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Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer. Metohds Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progression-free survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy. Results In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p=0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group. Conclusion This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.

Background: Anatomical esophageal position may affect the short-term outcomes after minimally invasive esophagectomy (MIE). A previous single-institutional retrospective study suggested that the presence of a left-sided esophagus (LSE) made MIE more difficult and increased the incidence of postoperative complications., Methods: The current study was a multicenter retrospective study of 303 patients with esophageal cancer who underwent MIE at six esophageal cancer high-volume centers in Kyushu, Japan, between April 2011 and August 2016. The patients were divided into the LSE (66 patients) and non-LSE groups (237 patients) based on the esophageal position on computed tomography images obtained with the patients in the supine position., Results: Univariate analysis showed that patients with LSE were significantly older than those with non-LSE (69 ± 8 vs. 65 ± 9 years; P = 0.002), had a significantly greater incidence of cardiovascular comorbidity (65.2% vs. 47.7%; P = 0.013), and a significantly longer operating time (612 ± 112 vs. 579 ± 102 min; P = 0.025). Logistic regression analysis verified that LSE was an independent risk factor for the incidence of pneumonia (odds ratio 3.3, 95% confidence interval 1.254-8.695; P = 0.016)., Conclusions: The presence of a LSE can increase the procedural difficulty of MIE and the incidence of morbidity after MIE. Thus, careful attention must be paid to anatomical esophageal position before performing MIE.

Approximately half of the patients with esophageal cancer are diagnosed at an advanced stage with inoperable disease. The technique of bypass surgery, which is one of the palliative procedures for esophageal cancer, usually requires the insertion of a drainage tube for clearing secretions from the blind remnant esophagus. Since the artificial drainage tube is sometimes problematic for the patient after discharge from the hospital, drainage tubeless (DRESS) surgery might be preferable. The authors demonstrated the utility of DRESS bypass surgery by adding esophagostomy in the right supraclavicular region in three patients with unresectable esophageal cancer with and without esophago-respiratory fistula. All patients had been able to take per-orally and discharged the hospital. Two of three patients are alive with per-oral intake at 1 year later. This DRESS bypass surgery technique, which has not hardly reported in the literature, could release the patients from the tube trouble after the discharge from the hospital and give the patients the better quality of life.

Purpose: The Geriatric Nutritional Risk Index (GNRI) is a new index recently introduced to predict the risk of nutrition-related complications and mortality. Our aim is to examine the association between the GNRI and long-term prognosis in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy., Methods: The present study enrolled consecutive 216 patients with ESCC who underwent esophagectomy. The GNRI at admission to the hospital was calculated as follows: (1.489 × albumin, g/l) + (41.7 × present/ideal body weight). The characteristics and long-term prognosis were compared between four groups: the severe risk (GNRI: <82), moderate risk (GNRI: 82 to <92), low risk (GNRI: 92 to <98) and no risk (GNRI: >98) groups. The 5-year overall survival and independent prognostic factors were investigated, respectively., Results: A decreased GNRI significantly correlated with unfavorable overall survival (p < 0.001). In all patients, a multivariate analysis demonstrated that the severe and moderate risk groups (GNRI: <92) (hazard ratio 0.50; p = 0.002), T factor (≥T2) (hazard ratio 0.52; p = 0.026), and N positive factor (hazard ratio 0.47; p = 0.004) were independent prognostic factors. In the subgroup analysis, which excluded patients with preoperative chemoradiotherapy, the severe and moderate risk groups (GNRI: <92) (hazard ratio 0.48; p = 0.0057), and T factor (≥T2) (hazard ratio; p = 0.021) were independent prognostic factors., Conclusions: GNRI is considered to be a useful prognostic factor in patients with ESCC undergoing esophagectomy., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Anastomotic leakage (AL) after esophagectomy is associated with high rates of postoperative morbidity and mortality. In cases with leakage, a refractory fistula (RF) is sometimes recognized after esophagectomy. The aim of this study was to evaluate the risk factors for RF after esophagectomy with gastric tube reconstruction., Methods: This study enrolled 244 consecutive esophageal cancer patients who had undergone esophagectomy with gastric tube reconstruction. RF was defined as a noncurative anastomotic site-cutaneous fistula that had been present for more than 2 months. We evaluated the risk factors for RF., Results: AL occurred in 30 patients (12.3%). There was one mortality case (0.4%) due to mediastinitis caused by AL in the present series. A multivariate analysis revealed that the subcutaneous route was an independent risk factor for AL (OR 4.42, 95% CI 1.42-13.8, p = 0.01), and that the subcutaneous route was an independent risk factor for RF (OR 13.30, 95% CI 2.50-71.30, p = 0.0024)., Conclusion: The results of this retrospective study suggest that subcutaneous route was associated with an increased risk of RF after esophagectomy with gastric tube reconstruction. The preoperative identification of risk factors may contribute to the prevention of postoperative AL and RF., (© 2016 S. Karger AG, Basel.)

Background/aims: Patients with postoperative pulmonary complications after esophagectomy often have increased mortality. The purpose of the study was to examine the efficacy of preventing postoperative pulmonary complications by an intensive preoperative respiratory rehabilitation (PR) program for esophageal cancer patients., Methods: This study was a prospective randomized controlled study. Thirty patients in the PR group and 30 patients in the no preoperative respiratory rehabilitation (NPR) group were included. The PR group received preoperative rehabilitation for more than 7 days, while the NPR group did not receive any preoperative rehabilitation. All patients underwent postoperative rehabilitation from the first postoperative day. The postoperative pulmonary complications were evaluated using the Clavien-Dindo classification (CDC) and the Utrecht Pneumonia Scoring System (UPSS)., Results: The CDC grade in the PR group was significantly lower than that in the NPR group (p = 0.014). The UPSS score in the PR group was significantly lower than that in the NPR group at postoperative day 1 (p = 0.031). In the multivariate analysis, NPR was an independent risk factor for postoperative pulmonary complications greater than CDC grade II (OR: 3.99, 95% CI: 1.28-12.4, p = 0.017)., Conclusions: This study showed that the intensive PR program was capable of reducing the postoperative pulmonary complications in esophageal cancer patients., (© 2015 S. Karger AG, Basel.)

Background: The Geriatric Nutritional Risk Index (GNRI) is a new index recently introduced for predicting the risk of nutrition-related complications. The GNRI has mainly been reported as a simple and accurate tool to assess the nutritional status and prognosis of elderly patients. So far, there have been no reports of the GNRI in patients with gastrointestinal cancer. Our objective was to examine the association between the GNRI and short-term outcomes, especially postoperative complications, in patients with esophageal cancer who underwent esophagectomy and gastric tube reconstruction., Materials and Methods: The present study enrolled 122 consecutive patients with esophageal cancer who underwent esophagectomy and gastric tube reconstruction. The GNRI at admission to the hospital was calculated as follows: (1.489 × albumin in g/l) + (41.7 × present/ideal body weight). The characteristics and short-term outcomes were compared between two groups: the high (GNRI ≥90) and the low (GNRI <90) GNRI group. The mortality and morbidity rates, especially the rates regarding respiratory complications and anastomotic leakage, were investigated., Results: The mean age of the 122 patients was 63.9 ± 9.1 years (range 43-83). There were no significant differences in either patient or operative characteristics. The low GNRI group had a significantly higher rate of respiratory complications (p = 0.002). A multivariate analysis demonstrated that the GNRI was the only independent significant factor predicting respiratory complications (hazard ratio 3.41, 95% confidence interval 1.19-9.76; p = 0.022)., Conclusion: The GNRI is considered to be a clinically useful marker that can be used to assess the nutritional status and predict the development of postoperative respiratory complications in patients with esophageal cancer undergoing esophagectomy and gastric tube reconstruction., (2015 S. Karger AG, Basel.)

A 69-year-old woman underwent 4 months of imatinib mesylate chemotherapy for a diagnosed gastrointestinal stromal tumor of the esophagus. This treatment was suspended because of its side effects and because radiological examinations showed that the tumor had not changed or had even increased slightly in size. Thus, we performed esophagectomy via left thoracotomy and removed a tumor that measured 18 × 17 × 10 cm. Immunohistochemical examination revealed positive reactions for c-kit and CD34, suggestive of a high-risk malignancy. The patient was discharged from hospital on postoperative day 30, and has remained well with no sign of tumor recurrence for more than 5 years, without adjuvant chemotherapy.

Small-cell carcinoma of the esophagus (SCCE) is a rare and rapidly progressive malignant tumor with an extremely unfavorable prognosis. We report a case of long-term survival and review similar cases in the literature. An 84-year-old Japanese woman visited a clinic complaining of tarry stools. Type-1 tumor was detected in the left posterior wall of the middle thoracic esophagus on endoscopic examination, and the pathological diagnosis following immunohistochemical examination was SCCE. Chemoradiotherapy was adopted after taking the characteristics of poor prognosis, rapid progression, and patient age into consideration. Chemoradiotherapy comprised 56 Gy of irradiation over 43 days and two courses chemotherapy with cisplatin and vincristine. Therapeutic effect was evaluated as complete response after endoscopic examination and computed tomography at one month after treatment. No recurrence or metastasis has been identified as of more than five years after achieving complete response, with endoscopic examination every six months and computed tomography every three months. To date, long-term survival has only been reported in octogenarian patients with SCCE, and the present case describes the oldest patient for whom successful radical therapy has been reported.

Background/aims: The aim of the present study was to clarify the results and feasibility of surgical approaches for cancer, which is mainly occupied by squamous cell carcinoma (SCC), of the lower esophagus., Methodology: Forty-four patients (34 men, 10 women) with cancer located at the lower esophagus were enrolled in this study. SCC was diagnosed in 36 cases and adenocarcinoma (ADC) in 8 cases. Thirteen patients underwent transhiatal esophagectomy, 18 underwent lower thoracic esophagectomy by left thoracotomy, and 13 underwent esophagectomy with a right thoracic approach by open thoracotomy or thoracoscopy., Results: Ten cases (ADC, n = 2; SCC, n = 8) showed involvement of mediastinal lymph nodes, although lymph node dissection varied with each surgical approach. Five-year survival rates were 75% for ADC and 31.9% for SCC, and ADC tended to be associated with a more favorable prognosis than SCC (p = 0.058). Transhiatal esophagectomy was performed more often in older patients (p < 0.05), but no other clinicopathological parameters appeared to affect the selection of surgical approach. No significant prognostic differences existed between surgical approaches (p = 0.35), even though the examination was limited to SCC (p = 0.98)., Conclusions: No significant prognostic differences were identified between transhiatal and left and right transthoracic approaches for lower esophageal cancer.

Background/aims: Reconstruction using a free jejunal graft (FJG) after resection of the cervical esophagus has become common, but postoperative morbidity remains. We report herein our procedure and the results of reconstruction for neck cancer using FJGs., Methodology: Twenty-four patients underwent FJG reconstruction after laryngo-pharyngo-esophagectomy. We perform a mini-laparotomy with a 5-cm para- or trans-rectus muscle incision. The FJG is then harvested from the jejunum supplied by the second or third mesenteric artery, and a jejunostomy is created. Pharyngo-jejunal anastomosis is performed using an Albert-Lembert suture and jejunal-esophageal anastomosis by a circular stapling technique. The facial artery or suprathyroid artery is used as the feeding artery, and the common facial vein or external jugular vein as the drainage vein. Vascular anastomosis is performed microsurgically., Results: In terms of postoperative morbidity, minor anastomosis leakage of the pharyngo-jejunal anastomosis was observed in one patient, stricture of the jejunal-esophageal anastomosis in four, and wound infection in one. No cases of passage disorder due to graft bending were seen, and no patients died., Conclusions: The procedure using FJG harvested via mini-laparotomy is minimally invasive and is a feasible procedure for reconstruction after laryngo-pharyngo-esophagectomy, resulting in low morbidity.

Background: The present study aimed to clarify the long-term prognostic impact and oncologic feasibility of thoracoscopic esophagectomy (TSE) in patients with esophageal cancer in comparison with open thoracic esophagectomy (OTE)., Methods: Patients with esophageal cancer underwent surgically curative esophagectomy without neoadjuvant therapy from January 1991 to December 2008 and were analyzed retrospectively. Of 257 patients, 91 underwent TSE and 166 had OTE. Relations between the long-term prognosis after surgery, the surgical procedure, and clinicopathologic parameters were analyzed statistically. The propensity scores were calculated for all patients through a multiple logistic regression model that was optimized with Akaike's Information Criterion. Using Cox's proportional hazard model with prognostic variables and the propensity scores, we implemented a multivariate analysis for comparing the performance of two surgical methods., Results: Patient characteristics and the incidence of perioperative morbidity or hospital death were similar for the TSE and OTE groups. Significantly more lymph nodes were dissected in the TSE group than in the OTE group (total p = 0.013; thoracic p = 0.0094; recurrent laryngeal p < 0.0001). The TSE group exhibited a more favorable prognosis after surgery than the OTE group in terms of overall survival (p = 0.011) and disease-specific survival (DSS) (p = 0.0040). Particularly in subgroup analysis of DSS, the TSE group had a favorable prognosis in upper thoracic esophageal cancer (p = 0.0053), invasive cancer (p = 0.046), node-positive cancer (p = 0.020), progressive cancer (p = 0.0052), cancer with lymphatic vessel invasion (p = 0.0019), and cancer without blood vessel invasion (p = 0.0081). In terms of DSS, the TSE group exhibited a more favorable prognosis than the OTE group regardless of the presence or absence of metastasis to lymph nodes around the thoracic (p < 0.0001) or recurrent laryngeal (p < 0.0001) nerves. TSE (p = 0.0430), lymph node metastasis (p = 0.0382), lymphatic invasion (p = 0.0418), and p stage (p = 0.0047) were independent prognostic parameters in the Cox's proportional hazard model with the propensity scores., Conclusions: TSE can contribute to prolonged survival after surgery in patients with esophageal cancer by enabling precise thoracic lymph node dissection based on a magnified surgical field. TSE might have maximum oncologic benefit and minimum invasiveness for patients with esophageal cancer.

Aim: The aim of the present study was to clarify differences in node metastasis mode and clinical outcomes based on tumor location in patients with esophageal squamous cell carcinoma (ESCC)., Patients and Methods: Participants comprised 228 patients with ESCC who underwent radical esophagectomy without preoperative supplement therapies. Lymph nodes were harvested from three fields: the neck, thorax, and abdomen. Patients were divided into three groups depending on tumor location [upper esophagus (UE), middle esophagus, or lower esophagus (LE)] and analyzed clinicopathologically., Results: The LE group showed significantly more progressive ESCC in terms of tumor invasion (p = 0.025), node metastasis (p = 0.0071), and TNM stage (p = 0.0043). The LE group revealed a tendency to metastasize to extrathoracic (especially abdominal) nodes (p = 0.0008). Recurrent laryngeal node metastasis was increased in the UE group (p = 0.016). However, no prognostic differences were detected between groups according to tumor location. Likewise, subgroup analyses by surgical approach (open thoracotomy vs. thoracoscopy) and cancer stage (stage I/II, III, and IV) did not reveal any significant prognostic impact of tumor location., Conclusion: Lymphatic spread varied by tumor location, but no prognostic impact of tumor location could be detected in patients with ESCC in spite of surgical approach or cancer stage., (© 2013 S. Karger AG, Basel.)

We report a case in which rabeprazole cured gastric tube ulcer after esophagectomy for esophageal squamous cell carcinoma (ESCC). A 47-year-old Japanese man was referred to our hospital with refractory ulcer of the reconstructed gastric tube one year after esophagectomy for ESCC. The ulcer proved refractory to healing by the administration of omeprazole or lansoprazole, or eradication of Helicobacter pylori after examinations concerning ischemia, acid over-secretion and H. pylori infection. Finally, metabolizer type was examined for proton pump inhibitors (PPIs), revealing the patient as a hetero-extensive metabolizer for the CYP2C19 genotype. This suggested sensitivity to rabeprazole, but resistance to omeprazole and lansoprazole. The refractory ulcer was subsequently cured after changing the PPI to rabeprazole. Examination of PPI metabolizer type might thus be important, along with an investigation of ischemia, acid secretion and H. pylori infection in the treatment of refractory gastric tube ulcer after esophagectomy.

Purpose: The present study examined the clinicopathological impact of survivin expression in oesophageal squamous cell carcinoma (ESCC). In addition, the biological role of anti-apoptosis parameter in ESCC was examined immunohistochemically., Patients and Method: Subjects comprised 71 patients followed up for 5 years after surgery for ESCC and analysed immunohistochemically to examine the clinicopathological impact of survivin expression. Separately, 37 fresh frozen samples of ESCC obtained recently were examined concerning splicing variant expression of survivin using reverse-transcription polymerase chain reaction (RT-PCR)., Results: Immunohistochemical survivin expression was detected in the nuclei of 10 ESCC specimens (14.1%) and cytoplasm of 22 specimens (31.0%). Nuclear expression displayed no clinicopathological implications, but cytoplasmic expression correlated with histological differentiation (p=0.002) and tumour invasion (p=0.073) and showed prognostic impacts in univariate (p=0.0184) and multivariate (p=0.0299) analyses. Survivin, survivin-2B and survivin-deltaEx3 mRNA were amplified in 31 (83.8%), 23 (62.2%) and 26 (70.3%) specimens, respectively, by RT-PCR. Survivin-2B level related significantly with histological differentiation (p=0.038), but no other significant implication was identified between any mRNA and clinicopathological factors., Conclusion: As a molecular biological anti-apoptotic factor, survivin expression was of use in assessing prognosis in ESCC. Inhibition of survivin may be useful as a molecular biological therapy in ESCC., (Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

In patients with superficial esophageal cancer, especially in those with tumor invasion above the muscularis mucosae, lymph node metastasis is very rare. We report a case of superficial esophageal cancer who presented with lymph node metastasis. In another hospital a 49-year-old man was found to have a bulky tumor adjacent to the cardiac area of the stomach and a total gastrectomy was carried out. Postoperatively, the tumor was identified as a lymph node containing metastatic squamous cell carcinoma. The main lesion could not be identified on fluorodeoxyglucose positron emission tomography. On esophagogastric endoscopy, using the iodine spray technique, we found an unstained lesion about 32 cm from the incisor teeth. The tumor was removed using endoscopic mucosal resection. The entire resected specimen was examined histopathologically; the depth of the tumor was above the muscularis mucosae. Thirty-four months after endoscopic mucosal resection, there is no sign of tumor recurrence or metastasis.

Background/aims: Esophagectomy for esophageal cancer is one of the most invasive surgical procedures. However, with the recent aging of the population, clinicians are increasingly encountering patients with advanced age (over 80 years) who require treatment for esophageal cancer. Patients in this age group tend to be regarded as at high risk in terms of surgical treatment. In the present study, the authors examined perioperative complications and clinical outcome in esophagectomy in patients aged over 80 years compared with those aged 70-79 and discuss the risk and appropriateness of esophagectomy in the older group., Methodology: Of patients with esophageal cancer at our institute, 25 were aged over 80 years, while 95 were aged 70-79 years. We statistically compared those who underwent esophagectomy; 8 in the older group and 62 in the younger group. The oldest patient was an 84-year-old man. Among the 8 older patients, 7 were male and 1 was female. All cases were histologically confirmed as squamous cell carcinoma and this series included 1 case in Stage 0, 3 in Stage I and 4 in Stage III. Total thoracic esophagectomy was performed in 5 patients, transhiatal blunt dissection in 2 and lower thoracic esophagectomy in 1., Results: Rate of surgical treatment was significantly lower in the older group than in the younger group (32.0% vs. 65.3%, p < 0.001). No significant difference was observed in postoperative complications or mortality. Regarding clinical postoperative outcome in the older group, there were 5 deaths: 1 related to surgery, 2 to other causes (at 5 and 12 months), 2 to cancer (4 and 11 months). The remaining patients were alive at 31, 60, and 88 months. No significant difference was observed in overall or disease specific survival after surgery between the 2 groups., Conclusion: No statistically significant differences were apparent in morbidity, mortality or clinical outcome in the 2 groups. Since surgery seems to confer similar symptomatic improvements and survival in patients aged over 80 to those expected for patients aged 70-79, we believe that surgeons should not withhold esophagectomy in patients aged over 80 years because of advanced age alone.

The purpose of this study was to analyze loss of p16 expression and its relationship to hypermethylation, clinicopathological parameters and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Tissue samples from 60 ESCC were subjected to histological analysis. Immunohistochemical staining for p16 expression was performed. DNA was extracted from these primary esophageal tumors and from sera from another 38 ESCC patients. The DNA was modified with bisulfite and analyzed for p16 promoter methylation by methylation-specific polymerase chain reaction. Twelve out of the 60 tumors (20%) were methylated at the p16 promoter and 48 tumors (80%) were unmethylated. There were no significant correlations between the methylation of the p16 promoter and clinicopathological parameters. Immunohistochemical staining revealed that 41 of the 60 tumors (68.3%) were p16-negative and 19 tumors (31.7%) were p16-positive. The correlation between negative p16 immunohistochemical staining and methylation was statistically significant (P = 0.0084). No instances of p16 methylation and p16 positive immunostaining were found. There was a close correlation between loss of p16 expression and poorer prognosis in ESCC (P = 0.0517 in overall survival, P = 0.0478 in disease-free survival). The p16 gene promoter hypermethylation was detected in the serum of two of 38 (5.2%) patients with ESCC. This indicates that p16 promoter methylation suppresses p16 expression and that the loss of expression has a close relationship with poor prognosis in patients with ESCC. The present results may lead to the development of new therapeutic strategies, such as p16(INK4A) gene therapy, to treat patients with ESCC.

A 70-year-old woman, who had undergone esophagectomy for cervical esophageal squamous cell carcinoma (pT3pN2M0, Stage III) 9 months earlier, was diagnosed as mediastinal lymph node recurrence by CT and endoscope. Patients underwent radiochemotherapy with 5 cycles of docetaxel 10 mg/m(2) on day 1 and 5-FU 250 mg/m(2) on day 1 to day 5, together with concurrent radiation (50 Gy/25 Fr) for mediastinum. After this treatment, a complete response (CR) was achieved, and there was no recurrence 9 months after the treatment. No severe adverse effects were observed. Concurrent radiochemotherapy with docetaxel and 5-FU is considered effective without serious side effects for postoperative recurrence in esophageal cancer.

Background: The aim of this study was to assess the clinical outcome in patients with esophageal squamous cell carcinoma (ESCC) by using molecular biological classification based on immunohistochemical analysis in addition to tumor, node, metastasis system (TNM) classification., Methods: Samples from 71 patients with ESCC who underwent surgery were analyzed immunohistochemically. Cyclin B1, E-cadherin, Bag-1, and heat-shock protein 70 were selected as the molecular biological parameters. The utility of molecular biological classification on clinical impact was examined and compared with TNM classification., Results: Three patients were diagnosed as stage 0, 14 as stage I, 20 as stage II, 19 as stage III, and 15 as stage IV by TNM classification. Thirteen patients were classified as stage 0, 17 as stage I, 21 as stage II, 18 as stage III, and 2 as stage IV by molecular biological classification. Molecular biological stage (P < .0001) and TNM stage (P < .0001) were statistically significant prognostic parameters in univariate analysis. Twenty (28.2%) of 71 patients were assigned to the same stage by both classifications, and a significant correlation was identified between the two classifications (P = .0002). Molecular biological classification (P < .01) and TNM classification (P < .0001) were independent prognostic parameters in multivariate analysis. Combined TNM and molecular biological classification accurately reflected clinical outcome (P < .0001)., Conclusions: Molecular biological classification combined with TNM classification is useful for assessing the prognosis of patients with ESCC.

Background: Amplification of the chromosome 3q seems to occur frequently in esophageal squamous cell carcinoma (ESCC). This study analyzed the clinical effect of messenger RNA (mRNA) expression for PIK3CA (the gene that encodes phosphatidylinositol-3 kinase catalytic alpha-polypeptide) and TFRC (the gene that encodes the transferrin receptor), which map within chromosome 3q in ESCC., Methods: Formalin-fixed, paraffin-embedded ESCC tissues were examined. Total RNAs were extracted, and reverse transcription products were subjected to polymerase chain reaction amplification of beta-actin, PIK3CA, and TFRC., Results: Expression of beta-actin mRNA was detected in 67 (55.8%) of 120 samples, with PIK3CA mRNA expression in 22 (32.8%) of these 67 samples and TFRC mRNA expression in 15 (22.4%) of the 67 samples. PIK3CA mRNA expression correlated with regional lymph node metastasis (P = .04). TFRC mRNA expression correlated with distant metastasis (P = .04). Patients with positive results for either PIK3CA or TFRC mRNA displayed a significantly worse prognosis than patients with negative results (PIK3CA, P = .045; TFRC, P = .009). TFRC mRNA expression represented an independent prognostic factor in multivariate analysis (P = .0233), but PIK3CA did not (P = .7585)., Conclusions: PIK3CA and TFRC mRNA represent prognostic factors in patients with ESCC. TFRC mRNA offers an independent prognostic factor, and expression may have clinically important implications.

The p63 gene is a member of the p53 family that plays a role in cell differentiation, development and carcinogenesis. The relationship between p63 expression and the prognosis of esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examines the clinical impact of p63 in patients with ESCC. Resected specimens from 180 patients with ESCC were immunostained for p63 and p53. After establishing a cut-off value for p63 expression, we statistically examined its clinical impact and relationship to p53 expression. At a 50% cut-off value for p63 expression, the 5-year overall survival was significantly longer in p63-positive (46.4%) than -negative patients (11.1%, p=0.05). Among the 180 ESCC patients, 171 (95.0%) were p63 immunoreactive and only 9 (5.0%) were negative. The correlation between p63 status and clinicopathological parameters was not significant, although p63-negativity tended to correlate with distant metastasis (p=0.06) and clinical stage (p=0.08). Univariate analysis demonstrated significant correlations between patient survival and tumor diameter, depth of invasion, lymphatic invasion, vascular invasion, lymph node metastasis and distant metastasis. The survival of patients who did not express p63 and p53 was obviously unfavorable (p=0.03). Multivariate analysis revealed that only lymph node metastasis was a critical independent prognostic marker for overall survival (p=0.0015). Expression of p63 was not an independent prognostic factor for overall survival in this study (p=0.69). These data suggest that, although a reduced expression of p63 is infrequent, it has a prognostic impact upon patients with ESCC.

Expression of galectin-3, a member of the beta-galactosidase binding lectin family, is reported to correlate with cell adhesion. The present immunohistochemical study was performed to clarify the impact of galectin-3 expression on patients with esophageal squamous cell carcinoma. Galectin-3 expression was examined immunohistochemically in 154 patients with esophageal squamous carcinoma, who had undergone surgery without preoperative supplemental therapy at the Department of Surgery II in the Hospital of the Faculty of Medicine, Oita University, between 1990 and 2000. The cases with > or =30% nuclear-stained cancer cells were considered high nuclear expression cases. In contrast, the cases with > or =45% cytoplasm-stained cancer cells were considered high cytoplasm expression cases. Twenty-three of 154 ESCC cases were regarded as high nuclear expression (14.9%) and 72 of 154 cases were regarded as high cytoplasm-expression (46.5%). High expression of galectin-3 in the nuclei inversely correlated with vascular invasion (p=0.030) and histological differentiation (p=0.0064). In contrast, cytoplasmic expression of galectin-3 revealed no significant impact on clinicopathological factors. Neither nuclear nor cytoplasmic expression of galectin-3 was a prognostic indicator in ESCC. Elevated expression of galectin-3 in the nuclei but not the cytoplasm may be an important biological parameter related to histological differentiation and vascular invasion in patients with ESCC.

A flexible nitinol stent was inserted to treat malignant stricture of the esophagus in 28 patients. Stenting was successful in all 28 patients, leading to an improved oral intake that was maintained for >80% of the survival period in 26 patients. Patients with tumors arising in the esophagus (n=24) were divided into two groups to compare complications and prognosis: patients who underwent stenting only (n=10); and patients who underwent stenting after radiochemotherapy (n=14). Fatal complications associated with stenting were seen in four patients (28.6%) who underwent stenting after radiochemotherapy and in one patient (10.0%) who underwent stenting only. Although survival was significantly longer for patients who underwent prior radiochemotherapy than for patients who did not, the incidence of fatal complications tended to be higher. No significant differences in background factors other than radiochemotherapy before stenting were observed between patients with fatal and non-fatal complications. Stenting was shown to represent a useful treatment for malignant stricture of the esophagus, as oral intake improved and was maintained for a long period of time in most patients. However, incidence of fatal complications was high among patients who underwent radiochemotherapy, and caution must be exercised due to the difficulty in predicting fatal complications.

Hypermethylation in the E-cadherin promoter region and expression of the transcription factor Snail were analyzed in 41 cases of esophageal squamous cell carcinoma (ESCC) and paired normal squamous epithelium by methylation-specific polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) to clarify the mechanism regulating E-cadherin deletion; 93 cases of ESCC were analyzed immunohistochemically to determine the clinicopathologic impact of E-cadherin deletion. Hypermethylation of the E-cadherin promoter and Snail overexpression were detected in 25 cases (61%) by methylation-specific PCR and 34 cases (83%) by RT-PCR, respectively. Reduced E-cadherin expression, observed immunohistochemically in 55 cases (59%), correlated with hypermethylation (P = .0011) but not Snail overexpression (P = .685). Hypermethylation and Snail overexpression correlated significantly with E-cadherin deletion (P = .0018). Snail overexpression was unrelated to clinicopathologic factors. Reduced E-cadherin expression correlated with tumor invasion (P = .019) and vascular invasion (P = .052) but not other factors. E-cadherin deletion had prognostic impact in univariate (P = .023) and multivariate (P = .034) analyses. E-cadherin deletion was regulated by hypermethylation and Snail expression. Examination of reduced E-cadherin expression is important for assessing biologic behavior, including clinical outcome, in patients with ESCC.

Aggressive surgery including extensive lymph node dissection is considered necessary to improve the long-term survival of patients with esophageal carcinoma. While three-field lymph node dissection is widely performed for patients with thoracic esophageal carcinoma, cervical lymph node metastasis is uncommon. In order to reduce surgical stress, we have developed a two-step three-field lymph node dissection procedure for thoracic esophageal carcinoma. In the first-step operation, total thoracic esophagectomy through a right thoracotomy is performed. Mediastinal and abdominal lymph node dissection is performed synchronously. When recurrent nerve lymph node metastasis is pathologically positive, cervical lymph node dissection is performed about 3 weeks after the first operation (second step). Of 343 patients with carcinoma of the esophagus surgically treated in our department between 1990 and 2001, 146 underwent the operation described above. Three-field dissection was performed in 68 patients (group A), while two-field dissection was performed in 78 patients (group B). In the 68 group A patients, cervical lymph node metastasis was positive in 15 patients (22%). There was no marked difference in the onset of major complications between the two groups. The 5-year survival rate was 58% for group A and 61% for group B, not a statistically significant difference. In 78 of the 146 patients, it was possible to avoid cervical lymph node dissection without negatively affecting therapeutic outcomes. Two-step three-field lymph node dissection can reduce surgical stress of patients with good clinical outcome., (Copyright 2004 ISDE)

Macrophages have been reported to play an important role in suppressing tumor growth, and heat shock protein 70 (HSP70) in presenting tumor specific antigens. The objective of the present study was to investigate the relationship between lymph node metastasis and these two molecular biological markers in superficial esophageal carcinoma. Subjects were 37 patients with untreated submucosal esophageal carcinoma who underwent curative surgery. Among these patients, expression of CD68-positive macrophages in the tumor stroma and expression of HSP70 in tumor cells were analyzed. The results demonstrated that expression of CD68-positive macrophages was significantly greater among patients without lymph node metastasis (p<0.0001), and a significant correlation existed between HSP70 expression and CD68 expression (p=0.0125). In superficial esophageal carcinoma, lymph node metastasis is correlated with expression of CD68-positive macrophages in tumor stroma and expression of HSP70 in tumor cells. These two markers may therefore prove useful for therapy planning.

DNA copy number changes were analyzed by comparative genomic hybridization (CGH) in 53 esophageal squamous cell carcinomas (ESCC) to clarify the relationship between DNA sequence copy number aberrations and clinicopathological factors. Changes in DNA copy number were observed in all 53 ESCC patients. The average number of DNA copy number gains was 9.32 (range 1-23), most frequently located on chromosomes 3q, 5p, 8q, 11q and Xq in over 40% of tumors. Loss of DNA copy number was detected on 3p, 5q, 4p, 1p and Xp in over 20% of tumors. No statistically significant differences in the frequency of DNA copy number changes were observed. However, some loci showed correlation with clinicopathologic factors: 8q gain correlated with the pattern of tumor infiltration, 3q gain correlated with pT, 2p gain, 1p loss and 16p loss correlated with lymphatic invasion, and 3q gain correlated with clinical stage. Thus, in ESCC, gain of 3q is the only specific recurrent pattern of DNA aberration that correlates with clinicopathologic parameters, although no particular loci correlated with patient prognosis. Further CGH analysis may reveal new, recurrent genetic changes in ESCC affecting chromosomes sites that harbor genes known to participate in tumorigenesis and progression of several human malignant neoplasms.

A 69-year-old Japanese man undergoing total gastrectomy for multiple gastric ulcers at age 46 was found endoacopically to have multiple esophageal cancers in the upper, mid, and lower esophagus. Esophageal mucosa associated with tumors was replaced with columnar epithelium. He underwent total esophagectomy combined with laryngectomy, pharyngectomy, and lymph node dissection using the large bowel for reconstruction. The resected esophagus had multiple cancers, including well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and small-cell carcinoma. Barrett's mucosa consisted mainly of specialized columnar epithelium while both junctional and fundic Barrett's epithelium was observed partially but not clearly. This case is indicative of the high and totipotential carcinogenetic risk of Barrett's epithelium and the relationship between duodenal content reflux and esophageal carcinogenesis after total gastrectomy.

In the present study, micrometastasis in the rib marrow of 24 patients with esophageal cancer was examined using RT-PCR. RT-PCR was done using primers corresponding to cytokeratin 18 (CK18), squamous cell carcinoma antigen (SCC), and carcinoembryonic antigen (CEA). In 18 cases, CK18 was also detected in the rib marrow. Only one patient exhibited CEA amplification in the rib marrow. No cases demonstrated SCC amplification as a marker of micrometastasis in the rib marrow. The information from micrometastasis detected in the rib marrow using RT-PCR is useful in deciding whether or not adjuvant therapy is necessary after surgery. However, combined analysis using plural markers should be required since sensitivity or specificity of each marker may vary. Further follow-up of the patients is necessary to clarify the clinical impact of micrometastasis in rib marrow.

The expression of the fragile histidine triad (FHIT) gene has been proposed to play an important role in early events of carcinogenesis and to be correlated with the progression or clinical outcomes of various cancers. Attention has focused recently on the regulation of FHIT expression, and loss of heterozygosity or hypermethylation of the CpG island in the promoter region has been suggested as clues to a possible mechanism. Methylation status and FHIT expression were investigated in the present study to clarify the clinicopathologic impact of FHIT in vivo. One hundred and five patients with esophageal cancer were admitted to the study. Cancer tissues were immunohistochemically stained for FHIT, and FHIT methylation status was examined in 36 patients by the methylation-specific polymerase chain reaction. FHIT methylation and expression were analyzed with respect to both clinicopathologic parameters and their interactions. Tissue specimens from 35 of the 105 patients (33.3%) stained positively for FHIT. In contrast, the CpG island in the FHIT promoter region was hypermethylated in 25 of the 36 (69.4%) analyzed cases of esophageal cancer. Hypermethylation was significantly correlated with the deletion of FHIT protein expression (P<0.001). FHIT hypermethylation was not associated with any clinicopathologic parameters. In contrast, deletion of FHIT expression significantly promoted tumor invasion (P<0.05) and lymphatic vessel invasion (P<0.01). Lymph node metastasis also appeared higher in the absence of FHIT protein expression, but the result was not significant (P=0.069). Patients with a preserved FHIT gene expression possibly exhibited an improved prognosis compared with those with deleted FHIT expression (P=0.093). Hypermethylation of the FHIT promoter region may be a mechanism for regulating FHIT expression. FHIT gene expression was closely correlated with cancer progression, as indicated by tumor invasion and lymphatic spread, and it may provide insight into the mechanism of progression of esophageal cancer.

Reconstruction of cervical esophagus and hypopharynx following cervical esophagectomy and laryngopharyngectomy is generally performed using jejunal autograft interposition. However, this method has some disadvantages and is not suitable for optimal swallowing function. In our institution, free transverse colonic graft has been successfully applied for reconstructive purposes in 12 cases since 1986. The present report describes a case of upper esophageal web accompanying superficial squamous cell carcinoma and details the operative techniques utilized.

Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine to 5'-fluorouracil, which exerts an anticancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). Recently, PyNPase has been shown to be identical to a potent angiogenic factor, platelet-derived endothelial cell growth factor. We analyzed the concentration of PyNPase and DPD in 33 patients with esophageal squamous cell carcinoma in fresh-frozen samples by enzyme-linked immunosorbent assay. In addition, we evaluated the clinical significance and prognostic value of PyNPase expression in esophageal carcinoma. The PyNPase concentration of tumor tissue was statistically higher than that of normal tissue of the esophagus (248 +/- 146 U/mg protein vs 73 +/- 63 U/mg protein, P = 0.0001), whereas DPD showed no difference (90 +/- 62 U/mg protein vs 88 +/- 62 U/mg protein, P = 0.825). The ratio of PyNPase to DPD of tumor tissue was statistically higher than that of normal tissue of the esophagus (3.3 vs 0.95, P = 0.0001). There were no significant differences between the group with high tumor to normal tissue ratios of PyNPase concentration and the low-ratio group in terms of the tumor length, depth, lymph node metastasis, lymph vessel invasion, vascular invasion, stage and survival. In conclusion, 5'-deoxy-5-fluorouridine may be effective on esophageal carcinoma and PyNPase concentration in esophageal carcinoma may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.

Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery.

Small cell carcinoma arising in the esophagus is a relatively rare disease. In the more common small cell carcinoma of the lung, the diagnostic significance of several new markers has been recently reported. This study used immunohistochemical techniques in addition to clinicopathological analysis, in order to clarify the utility of newer markers as biological parameters or as diagnostic tools. Six patients with small cell carcinoma of the esophagus were clinicopathologically analyzed. Immunohistochemical staining was performed using primary antibodies for bombesin, CD56 and CD57 in addition to conventional endocrine markers chromogranin A, neuron specific enolase and synaptophysin. All patients died within 2 years of surgery due to cancer recurrence, whether or not they had received adjuvant therapy. Pathological stages ranged from IIa to IVb and lymph node metastasis was observed in five cases. Of the six cases, four showed a positive reaction for bombesin and five were positive for CD57. In contrast, no cases revealed a positive reaction for CD56. The one case to survive 24 months after surgery was not shown to express bombesin, CD56 or CD57. Small cell carcinoma of the esophagus demonstrated an unfavorable prognosis. The study suggested that in this disease, bombesin and CD57 (but not CD56) were useful as biological markers, predicting clinical outcome rather than having diagnostic significance.

The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2% vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma.

Background: It would be of considerable benefit to patients with esophageal cancer to be able to predict the effect of CRT before therapy, because critical side effects could be avoided and the therapeutic cost of CRT-resistant cases could be reduced. One of the biological parameters with the potential to indicate radioresponse is the DNA double-strand break repair enzyme DNA-PKcs. This study aims to clarify the correlation between DNA-PKcs expression and CRT effect., Methods: Sixty-seven patients with progressive esophageal cancer treated with CRT were included in this study. The relationship between the expression of DNA-PKcs and the effect of CRT was examined by using immunohistochemistry. The relationships between DNA-PKcs expression, clinicopathologic parameters, and CRT effect were investigated statistically., Results: A significant correlation was found between the expression of DNA-PKcs and the effect of CRT (P =.0149). The high-DNA-PKcs expression group showed greater therapeutic sensitivity than the low-expression group. Clinicopathologic factors had no relationship with DNA-PKcs expression or CRT effect., Conclusions: This study suggests that high expression of DNA-PKcs correlates with CRT effect. DNA-PKcs expression could, therefore, be useful for predicting the effect of CRT. In addition, these results may make it possible to plan therapy taking patients' quality of life into consideration.

Primary adenocarcinoma of the esophagus is rare in Japan and, in most cases, arises from Barrett's esophagus epithelium. A 72-year-old man reporting heartburn and dysphagia and preoperatively diagnosed with adenosquamous carcinoma arising from Barrett's esophagus underwent thoracic esophagectomy and lymph node dissection in curative resection. Pathological diagnosis of the resected specimen showed adenosquamous carcinoma (coexistent adenocarcinoma and squamous cell carcinoma) invasive to the submucosal layer; metastasis was found in regional lymph nodes. Pathological staging was pT1bN1M0, stage II. Unfortunately, the man died of liver and lung metastasis 17 months postoperatively. To our knowledge, this rare case is only the fifth reported in the English literature on adenosquamous carcinoma arising from Barrett's esophagus.

This study divided patients with esophageal cancer and multiple primary cancers into two groups, a head and neck cancer (HNC) group and a non-head and neck cancer (NHNC) group. These groups were then evaluated on the basis of clinical and pathological studies. Among 92 patients with esophageal cancer as one of multiple primary cancers, 38 (41.8%) were assigned to the HNC group. The following characteristics distinguished patients in the HNC group from those in the NHNC group: (1) younger age; (2) shorter interval between diagnosis of metachronous cancers; (3) many displayed superficial esophageal cancer. Among the cases in which esophageal cancer was discovered synchronously with head and neck cancer, head and neck cancers were discovered before esophageal cancer; and (4) many patients displayed esophageal dysplasia, and many had multiple esophageal cancers. In the present study, we demonstrated the necessity of screening for multiple primary cancers in patients with esophageal cancer.

Vascular endothelial growth factor C (VEGF-C) is known to act in lymphangiogenesis. Recent reports suggest VEGF-C plays a role in the spread of several cancers to the lymph system. Lymphatic spread is a critical prognostic factor in esophageal cancer, however, the molecular mechanism involved in the spread of cancerous cells remains unclear. In the present study the clinicopathological implication of VEGF-C was analyzed using immunohistochemistry. Seventy-one patients with esophageal squamous cell carcinoma (ESCC) resected in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for VEGF-C and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically. Only histological grade (differentiation) was shown to have a statistically significant correlation with VEGF-C expression (p=0.028). Age (p=0.064), lymph node metastasis (pN) (p=0.085) and vascular invasion (p=0.092) tended to correlate with VEGF-C expression although on analysis this correlation was not statistically significant. The results suggested there is no prognostic implication for VEGF-C in ESCC (p=0.80). There is no significant correlation between VEGF-C expression and clinicopathological parameters involved in lymphatic spread. However, VEGF-C expression might play an important role in metastasis of ESCC since histological grade was closely related to lymph node metastasis and distant metastasis.

Background: The aim of the present study was to use immunohistochemical methods to clarify the clinical implication of heat shock protein (HSP) 70 expression in esophageal squamous cell carcinoma and to investigate the function of HSP70 as a chaperone for p53., Methods: Seventy-one patients with esophageal squamous cell carcinoma were admitted in the present study. Expression of HSP70 was analyzed by immunohistochemistry and correlated with TNM classification, vessel invasion, p53 expression, and clinical outcome after operation., Results: Overexpression of HSP70 was related to sex (p < 0.05), tumor configuration (p < 0.05), lymph node metastasis (p < 0.01), and lymphatic vessel invasion (p < 0.05). Expression of p53 and HSP70 were not correlated with each other (p = 0.824). Esophageal squamous cell carcinoma with HSP70 expression exhibited a significantly better prognosis compared with HSP70-negative esophageal squamous cell carcinoma in univariate analysis (p < 0.05), but no significance was found in multivariate analysis., Conclusions: We suggest that HSP70 expression might be of use to assess the progression, lymph node metastasis, and lymphatic vessel invasion of esophageal squamous cell carcinoma. Inasmuch as both lymph node metastasis and HSP70 expression are prognostic variables in esophageal squamous cell carcinoma, examination of HSP70 expression may be of use to assess clinical outcome after operation.

Background: It has been reported that p53 regulates the G2-M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC)., Methods: Tissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry., Results: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC., Conclusions: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC., (Copyright 2002 American Cancer Society.)

Most esophageal malignancies are either squamous cell carcinomas or adenocarcinomas arising from Barrett's esophagus. We report a case of adenocarcinoma of the upper esophagus (cervical esophagus) that was derived from heterotopic gastric mucosa. In a 73-year-old man cervical esophagectomy was performed, followed by pharyngectomy, laryngectomy, and palliative dissection of lymph nodes on both sides of the neck, after an accurate diagnosis has been made by esophagography and endoscopy. The resected tumor was smoothly elevated (2.5 cm x 2.0 cm) and was microscopically identified as a well differentiated adenocarcinoma with invasion to the submucosa. The origin of the carcinoma was found to be a heterotopic gastric mucosa, by hematoxylin-eosin (H&E), immunohistochemical, and enzyme histochemical staining. To our knowledge, only 18 similar cases have been reported previously.

It is reported that macrophages and CD4+ or CD8+ cytotoxic T cells have an important role in the suppression of cancer progression. The aim of this study was to clarify these immune responses in patients with esophageal cancer. We enrolled 28 patients with pT2 esophageal cancer that had been resected without preoperative adjuvant therapy. The correlations between the numbers of infiltrating CD4+, CD8+ and CD68+ cells, the expression of heat shock protein 70 (hsp70) and a variety of clinicopathologic factors were analyzed. The numbers of CD8+ T cells and CD68+ macrophages showed a significant positive correlation with tumor diameter (p = 0.01, p = 0.037) and the expression of hsp70 (p = 0.01, p = 0.02) and a negative correlation with lymph node metastasis (p = 0.0079, p < 0.0001). The expression of hsp70 exhibited a negative correlation with lymph node metastasis (p = 0.023). CD8+ T cells and CD68+ macrophages might have a suppressive function against esophageal cancer progression. Our results suggested that hsp70 might play an important role in the presentation of tumor specific antigens.

Recently, neoadjuvant chemotherapy combined with radiation (NAT) has been used in the active treatment of progressive esophageal cancer (T4). However, many patients are resistant to supplemental therapy, and it is necessary to to be aware that side-effects may occur. Accordingly, to minimize adverse reactions and cost, it is important to determine the indications for NAT. We investigated 34 patients with T4 esophageal squamous cell carcinoma and examined the relation between the effects of NAT and immunohistochemical or additional clinicopathologic factors. There was no relation between clinicopathologic factors and immunohistochemical findings (p53 or hsp27 expression), and no clinicopathologic factors showed a relation to a supplemental therapeutic effect. In addition, there was no correlation between p53 staining and therapeutic effects (P=0.734). In contrast, there was a correlation (P=0.0058) between hsp27 staining and therapeutic effect. In conclusion, the usefulness of hsp27 immunostaining in predicting the therapeutic effect of NAT was confirmed in T4 esophageal squamous cell carcinoma.

In Japan, Barrett's esophageal cancer is a very rare disease. We examined clinicopathologically and immunohistologically 4 patients with Barrett's esophageal cancer who underwent surgical resection in our department. Barrett's esophageal mucosa was classified into 3 types for detailed observation. Specialized columnar epithelium (SCE) remained on the orifice side of carcinoma, and progression to adenocarcinoma was observed in some dysplastic glands. positive findings were detected on p53 immunohistochemical staining, and the ki-67 labeling index was higher than other types. SCE-type Barrett's esophagus may be a precancerous lesion arising prior to the development of adenocarcinoma.

We examined the immunohistochemical expression of proliferating-cell nuclear antigen (PCNA) and p53 proteins in dysplasia and intramucosal carcinoma of the esophagus. Immunohistochemistry was performed with monoclonal antibodies directed against PCNA and p53. We used surgically resected specimens from 29 patients who had a total of 55 lesions of severe dysplasia (n = 16), intraepithelial carcinoma (n = 21), and mucosal carcinoma (n = 18). The mean PCNA index with immunoreactivity for p53 was 48.9 +/- 6.5 in areas of severe dysplasia (n = 7), 58.2 +/- 7.3 in areas of intraepithelial carcinoma (n = 10), and 71.4 +/- 9.3 in the invasive areas of mucosal carcinoma (n = 10). The mean PCNA index without immunoreactivity for p53 was 41.2 +/- 5.5 in areas of severe dysplasia (n = 9), 48.0 +/- 7.4 in areas of intraepithelial carcinoma (n = 11), and 63.7 +/- 9.1 in invasive areas of mucosal carcinoma (n = 8). The PCNA indices of the areas of severe dysplasia with immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma with immunoreactivity for p53. Similarly, the PCNA indices of severe dysplasia without immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma without immunoreactivity for p53. These results thus suggest that severe dysplasia has a lower proliferative potential than carcinoma and may therefore represent a precancerous lesion.