Intraperitoneal Paclitaxel Combined with S-1 Plus Oxaliplatin for Advanced Gastric Cancer with Peritoneal Metastasis: a Phase I Study

Purpose@#We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. @*Materials and Methods@#Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m2 /day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m2 on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m2 , and the dose escalation was set in units of 20 mg/m2 up to 80 mg/m2 . Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. @*Results@#Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m2 . Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. @*Conclusions@#The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m2 , when combined with a systemic SOX regimen.

Clinical Implications of Microsatellite Instability in Early Gastric Cancer

PURPOSE: We aimed to evaluate the clinical characteristics of microsatellite instability in early gastric cancer.MATERIALS AND METHODS: The microsatellite instability status of resected early gastric tumors was evaluated using two mononucleotide repeat markers (BAT25 and BAT26) and three dinucleotide repeat markers (D5S346, D2S123, and D17S250). Tumors with instability in two or more markers were defined as microsatellite instability-high (MSI-H) and others were classified as microsatellite stable (MSS).RESULTS: Overall, 1,156 tumors were included in the analysis, with 85 (7.4%) classified as MSI-H compared with MSS tumors. For MSI-H tumors, there was a significant correlation with the female sex, older age, tumor location in the lower gastric body, intestinal histology, lymphovascular invasion (LVI), and submucosal invasion (P<0.05). There was also a trend toward an association with lymph node (LN) metastasis (P=0.056). In mucosal gastric cancer, there was no significant difference in MSI status in tumors with LN metastasis or tumors with LVI. In submucosal gastric cancer, LVI was more frequently observed in MSI-H than in MSS tumors (38.9% vs. 25.0%, P=0.027), but there was no difference in the presence of LN metastases. The prognosis of MSI-H tumors was similar to that of MSS tumors (log-rank test, P=0.797, the hazard ratio for MSI-H was adjusted by age, sex, pT stage, and the number of metastatic LNs, 0.932; 95% confidence interval, 0.423–2.054; P=0.861).CONCLUSIONS: MSI status was not useful in predicting prognosis in early gastric cancer. However, the frequent presence of LVI in early MSI-H gastric cancer may help guide the appropriate treatment for patients, such as endoscopic treatment or limited LN surgical dissection.

Similar Operative Outcomes between the da Vinci Xi® and da Vinci Si® Systems in Robotic Gastrectomy for Gastric Cancer

PURPOSE: The robotic system for surgery was introduced to gastric cancer surgery in the early 2000s to overcome the shortcomings of laparoscopic surgery. The more recently introduced da Vinci Xi® system offers benefits allowing four-quadrant access, greater range of motion, and easier docking through an overhead boom rotation with laser targeting. We aimed to identify whether the Xi® system provides actual advantages over the Si® system in gastrectomy for gastric cancer by comparing the operative outcomes. MATERIALS AND METHODS: We retrospectively reviewed all patients who underwent robotic gastrectomy as treatment for gastric cancer from March 2016 to March 2017. Patients' demographic data, perioperative information, and operative and pathological outcomes were collected and analyzed. RESULTS: A total of 109 patients were included in the Xi® group and 179 in the Si® group. Demographic characteristics were similar in both groups. The mean operative time was 229.9 minutes in the Xi® group and 223.7 minutes in the Si® group. The mean estimated blood loss was 72.7 mL in the Xi® group and 62.1 mL in the Si® group. No patient in the Xi® group was converted to open or laparoscopy, while 3 patients in the Si® group were converted, 2 to open surgery and 1 to laparoscopy, this difference was not statistically significant. Bowel function was resumed 3 days after surgery, while soft diet was initiated 4 days after surgery. CONCLUSIONS: We found no difference in surgical outcomes after robotic gastrectomy for gastric cancer between the da Vinci Xi® and da Vinci Si® procedures.

Prognostic Impact of Extended Lymph Node Dissection versus Limited Lymph Node Dissection on pN0 Proximal Advanced Gastric Cancer: a Propensity Score Matching Analysis

PURPOSE: Splenic hilar lymph node dissection (LND) during total gastrectomy is regarded as the standard treatment for proximal advanced gastric cancer (AGC). This study aimed to investigate whether splenic hilar LND or D2 LND is essential for proximal AGC of pT2-4aN0M0 stage. MATERIALS AND METHODS: Data of curative total gastrectomies (n=370) performed from 2000 to 2010 for proximal AGC of pT2-4aN0 stage were retrospectively reviewed. Clinicopathological characteristics and long-term outcomes were compared using propensity score matching between patients who underwent splenectomy (n=43) and those who did not (n=327) and between patients who underwent D2 LND (n=122) and those who underwent D1+ LND (n=248). RESULTS: Tumors of larger size and a more advanced T stage and significantly lower overall and relapse-free survival (P<0.001) were observed in the splenectomy group than in the 2 spleen-preserving groups. Before propensity score matching, worse overall and relapse-free survival (P<0.001) was observed in the splenectomy group than in the non-splenectomy group. After matching, although the overall survival became similar (P=0.123), relapse-free survival was worse in the splenectomy group (P=0.021). Compared with D1+ LND, D2 LND had no positive impact on the overall (P=0.619) and relapse-free survival (P=0.112) after propensity score matching. CONCLUSIONS: Splenic hilar LND with or without splenectomy may not have an oncological benefit for patients with pathological AGC with no LN metastasis.

Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial

PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.

Modification of the TNM Staging System for Stage II/III Gastric Cancer Based on a Prognostic Single Patient Classifier Algorithm

PURPOSE: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. MATERIALS AND METHODS: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. RESULTS: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P < 0.001) and 2.54 (95% CI, 1.84–3.50; P < 0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P < 0.001). CONCLUSIONS: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

The Statistical Analysis on the Postmortem Inspection Cases of National Forensic Service Seoul Institute in 2016 / 대한법의학회지

From January 1, 2016 to December 31, 2016, a total of 1147 postmortem inspection cases in Area 8, Seoul Metropolitan Police Agency (Gangseo, Yangcheon, and Guro police stations) were statistically analyzed. Autopsies were performed in 205 cases (17.9%), and the autopsy rates were 17.6% (75/426 cases) in the Gangseo police station, 9.5% (34/357 cases) in the Yangcheon police station, and 24.3% (82/337 cases) in the Guro police station. For 288 cases with an unknown cause of death, the autopsy rates were 70.0% (60/87 cases) in the Gangseo police station, 28.6% (26/91 cases) in the Yangcheon police station, and 63.1% (65/103 cases) in the Guro police station. For 65 cases due to fall from height, the autopsy rate was 7.7% (n=5). Of the 187 cases due to hanging, 155 cases were classified as suicide at the scene with a 4.5% (n=7) autopsy rate and 32 cases were classified as an undetermined manner of death at the scene with a 15.6% (n=5) autopsy rate. The distribution of the “manner of death” was natural death, 45% (n=516); unnatural death, 29.9% (n=343); and other and undetermined, 25.1% (n=288). Proportions of dispatch times were 50.9% (584 cases) during work hours (09:00–18:00), 13.8% (n=158) during evening hours (18:00–21:00), 13.4% (n=154) at night (21:00–00:00), 11% (n=126) at dawn (00:00–06:00), and 10.9% (n=125) during morning hours (06:00–09:00). The male-to-female ratio was 1.86:1 (746:401). These statistics are valuable for the evaluation of postmortem inspections by experts.

A pictorial review of signature patterns living in musculoskeletal ultrasonography

The musculoskeletal system is mainly composed of the bones, muscles, tendons, and ligaments, in addition to nerves and blood vessels. The greatest difficulty in an ultrasonographic freeze-frame created by the examiner is recognition of the targeted structures without indicators, since an elephant's trunk may not be easily distinguished from its leg. It is not difficult to find descriptive ultrasonographic terms used for educational purposes, which help in distinguishing features of these structures either in a normal or abnormal anatomic condition. However, the terms sometimes create confusion when describing common objects, for example, in Western countries, pears have a triangular shape, but in Asia they are round. Skilled experts in musculoskeletal ultrasound have tried to express certain distinguishing features of anatomic landmarks using terms taken from everyday objects which may be reminiscent of that particular feature. This pictorial review introduces known signature patterns of distinguishing features in musculoskeletal ultrasound in a normal or abnormal condition, and may stir the beginners' interest to play a treasure-hunt game among unfamiliar images within a boundless ocean.

A pictorial review of signature patterns living in musculoskeletal ultrasonography

The musculoskeletal system is mainly composed of the bones, muscles, tendons, and ligaments, in addition to nerves and blood vessels. The greatest difficulty in an ultrasonographic freeze-frame created by the examiner is recognition of the targeted structures without indicators, since an elephant's trunk may not be easily distinguished from its leg. It is not difficult to find descriptive ultrasonographic terms used for educational purposes, which help in distinguishing features of these structures either in a normal or abnormal anatomic condition. However, the terms sometimes create confusion when describing common objects, for example, in Western countries, pears have a triangular shape, but in Asia they are round. Skilled experts in musculoskeletal ultrasound have tried to express certain distinguishing features of anatomic landmarks using terms taken from everyday objects which may be reminiscent of that particular feature. This pictorial review introduces known signature patterns of distinguishing features in musculoskeletal ultrasound in a normal or abnormal condition, and may stir the beginners' interest to play a treasure-hunt game among unfamiliar images within a boundless ocean.

Comparison of Ramosetron Plus Dexamethasone with Ramosetron Alone on Postoperative Nausea, Vomiting, Shivering and Pain after Thyroid Surgery

BACKGROUND: Postoperative nausea and vomiting (PONV), postanesthetic shivering and pain are common postoperative patient complaints that can result in adverse physical and psychological outcomes. Some antiemetics are reported to be effective in the management of postoperative pain and shivering, as well as PONV. We evaluated the efficacy of dexamethasone added to ramosetron on PONV, shivering and pain after thyroid surgery. METHODS: One hundred and eight patients scheduled for thyroid surgery were randomly allocated to three different groups: the control group (group C, n = 36), the ramosetron group (group R, n = 36), or the ramosetron plus dexamethasone group (group RD, n = 36). The patients were treated intravenously with 1 and 2 ml of 0.9% NaCl (group C); or 2 ml of 0.15 mg/ml ramosetron plus 1 ml of 0.9% NaCl (group R); or 2 ml of 0.15 mg/ml ramosetron plus 1 ml of 5 mg/ml dexamethasone (group RD) immediately after anesthesia. RESULTS: Incidence of nausea and the need for rescue antiemetics, verbal rating scale (VRS) 1 hour pain value, ketorolac consumption, and incidence of shivering were significantly lower in group R and group RD, than in group C (P < 0.05). Moreover, these parameters were significantly lower in group RD than in group R (P < 0.05). CONCLUSIONS: Combination of ramosetron and dexamethasone significantly reduced not only the incidence of nausea and need for rescue antiemetics, but also the VRS 1 hour pain value, ketorolac consumption, and the incidence of shivering compared to ramosetron alone in patients undergoing thyroid surgery.