Prognostic impact of surgery after chemotherapy for type 4 gastric cancer.

PURPOSE: To assess the clinical indications for, and prognostic impact of surgery after, chemotherapy for type 4 gastric cancer. METHODS: The subjects of this retrospective study were 67 patients who received chemotherapy for type 4 gastric cancer. The patients were grouped into those with progressive disease (PD group) and those without PD (non-PD group), according to the tumor response to chemotherapy. RESULTS: Distant metastases developed in 58 patients. With regard to tumor response, there were 16 patients in the PD group and 51 patients in the non-PD group. The prognosis of the PD group patients was significantly poorer than that of the non-PD group patients (p < 0.0001). R0 resection was performed for 21 of 23 patients who underwent surgery after chemotherapy. Multivariate analysis revealed tumor response and surgery as independent prognostic factors (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis of the surgery group revealed that metastatic nodal status (N0-1 vs. N2-3) and residual tumor status (R0 vs. R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). CONCLUSION: The findings of this study suggest that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status, who undergo curative R0 resection.

Clinical Significance of Conversion Surgery for Gastric Cancer with Peritoneal Dissemination: A Retrospective Study.

OBJECTIVE: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. METHODS: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. RESULTS: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). CONCLUSION: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.

Indication and Prognostic Significance of Conversion Surgery in Patients with Liver Metastasis from Gastric Cancer.

OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.

Response Rate and Prognostic Impact of Salvage Chemotherapy after Nivolumab in Patients with Advanced Gastric Cancer.

OBJECTIVE: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. METHODS: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. RESULTS: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. CONCLUSION: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.

Evaluation of postoperative quality of life by PGSAS-45 following local gastrectomy based on the sentinel lymph node concept in early gastric cancer.

BACKGROUND: The usefulness of sentinel node navigation surgery (SNNS) for early gastric cancer has been demonstrated in a multicenter prospective study. However, quality of life (QOL) after local resection remains unclear. This present study investigated QOL after local resection and distal gastrectomy. METHODS: We examined 69 patients who underwent laparoscopic distal gastrectomy (LADG) (n = 44) and laparoscopic local resection (LLR) (n = 25) in our hospital between September 2011 and May 2018. We conducted a combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) with SNNS as LLR. All patients had pStage I or II and none had received adjuvant chemotherapy. We evaluated QOL using the postgastrectomy syndrome assessment scale questionnaire (PGSAS-45) 1, 6, and 12 months after surgery. RESULTS: In PGSAS-45, no significant differences were observed between LLR and LADG at 1 and 6 months after surgery. At 12 months, the LLR group scored better for some of the subscales (SS). In the endoscopic evaluation, the LLR group showed significant improvements in residual gastritis at 6 months (P = 0.006) and esophageal reflux and residual gastritis at 12 months (P = 0.021 and P = 0.017). A significant difference was observed in the prognostic nutritional index, which was assessed using serum samples, between the two groups at 6 months (P = 0.028). The body weight ratio was better in the LLR group than in the LADG group at 6 and 12 months (P = 0.041 and P = 0.007, respectively). CONCLUSIONS: CLEAN-NET with SNNS preserved a better QOL and nutrition status than LADG in patients with early gastric cancer.

Combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with advanced gastric cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are representative blood markers of systemic inflammatory responses. However, the clinical significance of the combination of these markers is unclear. This study aimed to investigate the NLR and PLR in patients with advanced gastric cancer treated with chemotherapy and assess the clinical utility of a new blood score combining the NLR and PLR (NLR-PLR score) as a predictor of tumor response and prognosis. METHODS: We retrospectively analyzed 175 patients with gastric cancer receiving chemotherapy or chemoradiotherapy. These patients were categorized into progressive disease (PD) and non-PD groups according to tumor response. The NLR and PLR before treatment were examined, and the cut-off values were determined. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (> 2.461) and high PLR (> 248.4); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. RESULTS: With regard to tumor response, 64 and 111 patients had PD and non-PD, respectively. The NLR-PLR score was significantly higher in patients with PD than in those with non-PD (p = 0.0009). The prognosis was significantly poorer in patients with a higher NLR-PLR score than in those with a lower NLR-PLR score (p <  0.0001). Multivariate analysis demonstrated that the NLR-PLR score was an independent prognostic factor for prediction of overall survival (p = 0.0392). CONCLUSION: Low-cost stratification according to the NLR-PLR score might be a promising approach for predicting tumor response and prognosis in patients with advanced gastric cancer.

[A Case of Advanced Gastric Cancer Showing Pathological Complete Response after Neoadjuvant Chemotherapy with S-1 and Oxaliplatin].

A 57-year-old woman was admitted to our hospital for treatment of gastric cancer presenting as a type 2 tumor in the lower third of the stomach. According to pre-therapeutic imaging examinations and laparoscopy, she was diagnosed with advanced gastric cancer, cT4a(SE)N2M0, Stage Ⅲ. Therefore, neoadjuvant chemotherapy was planned, and she received the SOX regimen. After 3 courses of chemotherapy, post-therapeutic imaging examinations showed that the primary gastric tumor and metastatic lymph nodes had reduced in size. We performed distal gastrectomy with D2 lymphadenectomy. Final pathological examinations demonstrated that no viable tumor cells remained in the resected stomach and dissected lymph nodes (Grade 3). SOX may be useful as neoadjuvant chemotherapy to improve prognosis in patients with advanced gastric cancer. Herein, we report a case of advanced gastric cancer with pathological complete response after neoadjuvant chemotherapy with the SOX regimen.

Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer.

Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis. This study assessed the clinical significance of PD-L1 mRNA expression in blood specimens obtained from patients with gastric cancer. Peripheral blood specimens were collected before treatment from 124 patients with gastric cancer. The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death-ligand 1 mRNA expression was significantly higher in patients with advanced gastric cancer than in patients with early gastric cancer (P = .002). Moreover, PD-L1 expression correlated significantly with depth of tumor invasion, distant metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients with high PD-L1 expression showed significantly poorer prognosis than those with low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1 expression as an independent prognostic factor. Expression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer.

Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma.

BACKGROUND: While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not. METHODS: Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis. RESULTS: The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor. CONCLUSION: Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

Quantitative assessment of fluorescence intensity of ICG in sentinel nodes in early gastric cancer.

BACKGROUND: The sentinel node (SN) detection by dual tracer method using indocyanine green (ICG) and a radioisotope (RI) has been recommended for early gastric cancer. However, institutions are limited due to radioactivity in the RI method. The greatest advantage of the RI method is that it objectively assesses RI uptake as a numerical value. The aim of the present study was to verify the usefulness of ICG fluorescence intensity in SN. METHODS: Seventeen patients with early gastric cancer were enrolled in this study. RI uptake by each lymph node was measured using Navigator GPS and fluorescence nodes were identified using the hyper eye medical system (HEMS). Fluorescence intensity in fluorescence nodes was evaluated using ICG intensity imaging software (Mizuho, Japan) of the HEMS. RESULTS: The total number of dissected lymph nodes was 227, with an average of 13.3 per patient. The numbers of HN, FN-S, and FN-B were 64, 77, and 34. RI uptake was significantly greater by FN-S than by non-FN-S (P = 0.0016). The median fluorescence intensity value was higher in HN than in non-HN (P < 0.001). A correlation was observed between RI uptake and fluorescence intensity. Dissecting FNs with fluorescence intensity levels of 1-6 resulted in 92.1% dissection of HNs. CONCLUSION: It is possible that the evaluation of fluorescence intensity is useful for selected SNs instead of RI tracer. If fluorescence intensity is measurable in surgery, an infrared fluorescence method using ICG may be useful and safe for the detection of SN in early gastric cancer.

Combined fibrinogen and neutrophil-lymphocyte ratio as a prognostic marker of advanced esophageal squamous cell carcinoma.

Patients with advanced esophageal squamous cell carcinoma (ESCC) is received chemoradiotherapy or chemotherapy for clinical management. However, it is difficult to predict tumor response and prognosis using blood markers before starting treatments. The purpose of this study was to investigate the pre-treatment plasma fibrinogen and neutrophil-lymphocyte ratio (NLR) in patients with advanced ESCC treated with chemoradiotherapy or chemotherapy, and to assess the clinical utility of a combined score using these blood markers, named as the F-NLR (fibrinogen and NLR) score, as a predictor of tumor response and prognosis. A total of 98 advanced ESCC patients, treated with chemoradiotherapy or chemotherapy, were classified into three groups: F-NLR score of 2, having both hyperfibrinogenemia (>400 mg/dL) and high NLR (>3.0), score of 1, one of these hematological abnormalities, and score of 0, having neither hyperfibrinogenemia nor high NLR. Fibrinogen and NLR were significantly higher in the progressive disease (PD) group than the non-PD group (P = 0.0419, and P = 0.0001, respectively). A significantly higher F-NLR score was found in the PD group than the non-PD group (P = 0.0140). Overall survival was significantly lower in patients with an F-NLR score of 2 than in those with an F-NLR score of 0 or 1 (P < 0.0001). Multivariate analysis showed that the F-NLR score was one of the independent prognostic factors (P = 0.0081). Our study demonstrates that the F-NLR score is promising as a predictive marker for therapeutic effects and prognosis in patients with advanced ESCC.

As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Cysteine/histidine-rich 1 (CYHR1) was first discovered in a yeast two-hybrid screen with murine galectin-3, and no previous reports have described a relationship between the CYHR1 gene and human cancer. The current study evaluated the role and significance of CYHR1 in esophageal cancer. METHODS: The human esophageal squamous cell carcinoma (ESCC) cell line TE-8 and the CYHR1 knock-down cell line TE-8/small interfering (si)-CYHR1 were used for in vitro and in vivo assays. For clinical study, ESCC tissues (n = 104) were used. RESULTS: Compared with parental cells, TE-8/si-CYHR1 cells had suppressed proliferation and invasion activities. In the in vivo assay, the tumors from TE-8 cells treated with si-CYHR1 had abrogated tumorigenicity. In the clinical study, the expression of CYHR1 mRNA was associated with lymph node metastasis and stage and shown to be an independent prognostic factor. CONCLUSIONS: As the findings show, CYHR1 may represent not only a valuable prognostic marker but also a therapeutic target for ESCC patients.

The clinical usefulness of the intraoperative detection of sentinel lymph node metastases by a rapid RT-PCR system in patients with gastric cancer.

BACKGROUND: The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses. METHODS: A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer. RESULTS: SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively. CONCLUSIONS: The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer.

A Novel Scoring System Based on Fibrinogen and the Neutrophil-Lymphocyte Ratio as a Predictor of Chemotherapy Response and Prognosis in Patients with Advanced Gastric Cancer.

OBJECTIVE: We assessed the clinical applicability of the F-NLR score, which is based on fibrinogen (F) and the neutrophil-lymphocyte ratio (NLR), and the Glasgow Prognostic Score (GPS) to predict the therapeutic effects of chemotherapy or chemoradiotherapy on advanced gastric cancer and the prognoses of patients. METHODS: Sixty-eight patients with advanced gastric cancer treated with first-line chemotherapy or chemoradiotherapy were classified into two groups based on tumor response. Furthermore, we categorized patients according to cutoff F-NLR scores of 2 [hyperfibrinogenemia (>400 mg/dl) and high NLR (>3.0)], 1 [one of these hematological abnormalities], and 0 [neither hyperfibrinogenemia nor high NLR]. RESULTS: A total of 27 patients had progressive disease (PD) and 41 did not. The F-NLR scores were significantly higher in the PD than in the non-PD group (p = 0.003). Survival was significantly shorter for patients with high F-NLR scores and GPS (p = 0.0071 and p = 0.0065, respectively). Multivariate analysis selected the F-NLR score as an independent prognostic factor (p = 0.017). CONCLUSION: A novel grading system based on F-NLR scores, as well as the GPS, appears to have value as a clinical predictor of the therapeutic response of advanced gastric cancer to chemotherapy or chemoradiotherapy and the prognoses of patients.

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

BACKGROUND: The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. PATIENTS AND METHODS: We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. RESULTS: Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. CONCLUSIONS: To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Therapeutic mammoplasty combining partial mastectomy with nipple-areola grafting for patients with early breast cancer: a case series.

PURPOSE: Therapeutic mammoplasty (TM) for breast cancer is a widely practiced oncoplastic technique. Intraductal spread towards the nipple or the location of the cancerous lesion on the central breast may become a contraindication for breast-conserving surgery. We herein report the results of TM in such cases. METHODS: Six patients underwent TM that combined partial mastectomy with free nipple-areola (NA) grafting. The nipple was removed together with the cancerous lesions, and the areola was preserved for NA reconstruction. The tumors were located in the lower quadrant (n = 1), the central area (n = 1), the upper-outer area (n = 2), and the upper-inner area (n = 2). The types of mammoplasty that were performed included: amputation (n = 1), inverted T mammoplasty (n = 3), and L mammoplasty (n = 2). With the exception of one patient, all patients underwent inverted T mammoplasty on the contralateral breast in order to achieve symmetry. RESULTS: The total surgical and plastic periods ranged from 155 to 235 min (mean 207 min) and 100 to 150 min (mean 121 min), respectively. Oncological safety and excellent cosmetic results were achieved. CONCLUSIONS: TM combining partial mastectomy with NA grafting was successfully performed in patients with early-stage cancer in all quadrant areas.

[A Case of Recurred Gastric Cancer of the Anastomosis Completely Responding to Docetaxel, Cisplatin, and S-1 Triplet Therapy].

A 51-year-old man who had undergone distal gastrectomy for gastric cancer was admitted in Kagoshima University Hospital under the diagnosis of anastomotic recurrence of gastric cancer. From abdominal CT results, the recurred tumor was suspected to invade into the pancreas with regional node metastases. Because of the intense radicality of surgical intervention, we planned 3 courses of docetaxel, cisplatin, and S-1 triplet therapy(DCS therapy). After the chemotherapy, the recurred tumor and lymph node metastases shrunk drastically. Segmental gastrectomy with lymph node dissection was performed with curative intent. Final pathology revealed complete regression of both the recurred tumor and lymph node metastases. The patient's postoperative course was uneventful without tumor relapse. DCS therapy seems to be suitable to obtain drastic tumor regression before surgical intervention as a neoadjuvant chemotherapy for locally advanced gastric cancer.

Clinical Significance of Circulating Tumor Cells in Peripheral Blood of Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma is an aggressive gastrointestinal tract cancer. To date, the presence of circulating tumor cells (CTC) has been reported as a prognostic factor in peripheral blood from patients with gastrointestinal cancers. METHODS: The CellSearch system was used to isolate and enumerate CTCs. A total of 90 patients with esophageal squamous cell carcinoma who received chemotherapy or chemoradiotherapy were enrolled. Peripheral blood specimens were collected before and after treatments. RESULTS: At baseline analysis, CTCs were detected in 25 patients (27.8 %). Overall survival was significantly shorter in patients with than without CTCs. Follow-up blood specimens were obtained from 71 patients. Partial response, stable disease, and progressive disease after treatment were seen in 32, 12, and 27 patients, respectively. CTC positivity after treatment in the progressive disease group (40.7 %) was significantly higher than that of the partial response group (6.3 %). Patients with a change in CTC status from positive to negative had a good prognosis as well as patients without baseline CTCs. CONCLUSIONS: Evaluation of CTCs may be a promising indicator for predicting tumor prognosis and the clinical efficacy of chemotherapy or chemoradiation therapy in patients with esophageal squamous cell carcinoma.

Correlation of Aurora-A expression with the effect of chemoradiation therapy on esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC). However, because some patients respond well to CRT and others do not, it is important to be able to predict response to CRT before beginning treatment by using markers. Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions in centrosome maturation and chromosome segregation. In this study, we investigated the relationship between the expression of Aurora-A and the response to CRT in patients with ESCC. METHODS: We immunohistochemically investigated the expression of Aurora-A in biopsy specimens of untreated primary tumors of 78 patients with ESCC and determined the relationship between Aurora-A levels and patient responses to CRT, which consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. RESULTS: Tumors were judged as Aurora-A positive when more than 10% of the cancer cells displayed a distinct positive nuclear anti-Aurora-A immunoreaction by immunohistochemical evaluation. The tumors of 46 of 78 patients (58.9%) displayed positive expression of Aurora-A. In terms of clinical response the percentage of patients showing complete response (CR), incomplete response/stable disease of primary lesion (IR/SD), and progressive disease (PD) was 19.2, 69.2, and 11.5%, respectively. In terms of histological response the tumor grade of the 41 patients who underwent surgery was as follows: grade 1, 48.8%; grade 2, 29.2%; grade 3, 22.0%. CRT was effective for patients who had Aurora-A (+) tumors (clinically: P = 0.0003, histologically: P = 0.036). CONCLUSIONS: Our results suggest that Aurora-A expression in biopsy specimens of primary tumors is associated with CRT efficacy in patients with ESCC. Assessment of Aurora-A expression in biopsy specimens maybe useful for regarding the potential utility of CRT therapy for patients with ESCC before treatment.

Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2 (Nrf2) expression in gastric cancer.

BACKGROUND: The transcription factor nuclear factor (erythroid-2)-related factor 2 (Nrf2) was originally identified as a critical regulator of intracellular anti-oxidants and of phase II detoxification enzymes through its transcriptional up-regulation of many anti-oxidant response element (ARE)-containing genes. Nrf2 protects not only normal cells but also cancer cells from cellular stress, and enhances cancer cell survival. Some studies have shown that Nrf2 expression in cancer patients has clinical significance. However, there has been no comprehensive analysis of the nuclear expression level of Nrf2 in gastrointestinal cancer cells. In this study we aimed to immunohistochemically evaluate the expression of Nrf2, and to assess its clinical significance in gastric cancer. METHODS: A total of 175 gastric cancer patients who received R0 gastrectomy with standard lymph node dissection were enrolled. We immunohistochemically evaluated Nrf2 expression in the paraffin-embedded surgically resected specimens of these 175 patients. Group differences were analyzed using the χ (2) test, Fisher's exact test, and the Mann-Whitney U test. Associations between Nrf2 expression and clinicopathological features, including clinical outcome, were assessed using univariate and multivariate analyses, and Kaplan-Meier curves with the log-rank test, respectively. RESULTS: Nrf2 immunoreactivity was predominantly identified in the nucleus of gastric cancer cells. Nrf2 positivity was closely associated with tumor size, tumor depth, lymph node metastases, lymphovascular invasion, histology and stage (p < 0.05 for all). A log-rank test indicated that the overall survival of the Nrf2-positive group was significantly poorer than that of the Nrf2-negative group (p < 0.01). And, positive Nrf2 expression was significantly associated with resistance to 5FU-based adjuvant chemotherapy (p = 0.024). CONCLUSIONS: Nrf2 expression was positively associated with aggressive tumor behavior in gastric cancer. This result suggests that Nrf2 expression in gastric cancer is a potential indicator of worse prognosis.