Staging Paradox and Discrepancy in Adjuvant Chemotherapy in Patients with T4N0, T1-2N1, and T3N1 Colon Cancer.

BACKGROUND: A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages. METHODS: Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors. RESULTS: The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor. CONCLUSIONS: T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients.

Clinical safety and efficacy of neoadjuvant combination chemotherapy of tranilast in advanced esophageal squamous cell carcinoma: Phase I/II study (TNAC).

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) was previously shown to play an important role in the maintenance of cancer stem cells, and its specific inhibitor, tranilast, also has potential as a targeted therapeutic agent for esophageal squamous cell carcinoma (ESCC). The present study is being conducted to confirm the safety and efficacy of the additional use of tranilast with conventional preoperative adjuvant chemotherapy for patients with advanced ESCC. PATIENTS AND METHODS: Between 56 and 59 patients aged between 20 and 74 years with clinically diagnosed Stage II or Stage III ESCC will be enrolled. Eligible patients will receive preoperative adjuvant chemotherapy, 2 cycles of combination therapy with cisplatin, 5-fluorouracil, and tranilast. Recruitment started in November 2019, with the final follow-up being planned for March 2029. One subject has been enrolled since October 21, 2020. The pathological therapeutic effect is the primary endpoint. The objective response rate, safety of preoperative adjuvant chemotherapy, recurrence-free survival (RFS), and overall survival (OS) are the secondary endpoints. RFS and OS will be calculated as the time from surgery to first recurrence and all-cause death, respectively. ETHICS AND DISSEMINATION: This protocol has been approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine and all participating hospitals in August 30, 2019 (Number: CRB5180001). Written informed consent will be obtained from all patients before their registration, which is in accordance with the Declaration of Helsinki. The results of the present study will be disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number jRCTs051190076.

Clinical Significance of Prognostic Nutritional Index in the Treatment of Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The prognostic nutritional index (PNI) is reported to affect postoperative complications and survival of patients with esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the clinical significance of PNI in treatment of ESCC. PATIENTS AND METHODS: Two hundred and sixty-three patients who underwent radical esophagectomy were retrospectively analyzed. PNI was calculated in the pretreatment (pre-Tx), post-neoadjuvant chemotherapy (post-NAC), and postoperative periods. RESULTS: Pre-Tx PNI positively correlated with prognosis irrespective of undergoing NAC (p<0.05). In the patients with NAC, pre-Tx PNI was one of the independent prognostic factors (p=0.04). In patients with low pre-Tx PNI, the prognosis was improved by increase of PNI after NAC (p=0.08), and two cycles of NAC significantly correlated with high post-NAC PNI (p=0.04). CONCLUSION: Pre-Tx PNI is an independent prognostic factor irrespective of NAC. Patients in whom the post-NAC PNI can be improved have a high probability of obtaining a good prognosis.

Significance of GSTP1 for predicting the prognosis and chemotherapeutic efficacy in esophageal squamous cell carcinoma.

Glutathione S-transferases (GSTs) have been reported to be activated in several types of cancers, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate whether GSTP1 protein expression is a useful predictor of the clinical outcome or drug resistance in ESCC. Immunohistochemistry was conducted with 75 ESCC resected specimens using a monoclonal antibody against GSTP1. The patients were divided into two groups according to the degree of GSTP1 staining, and the relationship between the GSTP1 level and the clinicopathological features was examined. Seventy-five patients were divided into low (grade 1, n=36) and high (grade 2, n=39) GSTP1 expression groups. The overall survival was significantly worse in the grade 2 patients than in the grade 1 patients (5­year survival rate, 78.5 vs. 51.2%; p=0.027). Cox proportional hazard analysis revealed that macroscopic type 3 or 4 disease (p=0.001), lymph node metastasis (p=0.010), and high GSTP1 expression (p=0.029) were independent predictors of a poor prognosis. With regard to the subgroup analysis among the 31 patients undergoing adjuvant chemotherapy, the grade 2 patients had a worse prognosis than did the grade 1 patients (5­year survival rate, 45.0 vs. 81.8%; p=0.081). This tendency was not observed in the subgroup without adjuvant chemotherapy (5­year survival rate, 51.7 vs. 59.9%; p=0.979). In conclusion, the GSTP1 expression is a good predictor of prognosis, and it may be closely related to the chemotherapeutic efficacy of 5-FU plus cisplatin in ESCC patients.

Case involving long-term survival after esophageal cancer with liver and lung metastases treated by multidisciplinary therapy: report of a case.

A 57-year-old male with lower esophageal cancer underwent subtotal esophagectomy with lymphadenectomy. The histopathological diagnosis was poorly differentiated squamous cell carcinoma, pT2N1M0 pStageIIB. After one course of postoperative adjuvant chemotherapy involving low-dose CDDP/5FU, a PET-CT scan obtained 12 months after surgery revealed a solitary liver metastasis in the S2 area. The patient then underwent five courses of docetaxel chemotherapy (80 mg/body, tri-weekly), and a partial response was observed. We also performed radiofrequency ablation (RFA), after which a complete response was observed. Twenty months after surgery, we detected local liver recurrence in the same position and performed additional RFA. Twenty-four months after surgery, a solitary lung metastasis was detected in the left S2 area and the patient was administered five additional courses of docetaxel therapy. Subsequently, PET-CT revealed growth of lung and liver tumors without recurrence in other areas. Twenty-nine months after surgery, we partially excised metastatic liver and lung tumors, and no subsequent recurrence has since been detected. The prognoses of patients who suffer from esophageal cancer organ recurrence are known to be extremely poor, and optimal therapeutic strategies for treating these patients have not been established. This long-term survival case suggests that multidisciplinary therapy for the treatment of liver and lung recurrence after esophagectomy is effective.

[PSK-mediated growth suppression and enhancement of 5-FU/docetaxel-induced cytotoxicity in human esophageal cancer cell lines].

PSK, a protein-bound polysaccharide, is widely used for treating cancer patients as an immunostimulant. However, its direct action on cancer cells is not fully understood. In the present study, we investigated direct effects of PSK alone or in combination with 5-FU, CDDP and docetaxel on tumor growth by using esophageal cancer cell lines, KYSE170 and TE13. Cells were incubated with different concentrations of PSK for 72 hour, and cell viability was determined by WST-8 assay, and cell cycle was analyzed by flow cytometry. As a result, PSK of 100 microg/mL induced growth suppression dose-dependently in the both cell lines, and flow cytometric analysis showed a PSK dose-dependent increase of sub-G1 cells indicating apoptotic cells. In addition, when cells were incubated with different concentrations of 5-FU and docetaxel in the presence of PSK at the dose of 5 microg/mL showing no growth suppression, cytotoxicity induced by 5-FU and docetaxel was significantly enhanced. These results indicate that PSK not only shows tumor growth suppression by apoptosis induction, but also enhances 5-FU and docetaxel-induced cytotoxicity.

[Plasma methylation-specific polymerase chain reaction as a diagnostic tool for esophageal cancer patients].

This study was designed to perform methylation-specific polymerase chain reaction (MS-PCR) assay for p16, E-cadherin, and retinoic acid receptor beta genes on peripheral blood samples from patients with esophageal squamous cell cancers, and compare the results of MS PCR with conventional serum tumor markers and the CEA-specific reverse transcriptase polymerase chain reaction (RT-PCR) assay. Preoperative blood samples were obtained from 30 patients with esophageal cancer, and were subjected to MS PCR and RT-PCR assays. Eleven patients (37%) showed aberrant methylation of the promoter region of at least one gene. On the other hand, circulating tumor cells were detected in 11 patients (37%). There was no correlation between both results and conventional tumor markers. The MS-PCR and RT-PCR assays can serve as complementary diagnostic markers for screening and monitoring patients with esophageal cancers.

Comparison of serum aberrant methylation and conventional tumor markers in gastric cancer patients.

BACKGROUND/AIMS: This study was designed to compare a methylation-specific polymerase chain reaction (MSP) assay for three genes [p16, E-cadherin, and retinoic acid receptor beta (RARbeta)] and conventional serum tumor markers using blood samples from gastric cancer patients. METHODOLOGY: Preoperative blood samples obtained from 63 consecutive patients with gastric cancer were subjected to MSP and conventional serum marker assays. RESULTS: MSP assay detected hypermethylation of p16 in 17 patients (27%), E-cadherin in 15 patients (24%), and RARbeta in 11 patients (17%). Altogether, 32 patients (51%) showed hypermethylation in serum samples. By contrast, only 21 (33%) patients exhibited elevations of serum carcinoembryonic antigen or carbohydrate antigen 19-9. There was no correlation between MSP results and conventional tumor markers. CONCLUSIONS: The detection rate for MSP was higher than that of conventional tumor markers in serum of gastric cancer patients. Both assays can serve as complementary markers that allow for selection of cases requiring more intensive screening or aggressive postoperative treatment.