Background
Preoperative chemotherapy with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for ...advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis. In the JCOG1002, we added docetaxel to CS (DCS) to further improve long-term outcomes. However, the primary endpoint, clinical response rate (RR), did not reach the expected level (Ito et al. in Gastric Cancer 20:322–31, 2017). Herein, we report our long-term survival results.
Methods
Patients with BN and/or PAN metastasis received 2 or 3 cycles of DCS therapy (docetaxel at 40 mg/m
2
and cisplatin at 60 mg/m
2
on day 1 and S-1 at 80 mg/m
2
per day for 2 weeks, followed by a 2-week rest) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year.
Results
Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% had both PAN and BN metastasis, and the rest had either PAN (26.4%) or BN (56.6%) metastasis. Among all eligible patients, the 5-year overall survival was 54.9% (95% confidence interval 40.3–67.3%) at the last follow-up in May 2018. Among 44 eligible patients with R0 resection, the 5-year relapse-free survival was 47.7% (95% confidence interval 32.5–61.5%).
Conclusions
Adding docetaxel to CS in preoperative chemotherapy for extensive nodal metastasis improved neither short-term outcomes nor long-term survival. Preoperative chemotherapy with CS followed by D2 + PAN dissection and postoperative S-1 remains the standard of care for patients with extensive nodal metastasis.
Scab, caused by
Venturia nashicola
, is the most important disease of Asian pears. In Japan, the most popular and widely grown pear cultivar (cv.) Kousui is resistant to black spot, caused by the ...Japanese pear pathotype of
Alternaria alternata
, but highly susceptible to scab. Recently, a new interspecific pear cv. Yutaka carrying high fruit quality was registered officially after a cross between the Chinese pear cv. Hongli and the Japanese pear cv. Housui. Accordingly, tests were conducted to assess resistance of cv. Yutaka to scab, black spot and anthracnose. When conidial suspensions of
V. nashicola
were spray inoculated onto potted trees, leaves of cv. Yutaka showed no disease symptoms although severe scab development was recorded on the susceptible reference cv. Kousui. Furthermore, neither black spot symptoms nor necrosis formation were observed when leaves of cv. Yutaka were inoculated with conidial suspensions of the
A. alternata
Japanese pear pathotype or treated with a culture filtrate containing the host-specific AK-toxin of this pathogen, respectively. These results strongly indicate that cv. Yutaka is highly resistant to scab and black spot. Inoculation tests also suggested the potential high levels of resistance of cv. Yutaka to anthracnose caused by
Colletotrichum gloeosporioides
sensu lato. The introduction of this new pear cultivar will reduce fungicide applications in pear orchards and thus lower the risk of fungicide resistance development in these pathogens.
In-situ reflectance interferometry was utilized in this study to understand the characteristics of the reflectance profile for the growth of heteroepitaxial diamonds. We observed the time-resolved ...Fabry-Pérot oscillation of the growing heteroepitaxial diamond. Oscillations in the reflectance profile provided information on the grown thickness and provided the growth rate in real-time. The obtained in-situ profile was experimentally compared with the actual growth status via ex-situ observations and the strong correlation between the in-situ profile and the actual growth status was suggested. The analysis of the profiles provided a reasonable prediction to whether there would be any unexpected growth behavior in real-time for heteroepitaxial diamond growth.
Display omitted
•In-situ reflectance interferometry was demonstrated for heteroepitaxial diamonds.•Time-resolved Fabry-Pérot oscillation was observed in the reflectometry.•Growth rate estimation of heteroepitaxial diamonds was possible in real-time.•Important growth event such as layer coalescence was observed in real-time.
Adiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to ...evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity.
Overall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples.
The serum adiponectin level was 2.9 μg/mL (1.7-4.1 μg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1-2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001).
The serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass.
IL-1 functions as an essential pro-inflammatory mediator for the sensitisation of allergic contact dermatitis (ACD). However, studies conducted to date have typically used a limited number of haptens ...and examined their effects only on murine ACD or murine dendritic cells (DCs). It therefore remains unclear whether IL-1α and/or IL-1β is produced in ACD induced by haptens other than those commonly used in mouse ACD models, and whether they are essential for sensitisation leading to ACD in humans. In addition, it is unclear whether human DCs also produce IL-1α or IL-1β after stimulation by haptens in general. Here, we first demonstrated that 10 haptens (3 extreme, 1 strong, 3 moderate and 3 weak) increased both IL-1α mRNA and IL-1β mRNA expression by the human monocyte cell line THP-1, a commonly used surrogate of DCs in in vitro skin sensitisation tests. Next, we constructed an in vitro skin sensitisation test using a stable IL-1β reporter cell line, THP-G1b, and evaluated whether 88 haptens and 34 non-haptens increase IL-1β reporter activity. We found that 94% of 77 haptens evaluated after considering their applicability domain and solubility in the chosen media stimulated reporter activity. These studies demonstrated that most haptens, irrespective of their potency, increased IL-1β mRNA expression by THP-1 cells, confirming that human DCs also produce IL-1β after stimulation by most haptens. The luciferase assay using THP-G1b cells is thus another skin sensitisation test based on the adverse outcome pathway with reasonable performance.
To investigate the residual pattern of esophageal cancer in the esophageal wall after neoadjuvant chemotherapy (NAC) and its clinical significance.
NAC is a standard treatment for locally advanced ...esophageal cancer; however, residual tumor patterns in resected specimens after NAC and their clinico-pathological characteristics remain unknown.
One hundred twenty consecutive patients with cT3 or deeper esophageal cancer underwent curative esophagectomy after NAC and achieved grade 2 histological responses between 2000 and 2016. Hematoxylin-eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations between these Types and clinico-pathological factors, including prognosis.
Forty-five (38%) specimens had no residual tumor cells in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3, and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9 (8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4 more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the 4 Types.
After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but approximately 40% of specimens showed no tumor cells in the mucosal layer. Deep and diffuse remnant patterns were associated with high risks of pleural dissemination and distant metastasis.
To evaluate pathological response to NAC in metastatic LNs, and assess its clinical prognostic significance in patients with EC.
The pathological response to preoperative treatment is commonly ...evaluated in the PT. However, LN metastases strongly correlate with systemic micro-metastases. Thus, pathological evaluation of LN response could more accurately predict prognosis in EC patients undergoing NAC before surgery.
We enrolled 371 consecutive patients who underwent triplet NAC followed by surgery for EC between January 2010 and December 2016. Pathological LN regression grade was defined by the proportion of viable tumor area within the whole tumor bed area for all metastatic LNs: grade I, >50%; II, 10%-50%; III, <10%; and IV, 0%. We analyzed the correlation of grade with clinico-pathological parameters.
Among 319 patients with clinically positive LNs, pathological LN regression grades were I/II/III/IV in 115/51/58/95 patients, and 191 patients (59.9%) showed discordance between the PT and LN pathological regression grades. LN regression grade significantly correlated with cN positive number, ypTNM, lymphovascular invasion, and clinical/pathological PT response. Multivariate analysis for recurrence-free survival revealed that LN regression grade hazard ratio (HR) = 2.25, P < 0.001, ypT (HR = 1.65, P = 0.005), and ypT (HR = 1.62, P = 0.004) were independent prognostic factors, but not pathological PT regression grade (P = 0.67).
Compared to PT response, pathological LN response better predicted long-term survival in EC patients who received NAC plus curative surgery.
False-negative judgment due to poor chemical solubility is a problem with in vitro skin sensitisation tests. Water-insoluble chemicals are typically dissolved in DMSO in most sensitisation tests but ...precipitate when diluted with medium beyond their solubility in water. Such tests lack procedures to rule out false-negative judgments due to poor solubility. The IL-8 Luc assay (OECD442E) is unique in that if chemicals do not dissolve at 20 mg/mL in medium and have no effect on IL-8 luciferase activity (IL8LA), they are classified as indeterminate. The purpose of the present study was to reduce the number of indeterminate chemicals and improve assay performance. The IL-8 Luc assay can simultaneously examine glyceraldehyde 3-phosphate dehydrogenase luciferase activity (GAPLA) and IL8LA, and thus we examined the correlation between the reduction of GAPLA (defined as Inh-GAPLA) and the reduction of propidium iodide (PI)-excluding cells for three sensitizers and three non-sensitizers. We observed a significant correlation between luciferase activity driven by the GAPDH promoter of THP-G8 cells and the number of viable cells. Furthermore, chemicals providing an Inh-GAPLA value below 0.8 always reduced the ratio of PI-excluding cells to less than 0.6. Using the modified criteria, indeterminate chemicals are judged as negative if they provide Inh-GAPLA values below 0.8. This modification reduced the number of indeterminate chemicals and increased specificity, highlighting the unique advantage of the IL-8 Luc assay.
Background
The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection.
Methods
In this six-institution, matched-cohort study, ...2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns.
Results
Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (
p
= 0.0078), 41.0% (
p
= 0.0297), and 55.3% (
p
= 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (
p
= 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (
p
= 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (
p
= 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (
p
= 0.0183).
Conclusions
Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.
Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. We aimed to clarify whether perioperative exercise capacity was related to long-term ...survival in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy. One hundred-six patients with hepatocellular carcinoma underwent pre- and postoperative cardiopulmonary exercise testing to determine their anaerobic threshold, defined as the point between carbon dioxide production and oxygen consumption per unit of time. Testing involved 35 items including blood biochemistry analysis, in-vivo component analysis, dual-energy X-ray absorptiometry, and cardiopulmonary exercise testing preoperatively and 6 months postoperatively. We classified patients with anaerobic threshold ≥ 90% 6 months postoperatively compared with the preoperative level as the maintenance group (n = 78) and patients with anaerobic threshold < 90% as the decrease group (n = 28). Five-year recurrence-free survival rates were 39.9% vs. 9.9% (maintenance vs. decrease group) (hazard ratio: 1.87 95% confidence interval: 1.12-3.13; P = 0.018). Five-year overall survival rates were maintenance: 81.9%, and decrease: 61.7% (hazard ratio: 2.95 95% confidence interval: 1.37-6.33; P = 0.006). Multivariable Cox proportional hazards models showed that perioperative maintenance of anaerobic threshold was an independent prognostic indicator for both recurrence-free- and overall survival. Although the mean anaerobic threshold from preoperative to postoperative month 6 decreased in the exercise-not-implemented group, the exercise-implemented group experienced increased anaerobic threshold, on average, at postoperative month 6. The significant prognostic factor affecting postoperative survival for chronic liver injury patients with HCC undergoing hepatectomy was maintenance of anaerobic threshold up to 6 months postoperatively.
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