Evaluation of subcarinal lymph node dissection and metastasis in transmediastinal radical esophagectomy

Background

The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer.

Methods

Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail.

Results

The median of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p?=?0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis, whereas only 7 (26.9%) of those with metastasis were preoperatively diagnosed as positive. In addition, all patients with subcarinal lymph node metastasis had other non-subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥?30 mm) and deeper (T3/T4a) primary lesions (p?=?0.02 and 0.02, respectively), but it was not found in 49 patients with the primary lesion located in the upper thoracic esophagus.

Conclusions

Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.

     

The carina is not a landmark for central venous catheter placement in neonates

BACKGROUND: Cardiac tamponade is rare but one of the most serious complications in relation to central venous catheters (CVC). The tip of the CVC should be placed outside the pericardium to avoid tamponade. In adults, the carina is always located above the pericardium; therefore, the carina is a reliable landmark for CVC placement. We examined whether the carina could also be an adequate landmark for CVC placement in neonates. METHODS: The study was conducted using nine fresh neonatal cadavers. The longitudinal distance between the carina and the pericardium as it transverses the superior vena cava (the pericardial reflection: PR) was measured. RESULTS: The median postconceptional age (gestational age in weeks + weeks after delivery) at autopsy was 35 (range: 23-42) weeks. The PR was located at a distance of 4 mm above to 5 mm below the carina. Unlike in adults, the position of the PR varies in relation to the carina in neonates. In seven of the nine subjects, the location of the PR was above the carina. CONCLUSIONS: In neonates, the carina is not always located above the pericardium, as it is in adults; therefore, the carina is not an appropriate landmark for CVC placement.     

Absence of beta-catenin alteration in hepatic tumors induced by p-nitroanisole in Crj:BDF1 mice

In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) approach. Genomic DNA was isolated from paraffin sections of a total of 53 liver tumors. Immunohistochemical analysis revealed no abnormal accumulation of the beta-catenin protein in any of the cases. No mutations (0/13), 20% silent mutations (3/15) and 8% silent plus 12% functional mutations (2 + 3/25), not in the multiple phosphorylation sites of beta-catenin, were observed in hepatocellular adenomas, carcinomas and hepatoblastomas, respectively. The results indicate that beta-catenin does not play an important role in development of hepatic tumors induced by pNA in Crj:BDF1 mice.     

Existence of no hepatocarcinogenic effect levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with or without coadministration with ethanol

There is increasing evidence of the existence of no effect levels for genotoxic carcinogens. However, only limited information is available regarding dose-response curves for combination effects of multiple carcinogens at low dose. In the present study, 280 male F344 rats were divided into 14 groups to determine the effects of co-administration of various doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 10% ethanol on the development of glutathione S-transferase placental form (GST-P)-positive foci in the liver. The results provided concrete evidence for the existence of no effect levels for hepatocarcinogenicity of MeIQx either in presence or absence of ethanol and, therefore, for a practical threshold for this genotoxic carcinogen.     

Role of CYP2E1 in diethylnitrosamine-induced hepatocarcinogenesis in vivo

CYP2E1 metabolizes many low-molecular weight toxins and carcinogens. Some in vitro experiments suggest that CYP2E1 may be involved in the metabolic activation of diethylnitrosamine. However, there has been no direct evidence demonstrating a role for CYP2E1 in diethylnitrosamine-mediated carcinogenesis in vivo. To clarify this, we carried out a diethylnitrosamine-induced hepatocarcinogenesis experiment using Cyp2e1-null mice. Male 14-day-old wild-type and Cyp2e1-null mice were treated with diethylnitrosamine (10 mg/kg of body weight) and killed at weeks 24 and 36 after diethylnitrosamine treatment for investigation of tumors and at 6, 24, and 48 h for examination of apoptosis and gene expression. Liver weights of Cyp2e1-null mice were significantly different at weeks 24 and 36 compared with wild-type mice (P < 0.01). Liver tumor incidences of Cyp2e1-null mice were significantly decreased at weeks 24 and 36 compared with wild-type mice (P < 0.01). Cyp2e1-null mice showed significant decrease in the multiplicities of hepatocellular adenoma at weeks 24 and 36 (P < 0.05 and P < 0.01, respectively), and of hepatocellular carcinoma at week 36 (P < 0.01) compared with wild-type mice. Apoptotic index and caspase-3 and/or Bax mRNA expression of Cyp2e1-null mice were significantly different at 6, 24, and 48 h after diethylnitrosamine treatment compared with wild-type mice (P < 0.05). We conclude that Cyp2e1-null mice show lower tumor incidence and multiplicity compared with wild-type mice in diethylnitrosamine-induced hepatocarcinogenesis. It is suggested that CYP2E1 completely participates in diethylnitrosamine-induced hepatocarcinogenesis, and high frequency of tumors in wild-type mice could be associated with the increased apoptosis.     

Quantification of circulating plasma DNA fragments as tumor markers in patients with esophageal and gastric cancer

The quantity and quality of circulating DNA fragments was analyzed by quantitative real-time polymerase chain reactions (qPCR) in plasma from patients with esophageal and gastric cancer, in order to assess their diagnostic value. Plasma was collected preoperatively from 24 patients with esophageal cancer 53 patients with gastric cancer and from 21 healthy controls. qPCR was performed using two primer sets for the BETA-actin gene, amplifying short (102 bp) and long (253 bp) segments. The DNA concentrations in both the short and long segment assays of both cancer patients were significantly higher than the controls. The difference of concentrations between disease group and controls was more significant in esophageal cancer patients. The area under the receiver-operating characteristic curve was 0.83 (short) and 0.91 (long) for esophageal cancer patients, and 0.75 (short) and 0.67 (long) for gastric cancer versus the controls. There was also a significant difference in DNA integrity (short/long) between esophageal cancer patients and the control group (p = 0.001). qPCR assays for plasma DNA concentrations and their integrity can serve as new diagnostic markers for screening and monitoring patients with esophageal and gastric cancer.     

Inhibitory effects of 1,3-diaminopropane, an ornithine decarboxylase inhibitor, on rat two-stage urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine

Overexpression of ornithine decarboxylase (ODC) has been shown to be characteristic of tumor development and progression in humans and experimental animals. Therefore, we have examined the effects of 1, 3-diaminopropane dihydrochloride (DAP), a potent inhibitor of ODC, on rat two-stage urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In experiment 1 (36 weeks), 6-week-old F344 male rats were administered 0.05% BBN in drinking water for 4 weeks and then divided into four groups. Animals of groups 1 and 2 received basal diet and drinking water supplemented with or without DAP (2 g/l). Groups 3 and 4 were given diet containing 5% sodium L-ascorbate (NaAsA), a typical urinary bladder tumor promoter, and drinking water with or without DAP. Administration of DAP to group 1 significantly reduced tumor size, multiplicity and incidence, particularly of papillomas, when compared with group 2 values. DAP together with NaAsA (group 3) also decreased tumor size relative to the group 4 case. To determine the effects of DAP on the early stages of bladder carcinogenesis and its mechanisms, a similar protocol was conducted (experiment 2) with death after 20 weeks. DAP treatment caused complete inhibition (0% incidence) of papillary and/or nodular hyperplasia in group 1 but was without influence in group 3, as compared with the respective controls. Moreover, the ODC activity, bromodeoxyuridine labeling indices and mRNA expression levels of cyclin D1 in the urinary bladder mucosa, determined by northern blotting, were markedly lower in group 1 than in group 2, but values were comparable for both groups administered NaAsA. Assessment of mRNA expression levels of the angiogenic vascular endothelial growth factor suggested no involvement in the inhibitory effects of DAP on urinary bladder carcinogenesis. The results indicate that inhibition of ODC could reduce urinary bladder carcinogenesis in rats, particularly in the early stages, through antiproliferative mechanisms.     

Postoperative adjuvant chemotherapy with cisplatin, etoposide, and pirarubicin for endometrial carcinoma patients with lymph node metastasis: A pilot study

We evaluated the effects of a combined chemotherapy regimen on endometrial carcinoma in 14 patients with lymph node metastasis. After surgery, the patients were treated with 3 cycles of chemotherapy (PVP regimen) every 4 weeks. The PVP regimen consisted of 75 mg/m2 cisplatin on day 1, 40 mg/m2 pirarubicin (P) on day 1, and 75 mg/m2 etoposide (VP-16: V) on days 2, 3 and 4. The effect of adjuvant chemotherapy was evaluated based on progression-free survival (PFS), overall survival (OS), and adverse effects. The 5-year PFS rate was 52% [95% confidence interval (CI), 10-94%], and the 5-year OS rate was 50% (95% CI, 16-84%). The major toxicity was myelosuppression. One hundred percent of patients had neutropenia above grade 3, but all recovered from myelosuppression. PVP therapy may be an effective adjuvant therapy for endometrial carcinoma patients with lymph node metastasis used as an alternative to radiation therapy.     

Gastrointestinal stromal tumor mimicking gynecological disease

Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors of the digestive tract. These tumors occasionally present a pelvic mass and leading to the misdiagnosis of gynecologic diseases. Two patients with GIST in the small intestine giving an impression of an ovarian fibroma and a uterine leiomyoma respectively were diagnosed correctly at the surgery. In the patients with a pelvic mass, especially if unusual symptoms and laboratory data being not compatible with gynecological disease, the possibility of diseases other than a gynecologic disease has to be considered.