Reflux esophagitis after esophagectomy: impact of duodenogastroesophageal reflux.

Reflux esophagitis (RE) is a known complication disturbing patients' quality of life after esophageal resection. It is generally recognized that bile reflux as well as acid reflux cause RE. However, the clinical influence of acid and bile reflux, and Helicobacter pylori (H. pylori) infection on RE in the cervical esophagus after esophagectomy is not yet clarified. Sixty patients who underwent cervical esophagogastrostomy following esophagectomy were enrolled in this study. They underwent examination for H. pylori infection, endoscopic examination, and continuous 24-hour pH and bilirubin monitoring, at 1 month after surgery. The influence of acid and/or bile reflux, H. pylori infection, and others on the development of RE were investigated. RE was observed in 19 patients (32%) at 1 month after esophagogastrostomy, mild RE in 16 (27%), and severe RE in 3 (5%). The percentage of time duration of both acid and bile reflux into the cervical esophagus was higher in patients with RE than in those without (P = 0.027, P < 0.001). A significant difference in %time pH < 4 acid reflux was found between mild RE and severe RE (P = 0.014), and a statistical difference in %time abs. > 0.14 between non-RE and mild RE (P = 0.017). Acid and/or bile reflux was observed in 31 patients (52%), acid-only reflux in 6 (10%), bile-only reflux in 15 (25%), and acid-and-bile reflux in 10 (17%). Severe RE was observed only in patients having acid-and-bile reflux. On the univariate analysis, no infection of H. pylori, acid reflux, and bile reflux were determined to be the influencing factors to RE among the clinical factors including age, gender, route of esophageal reconstruction, H. pylori infection, and acid-and-bile reflux. In the subanalysis using the logistic model, there were significant correlations between bile reflux and RE irrespective of the presence of H. pylori infection (P = 0.016, P = 0.007). On the other hand, there was a significant correlation between acid reflux and RE only in patients without H. pylori infection (P = 0.039). In the early period after esophagogastrostomy, bile reflux could cause RE irrespective of H. pylori infection, while acid reflex could cause RE only in patients without H. pylori infection. There is a possibility that bile reflux plays an important role in the development of RE after esophagectomy.

Thoracic endovascular aortic repair for aortic complications after esophagectomy for cancer: report of three cases.

Aortic complications after esophageal cancer surgery are rare and usually fatal. Here, we report three patients who underwent thoracic endovascular aortic repair (TEVAR) for aortic complications after esophagectomy for cancer. In the first case, aortic rupture was caused by pyothorax due to residual tumor after esophagectomy. In the second case, aortic rupture was caused by pyothorax due to anastomotic leakage. In the third case, a pseudoaneurysm was caused by surgical injury during esophagectomy. TEVAR was safe and effective for severe aortic complications when graft infection was avoided. The first case died of sepsis on the 84th postoperative day, and the other two cases have survived 4 years and 2 years to date.

What influences the acidity in the gastric conduit in patients who underwent cervical esophagogastrostomy for cancer?

The aim of this study was to determine the factors influencing acidity in the gastric conduit after esophagectomy for cancer. Acidity and bile reflux in the stomach and in the gastric conduit were examined by 24-h pH monitoring and bilimetry in 40 patients who underwent transthoracic subtotal esophagectomy followed by esophageal reconstruction using a gastric conduit, which was pulled up to the neck through a posterior mediastinal route in 17 patients, through a retrosternal route in 10 patients, and through a subcutaneous route in 13 patients. They were examined at 1 week before surgery, at 1 month after surgery, and at 1 year after surgery. Helicobacter pylori infection was examined pathologically and using the (13) C-urea breath test. The factors influencing acidity of the gastric conduit were analyzed using the stepwise regression model. Gastric acidity assessed by percentage (%) time of pH < 4 was reduced after surgery and was significantly less in patients with H. pylori infection compared with those without H. pylori infection throughout the period from 1 week before surgery to 1 year after surgery. Duodenogastric reflux (DGR) assessed by % time absorbance > 0.14 into the lower portion of the gastric conduit was significantly increased after surgery throughout the period from 1 month after surgery to 1 year after surgery. Multivariate analysis showed that the acidity in the gastric conduit was influenced by H. pylori infection and DGR at 1 month after surgery, and by H. pylori infection and the route for esophageal reconstruction at 1 year after surgery. Acidity in the gastric conduit was significantly decreased after surgery. Acidity in the gastric conduit for esophageal substitutes is influenced by H. pylori infection and surgery. DGR influences the gastric acidity in the short-term after surgery, but not in the long-term after surgery.

Reflux esophagitis and columnar-lined esophagus after cervical esophagogastrostomy (following esophagectomy).

Reflux esophagitis (RE) and columnar-lined esophagus (CLE) are frequently observed after esophagectomy. The incidence of these conditions according to time and to the route of esophageal reconstruction after esophagectomy remains unknown. The aim of this study was to clarify any changes and differences of the incidence of RE and CLE in patients who underwent gastric tube reconstruction after esophagectomy. A hundred patients who underwent cervical esophagogastrostomy after resection of the thoracic esophagus were included in this study. We reviewed their endoscopic findings at 1 month, at 1 year and at 2 years after surgery, and compared the incidence rates of RE and CLE with the passage of time and among the three reconstruction routes; a subcutaneous route, a retrosternal route, and a posterior mediastinal route. The incidence rate of RE was 42%, 37% and 38%, at 1 month, 1 year and at 2 years after surgery, respectively. There was no significant difference in the incidence of RE according to the time after surgery. The incidence rate of severe RE (Grade C and D in the Los Angeles Classification) was 9% percent at 1 month after surgery, 18% at 1 year after surgery and 22% at 2 years after surgery, significantly increasing with passage of time. The incidence rate of CLE was 0% at 1 month after surgery, 14% at 1 year after surgery and 40% at 2 years after surgery, significantly increasing with passage of time. No difference was observed in the incidence of RE and that of CLE among the three routes of esophageal reconstruction. Severe RE and CLE increase with passage of time after cervical esophagogastrostomy. Therefore, careful endoscopic follow-up is necessary for such patients irrespective of the route of esophageal reconstruction.

Outcomes of multimodality therapy for stage IVB esophageal cancer with distant organ metastasis (M1-Org).

Esophageal cancer patients with distant organ metastasis have usually been treated only to palliate symptoms without multimodality therapy. The current study evaluates the role of multimodality therapy in esophageal squamous cell cancer patients with distant organ metastasis. Between February 1988 and January 2007, 80 esophageal squamous cell cancer patients with distant organ metastases were treated at our institution. Multimodality therapy was performed in 58 patients: 43 patients received chemoradiotherapy, 13 underwent surgery followed by chemotherapy and/or radiation therapy, and two received chemotherapy or chemoradiotherapy followed by surgery. Thirteen patients received single-modality therapy; chemotherapy, radiotherapy, or surgery alone. The remaining nine patients received best supportive care alone. The metastatic organ was the liver (n= 40), the lungs (n= 33), bone (n= 10), and other (n= 6). Nine patients had metastasis in two organs. There was no difference in the median survival among the sites of organ metastasis, lung, liver, or bone (P= 0.8786). The survival of patients treated with multimodality therapy was significantly better than that of the patients who received single-modality therapy or best supportive care alone (P < 0.0001). In patients treated with multimodallity therapy, there was no difference in survival for patients treated with surgery compared with patients treated without surgery (P= 0.1291). This retrospective study involves an inevitable issue of patient selection bias. However, these results suggested that multimodality therapy could improve survival of the esophageal squamous cell cancer patients with distant organ metastasis.

Endoscopic classification for reflux pharyngolaryngitis.

The quality of life in patients who have undergone surgery for esophageal cancer is frequently disturbed by postoperative gastroesophageal reflux disease or pharyngolaryngeal reflux disease. Recently, there have been many reports on gastroesophageal reflux disease after esophagectomy, and only a few on pharyngolaryngeal reflux disease. There is not yet any convenient endoscopic classification of reflux pharyngolaryngitis. We designed a new classification for reflux pharyngolaryngitis based on endoscopic findings. Our new classification consists of the five grades from 0 to IV based on (i) the extent and severity of erythema and/or edema in the pharynx and the larynx, and (ii) the extent and severity of granulation or scarring stenosis in the vocal cords. Ninety-three patients after cervical esophagogastrostomy after esophagectomy (the CEG group) and 28 patients after intrathoracic esophagogastrostomy (the TEG group) were reviewed in this study. We investigated the relation between the severity of reflux pharyngolaryngitis and clinical symptoms in these patients, and the correlation between this new classification of reflux pharyngolaryngitis and the Los Angeles classification of reflux esophagitis. Reflux esophagitis was more severe in the TEG group than in the CEG group, while there was no difference in the grading of reflux pharyngolaryngitis between the two groups. The pharyngolaryngeal symptoms and F-scale scores were not correlated with the severity of reflux pharyngolaryngitis in each group. The grading of reflux pharyngolaryngitis and that of reflux esophagitis was correlated in each group (P<0.001 in the CEG group and P=0.002 in the TEG group). We proposed a new endoscopic classification of reflux pharyngolaryngitis. The new classification of reflux pharyngolaryngitis correlated fairly well with the Los Angeles classification of reflux esophagitis, although this classification did not correlate with the clinical symptoms in patients who underwent esophagectomy. Follow-up attention including upper endoscopy should be paid to reflux pharyngolaryngitis in patients after esophagogastrostomy as well as reflux esophagitis, because there is often a lack in symptoms regardless of high incidence of pharyngolaryngitis.

Surgical management for small cell carcinoma of the esophagus.

Esophageal small cell carcinoma (SmCC) has been regarded as a rare and aggressive tumor with early metastasis. The optimal treatment has not yet been established, and the role of surgery has remained controversial. In this retrospective study, we report seven cases studies of SmCC of the esophagus and analyze the clinical outcomes after surgery. Between 1986 and 2007, there were seven patients with esophageal SmCC treated surgically in our institution. All the patients with clinically limited disease underwent transthoracic esophagectomy with lymphadenectomy. Lymph node involvement was found in all cases irrespective of the depth of tumor invasion. Three of the seven patients were diagnosed as having an extensive disease on pathological examination after esophagectomy. Five patients received postoperative chemotherapy. Two patients are alive with no recurrence at 16 months and at 45 months after surgery. Another one without chemotherapy survived 93 months and died of another disease. The remaining four patients died of recurrent disease or another disease. The median overall survival to date of these patients was 16 months (range 12-93 months). Esophagectomy with lymphadenectomy resulted in a relatively better survival in some patients with esophageal SmCC. We concluded that surgery may be helpful as part of multimodality treatment in selected patients with esophageal SmCC.

Pharyngolaryngeal reflux in patients who underwent cervical esophago-gastrostomy following esophagectomy.

Pharyngolaryngeal reflux has been generally accepted as a cause for pharyngolaryngitis, hoarseness, aspiration pneumonia, chronic cough, and nocturnal asthma. Although patients who have undergone gastric conduit reconstruction after esophagectomy are at a high risk to pharyngolaryngeal reflux disease (PLRD), PLRD after esophagectomy is still unknown. The aim of this study is to investigate the correlation between reflux pharyngolaryngitis and acid reflux into the hypopharynx and into the cervical esophagus in patients who have undergone cervical esophagogastrostomy. We enrolled 62 patients who received follow-up endoscopy and 24-h pH monitoring after cervical esophagogastrostomy. These included 26 at 1 month after surgery and 36 at 1 year or more after surgery. We investigated: (i) the correlation between the extent of reflux pharyngolaryngitis and that of reflux esophagitis based on endoscopic findings; and (ii) the correlation between the extent of reflux pharyngolaryngitis and that of acid exposure -'% time pH < 4' measured by 24-h pH monitoring - in the hypopharynx and in the cervical esophagus, and of acidity in the gastric conduit. There was no difference in acid exposure between the hypopharynx and the cervical esophagus according to time after surgery. However, the acidity in the gastric conduit was significantly more at one year or more after surgery compared with acidity at 1 month after surgery (P= 0.001). There was a significant correlation between acid exposure in the hypopharynx and that in the cervical esophagus (P < 0.001), although acid exposure in the hypopharynx was significantly less than that in the cervical esophagus (P < 0.001). A significant correlation between reflux pharyngolaryngitis and reflux esophagitis was observed (P < 0.001). There was a significant correlation between reflux pharyngolaryngitis and acid exposure in the hypopharynx (P= 0.021), and also that in the proximal esophagus (P= 0.001). The correlation between the extent of reflux pharyngolaryngitis and the acidity in the gastric conduit was not observed. These findings are consistent with pharyngolaryngitis being caused by gastro-esophago-pharyngolaryngeal reflux in patients after cervical esophagogastrostomy, despite the upper esophageal sphincter strongly preventing acid reflux from the cervical esophagus into the hypopharynx.

Identification of EGFR mutations in esophageal cancer.

BACKGROUND: It is well known that the prognosis for esophageal cancer is worse than for other digestive cancers in spite of multimodality treatment, and there is an urgent need to improve this situation. The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, was approved in Japan to treat advanced non-small cell lung cancer patients and several papers have since reported that the successfully treated patients had genetic mutations in EGFR. PURPOSE: The aim of this study was to investigate the existence of EGFR mutations in esophageal cancer cell lines and primary lesions, and also to explore the possibility of treating esophageal cancer using gefitinib. MATERIALS AND METHODS: Nineteen esophageal cancer cell lines were cultured and DNA was extracted using an ultracentrifugation method. Fifty cases of primary cancer and corresponding normal tissue samples were obtained and DNA was extracted using the same protocol. Nested PCR and DNA sequencing targeting exons 18, 19, 20 and 21 of EGFR were performed to investigate the presence of mutations in esophageal cancer cell lines and primary tumors. RESULTS: Three of the 19 cell lines had the same silent mutation at nucleotide 2607, a G-to-A substitution in exon 20. One of the 50 patients had an EGFR mutation in codon 719, resulting in an amino acid substitution from glycine to aspartic acid. CONCLUSION: EGFR mutations in esophageal carcinoma are rare but do exist, and thus gefitinib could be included in esophageal cancer treatment regimens by selecting those patients who possess such mutations.

Metronomic chemotherapy using weekly low-dosage CPT-11 and UFT as postoperative adjuvant therapy in colorectal cancer at high risk to recurrence.

This study was designed to evaluate the antitumor efficacy and feasibility of postoperative adjuvant metronomic chemotherapy using weekly low-dosage CPT-11 and UFT in colorectal cancer at high risk to recurrence. A total of 49 patients (24 stage IIIb and 25 distant metastasis) who underwent a R0 operation were enrolled in this prospective study. Forty mg/m2 of CPT-11 were administered on day 1, day 8, and on day 15 in 28-day cycles. A dosage of 335 mg/m2/day of UFT was given perorally on daily schedule. Cycles were repeated for 6 months, and were followed by UFT alone for further 6 months. One or more adverse effects were seen in 43 of the 49 patients. However, most of these effects were mild at grade 1 or 2: with only nausea in 3 patients, vomiting in 2, leucopenia in 2 and neutropenia in 2 at grade 3. The overall survival rates were favorable both in the stage IIIb group (5-year: 73%) and in the distant metastases group (5-year: 62%). Postoperative adjuvant metronomic chemotherapy using weekly low-dosage CPT-11 and UFT might be safe and feasible and prolong survival time in colorectal cancer at high risk to recurrence.

Functional outcome after sphincter excision for ultralow rectal cancer.

This article shows a prospective study investigating bowel function after transanal rectal resection with internal and external sphincterectomy for low rectal cancer. Eight patients underwent standard low anterior resection with colonic J-pouch anal anastomosis (LARJ), and eight patients underwent transanal rectal resection with internal and external sphincter resection (IESR). Manometry, manovolumetry, transit time study, and a questionnaire were performed before and after the operation. Six and 12 months after the operation, maximum resting pressure and squeezing pressure were significantly lower in IESR group than in LARJ group, whereas there was no significant difference between the two groups in terms of constant sensation, maximum tolerable volume, or neorectal compliance. Although the functional score of the IESR group remained low at 6 months after the operation in comparison with the LARJ group, it improved at 12 months after the operation. Transanal rectal resection with internal and external sphincterectomy showed usefulness in preserving bowel function and avoiding permanent colostomy.

Identification of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA-A24-restricted cytotoxic T lymphocytes in cancer patients.

Genes encoding tumor epitopes that are capable of inducing CTLs against adenocarcinomas and squamous cell carcinomas, two major human cancers histologically observed in various organs, have rarely been identified. Here, we report a new gene from cDNA of esophageal cancer cells that encodes a shared tumor antigen recognized by HLA-A2402-restricted and tumor-specific CTLs. The sequence of this gene is almost identical to that of the KIAA0156 gene, which has been registered in GenBank with an unknown function. This gene encodes a Mr 140,000 protein that is expressed in the nucleus of all of the malignant tumor cell lines tested and the majority of cancer tissues with various histologies, including squamous cell carcinomas, adenocarcinomas, melanomas, and leukemia cells. However, this protein was undetectable in the nucleus of any cell lines of nonmalignant cells or normal tissues, except for the testis. Furthermore, this protein was expressed in the cytosol of all of the proliferating cells, including normal cells and malignant cells, but not in normal tissues, except for the testis and fetal liver. Two peptides of this protein were recognized by HLA-A2402-restricted CTLs and were able to induce HLA-A24-restricted and tumor-specific CTLs from peripheral blood mononuclear cells of most of HLA-A24+ cancer patients tested, but not from peripheral blood mononuclear cells of any healthy donors. These peptides may be useful in specific immunotherapy for HLA-A24+ cancer patients with various histological types.

Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides.

The tumor-rejection antigen SART3 possesses two antigenic epitopes (SART3(109-118) and SART3(315-323)) capable of inducing HLA-A24-restricted and tumor-specific CTLs. To determine its safety and ability to generate antitumor immune responses, 12 patients with advanced colorectal cancer were administered s.c. vaccinations of these peptides. No severe adverse events were associated with the vaccinations. Significant levels of increased cellular immune responses to both HLA-A24+ colon cancer cells and the vaccinated peptide were observed in the postvaccination peripheral blood mononuclear cells in 7 of 11 and 7 of 10 patients tested, respectively, and the higher responses were observed in those patients vaccinated with the highest dose (3 mg/injection) of the peptides. These results encourage further development of SART3 peptide vaccine for colorectal cancer patients.

MDM2 interacts with MDMX through their RING finger domains.

The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2.

The effect of thrombospondin on hepatocellular carcinoma cell proliferation.

We report the effects of thrombospondin (TSP) on the proliferation of four different human hepatocellular carcinoma (HCC) cell lines (HuH-7, KIM-I, KYN-2, and KYN-3) and report the proliferative activity of HuH-7 cell using microspectrophotometry. The addition of anti-TSP neutralizing antibody (150, 1500, or 15000 ng/ml) to cultured medium showed marked suppression of cell proliferation in all cell lines. On the other hand, the addition of exogenous TSP (20 or 40 mu g/ml) to culture medium stimulated cell proliferation, in KYN-2 and KYN-3 but not in HuH-7 or KTM-1. Furthermore, in DNA measurements on HuH-7 cells, the effect of the anti-TSP neutralizing antibody induced growth arrest in the G(0)/G(1) phase of the cell cycle and decreased DNA synthesis. In conclusion, TSP promoted the proliferation of HCC cells, and based on our results it is predicted that TSP might act through an autocrine or paracrine growth-supportive mechanism in the extracellular matrix.

Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus.

To determine the crucial abnormality in the cell cycle regulatory proteins in human squamous cell carcinoma of the esophagus, we examined the cell growth ratio (CGR) and basal expression levels of G1 cyclins (cyclin D1, cyclin E), cyclin-dependent kinase (cdk) 2, cdk4, proliferating cell nuclear antigen (PCNA), and p21Waf-1 using 9 cell lines (KE3, KE4, TE8, TE9, TE10, TE11, YES1, YES2, and YES6). Western blotting revealed an inverse linear correlation between the basal levels of p21Waf-1 expression and CGR. The protein levels of G1 cyclins, cdks, and PCNA did not coordinately reflect the CGR. There was no relationship between p21Waf-1 expression levels and mutation of the p53 gene. Next, when the cells were stimulated with serum 48 h after the starvation, stimulated levels of the above G1 cell cycle markers were variously observed among cell lines irrespective of CGR. Serum stimulation markedly induced phosphorylated Rb in TE9 (a high CGR cell line, CGR>2.0), but not in KE4 (a low CGR cell line, CGR<1.5). Furthermore, adenovirus-mediated expression of exogenous p21Waf-1 effectively reduced cell growth in KE3 and TE9 (high CGR cell lines), but not in KE4 and TE11 (low CGR cell lines). p21Waf-1-mediated growth suppression was associated with the induction of involucrin, a marker of squamous cell differentiation. Our data suggested that the basal level, but not the stimulated level, of p21Waf-1 expression play a pivotal role in abnormal growth in human squamous cell carcinoma of the esophagus.

Clinicopathologic study of multiple primary superficial carcinoma of the esophagus.

Endoscopic examination with iodine staining has led to the easy detection of multiple superficial esophageal carcinoma (MSEC). The purpose of this study was to better understand the characteristics of MSEC. Of 49 patients with multiple esophageal carcinomas, 19 had superficial carcinoma. Multiple esophageal carcinomas were more often found in superficial carcinomas (31.1%) than in advanced carcinomas (14.4%). Comparing the depth of invasion of multiple esophageal carcinomas, the secondary lesions represented relatively early stages. Ki-67-positive cells were seen significantly more frequently in the main lesion of MSEC than in the secondary lesions, but proliferating cell nuclear antigen positivity and p53 expression did not differ significantly. Since multiple carcinoma occurs more frequently, care should be taken to look for small secondary lesions when treating superficial esophageal carcinoma. Ki-67 immunohistochemistry suggested that tumor cells proliferate more slowly in secondary lesions than in main lesions of MSEC.

Experimental study of the histocompatibility of covered expandable metallic stents in the trachea.

STUDY OBJECTIVES: To evaluate the histocompatibility of four different materials used to cover expandable metallic stents. DESIGN: Prospective, randomized, unblinded study. SETTING: Animal research laboratory of Kurume University. PATIENTS OR PARTICIPANTS: Twenty 12- to 18-kg mongrel dogs. INTERVENTIONS: Handmade Gianturco-type stents with six bends, 20 mm in length, and 15 to 20 mm in diameter were covered using four different materials: polypropylene mesh, silicone-coated mesh, polyester mesh, and ePTFE. Covered stents were inserted into the trachea after i.v. anesthesia. Five animals were used in each group. MEASUREMENTS AND RESULTS: Postinsertion status was observed using clinical and bronchoscopy measures 7, 14, 28, and 56 days after intervention. Eight weeks after stent insertion, the tracheal specimens were studied pathologically. A scoring system was used to evaluate the histocompatibility of covered stents in each study group. The mean of clinical scores in the polypropylene group was 1.84+/-0.36, which was significantly higher than those in the groups of silicone, polyester, and ePTFE. The means of histopathologic scores in the polypropylene group and the silicone group were 1.60+/-0.55, which were significantly higher than those in groups of polyester and ePTFE. CONCLUSIONS: Polypropylene mesh cover was more suitable than silicone-coated mesh, polyester mesh, and ePTFE because of its excellent histocompatibility.

Preoperative evaluation of cardiopulmonary reserve with the use of expired gas analysis during exercise testing in patients with squamous cell carcinoma of the thoracic esophagus.

OBJECTIVE: We evaluated the usefulness of analyzing expired gas during exercise testing for the prediction of postoperative cardiopulmonary complications in patients with esophageal carcinoma. BACKGROUND DATA: Radical esophagectomy with 3-field lymphadenectomy is performed in patients with thoracic esophageal carcinoma but has a high risk of postoperative complications. To reduce the surgical risk, we performed preoperative risk analysis using 8 factors. Although hospital mortality was decreased when this risk analysis was used, severe cardiopulmonary complications still occurred. METHODS: The study group consisted of 91 patients who had undergone curative esophagectomy with 3-field lymphadenectomy. The maximum oxygen uptake, anaerobic threshold, vital capacity, percent vital capacity, forced expiratory volume in 1 second, percent forced expiratory volume, V.(25)/HT, forced expired flow at 75% of forced vital capacity to height ratio (FEF(75%)/HT), forced expired flow at 50% to 75% of forced vital capacity ratio (FEF(50%)/FEF(75%)), percent diffusion capacity for carbon monoxide, and arterial oxygen tension were measured. Patients were divided into 2 groups on the basis of the presence or absence of postoperative cardiopulmonary complications. RESULTS: Only the maximum oxygen uptake was significantly different between the 2 groups. All patients were grouped according to the value of the maximum oxygen uptake, and the occurrence of postoperative cardiopulmonary complications was calculated for each group. A cardiopulmonary complication rate of 86% was found for patients with a maximum oxygen uptake of less than 699 mL. min(-1). m(-2); for those with a value of 700 to 799 mL. min(-1). m(-2), the complication rate was 44%. CONCLUSIONS: The maximum oxygen uptake obtained by expired gas analysis during exercise testing correlates with the postoperative cardiopulmonary complication rate. On the basis of these results, esophagectomy with 3-field lymphadenectomy can be safely performed in patients with a maximum oxygen uptake of at least 800 mL. min(-1). m(-2).

A preoperative alternating chemotherapy and radiotherapy program for patients with stage IIIA (N2) non-small cell lung cancer.

The objective of the present study was to evaluate the feasibility and toxicity of a preoperative alternating chemotherapy and radiotherapy program followed by surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response, resection rate, tumor/lymph node downstaging, and survival were also evaluated. The positive predictive value (PPV) in the diagnosis of mediastinal lymph node metastasis was 81% using conventional magnetic resonance imaging (MRI) with short inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria. Eligible patients had clinical N2 lesions (stage IIIA) and a World Health Organization (WHO) performance status of 0-2. The treatment program consisted of two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating with radiotherapy, including two courses of 20 Gy radiation. Surgery was performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study. Hematologic and other toxicities were within an acceptable range. Surgery was not indicated for two patients because of distant metastasis; one patient with renal dysfunction and one with pancytopenia during this treatment underwent surgery subsequently. The clinical response rate was 50% (partial response in 11/22). Definitive surgery was indicated for 18 patients resulting in 17 patients with complete resection and one exploratory thoracotomy. A pathologic complete response of the primary tumor occurred in 41% of the patients (seven of 17; without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median survival was 33 months with an actuarial 4-year survival rate of 33% in 17 patients with complete resection and 30 months with 28% 4-year survival rate in all entered patients. A randomized phase-III study using this approach for stage IIIA (clinical N-2 disease) is warranted.