)H(2))PA peptides on titanium surfaces.

The purpose of this study was to characterize the chemical interaction between titanium surfaces and the peptide RGDS(PO(3)H(2))PA (P-RGD) synthesized from RGD peptide (RGD) and o-phospho-L-serine (P-Ser), and to determine the degree of peptide immobilization on the titanium surface. X-ray photoelectron spectroscopy showed that the adsorption amount of RGD was significantly smaller than those of P-Ser and P-RGD (p<0.05). Furthermore, although it appeared that P-RGD bonded to the surface, ultrasonic rinsing with water caused it to dissociate, releasing RGD and leaving only S(PO(3)H(2))PA bonded to the surface. These findings show that although it remains difficult to obtain a stable P-RGD layer, the phosphate functional group greatly improves immobilization of the molecule on titanium surfaces.

The quasi-three-dimensional marginal leakage of full-coverage crowns: resin coating versus sodium hypochlorite treatment.

This study compared the effects of various surface treatments and techniques on the marginal leakage of full-coverage crowns using a quasi-three-dimensional evaluation. Crowns were cast using a gold-silver-palladium alloy by means of the lost-wax technique. Twenty-eight recently extracted human molars were divided randomly into four groups according to surface treatment before crown cementation: (1) no pretreatment (negative control), (2) primer (positive control), (3) resin coating and primer, and (4) phosphoric acid, sodium hypochlorite, and primer. All specimens were cemented with composite cement. The lowest marginal leakage was observed in group 4. Variation in marginal leakage between specimens originating from the same tooth was observed.

Stress distribution prevents ischaemia and bone resorption in residual ridge.

OBJECTIVE: Intensive mechanical stress and/or inflammation are known to induce alveolar bone resorption. This study investigated whether a distribution of mechanical stress would reduce residual ridge resorption or improve ischaemia. DESIGN: Thirty rats were divided into six experimental groups (n=5). The control group received no intentional stimulation, but rats in the experimental groups wore denture stimulators made of acrylic resin or a soft lining material. The stimulator transmitted masticatory pressure to the rats' palates for four weeks. The four types of soft lining materials investigated in this study dispersed the applied pressure, with compressive stress ranging from 20.8 to 90.8kPa. Volumes of blood flow and bone resorption of denture foundations were measured every week for 4 weeks. Statistical evaluation of these results was performed using two-way ANOVA and Holm-Sidak test within 5% error limits. RESULTS: Non-viscoelastic material clearly induced bone resorption and ischaemia of denture foundations, while viscoelastic materials reduced these phenomena to different extents according to their viscoelastic properties. Ischaemia in the alveolar ridge preceded residual ridge resorption, because the amount of residual ridge resorption and blood flow rate showed a simple linear regression. CONCLUSION: Animal model of this study suggested that a distribution or reduction of mechanical stress could improve blood flow and decrease alveolar ridge resorption.

Visible light-induced crosslinkable gelatin.

A novel visible light-crosslinkable porcine gelatin was prepared for gelation and micropatterning. The preparation employed a photo-oxidation-induced crosslinking mechanism. First, furfuryl groups were incorporated into the gelatin. Second, the modified gelatin was mixed in water with Rose Bengal, which is a visible light sensitizer. Irradiation by visible light solidified the aqueous solution. In addition, when the solution was cast on a plate, dried and photo-irradiated in the presence of a photomask a micropattern was formed that matched the micropattern on the photomask. The gelatin-immobilized regions enhanced cell adhesion. It was also confirmed that the gelatin incorporating furfuryl and Rose Bengal have no significant toxicity. The photo-crosslinkable gelatin was employed as a direct pulp capping material in the dental field. Considering these results, this system could be useful as a new type of visible light-induced crosslinkable biosealant.

Mechanical properties of a resin-modified glass ionomer cement for luting: effect of adding spherical silica filler.

This study investigated the effects of spherical silica filler (SSF) on the workability and mechanical properties of resin-modified glass ionomer cements for luting (RMGICL). Varying powder/liquid ratios (P/L=2.0, 2.2, 2.4, and 2.6) of a commercially available glass ionomer cement (Fuji Lute, GC Corp.) were mixed with SSF at different weight percentages (5, 7.5, and 10%). On film thickness, statistically significant effects of SSF addition were noted at 2.5 minutes after mixing started, notably at P/L=2.4 and 2.6 when 7.5 and 10 wt% of SSF were added. The same result was also obtained for consistency evaluation. On mechanical and bonding strengths to the tooth substrate, no statistically significant differences were observed among all the SSF weight percentages within each P/L ratio. SSF-added RMGICL at a higher powder/liquid ratio exhibited increased mechanical and bonding strengths when compared to a control without SSF addition, but nonetheless maintained the film thickness with no further increase.

Nano-controlled molecular interaction at adhesive interfaces for hard tissue reconstruction.

Although decayed/fractured teeth can be reconstructed minimally invasively and nearly invisibly using adhesive technology, the clinical longevity of dental composite restorations is still too short. Water sorption is thought to be the principal cause of destabilization of the biomaterial-tooth bond. However, the actual mechanisms of interfacial degradation are far from understood. Here we report how nano-controlled molecular interaction at the biomaterial-hard tissue interface can improve bond durability. The use of functional monomers with a strong chemical affinity for the calcium in hydroxyapatite is essential for long-term durability. Correlative X-ray diffraction and solid-state nuclear magnetic resonance disclosed a time-dependent molecular interaction at the interface with stable ionic bond formation of the monomer to hydroxyapatite competing in time with the deposition of less stable calcium phosphate salts. The advanced tooth-biomaterial interaction model gives not only an insight into the mechanisms of bond degradation, but also provides a basis to develop functional monomers for more durable tooth reconstruction.