Prognostic Impact of Post-operative Infectious Complications in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: Post Hoc Analysis of a Randomized Controlled Trial, JCOG0501.

PURPOSE: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer. METHODS: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses. RESULTS: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456)). CONCLUSION: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected.

A Retrospective Study of Gemcitabine Plus Nab-Paclitaxel for Advanced Pancreatic Cancer Refractory to Gemcitabine Monotherapy.

BACKGROUND/AIM: This study aimed to investigate the efficacy and safety of gemcitabine (GEM) plus nab-paclitaxel (nab-PTX), termed GnP, which is limited, in patients with advanced pancreatic cancer (PC) who show good tolerance to GEM monotherapy prior to being refractory to it. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced or metastatic PC who received GEM followed by GnP between December 2014 and March 2019, regardless of the treatment line. RESULTS: A total of 14 patients who received GnP after becoming refractory to GEM were included in this study. Eight patients were included in the nab-PTX-naïve group, seven of whom were treated with GEM monotherapy as first-line chemotherapy, and one was refractory to GEM monotherapy after modified FOLFIRINOX treatment. The other six patients were included in the nab-PTX reintroduction group. In this group, all patients received GnP followed by GEM maintenance therapy to prevent adverse events, such as peripheral neuropathy and fatigue. Two patients in the nab-PTX-naïve group showed partial response and none in the reintroduction group; median progression-free survival was 7.6 and 1.4 months and median overall survival was 9.4 and 6.2 months, respectively. In the safety analysis, grade 3 anemia and peripheral neuropathy were observed in one patient in the nab-PTX reintroduction group, while the remaining adverse events were of grade 1 or 2. CONCLUSION: GnP is safe and effective even in patients with GEM-refractory PC, and GEM treatment followed by GnP can be an effective treatment option for patients with nab-PTX-naïve PC.

Prognostic effect of categorized tumor deposits in gastric cancer: A single-center retrospective study.

BACKGROUND: Tumor deposits are defined as all types of isolated cancer lesions without lymphocyte aggregates considered part of the lymph node. Tumor deposits have been reported as a negative prognostic factor. However, the survival significance of categorized tumor deposits is uncertain, particularly in gastric cancer. This study aimed to investigate the prognostic difference among categorized tumor deposits. METHODS: Patients who underwent gastrectomy for gastric cancer were enrolled. All tumor deposits were categorized into irregular nodule, irregular nodule star, smooth nodule, and vascular/neural invasion. There are some cases with more than 2 categorized tumor deposits. These cases were categorized as tumor deposit complex in the following analysis. We performed survival analysis between the patients with and without tumor deposits, and compared the survival among each categorized tumor deposit. RESULTS: Of 868 patients, there were 96 (11.1%) and 772 (88.9%) patients with and without tumor deposits. Vascular/neural invasion, smooth nodule, irregular nodule, irregular nodule star, and the tumor deposits complex was observed in 6 (6.3%), 15 (15.6%), 43 (44.8%), 1 (1.0%), and 31 (32.3%) patients. Patients with tumor deposits displayed poorer survival than those without; the 3-year overall survival: tumor deposits negative = 87.0%, tumor deposits positive = 53.2% (P < .001). Survival analysis revealed tumor deposits can be a prognostic risk factor (hazard ratio: 1.9854, 95% confidence interval: 1.393-2.830, P < .01). Irregular nodule and the tumor deposits complex demonstrated the worst prognosis (irregular nodule 3-year overall survival: 51.2%, tumor deposits complex 3-year overall survival: 41.9%, P = .001), whereas smooth nodule demonstrated better prognosis (smooth nodule 3-year overall survival: 80%). CONCLUSION: Tumor deposits exerted a negative survival effect in gastric cancer. Irregular nodule and the tumor deposits complex displayed a strong prognostic effect.

Clinical Complete Response of Recurrent Gastric Cancer after Third-line CPT-11 Chemotherapy.

A 75-year-old man underwent distal gastrectomy for advanced gastric cancer in September 2018. During the adjuvant chemotherapy, computed tomography (CT) revealed recurrence sites in the liver and para-aortic lymph nodes. Therefore, chemotherapy was initiated. After first-line (capecitabine with oxaliplatin) and second-line (paclitaxel with ramucirumab) treatments, nivolumab was used as third-line chemotherapy. This treatment showed a strong effect against the tumor. However, following an immune-related adverse effect (irAE) because of nivolumab, the therapy was halted. The irAE was diagnosed with central adrenal insufficiency that was controllable by oral intake of steroids. CPT-11 was started and showed a similarly strong effect to that observed for nivolumab. Eventually, the recurrent tumor lesions became too small to be detected by CT. We discontinued CPT-11 at the request of the patient. Even after discontinuation, no recurrent sites have been observed, allowing us to declare a case of clinical complete response (cCR). In conclusion, even if irAEs occur in a patient, continuing chemotherapy should be considered. However, if cCR is achieved, discontinuation of chemotherapy might be a strategic treatment option.

Discovery of TP0597850: A Selective, Chemically Stable, and Slow Tight-Binding Matrix Metalloproteinase-2 Inhibitor with a Phenylbenzamide-Pentapeptide Hybrid Scaffold.

Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase and a promising target for various diseases, including cancer and fibrosis. Herein, we report the discovery of a novel MMP2-selective inhibitor with high chemical stability and slow tight-binding features. Based on the degradation mechanism of our small-molecule-peptide hybrid 1, the tripeptide linker {5-aminopentanoic acid [Ape(5)]-Glu-Asp} of 1 was replaced by a shorter linker (γ-D-Glu). Phenylbenzamide was suitable for the new generation of MMP2 inhibitors as an S1' pocket-binding group. The introduction of (4S)-aminoproline dramatically increased the chemical stability while maintaining high subtype selectivity because of its interaction with Glu130. TP0597850 (18) exhibited high stability over a wide range of pH values as well as potent MMP2 inhibition (Ki = 0.034 nM) and ≥2000-fold selectivity determined using the inhibition constants. A kinetic analysis revealed that it possesses slow tight-binding nature with a long MMP2 dissociative half-life (t1/2 = 265 min).

Evaluating the optimal treatment strategy for early and advanced remnant gastric cancer.

BACKGROUND: This study assessed lymph node metastasis characteristics to investigate the optimal treatment strategy for early and advanced remnant gastric cancer (RGC). METHODS: Cases of completion gastrectomy for RGC were enrolled. The frequency of lymph node metastasis was investigated, and risk factors for metastasis were identified. The clinical significance of completion gastrectomy in early remnant gastric carcinoma cases was also examined. In advanced cases, 3-year survival was analysed to investigate the prognostic importance of lymph node dissection and splenectomy. RESULTS: Seventy-nine patients were included. Lymphatic invasion and pathological tumour depth were identified as risk factors for lymph node metastasis. There was no metastasis in the pT1 cases. In advanced cases, the incidence of lymph node #10 and jejunal lymph node metastasis was 8.3-10.0% and 17.6%, respectively. Prognosis was found to be unrelated with splenectomy. CONCLUSIONS: Lymphatic invasion and pathological T status were identified as risk factors for LN metastasis in RGC. Additional gastrectomy after ESD might not be mandatory for early RGC cases. For advanced RGC cases, splenectomy might not improve patient prognosis, however, lymph node dissection of jejunal and #10 lymph nodes should be considered due to its high incidence of metastasis.

Discovery of Aryloxyphenyl-Heptapeptide Hybrids as Potent and Selective Matrix Metalloproteinase-2 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis.

Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase that plays important roles in the degradation of extracellular matrix proteins. MMP2 is considered to be an attractive target for the treatment of various diseases such as cancer, arthritis, and fibrosis. In this study, we have developed a novel class of MMP2-selective inhibitors by hybridizing the peptide that binds to a zinc ion and S2-S5 pockets with small molecules that bind to the S1' pocket. Structural modifications based on X-ray crystallography revealed that the introduction of 2,4-diaminobutanoic acid (Dab) at position 4 dramatically enhanced MMP2 selectivity by forming an electrostatic interaction with Glu130. After improving the metabolic and chemical stability, TP0556351 (9) was identified. It exhibited potent MMP2 inhibitory activity (IC50 = 0.20 nM) and extremely high selectivity. It suppressed the accumulation of collagen in a bleomycin-induced idiopathic pulmonary fibrosis model in mice, demonstrating the efficacy of MMP2-selective inhibitors for fibrosis.

Assessing the Prognostic Value of Extranodal Extension in Esophageal Cancer from the Pathological Staging Perspective.

BACKGROUND: Extranodal extension (ENE) is a prognostic factor for several types of malignant tumors, including esophageal cancer. Although the prognostic value of ENE has been investigated in esophageal cancer, its clinical utility warrants further investigation. MATERIALS AND METHODS: This retrospective single-center study evaluated 105 patients who underwent esophagectomy and had histologically node-positive metastasis between January 2007 and June 2017. The abilities of ENE to predict overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank test, as well as Cox proportional hazard models. Subgroup analyses of ENE's prognostic value were performed according to each pathological tumor-node-metastasis category. RESULTS: Significant differences according to ENE status were observed in the Kaplan-Meier analyses of OS (p = 0.001) and DFS (p = 0.001), as well as in the Cox proportional hazards models for OS (p = 0.009) and DFS (p = 0.012). Relative to patients without ENE, patients with ENE had significantly poorer OS if they also had pT3 status, pN1 status, or pathological stage III disease. However, no significant differences were observed in the subgroup analyses of pN3 status and pathological stage IV disease. CONCLUSIONS: Among patients with esophageal cancer, ENE status can predict a poor prognosis and may be useful for patient stratification. However, the prognostic value of ENE status may be limited to patients with specific pathological factors.

Prognostic value of tumor regression grade following the administration of neoadjuvant chemotherapy as treatment for gastric/gastroesophageal adenocarcinoma: A meta-analysis of 14 published studies.

INTRODUCTION: The efficacy of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (GC) has recently been revealed. The use of tumor regression grade (TRG) has also been reported, where TRG has been positively correlated with prognosis. However, previous studies included several types of GC and treatments. The prognostic value of TRG in a specific population has not been well investigated. Therefore, a meta-analysis of studies on gastric adenocarcinomas treated with NAC that evaluate the prognostic impact of TRG on overall survival (OS) must be conducted to provide more accurate evidence. METHODS: A meta-analysis of studies reporting gastric cancer/gastroesophageal junction (GC/GEJ) adenocarcinoma treated with NAC was performed. Studies that calculate the number of responders and non-responders were considered eligible. The risk ratio (RR) was obtained from the eligible studies, and a random-effects model was used for pooled analysis. RESULTS: Fourteen studies, which included a total of 1660 patients, were included in the current study. The responders showed better OS (RR: 0.53, 95% confidence interval (CI): 0.46-0.60, P < 0.001). All subgroup analyses (Asian vs. non-Asian populations, different TRGs, GC/GEJ vs. GC) also revealed the statistical dominance of better TRG over better OS. However, the possibility of some publication bias remained. CONCLUSIONS: In this meta-analysis, better TRG was associated with better OS. However, the histology, configuration, and location of GC varied. Hence, a more subdivided analysis is recommended to obtain more solid evidence.

Intraoperative blood loss as an independent prognostic factor for curative resection after neoadjuvant chemotherapy for gastric cancer: a single-center retrospective cohort study.

PURPOSE: Surgery-induced factors such as postoperative infectious complications (PICs) and intraoperative blood loss (IBL) have a negative impact on the survival of patients undergoing surgery for gastric cancer. A recent study showed that neoadjuvant chemotherapy (NAC) could reduce the negative impact of PICs; hence, we conducted the present study to investigate if NAC can also reduce the negative prognostic impact of IBL. METHODS: We reviewed 115 gastric cancer patients treated with NAC and radical gastrectomy. The cut-off for IBL predicting the long-term survival was assessed by a receiver operating characteristic curve. The Cox proportional hazard model was used to evaluate the association between patient characteristics including IBL, overall survival, and disease-free survival. RESULTS: The cut-off for IBL was set at 990 ml. Twenty-six patients had excessive IBL exceeding 990 ml (22.6%) and PICs developed in 33 patients (28.7%). The body mass index, IBL, ypT, and ypN were significant independent prognostic predictors, but PICs were not. CONCLUSION: NAC did not decrease the risk induced by excessive IBL. The prophylactic effect of NAC on surgery-induced risk was inconsistent.

Laparoscopic mediastinal approach for retrosternal gastric conduit cancer after esophagectomy.

The prognosis of esophageal cancer has improved, but the incidence of gastric conduit cancer has increased. Gastric conduit cancer is difficult to treat because current treatment options are highly invasive; in particular, surgical procedures have high mortality and modality. Treatment through the retrosternal route usually requires sternotomy, which often causes lethal osteomyelitis. To prevent lethal complications and reduce invasiveness, we used the laparoscopic mediastinal approach. Here, we report a successful case using the laparoscopic mediastinal approach for the treatment of gastric conduit cancer through the retrosternal route. Despite a few concerns, this approach can be a treatment option for gastric conduit cancer through the retrosternal route.

Quantum Tunneling of a He Atom Above and Below a Benzene Ring.

Van der Waals (vdW) complexes with helium atoms have deserved much attention for their intriguing quantum nature relevant to microscopic superfluidity. However, tunneling splitting, the clear signature of quantum delocalization of He atoms, has rarely been identified in any of the He-containing complexes. Here, UV excitation spectra of benzene-He were extensively examined with almost full rotational resolution to identify two weak vibronic bands with vibrational excitation energies of only ∼13 and ∼16 cm-1. Each of rotational transitions appears to be split into doublets in the higher-frequency band. This splitting is attributed to quantum tunneling due to the delocalization of He spread over two minimum locations below and above the benzene ring. The magnitude of the tunneling splitting as well as the vibrational frequencies of the two vdW modes are compared with the reported theoretical prediction to quantitatively assess the intermolecular potential energy surfaces so far derived.

SPOCK1 induces adipose tissue maturation: New insights into the function of SPOCK1 in metabolism.

SPOCK1 is a calcium-binding matricellular proteoglycan that has been extensively studied in several cancer cells. Previously, we generated a mouse line overexpressing SPOCK1 (Spock1-Tg mouse) and showed that SPOCK1 might play an important role in drug-induced gingival overgrowth, indicating that it possesses physiological functions in non-cancer diseases as well. Although SPOCK1 was reported to be secreted from human adipocytes, its role in adipocyte physiology has not been addressed yet. In this study, SPOCK1 protein expression was confirmed in pancreas, adipose tissues, spleen, and liver of normal diet (ND)-fed mice. Interestingly, SPOCK1 was up-regulated in the pancreas and adipose tissues of the high-fat diet (HFD)-fed mice. Spock1-Tg mice fed with ND showed increased maturation in epididymal and inguinal adipose tissues. In addition, Spock1 overexpression strongly decreased expression of UCP-1 in adipose tissues, suggesting that SPOCK1 might regulate thermogenic function through suppression of UCP-1 expression. Finally, exogenous SPOCK1 treatment directly accelerated the differentiation of 3T3-L1 adipocytes, accompanied by the up-regulation of adipocyte differentiation-related gene expression. In conclusion, we demonstrated for the first time that SPOCK1 induced adipocyte differentiation via the up-regulation of adipogenesis-related genes.

Predictive value of the surgical Apgar score on postoperative complications in advanced gastric cancer patients treated with neoadjuvant chemotherapy followed by radical gastrectomy: a single-center retrospective study.

BACKGROUND: The surgical Apgar score (SAS) or modified SAS (mSAS) has been reported as a simple and easy risk assessment system for predicting postoperative complications in primary surgery for gastric cancer. However, few studies have described the SAS's utility in gastric surgery after neoadjuvant chemotherapy (NAC). METHODS: One hundred and fifteen patients who received NAC and radical gastrectomy from 2008 and 2015 were included in this study. The SAS was determined by the estimated blood loss (EBL), lowest intraoperative mean arterial pressure, and lowest heart rate. The mSAS was determined by the EBL reassessed using the interquartile values. The predictive values of the SAS/mSAS for postoperative complications were assessed with univariate and multiple logistic regression analyses. RESULTS: Among the 115 patients, 41 (35.7%) developed postoperative complications. According to analyses with receiver operating characteristic curves of the SAS and mSAS for predicting postoperative complications, the cut-off value of the mSAS was set at 8. The rates of anastomotic leakage, pancreatic fistula, and arrhythmia in patients with high mSAS (> 8) values were higher than in those with low (0-3) and moderate [1-4] mSAS values. A multiple logistic regression analysis showed that the operation time, body mass index, and diabetes mellitus were independent risk factors for postoperative complications. The mSAS was not a significant predictor. CONCLUSION: The predictive value of SAS or mSAS for morbidity may be limited in patients who undergo gastric cancer surgery after NAC. Future prospective studies with a large sample size will be needed to confirm the present results.

Determination of the optimal surgical procedure by identifying risk factors for pneumonia after transthoracic esophagectomy.

BACKGROUND: Esophagectomy is associated with a high risk of postoperative complications, and the respiratory complications are the most common. Therefore, stratification of patients based on preoperative risk factors is essential. This study aimed to identify the risk of postoperative pneumonia (POP) based on the preoperative factors and determine the optimal perioperative surgical management strategy. METHODS: This retrospective study involved 207 patients who underwent esophagectomy. The patients were divided into two groups, namely, with POP and without POP. To identify the risk factors for POP, the pre- and perioperative characteristics were analyzed. A receiver operating characteristics curve was used to determine a cutoff value of 2.40 L for the forced expiratory volume in 1 s (FEV1.0) and the cohort was divided into a high- and low-FEV1.0 group. A second analysis was then performed to determine the optimal surgical management for patients at a high risk for POP. RESULTS: POP occurred in 45 (21.7%) patients. A multiple logistic regression analysis showed that FEV1.0 was significantly lower in the POP (+) group (P = 0.020); thus, a low FEV1.0 was found to be a risk factor for POP. Multiple logistic regression analysis showed that open thoracotomy was a significant risk factor for POP in low FEV1.0 patients (P = 0.013). CONCLUSIONS: A low FEV1.0 and an open thoracotomy are risk factors for POP. Therefore, patients with low FEV1.0 should be managed carefully and video-assisted thoracic surgery should be considered.

THUMP domain containing 2 protein possibly induces resistance to cisplatin and 5-fluorouracil in in vitro human esophageal squamous cell carcinoma cells as revealed by transposon activation mutagenesis.

BACKGROUND: Although chemotherapy is a core treatment for esophageal cancer, some patients develop drug resistance. Gene screening with transposons (i.e. mobile genetic elements) is a novel procedure for identifying chemotherapy-resistant genes. Transposon insertion can randomly affect nearby gene expression. By identifying the affected genes, candidate genes can be found. The present study aimed to identify cisplatin (CDDP)/5-fluorouracil (5-FU)-resistant genes in in vitro human esophageal squamous cell carcinoma with transposons. METHODS: After establishing transposon-tagged cells, we obtained CDDP/5-FU-resistant colonies. A polymerase chain reaction and sequencing were used to identify the transposon inserted site and candidate CDDP/5-FU resistant genes. Focusing on one candidate gene, we confirmed CDDP/5-FU resistance by comparing the IC50 between drug-resistant and wild-type cells. Furthermore, we investigated gene expression by a real-time polymerase chain reaction. Finally, we mediated the candidate gene level with small interfering RNA to confirm the resistance. RESULTS: Thirty-nine candidate genes for CDDP/5-FU resistance were identified. Nineteen were for CDDP resistance and 27 were for 5-FU resistance. Seven genes, THUMP domain-containing protein 2 (THUMPD2), nuclear factor interleukin-3-regulated protein (NFIL3), tyrosine-protein kinase transmembrane receptor 2 (ROR2), C-X-C chemokine receptor type 4 (CXCR4), thrombospondin type-1 domain-containing protein 2 (THSD7B) alpha-parvin (PARVA) and TEA domain transcription factor 1 (TEAD1), were detected as candidate genes in both colonies. Regarding THUMPD2, its expression was downregulated and knocking down THUMPD2 suggested drug resistance in both drugs. CONCLUSIONS: Thirty-nine candidate genes were identified with transposons. The downregulation of THUMPD2 was suggested to play a role in multidrug resistance in in vitro esophageal squamous cell carcinoma.

A low surgical Apgar score is a predictor of anastomotic leakage after transthoracic esophagectomy, but not a prognostic factor.

BACKGROUND: The surgical Apgar score (SAS) has been a useful predictor of postoperative complications in several types of cancer. However, there are few reports about the correlation of SAS and esophageal cancer. This study aimed to examine the utility of SAS as a predictor of major complications, particularly anastomotic leakage, in patients who underwent transthoracic esophagectomy, and investigate the correlation between SAS and patient prognosis. METHODS: This is a single-center, retrospective observational study. A total of 190 patients who underwent esophagectomy for esophageal cancer in 2012-2016 were reviewed to find the correlation between SAS and postoperative complications (Clavien-Dindo classification III or higher). SAS was calculated based on intraoperative estimated blood loss, lowest mean arterial pressure, and lowest heart rate. Major complications included anastomotic leakage, respiratory, cardiac, recurrent nerve palsy, chylothorax, and other complications. We also reviewed how SAS was correlated with 3 year overall survival (OS) and recurrence-free survival (RFS). A high SAS was defined as ≥ 6, and a low SAS as < 6. RESULTS: On univariate analysis, SAS showed a statistical significance in all major complications and anastomotic leakage. On multiple logistic regression analysis, a low SAS was detected as a risk factor of the major complications and anastomotic leakage, with a significant difference. Moreover, we conducted survival analysis with SAS; however, we could not detect that a low SAS had a negative impact on OS and RFS. CONCLUSIONS: A low SAS can be a predictor of postoperative complications, especially anastomotic leakage. However, SAS was not correlated with OS or RFS.

Does neoadjuvant chemotherapy cancel out the negative survival impact induced by surgical complications after gastrectomy?

BACKGROUND: Postoperative infectious complications (ICs) are associated with a poor prognosis following gastric cancer surgery. Neoadjuvant chemotherapy (NAC) targeting scirrhous-type or bulky nodal disease reportedly exerts a prophylactic effect on the negative impact of ICs. However, a recent study clearly showed that NAC for scirrhous-type disease had no survival benefit. We investigated this prophylactic effect and significant interactions among subgroups of histological response, macroscopic type, and bulky nodal disease. METHODS: We examined 115 patients who received NAC followed by radical gastrectomy between January 2008 and December 2015. The overall survival (OS) and disease-free survival (DFS) were compared between those with and without ICs. Our cohort included 62 with type 4/giant type 3, 44 with bulky nodal disease/para-aortic nodal disease, and 25 with other diseases. RESULTS: A histological response was observed in 80 patients (69.5%). Thirty three (28.7%) developed ICs. There was no significant difference in the OS [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.47-1.99, p = 0.920] or DFS (HR 0.74; 95% CI 0.40-1.38, p = 0.342) by the presence of ICs. The HR was 1.00 in patients who had no response to NAC (grade 0/1a) and 0.95 in those who responded to NAC (grade 1b/2/3). No subgroups showed significant interactions for the OS. CONCLUSIONS: NAC may cancel out the negative impact of morbidity on the survival in advanced gastric cancer patients. The prophylactic effects by NAC do not depend on the tumor type or histological response.

Sub-Doppler electronic spectrum of the benzene-D2 complex.

Excitation spectrum of the benzene-D2 van der Waals complex in the vicinity of the S 1 ← S 0 60 1 vibronic transition of the monomer was recorded with sub-Doppler resolution by utilizing mass-selective two-color resonance-enhanced two-photon ionization. Contrary to the previous report on the benzene-H2 complex [M. Hayashi and Y. Ohshima, J. Phys. Chem. A 117, 9819 (2013)], both spin isomers correlating to para and ortho D2 (with rotational angular momentum j = 1 and 0, respectively) are identified by using a gas sample of normal D2. Three and two vibronic bands involving vdW-mode excitation were observed for the para and ortho species, respectively, in addition to their origin bands. Comparison of the results for the two spin isomers has allowed us to make unambiguous band assignments, and vibrational frequencies of all the three vdW modes have been determined for benzene-H2 and -D2. Among the three modes, the two-dimensional vdW twist is correlated to the hindered internal rotation of H2/D2 and the barrier for the internal rotation has been evaluated: 72 and 66 cm-1 for benzene-H2 and -D2, respectively. Vibronic-state dependence of the intermolecular distance between benzene and H2/D2 is discussed on the basis of precisely determined rotational constants. Homogenous line broadening has been identified for all the observed vibronic bands, and the corresponding upper-state lifetimes are determined to be in the range of 0.3-0.7 ns.