Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear.
We evaluated MRP2 ...expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines.
MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP.
Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients.
Background
The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient ...population.
Methods
A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures.
Results
Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (
n
= 159) or TG (
n
= 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (− 12.8% versus − 16.9%;
p
= 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min;
p
< 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%;
p
= 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%;
p
= 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively;
p
= 0.49).
Conclusions
Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.
Circulating tumour DNA (ctDNA) is an emerging candidate biomarker for malignancies and may be useful for monitoring the disease status of gastric cancer.
We performed targeted deep sequencing of ...plasma cell-free DNA (cfDNA) by massively parallel sequencing in patients with tumours harbouring TP53 mutations. The quantitative values of TP53-ctDNA during the clinical course were compared with the tumour status.
Three out of ten patients with TP53 mutations in primary tumours showed detectable TP53 mutation levels in preoperative cfDNA. Although the cfDNA concentrations were not always reflective of the disease course, the ctDNA fraction correlated with the disease status.
ctDNA may serve as a useful biomarker to monitor gastric cancer progression and residual disease.
Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not ...been elucidated.
Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line.
Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells.
High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.
Background
Several studies have examined the clinical significance of metabolic response in primary tumours by 18Ffluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) in patients with ...oesophageal cancer who undergo neoadjuvant therapy. The relevance of the metabolic response in lymph nodes is unclear.
Methods
Consecutive patients with oesophageal cancer who underwent neoadjuvant chemotherapy followed by surgery were studied. 18F‐FDG‐PET was performed before and 2–3 weeks after completion of neoadjuvant chemotherapy, assessing FDG uptake in primary tumours and lymph nodes considered to be metastatic.
Results
Before therapy, 156 (73·9 per cent) of 211 patients had PET‐positive nodes, of whom 89 (57.1 per cent) had no evidence of metabolic activity in these lymph nodes following chemotherapy. There was a significant relationship between post‐treatment lymph node status assessed by FDG‐PET and numbers of pathologically confirmed metastatic lymph nodes. Patients with post‐treatment PET‐positive nodes had shorter survival than those without (5‐year survival rate 25 versus 62·6 per cent; P < 0·001). There was no difference in survival between patients with PET‐positive nodes before but not after therapy and patients who had PET‐negative nodes throughout (5‐year survival rate 59 versus 71 per cent respectively; P = 0·207). Multivariable analysis identified post‐treatment nodal status assessed by FDG‐PET and tumour depth as independent prognostic factors.
Conclusion
Identification of PET‐positive lymph nodes after completion of chemotherapy is a predictor of poor prognosis of patients with oesophageal cancer scheduled for surgery. FDG‐PET lymph node status after neoadjuvant chemotherapy is more important than that before chemotherapy.
Merits further evaluation in squamous cell cancer
Summary
Although 3-field lymph node dissection (3-FLD) is often performed for thoracic esophageal squamous cell carcinoma (ESCC), the clinical effects of cervical lymph node dissection in addition to ...mediastinal and abdominal dissections on postoperative complications remain unclear. A total of 367 ESCC patients who underwent curative esophagectomy for thoracic esophageal cancer in our hospital from 2010 to 2015 were included in the study: 157 patients who underwent 2-field lymph node dissection (2-FLD) and 210 patients who underwent 3-FLD. Clinicopathological parameters and postoperative complications based on the Clavien–Dindo classification were compared between the two groups. We performed propensity score matching (PSM) analyses to compare the groups with well-balanced backgrounds. In terms of patient background, clinical T (p < 0.001), N (p < 0.001), and M (p = 0.002) stage of tumor was significantly more advanced; therefore, preoperative treatment was more frequently performed in the 3-FLD group than in the 2-FLD group (91.0% vs. 79.0%, P< 0.001). However, perioperative parameters including operation time, blood loss, and the number of dissected mediastinal and abdominal lymph nodes did not differ between the groups. In terms of postoperative complications, the occurrence rate of pneumonia increased significantly in patients with 3-FLD compared to 2-FLD (grade III or higher: 10.5% vs. 3.2%, P= 0.025). Although the duration of systemic inflammatory response syndrome (SIRS) was longer in the 3-FLD group than in the 2-FLD group (median 3 days vs. 2 days, P= 0.025), other postoperative parameters (including the highest level of postoperative serum C-reactive protein, intensive care unit stay, re-operation rate, and postoperative hospital stay) were similar between the groups. After PSM, the differences in the background between the groups disappeared. PSM analysis showed that there was no significant difference in each complication between the groups. The duration of SIRS tended to be longer in the 3-FLD group than in the 2-FLD group, but the difference was not significant. The field of lymphadenectomy negatively impacted the short-term outcome in ESCC patients in terms of pneumonia and inflammatory response. However, because the results of the PSM analyses indicate that the short-term outcome was similar between the two groups, 3-FLD could be as feasible as 2-FLD in ESCC patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
SUMMARY
Although no consensus is available on the treatment of esophageal squamous cell carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction treatments is crucial to ...altering an unresectable status and achieving curative resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil, cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC. Fifty patients without distant metastasis who underwent initial induction chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical response rate compared to 72.0% for induction CRT. CRT was also performed in another 24 (48.0%) patients in the DCF group in whom surgical resection was not indicated. The DCF group had significantly higher overall resectability than the CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during induction treatments was significantly lower in the DCF group than the CRT group (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146). Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal perforation and increased overall resectability, leading to better survival than CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for initial induction treatment of T4 ESCC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In general, visceral fat and adhesion greatly influence the technical difficulty in performing abdominal surgery. Body mass index (BMI) has been widely used to express the degree of obesity, but it ...does not always properly reflect the degree of visceral fat. This retrospective study investigated the impact of visceral fat on the operation time to examine whether a quantified visceral fat area (VFA) could be used as a sensitive predictor of technical difficulty in performing a laparoscopic resection of rectosigmoid carcinoma.
Between February 1999 and April 2004, 58 consecutive patients underwent a laparoscopically assisted sigmoidectomy or anterior resection. After a review of the medical charts, the relationship between the operation time and the following variables was analyzed: sex, depth of invasion, approach (medial-to-lateral, lateral-to-medial), subjectively graded degree of visceral fat and adhesion, history of previous abdominal surgery, and BMI. The correlations between VFA, VFA/body surface area (BSA) measured by the "FatScan," software package for quantifying the VFA from the preoperative CT images, and operation time were investigated. Next, the impact of the VFA amount on the early surgical outcome was examined.
According to the intraoperative findings, two patients with a severe adhesion required a significantly longer operation time. A history of previous abdominal surgery was not a significant factor in the operation time. Instead, the VFA/BSA had a stronger correlation with the operation time than the BMI. A significantly longer operation time (209 +/- 42 vs 179 +/- 37 min; p = 0.031) was observed for the patients in the high VFA/BSA group (> or =85 cm(2)/m(2)) group than in the normal VFA/BSA group (<85 cm(2)/m(2)).
For predicting the technical difficulty of performing a laparoscopic resection of rectosigmoid carcinoma, VFA/BSA may be a more useful index than BMI.
Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to ...assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21(WAF1/CIP1)) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage.
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