Background: A retrospective investigation was conducted to determine whether autologous blood collection could reduce allogenic transfusion after resection of esophageal cancer and whether allogenic ...transfusion influenced postoperative infection. Methods: Patients (n = 100) who met the criteria for hemoglobin, age, body weight, and serum protein donated 800 mL of autologous blood from May 1994 to December 1997. The control group (n = 248) was selected from patients who met the same criteria and did not donate autologous blood over the 10 years before the start of autologous blood collection. Results: Only three patients (3%) from the autologous group required allogenic transfusion versus 84 patients (33.7%) from the control group. Sixteen of the 26 patients who received more than 4 units of allogenic blood contracted postoperative infections compared with 25 of 165 patients who did not (P <.0001). Autologous blood transfusion significantly increased the probability of avoiding allogenic transfusion (odds ratio, 27.58), and allogenic transfusion was significantly related to postoperative infection (odds ratio, 1.19), according to logistic regression analysis. Conclusions: Autologous blood collection reduces the need for allogenic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogenic transfusion may reduce the risk of postoperative infection.(Surgery 2000;127:185-92.)
A 68-year-old female patient presented with advanced gastric cancer and multiple hepatic tumors. Upper GI endoscopy showed a type 3 lesion in the posterior wall of the gastric body. Abdominal ...computed tomography revealed multiple liver metastases, and staging laparoscopy identified peritoneal dissemination. She was diagnosed with clinical Stage Ⅳ gastric cancer(cT3N2M1H1). She received 3 courses of combined chemotherapy containing S-1 and cisplatin. The therapeutic response was PR. We performed total gastrectomy with D2 lymph node dissection and splenectomy. Histopathological examination revealed no residual cancer cells, indicating pCR. She continued S-1 adjuvant chemotherapy and has remained free from recurrence for 18 months.
Basaloid squamous cell carcinoma (BSCC) is a rare and poorly differentiated variant of typical squamous cell carcinoma, and is characterised in part by activation of the Wnt signalling pathway. We ...previously demonstrated that constitutive activation of the Wnt signalling pathway by epigenetic silencing of secreted frizzled-related protein 4 (SFRP4) is observed in this tumour. Increasing evidence shows that the Wnt signalling pathway cross-talks with other developmental pathways, including the Hedgehog (HH) pathway. The HH pathway is stimulated by inactivating mutations of PTCH1, which have a well-described oncogenic role in basal cell carcinoma (BCC) of the skin. We employed polymerase chain reaction followed by direct sequencing to detect inactivating mutations of PTCH1 using archival tissue samples of 30 oesophageal BSCCs. The frequency of PTCH1 mutation was compared to that of Wnt component genes that we reported previously. We found PTCH1 mutations in 53.3% (16/30) of cases, revealing T1195S as a hotspot mutation. This frequency is quite high for cancers other than BCC of the skin, and PTCH1 mutations were almost mutually exclusive with mutations in APC, Axin1 and Axin2. Considering the fact that activation of Wnt signalling via down-regulation of APC and SFRP5 due to promoter methylation is observed in BCC of the skin, Wnt signalling activation in oesophageal BSCC might be a secondary effect of the PTCH1-inactivating mutations. These findings suggest that the HH and Wnt pathways coordinately contribute to tumourigenesis in oesophageal BSCC. Furthermore, this study provides a potential therapeutic application for HH pathway inhibitors in oesophageal BSCC with highly malignant potential.
Several studies have evaluated associations between the characteristics of patients with esophageal and gastric cancer and survival, but these associations remain unclear. We described the ...distribution of demographic and lifestyle factors among patients with esophageal and gastric cancer in Japan, and investigated their potential effects on survival.
Between 2003 and 2007, 24- to 95-year-old Japanese patients with esophageal and gastric cancer were enrolled in the BioBank Japan Project. The analysis included 365 patients with esophageal squamous cell carcinoma (ESCC) and 1574 patients with gastric cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using medical institution-stratified Cox proportional hazards models.
During follow-up, 213 patients with ESCC (median follow-up, 4.4 years) and 603 patients with gastric cancer (median follow-up, 6.1 years) died. Among patients with ESCC, the mortality risk was higher in ever drinkers versus never drinkers (multivariable HR = 2.37, 95% CI: 1.24, 4.53). Among patients with gastric cancer, the mortality risk was higher in underweight patients versus patients of normal weight (multivariable HR = 1.66, 95% CI: 1.34, 2.05). Compared to patients with gastric cancer with no physical exercise habit, those who exercised ≥3 times/week had a lower mortality risk (multivariate HR = 0.75, 95% CI = 0.61, 0.93). However, lack of stage in many cases was a limitation.
Among patients with ESCC, alcohol drinkers have a poor prognosis. Patients with gastric cancer who are underweight also have a poor prognosis, whereas patients with physical exercise habits have a good prognosis.
•Among ESCC patients, alcohol drinkers had a poor prognosis.•Underweight gastric cancer patients had a poor prognosis.•Gastric cancer patients who exercised had a good prognosis.•No association between esophageal or gastric cancer and smoking was observed.
We attempt to clarify the problems of pulmonary thromboembolism (PTE), which occurs less frequently in Japan than in the West, regarding its special perioperative management and prophylaxis for PTE ...after esophagectomy. We studied 26 patients with PTE following esophagectomy among 1023 patients with esophageal cancer between 1984 and 1997. The presence of embolism was confirmed by pulmonary perfusion scintigraphy. The incidence, diagnosis, and other issues of PTE were all reviewed. The incidence of PTE was 2.5%, with patients showing a biphasic early and late onset. The main symptoms were dyspnea in 19 patients and tachycardia in 17. Scintigraphy demonstrated 154 lesions, 35.7% of which were located in the left lower lobe and 25.3% in the right lower lobe. Treatment mainly consisted of the administration of heparin and urokinase. Four of the 26 patients died. Intermittent pneumatic compression (IPC) with the administration of heparin has been used in our department since 1994 to prevent PTE and this has also helped to decrease the incidence from 3.2% to 0.7%. Because the incidence of PTE following esophagectomy is higher than expected, PTE should be considered whenever hypoxemia of some unknown cause is found. Both early diagnosis and treatment are essential. It is also important to prevent PTE by the use of IPC.
Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare variant of typical squamous cell carcinoma (SCC) associated with poor survival. A characteristic feature is nuclear accumulation of ...beta-catenin, without a mutation of the gene. We studied the methylation status of Wnt antagonist genes, such as secreted frizzled-related protein (sFRP) gene family members, Wnt inhibitory factor-1 (WIF-1), Dickkopf-1 (Dkk-1), and human Dapper protein-1 (HDPR-1), and alterations of the APC, Axin1, and Axin2 genes in 30 cases of esophageal BSCC. beta-catenin and sFRP (sFRP-1, sFRP-2, sFRP-4, sFRP-5) protein expression was examined by immunohistochemistry. APC, Axin1, and Axin2 gene mutations were detected in 3, 2, and 2 cases, respectively, and 6 cases (20 %) harbored at least 1 alteration in these genes. Methylation of the sFRP-2 promoter region was observed in all cases, and methylation was frequent in sFRP-1 and sFRP-5, but infrequent in Dkk-1, WIF-1, sFRP-4, and HDPR-1. sFRP-2 expression was almost completely absent in 25 cases (83 %), consistent with the methylation status. Nuclear accumulation of beta-catenin was observed in all cases. sFRP-5 expression was associated with a low nuclear beta-catenin labeling index. These results show that sFRP-2 is a target gene of hypermethylation in esophageal BSCC and suggest that sFRP-2 might contribute to BSCC tumorigenesis through the Wnt/beta-catenin signaling pathway.PUBLICATION ABSTRACT
SUMMARY
Squamous cell carcinoma of the esophagus (ESCC) has a poor prognosis among digestive tract cancers. Lymph node metastasis and distant metastasis are the major factors determining its ...prognosis. We used comparative genomic hybridization (CGH) to evaluate primary tumor lymph nodes and metastatic areas from ESCC patients in order to determine the relationship between abnormal chromosome regions and outcome. Tumor tissues and lymph nodes were collected from 51 patients with ESCC, and abnormal chromosome regions were detected by CGH. We searched for regions that were significantly more common in patients with lymph nodes metastases (n≥ 6) or distant metastases, and correlated those chromosomal changes with survival. Regions showing amplification in more than 65% of esophageal squamous cell cancers were as follows: 17q12 (90.2%), 17q21 (86.3%), 3q29 (82.4%), 3q28 (78.4%), 8q24.2 (76.5%), 22q12 (76.5%), 3q27 (74.5%), 8q24.3 (74.5%), 1q22 (70.6%), 5p15.3 (70.6%), 22q13 (70.6%), 3q26.3, 8q23, 8q24.1, 9q34, 11q13, 17p12, 17q25, 20q12, 20q13.1 (68.6%), 1q32, 1q42, and 20q13.2 (66.7%). Regions showing deletion in more than 50% of the tumors were as follows: Yp11.3 (62.7%), 3p26 (56.9%), Yq12 (54.9%), 13q21 (52.9%), 4q32 (51.0%), and 13q22 (51.0%). When Fisher's test was used to assess associations of these regions with metastases to lymph nodes, amplification at 2q12–14 (P= 0.012), 3q24–26 (P= 0.005), and 7q21–31 (P= 0.026) were significant. Survival was worse for patients with amplification at all 3 regions. In patients with distant organ metastases, amplification at 7p13–21 was significant (P= 0.008), and survival was worse. Chromosomal amplifications in ESCC at 2q12–14, 3q24–26, and 7q21–31 were associated with lymph node metastasis, while amplification at 7p13–21 was related to distant metastasis. Amplification at these regions correlated with worse survival. Genes involved in the phenotype of ESCC may exist in these regions. Identification of these genes is a theme for future investigation.
Gastric cancer is the second leading cause of cancer mortality in the world. It is important to develop biomarkers for detecting new cancers at an early stage and for treating them early during ...recurrence in order to guide optimal treatment. Fatty acid synthase (FAS) is highly expressed in numerous human cancers and thus could potentially serve as such a biomarker, but the potential utility of measuring FAS for detecting gastric cancer has not been previously investigated. The aim of the present study was to provide a preliminary assessment of serum FAS as a marker of gastric carcinoma. The study included 47 patients with gastric cancer and 150 healthy subjects. Blood samples were collected from each cancer patient prior to treatment. Serum FAS levels were measured by ELISA and compared across the two groups of patients. Significantly higher levels of serum FAS were found in the gastric cancer patients 95% confidence interval (CI), 30.37-52.46 compared with the healthy controls (95% CI, 1.331-2.131), with elevated levels even in patients with early-stage tumors. These results indicate that measuring serum FAS levels has strong potential to provide a biomarker for the detection of gastric cancer, with high sensitivity and specificity.
Post-operative pulmonary complications such as systemic inflammatory response syndrome (SIRS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are strongly associated with ...morbidity and mortality after esophagectomy. Post-operative administration of sivelestat sodium hydrate (sivelestat), a selective inhibitor of neutrophil elastase (NE), has been shown to improve the post-operative clinical course after esophagectomy. This study aimed to evaluate the effect of prophylactic administration of sivelestat on bronchial inflammatory responses. We randomized 24 patients into two groups. One group received 0.2 mg/kg/h sivelestat from the induction of anesthesia to post-operative day 1 (sivelestat group) and the other group received the same amount of physiological saline (control group). Bronchial alveolar epithelial lining fluid (ELF) samples were obtained from both groups at the induction of anesthesia and at the end of surgery. The serum and ELF levels of interleukin (IL)-6 and IL-8 were measured by enzyme-linked immunosorbent assay, and NE activity was spectrophotometrically determined using the same samples. Although IL-6 levels in the ELF significantly increased at the end of surgery compared with the pre-operative levels in both groups, the IL-8 levels and NE activity did not significantly increase at the end of the surgery compared to the corresponding pre-operative values in the sivelestat group. Moreover, IL-8 levels and NE activity in the ELF were significantly reduced at the end of surgery in the sivelestat group compared with corresponding values in the control group. The durations of ALI and ARDS were apparently shorter in the sivelestat group and the duration of SIRS was significantly shorter in the sivelestat group compared to the control group. We demonstrated that prophylactic use of sivelestat mitigated bronchial inflammation by suppressing NE activity and IL-8 levels in the ELF and shortened the duration of SIRS after transthoracic esophagectomy.
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