[Surgical Outcomes of the Patients with Gastric Cancer in Aged 85 and Older at Our Hospital].

We investigated the surgical outcomes of the patients with gastric cancer in aged 85 and older. There were 9 males and 8 females, with a median age of 86 years. All had comorbidities and 7 had double cancers. Type of surgery was distal gastrectomy in 14 and total gastrectomy in 3, respectively. Postoperative complications occurred in 8 cases, and case with adhesion ileus or mesenteric bleeding performed reoperation. The postoperative hospital stay was 15 days. The cause of death was recurrent diseases in 2 cases and other diseases in 4. The overall survival rate was 63.9% for 3 years and 42.6% for 5 years, respectively. Elderly patients with gastric cancer may be increase in Japan, but they have large individual differences about tolerance of surgical intervention. Therefore, it is important to evaluate the detail of general condition in such patients.

[Outcomes of Salvage Thoracoscopic Esophagectomy after Definitive Radiochemotherapy for Clinical Stage â £a Esophageal Cancer].

We investigated the clinical outcomes of salvage thoracoscopic esophagectomy for residual or recurrent cases after radical radiochemotherapy for cStage Ⅳa esophageal cancer. Thoracic procedure was started thoracoscopically in all cases, but converted to thoracotomy in 2 cases. The operation time was 315 minutes and the blood loss was 300 mL. Lymph node metastasis was diagnosed in 5 cases, and 2 cases were finished in R1or 2. Nine cases died of recurrence and 1 case died of pneumonia. The 2-year and 5-year survival rates(OS)of all cases were 46.1% and 28.3%, respectively. R1,2 cases and pN+ cases had significantly poor prognosis. Surgical treatment after radical radiochemotherapy for cStage Ⅳa esophageal cancer can be safely performed thoracoscopically. If R0 is not obtained, the long-term prognosis cannot be expected, and selection of R0 resectable cases is important.

Effect of substituting allogenic blood transfusion with autologous blood transfusion on outcomes after radical oesophagectomy for cancer.

BACKGROUND: The oncologic benefit of avoiding allogenic blood transfusion in oesophageal cancer resection has not been studied. METHODS: The medical records of 68 patients (Auto group) who underwent a potentially curative oesophageal cancer resection without allogenic blood transfusion from 1996 to 1999 receiving 800 g of autologous blood donated preoperatively, and 97 patients (Allo group) who underwent the same operation with allogenic blood transfusion from 1990 to 1995 were compared. RESULTS: There were no differences in age, gender, stage of disease, number of retrieved nodes, or perioperative hemoglobin concentration between the two groups. The survival of the 45 patients with nodal involvement in the Auto group was better than that of the 59 patients in the Allo group (p=0.0435), and the survival of the 35 patients with T3 or T4 lesions in the Auto group was better than that of the 61 patients in the Allo group (p=0.0408). According to logistic regression analysis, allogenic blood transfusion correlated with tumour recurrence in patients with either nodal involvement or a T3-4 lesion. The natural killer cell activity remained higher in the Auto group than in the Allo group (p<0.05). CONCLUSION: Avoidance of allogenic blood transfusion favorably effected the survival of patients with oesophageal cancer at risk for recurrence.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2003 and March 2004].

Tendency of isolated bacteria from infections in general surgery during the period from April 2003 to March 2004 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 455 strains including 14 strains of Candida spp. were isolated from 191(75.2%) of 254 patients with surgical infections. Two hundred and thirty-nine strains were isolated from primary infections, and 216 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria and aerobic Gram-negative bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. The isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and Staphylococcus aureus were higher from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa in this order, and from postoperative infections, E. coli was the most predominantly isolated, followed by P. aeruginosa, E. cloacae, and K. pneumoniae. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. The isolation rate of anaerobic Gram-positive bacteria from primary infections and that of aerobic Gram-positive bacteria from postoperative infections were high in the last several years. In this series, we noticed no vancomycin-resistant Gram-positive cocci, but a few strains of moderately arbekacin-resistant MRSA. Carbapenm-resistant P. aeruginosa was seen in less than 10 per cents. Last year we noticed that there were cefazolin-resistant E. coli producing extended spectrum beta-lactamase, but there was no highly cefazolin-resistant E. coli in this year. In the next series, increase of both anaerobic bacteria and Enterococcus spp. should be carefully followed up.

Evaluation of blood flow by color Doppler sonography in free jejunal interposition grafts for cervical esophageal reconstruction.

The failure of the vascular anastmoses is a devastating complication in free jejunum transplantation. We used color Doppler sonography to estimate blood flow in free jejunal grafts in 21 patients who underwent radical pharyngoesophagectomy. Fast Fourier transform (FFT) analysis of blood flow, the pulsatility index (PI) as a measure of peripheral vascular resistance, and thickening of the graft wall were evaluated for predictive value. The arterial wave patterns were classified into three types based on systolic-diastolic differences and magnitude of flow. Type I was physiologic flow, type III overtly pathologic, and type II intermediate. The three patients who required vascular reanastomoses intraoperatively had a type II pattern that degenerated to type III within 15 minutes. The PI increased to 3.5 to 4.5 over 1 hour. In the one patient who required retransplantation, the wave pattern became type III by 18 hours and had disappeared by 24 hours, at which point the PI could not be measured. Jejunal thickening increased from 1.0 mm to 5.0 mm after 24 hours, even in healthy grafts. Monitoring blood flow during the 24 hours after surgery is critical. A type III wave pattern or a PI >2.5 is an indication for reexploration. Doppler sonography offers a noninvasive way to measure blood flow in jejunal grafts semiquantitatively and can predict free jejunal graft failure.

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy.

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.

Duodenogastric reflux eradicates Helicobacter pylori after distal gastrectomy.

BACKGROUND/AIMS: Patients who undergo distal gastrectomy often develop duodenogastric reflux and preoperative H. pylori infection is eradicated spontaneously after distal gastrectomy in some patients. However, whether a causal relationship exists has not yet been studied. This report examines the correlation between H. pylori eradication and the amount of duodenogastric reflux following distal gastrectomy. METHODOLOGY: Among 72 consecutive patients who underwent curative distal gastrectomy with radical lymphadenectomy for gastric cancer, 37 patients had H. pylori infection preoperatively and were included in this study. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions on the 14th day after the surgery. Endoscopic examination was performed to determine the presence of H. pylori infection on week 12 after surgery. RESULTS: The percent time was higher in patients whose H. pylori infection had been eradicated after distal gastrectomy (58.1+/-9.2%) than in patients who had H. pylori infection after distal gastrectomy (33.8+/-5.7%). CONCLUSIONS: Duodenogastric reflux correlates with spontaneous eradication of H. pylori infection following distal gastrectomy.

Correlation between duodenogastric reflux and remnant gastritis after distal gastrectomy.

BACKGROUND/AIMS: Many patients who undergo distal gastrectomy develop remnant gastritis. This report describes the correlation between remnant gastritis and the amount of duodenogastric reflux and looks at the relationship between Helicobacter pylori infection and duodenogastric reflux in remnant gastritis. METHODOLOGY: Sixty-two patients who underwent curative distal gastrectomy for gastric cancer with radical lymphadenectomy were studied. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions. Remnant gastritis was semi-quantified using the neutrophil infiltration score based on the updated Sydney System, and the presence of H. pylori infection was determined 12 weeks after the surgery. RESULTS: Overall, the correlation was not significant between the neutrophil infiltration score and the percent time (p=0.08). Similarly, the correlation was not significant in patients with H. pylori infection (p=0.30), but it was significant in patients without H. pylori infection (p=0.03). CONCLUSIONS: Duodenogastric reflux after distal gastrectomy can cause remnant gastritis in patients without H. pylori infection. Reconstruction with biliary diversion is protective against the development of remnant gastritis.

Surgical repair of esophagobronchial fistula caused by radiation injury.

We present an unusual case of a benign esophagobronchial fistula caused by radiotherapy to treat esophageal carcinoma which was closed successfully. A 62-year-old man with superficial squamous cell carcinoma of the esophagus underwent radiotherapy, including 60 Gy externally and 10 Gy intraluminally from January to March 1995. Esophagography revealed a fistula between the esophagus and left main stem bronchus on January 14, 1996. No residual cancer existed. Neither stenting with a silicone tube nor with a covered flexible metallic stent occluded the fistula. Thoracic esophagectomy, closure of the esophagobronchial fistula using a 2-cm nubbin of esophageal wall, surrounding the orifice of the fistula and antesternal gastric pull-through reconstruction with mediastinal lymphadenectomy were performed. The postoperative course was uneventful and there is no evidence of recurrence of the fistula or the cancer 5 years postoperatively. Radiotherapy may cause esophagobronchial fistula even in cases of superficial esophageal cancer. Bypass surgery should be considered because stenting is not effective for benign fistula without stricture.

The prognostic factors after radical esophagectomy for esophageal cancer with positive preoperative CEA.

BACKGROUND/AIMS: We investigated in this paper the clinicopathological factors that affect the prognosis of esophageal cancer with preoperative positive CEA. METHODOLOGY: Out of 252 patients with thoracic esophageal cancer who received curative resection in our department, we selected 33 cases with esophageal cancer that had positive serum CEA level preoperatively. We analyzed the clinicopathological factors which affect the prognosis in these CEA positive cases. RESULTS: There were no differences in preoperative CEA levels according to the variant clinicopathological factors. The number of lymph nodes metastasis, depth of tumor involvement, lymphatic invasion, and preoperative SCC antigen level were the significant factors influencing survival. But, only preoperative SCC antigen level was independent and a significant prognostic factor on multivariant analysis. CONCLUSIONS: While sensitivities of SCC antigen and CEA are low in esophageal cancer, the cases having positive value in both CEA and SCC antigen preoperatively have high recurrence rates after radical esophagectomy.

Esophageal tuberculosis presenting with an appearance similar to that of carcinoma of the esophagus.

A case of esophageal tuberculosis presenting with an appearance similar to that of esophageal cancer is reported. The patient was an 82-year-old man with progressive dysphagia. Barium swallow and esophagoscopy revealed an elevated lesion with deep ulceration in the middle thoracic esophagus. Esophageal carcinoma, in particular, an undermining type of undifferentiated carcinoma, was suspected fluoroscopically and endoscopically. Histological examination of biopsy specimens revealed no malignancy, but there were epithelioid granulomas and a few Langhans' type multinucleated giant cells. Endoscopic ultrasonography clearly demonstrated an extramural lesion with calcification and direct infiltration of enlarged subcarinal lymph nodes into the esophageal wall. Ultrasonographic and histological findings indicated the possibility of esophageal tuberculosis. Although no bacteriological evidence was obtained, a therapeutic trial for tuberculosis, using antituberculous drugs, was started. After 2 weeks, the enlarged subcarinal lymph nodes were markedly reduced in size. The patient's symptoms improved gradually and had disappeared 8 weeks after he started treatment, when tubercle bacilli were isolated from sputum. A connection between the esophageal wall and its adjacent structures was clearly demonstrated by endoscopic ultrasonography. For patients with findings indicative of esophageal tuberculosis on endoscopic ultrasonography, a therapeutic trial for tuberculosis should be considered, even if polymerase chain reaction assay or culture is negative.

Quantitative determinations of duodenogastric reflux, prevalence of Helicobacter pylori infection, and concentrations of interleukin-8.

Billroth I or II reconstruction after distal gastrectomy often is associated with inflammation in the gastric remnant. We sought to determine which reconstructive procedure was most effective in preventing such remnant gastritis. Patients undergoing curative distal gastrectomy for cancer ( n = 82) were classified as group A (Roux-en- Y, n = 22); group B (Billroth I, n = 40); or group C (Billroth II, n = 20). Interleukin (IL)-8 concentrations in gastric mucosa were measured 3 months after surgery. In the absence of Helicobacter pylori infection, IL-8 concentrations were 13, 56, and 87 pg/mg protein in groups A, B, and C, respectively ( p < 0.05). In the presence of H. pylori infection, IL-8 concentrations were 61, 161, and 234 pg/mg protein in groups A, B, and C ( p < 0.01). Roux-en- Y reconstruction is better able to prevent remnant gastritis than either the Billroth I or II procedure as judged from IL-8 concentrations in gastric remnant mucosa.

Bronchoscopic ultrasonography for staging supracarinal esophageal squamous cell carcinoma: impact on outcome.

The precise, accurate diagnosis of malignant airway invasion is essential to determine the likelihood of complete resection and survival of patients with invasive carcinoma of the upper esophagus. The usefulness of ultrasonic scanning of the tracheobronchial wall by bronchoscopic ultrasonography (BUS) was studied, and results were compared with those of computed tomography (CT). Sixty-six consecutive patients with advanced squamous cell carcinoma of the upper esophagus treated from 1997 to 2000 were studied. The presence of tracheobronchial invasion was diagnosed by BUS based on an interruption in the most external hyperechoic layer of the tracheobronchus (corresponding to its adventitia). BUS was completed without any complication in all patients. The accuracy of diagnosis was validated intraoperatively, and it was better for BUS (90%) than for CT (62%) ( p = 0.001). Of the 26 patients diagnosed as being invasion-free by BUS, only 2 had invasion, compared to 7 of 22 patients who had invasion after CT scans had suggested they did not. Survival was worse for patients diagnosed as having invasion than not having it based on CT scans ( p = 0.0071), but the difference was more significant with BUS ( p < 0.0001). BUS is a safe, reliable staging modality for cancer in the upper esophagus. When surgery is considered, BUS is essential for determining whether a curative resection is possible.

Prognostic factors in patients with squamous oesophageal cancer associated with solitary lymph node metastasis after oesophagectomy and extended lymphadenectomy.

It is not fully understood whether oesophageal cancer, associated with solitary lymph node metastasis, is still a local disease or already a systemic one. Among 283 patients with squamous oesophageal cancer who underwent oesophagectomy and 3-field lymphadenectomy, 37 patients had single metastasized nodes. Clinicopathologic factors, following Japanese Guideline for the Clinical and Pathological studies on Carcinoma of the Esophagus, related to survival and pre-operative predictability of nodal involvement was studied. Five-year survival was 48%. Initial pattern of recurrence was mostly haematogenous. Among the factors related to survival, grade of lymph node metastasis (pN1 vs. pN2, pN3, p=0.006) was more closely related than depth of invasion (pT1, pT2 vs. pT3, pT4, p=0.037). Five-year survival was 71.7% for pN1 patients, whereas it was 22% for pN2 or pN3 patients. Of the metastasized nodes 65% were <10 mm, and 27% was <5 mm in the maximum diameter. Oesophageal cancer is still a local disease in half of the patients with a solitary metastasized node. For these patients, dissection along the recurrent laryngeal nerve is necessary to retrieve the node possibly metastasized.

Causes of death and pattern of recurrence after esophagectomy and extended lymphadenectomy for squamous cell carcinoma of the thoracic esophagus.

Improved understanding of how esophageal cancer behaves following curative resection, including knowledge of other causes of death, is essential for informed decision making. The medical records of 246 consecutive patients with squamous cell carcinoma of the thoracic esophagus who had undergone esophagectomy and lymphadenectomy of the neck, chest, and abdomen that was deemed macroscopically curative, were reviewed. Patients who had had other malignancies or anticancer treatment were excluded. Median follow-up period was 1289 days (minimum, 730 days). The initial patterns of recurrence were classified as intramediastinal, hematogenous, or lymphatic. Forty-two patients died of a cause other than recurrence. The in-hospital death rate was 3.6%, and 19 patients died of pulmonary disease. Sixteen patients developed a second primary, most of which were in the upper aerodigestive tract; five of those patients died. Ninety-eight patients developed recurrence. Depth of invasion and number of nodal metastases predicted recurrence. The pattern of recurrence was intra-mediastinal, lymphatic, and hematogenous in 11, 21, and 67 patients, respectively. The patients with lymphatic recurrence survived longer than the patients with either of the other types of recurrences. Eighty-three percent of recurrences presented within 24 months. The time-to-recurrence correlated with survival after recurrence. The disease recurred earlier in patients with advanced stage than unadvanced disease at the time of esophagectomy. The time-to-recurrence, and anticancer therapy after the recurrence related to the survival. Meticulous care must be taken to detect hematogenous recurrence as early as possible so that adjuvant therapy may be started. Maintaining a good performance status permits the use of aggressive therapy should there be a recurrence. Pulmonary physiotherapy and treatment of metachronous primary tumors may improve overall survival.

Reconstructive procedure after distal gastrectomy for gastric cancer that best prevents duodenogastroesophageal reflux.

Billroth I and II reconstructions are commonly performed after distal gastrectomy. Both may cause duodenogastric and duodenogastroesophageal reflux, conditions reported to have carcinogenetic potential. The aim of this study was to investigate which reconstructive procedure would most effectively prevent bile reflux into the gastric remnant and esophagus after distal gastrectomy. A group of 92 patients who underwent curative distal gastrectomy for gastric cancer were subjected and classified into three groups retrospectively by the reconstructive procedure undertaken: group A, Roux-en-Y (Roux-Y) reconstruction (n = 29); group B, Billroth I reconstruction (n = 41); group C, Billroth II reconstruction (n = 22). The bile reflux periods (percent time) for the gastric remnant and esophagus were measured with the Bilitec 2000 under standardized conditions. The percent time for the gastric remnant was significantly less in group A than in group B or C. In 61% of all patients, bile reflux into the esophagus was found to be more than 5.0% of the time; it was less in group A than in group B or C (p = 0.057). A questionnaire revealed a good correlation between the incidence of reflux symptoms and the percent time for the gastric remnant and esophagus. Roux-Y reconstruction is superior to either Billroth I or II reconstruction for preventing bile reflux into the gastric remnant and esophagus after distal gastrectomy.

Clinicopathologic and immunohistochemical features of surgically resected small cell carcinoma of the esophagus.

Esophageal small cell carcinoma (SmC) is considered an aggressive cancer carrying a poor prognosis, although the rarity of this tumor has impeded statistical evaluation. We reviewed records of 457 esophageal cancer patients treated in our department from 1986 to 2000, comparing clinicopathologic factors and post-treatment outcomes, for 9 patients with SmC, most undergoing esophagectomy including lymphadenectomy, with data from 128 patients with esophageal squamous cell carcinoma (SqC) invading to the muscular layer or beyond. Immunohistochemical features were compared between the SmC and 12 consecutive SqC. All patients studied had localized disease according to preoperative staging. SmC showed more ulcerative and infiltrative growth, and more aggressive lymphatic spread, than SqC. All SmC patients had lymph node metastasis (thoracic nodes, 9 patients: abdominal 6; cervical 1). All SmC specimens but no SqC were immunoreactive for neuron-specific enolase. Two and three SmC specimens were reactive for epithelial membrane antigen and keratin, respectively. Survival of SmC patients after esophagectomy (median, 11 months) was worse than for SqC patients (p=0.013). However, 1 SmC patient remains alive at 76 months. Survival was not related to any clinicopathologic or immunohistochemical features. While SmC shows aggressive behavior and worse outcomes than SqC, combining esophagectomy with chemotherapy or radiotherapy may prolong survival.

Ambulatory intraesophageal bilirubin monitoring in Japanese patients with gastroesophageal reflux.

BACKGROUND: The role of reflux of duodenal contents in gastroesophageal reflux in Japanese patients, which may be different from that in Western patients, was studied. METHODS: Intraesophageal pH and the bilirubin concentration were monitored, using the Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The percentage of the time that spectrophotometric absorbance was 0.15 or more and pH was less than 4.0 was defined as the holding times (HTs) of bilirubin and acid, respectively. Severity of esophagitis was classified using the Savary-Miller (S-M) classification. RESULTS: Esophagitis was present in 37 patients; 5, 10, 13, and 9 patients had S-M grades 1, 2, 3, and 4, respectively. Both HTs in the volunteers were less than 5%. Bilirubin HT was more than 5% in 3 of the 6 patients without esophagitis, but the acid HT was less than 5% in these 6 patients. Acid HT was less than 5% in 4, 2, 2, and 2 patients with S-M grades 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient with S-M grade 2 esophagitis. Bilirubin HT in patients with S-M grades 3 and 4 esophagitis (50.9 +/- 5.8%) was higher than that in grades 1 and 2 (14.9 +/- 2.9%) (P < 0.0001), but this was not so for acid HT. In 32 patients, bilirubin HT exceeded acid HT. Bilirubin HT did not correlate with acid HT. CONCLUSIONS: Duodenogastroesophageal reflux occurred independently of and exceeded acid reflux. The amount of duodenogastroesophageal reflux correlated with the severity of esophagitis.

Different genetic alterations in rat forestomach tumors induced by genotoxic and non-genotoxic carcinogens.

Human beings are exposed to a multitude of carcinogens in their environment, and most cancers are considered to be chemically induced. Here we examined differences in genetic alterations in rat forestomach tumors induced by repeated exposure to a genotoxic carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methylnitrosourethane (MNUR), and chronic treatment with a non-genotoxic carcinogen, butylated hydroxyanisole (BHA) or caffeic acid (CA). A total of 132, 6-week-old male F344 rats were employed. Forty rats were treated with MNNG by intragastric administration at a dose of 20 mg/kg body wt once a week for 32 weeks, and 20 rats received 20 p.p.m. MNUR in their drinking water for 48 weeks. Further groups of 20 animals were administered 2% BHA or 2% CA in the diet for 104 weeks. The remaining rats were maintained without any supplement as controls. Multiple forestomach tumors were observed in all rats of the MNNG-, MNUR-, BHA- and CA-treated groups. Histopathologically, MNUR- and CA-treated groups showed almost the same pattern. On polymerase chain reaction-single strand conformation polymorphism analysis, H-ras and p53 gene mutations were observed at high and relatively low frequencies, respectively, in forestomach tumors induced by MNNG and MNUR. Most H-ras gene mutations were G-->A transitions in codons 7 and 12 of exon 1. On the other hand, forestomach tumors due to the non-genotoxic carcinogens, BHA and CA, had almost no mutations of the H-ras and p53 genes. Moreover, relative overexpression of cyclin D1 and p53 was detected in forestomach tumors induced by the genotoxic carcinogens, while their non-genotoxic counterparts had a tendency to show low expression of those molecules. Mutations of the beta-catenin gene were not detected in any group. The present study demonstrates that rat forestomach tumors induced by genotoxic and non-genotoxic carcinogens have different underlying genetic alterations, even if their pathological features are similar.

p53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients.

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.