Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

Schematic diagrams of the signal cascade of EGF-induced DPD expression of EGFR-mutated type cells. TF, transcription factor; Mit A, mithramycin A. (JPG 130 kb

The significance of extended lymphadenectomy for colorectal cancer with isolated synchronous extraregional lymph node metastasis

SummaryBackground/ObjectiveThe significance of extended lymphadenectomy for colorectal cancer with extraregional lymph node metastasis, such as para-aortic lymph node metastasis, has not been established. The purpose of this study was to evaluate the significance of extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis.MethodsBetween July 2004 and December 2013, 16 patients with synchronous extraregional lymph node metastasis without other organ metastases underwent curative resection and extended lymphadenectomy (R0 group). The clinical characteristics and survival outcomes of the R0 group were compared with those of 12 patients with extraregional lymph node metastasis who underwent palliative surgery (control group).ResultsIn the R0 group, the 5-year cancer-specific survival (CSS) rate was 70.3% and the 5-year relapse-free survival (RFS) rate was 60.5%. The 5-year CSS differed significantly between the R0 and control groups (70.3% vs. 12.5%; p = 0.0003). Univariate analyses revealed that the total numbers of metastatic lymph nodes and metastatic regional lymph nodes present were significantly associated with RFS (p = 0.019 for both).ConclusionFindings from our study suggest that extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis might be effective in carefully selected patients

An experience of hepatopancreatoduodenectomy in patients with hepatobiliary malignancies

BACKGROUND/AIMS: In the advanced stage of hepatobiliary malignancies, concurrent hepatopancreatoduodenectomy (HPD) is necessary to accomplish curative resection, even though high rates of morbidity and mortality still remain. METHODOLOGY: We examined the surgical records and outcome in 11 patients undergoing HPD. RESULTS: In 11 patients, diseases included bile duct carcinomas in 7 patients, gallbladder carcinomas in 3, and ampullar carcinoma in one. Hemi-hepatectomy with resection of the caudate lobe was performed in 8 patients and resection of segment 4 and 5 of the liver in two. Pancreatoduodenectomy (PD) was performed in 3 patients and pylorus-preserving PD in 8. Curative resection was accomplished in 8 patients. Two patients underwent adjuvant photodynamic therapy because of a cancer-positive margin. Morbidity rate was 36% but no hospital deaths were reported. The tumor recurrence rate was 73% and 8 patients died of cancer. Patient prognosis of gallbladder cancers (12 +/- 1 months) tended to be shorter than in patients with bile duct cancers (19 +/- 11 months) (p=0.15). Three patients with bile duct cancers survived without tumor relapse over 12 months. CONCLUSIONS: Complete surgical resection (R0) by HPD could be safely performed for diseases of the hepatobiliary malignancies, which achieved longer survival in some patients

High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non?Small-Cell Lung Cancer Using 5-Fluorouracil

BackgroundIt has been shown that 5-fluorouracil (5-FU) sensitivity in patients with non?small-cell lung cancer (NSCLC) is associated with epidermal growth factor receptor (EGFR) mutation status. However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status.Patients and MethodsEGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines.ResultsAdenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P < .05). DPD immunopositive cases were more frequently observed in adenocarcinoma, in females, and in nonsmokers. DPD immunopositive cases were correlated with EGFR mutation status (P < .003). The prognoses of wild-type EGFR and mutated EGFR populations were similarly favorable with postoperative S-1 treatment, which overcomes the problem of 5-FU degradation in mutated EGFR. In vitro, EGFR-mutated cell lines showed high DPD mRNA and protein expression.ConclusionHigh DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. Clinicians should take this finding into consideration when using 5-FU to treat patients with NSCLC

Difficulty of predicting lymph node metastasis on CT in patients with rectal neuroendocrine tumors.

BACKGROUND:Surgical indications for rectal neuroendocrine tumors with potential lymph node metastasis remain controversial. Although accurate preoperative diagnosis of nodal status may be helpful for treatment strategy, scant data about clinical values of lymph node size have been reported. The aim of this retrospective study was to investigate the relationship between lymph node size and lymph node metastasis. METHODS:Participants comprised 102 patients who underwent rectal resection with total mesenteric excision or tumor-specific mesenteric excision and in some cases additional lateral pelvic lymph node dissection for rectal neuroendocrine tumor between June 2005 and September 2016. All lymph nodes from specimens were checked and measured. RESULTS:Pathological lymph node metastasis was confirmed in 37 patients (36%), including 6 patients (5.8%) with lateral pelvic lymph node metastasis. A total of 1169 lymph nodes in the mesorectum were retrieved from all specimens, with 78 lymph nodes (6.7%) showing metastasis. Mean length (long-axis diameter) of metastatic lymph nodes in the mesorectum was 4.31 mm, significantly larger than that of non-metastatic lymph nodes (2.39 mm, P<0.01). The optimal cut-off of major axis length for predicting mesorectal lymph node metastasis was 3 mm. We could predict lymph node metastasis in only 7 patients (21%) from preoperative multidetector-row computed tomography. CONCLUSIONS:Metastatic lymph nodes were small, so predicting lymph node metastasis from preoperative computed tomography is difficult. Alternative modalities with a scan width less than 3 mm may be needed to predict lymph node metastasis of rectal NET with low cost and labour requirements

Clinical significance of soluble programmed cell death-1 and soluble programmed cell death-ligand 1 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

BackgroundInhibition of the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis in combination with radiotherapy may be a promising approach to treat cancer. In the present study, we aimed to evaluate serum soluble PD-1/PD-L1 levels in patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).MethodsSerum soluble PD-L1 and PD-1 levels were measured using an enzyme-linked immunosorbent assay before and after CRT in 117 patients with low rectal cancer. Changes in the levels of sPD-L1/PD-1 after CRT, and the correlation between sPD-L1/PD-1 level and clinicopathological characteristics or disease-free survival (DFS) were evaluated.ResultssPD-L1 levels significantly increased after CRT (p ConclusionsSignificant increase of sPD-L1 levels after CRT suggests that anti-PD-L1 therapy might be a potential treatment strategy in combination with CRT in advanced rectal cancer

The significance of extended lymphadenectomy for colorectal cancer with isolated synchronous extraregional lymph node metastasis

Background/Objective: The significance of extended lymphadenectomy for colorectal cancer with extraregional lymph node metastasis, such as para-aortic lymph node metastasis, has not been established. The purpose of this study was to evaluate the significance of extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis. Methods: Between July 2004 and December 2013, 16 patients with synchronous extraregional lymph node metastasis without other organ metastases underwent curative resection and extended lymphadenectomy (R0 group). The clinical characteristics and survival outcomes of the R0 group were compared with those of 12 patients with extraregional lymph node metastasis who underwent palliative surgery (control group). Results: In the R0 group, the 5-year cancer-specific survival (CSS) rate was 70.3% and the 5-year relapse-free survival (RFS) rate was 60.5%. The 5-year CSS differed significantly between the R0 and control groups (70.3% vs. 12.5%; p = 0.0003). Univariate analyses revealed that the total numbers of metastatic lymph nodes and metastatic regional lymph nodes present were significantly associated with RFS (p = 0.019 for both). Conclusion: Findings from our study suggest that extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis might be effective in carefully selected patients

The Right Colon Patch Graft Procedure for Extensive Intestinal Aganglionosis

Extensive intestinal aganglionosis is rare and very difficult to diagnose and treat. The condition is often fatal. A 6-month-old boy who had undergone ileostomy for extensive intestinal aganglionosis was referred to our department. We applied an aganglionic right colon onlay patch to the aganglionic intestine to enhance absorption of water and electrolytes. Three months after the ileocolostomy, the definitive operation, a Swenson-type procedure, was performed. The mesocolon to the onlay patch could be divided because blood supply was adequate from the ileal mesentery via the intestinal wall. Postoperatively, the onlay patch segment appeared normal on colonoscopy and bowel habit was improved. Although the patient still requires parenteral nutrition support due to the short bowel, the right colon onlay patch procedure enables him to be cared for at home and provides an opportunity for normal growth and development