Reflux esophagitis after esophagectomy: impact of duodenogastroesophageal reflux.

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

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

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

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

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

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

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

Surgical management for small cell carcinoma of the esophagus.

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

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

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

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

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

Endoscopic classification for reflux pharyngolaryngitis.

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

Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer.

AIMS: 5-Fluorouracil (5-FU) is one of the most widely used anticancer drugs; however, the activity of 5-FU is determined by the presence of several enzymes that limit its activation or degradation, and these include dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), thymidine kinase (TK), thymidine phosphorylase (TP) and deoxyuridine triphosphatase (dUTPase). The aim of this study was to compare the expression levels of these enzymes between the primary colorectal cancer of patients with and without distant metastases. Furthermore, there was a comparison of these expression levels between the primary tumour and the corresponding metastasis. METHODS: Of 55 patients with colorectal cancer, 20 had no metastasis and the other 35 had distant metastasis. A strong expression was classified as positive, while weak to moderate or no expression was negative by immunohistochemistry. RESULTS: Of the six 5-FU-related enzymes, the numbers of patients with expression of dUTPase (54% versus 15%; p = 0.005), TK (26% versus 0%; p = 0.019) and DPD (17% versus 45%; p = 0.033) were significantly different in those with primary tumours with metastasis compared with those with non-metastasis, respectively. The altered expression of OPRT (34.3%), TS (40.0%) and dUTPase (42.9%) was significantly greater from primary to metastasis among the 35 patients with metastasis. By contrast, the expression of OPRT, TS and dUTPase was decreased in 6, 5 and 7 patients, respectively, in metastatic sites. CONCLUSIONS: From this comparative study of the six 5-FU-related enzymes in colorectal cancer, the expression of dUTPase was most significantly different between primary tumours and their corresponding metastatic tumour. It is suggested that dUTPase may be a predictive biomarker for the metastatic potential of colorectal cancer.

Helicobacter pylori infection influences the acidity in the gastric tube as an esophageal substitute after esophagectomy.

It is commonly considered that acidity in a gastric tube used as an esophageal substitute after esophagectomy decreases due to truncal vagotomy. However, there have been few, if any, studies on the factors influencing the acidity in the gastric tube. It is well known that Helicobacter pylori (H. pylori) plays an important role in acid secretion of the stomach. The aim of this study was to investigate whether or not H. pylori infection also influenced the acidity in the gastric tube as an esophageal substitute. We investigated the changes in the levels of gastric acidity and the status of H. pylori infection from the preoperative period to 1 year after surgery. In 65 Japanese patients who underwent resection of esophageal cancer followed by reconstruction using a gastric tube, 24-h gastric pH monitoring and examination of H. pylori infection using the 13C-urea breath test and biopsy specimen obtained from the gastric mucosa under upper gastrointestinal endoscopy were performed pre- and postoperatively. Twenty-seven among the 65 patients underwent the same examinations at 1 year after surgery. The levels of postoperative gastric acidity and at 1 year after surgery were significantly lower than that of preoperative gastric acidity (P = 0.031, P = 0.001, respectively). There was no difference in the levels of gastric acidity between 1.5 months and 1 year after surgery (P = 0.282). The levels of gastric acidity in the stomach and in the gastric tube were significantly influenced by H. pylori infection, while age, gender, and past history of peptic ulcer showed no influence. The level of gastric acidity in patients who had H. pylori infection pre- and postoperatively were significantly lower than that in patients who had no H. pylori infection pre- and postoperatively (P < 0.0001). H. pylori infection was indicated to be an important factor influencing the levels of gastric acidity in the reconstructed esophagus as well as in the stomach before surgery.

Functional outcome after sphincter excision for ultralow rectal cancer.

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

Identification of EGFR mutations in esophageal cancer.

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

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

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

Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma.

Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group protein family, plays a crucial role in the regulation of embryonic development and has been associated with the regulation of the cell cycle. Recently, several studies have shown that EZH2 is highly expressed in aggressive tumours, including human breast cancer, prostate cancer, and lymphomas. We thus analysed EZH2 expression using real-time reverse transcription-polymerase chain reaction, and correlated its expression status with various clinicopathological parameters in 66 patients with hepatocellular carcinoma (HCC). We found high expression of EZH2 in human liver cancer cell lines. Furthermore, EZH2 gene-expression levels in tumour tissue specimens (0.34+/-0.52) were significantly higher (P<0.0001) than those in the corresponding nontumour tissue specimens (0.07+/-0.09). The incidence of cancer cell invasion into the portal vein was significantly higher (P<0.001) in the high EZH2 expression group (26 of the 33, 79%) than in the low expression group (13 of the 33, 39%). However, there was no significant difference in the disease-free survival rate between the two groups. The findings of this study indicate that EZH2 mRNA expression was upregulated in human HCC and may play an important role in tumour progression, especially by facilitating portal vein invasion.

A new ultimate anus-preserving operation for extremely low rectal cancer and for anal canal cancer.

To avoid permanent colostomy, we perform a new ultimate anus preserving operation for extremely low rectal cancer or for anal canal cancer. According to our pathologic study, two different removal methods of anal canal were theoretically considered. One is internal sphincter resection (ISR method), and the other is both deep-superficial external sphincter and internal sphincter resection (ESR method). Six patients received ISR and ten patients ESR. No severe intraoperative complications occurred and the postoperative course was uneventful. All patients receiving ISR had excellent anal function without soiling. Some patients receiving ESR sometimes complained of night soiling but satisfied the anus preservation. The median follow-up was 15 months, (range, 3-28 months). We had recurrences in two female patients receiving ISR. One had para-aortic and lateral lymph node recurrences without anastomotic recurrence. She underwent lateral and para-aortic lymphadenectomy, but died of lung metastasis, regardless of intensive chemotherapy. Another had pelvic recurrence with abdominal dissemination. She underwent abdominoperineal resection and is alive with pelvic re-recurrence. ISR and ESR are excellent procedures for anus preservation, but ISR needs a strict indication.

Esophageal perforation caused by a press through pack.

A 73-year-old woman complaining of sudden hoarseness visited our hospital 17 days after the onset. The upper gastrointestinal contrast study showed a shallow ulcer crater with moderate bulging in the upper thoracic esophagus. Endoscope and computed tomography revealed an esophageal foreign body, a Press Through Pack (PTP), in the esophageal ulcer. The PTP could be removed endoscopically. Two months after extraction of the PTP, the patient was taking normal food orally and was discharged. The esophageal perforation, looking like a diverticle, was still present more than 1 year after the onset.

Video-assisted gasless transanal endoscopic microsurgery: a review of 217 cases of rectal tumors over the past 10 years.

BACKGROUND: Transanal endoscopic microsurgery (TEM) has been suggested as a minimally invasive procedure of low morbidity for rectal tumor excision. However, the complicated setup of TEM instruments and the expensive cost are disadvantages to wider acceptance. The aims of this study are to introduce a new modality of modified video-assisted gasless TEM (V-TEM) using a video system and no CO(2) insufflation of the rectum, and discuss our experience during past 10 years. METHODS: 217 patients, with a mean follow-up of 61 months, underwent V-TEM for adenoma (n = 102), Tis (n = 83), T1 (n = 28) and T2 (n = 4) rectal tumors, located 3-20 cm from the dentate line. RESULTS: The mean size of the tumor was 39 mm, and the mean duration of the operation was 63 min including setup time, and the mean duration of hospital stay was 5.8 days. Seven (3.2%) patients underwent conversion to radical surgery owing to T1 with massive invasion or T2 tumors histopathologically. Two (0.9%) patients had recurrent disease which was managed by repeat V-TEM. The postoperative course in all patients was free from any significant complications. Transient fecal soiling was present in 12 (5.5%) patients. The cost of V-TEM was decreased compared to that of conventional TEM (USD 40000). CONCLUSION: V-TEM was a cheap, safe, simple and minimally invasive procedure for benign and early cancer in the proximal rectum.

A novel strategy for remission induction and maintenance in cancer therapy.

The p53 tumor suppressor gene plays an important role in protecting cells from developing undesirable proliferation. The mutant p53 gene or malfunctioning p53 protein found in more than 50% of cancer cells impedes DNA repair or apoptosis induction. This may be why some cancers gain resistance to chemotherapy and radiation and become more resistant after frequent cancer treatments. A non-toxic p53 gene activator would induce cancer cell apoptosis and help damaged cancer cells to recover. Therefore, the combination use of chemotherapeutics or radiation with a non-toxic p53 gene activator will be crucial in cancer therapy, damaging DNA with chemotherapeutics or radiation on the one hand and promoting apoptosis induction with p53 gene activator on the other. This strategy would be most efficient for remission induction and maintenance in cancer therapy. Antineoplastons are naturally occurring peptides and amino acid derivatives that control neoplastic growth. Antineoplaston A10 and AS2-1 are chemically identified and synthesized antineoplastons proven to inhibit cancer cell growth by arresting the cell cycle in the G1 phase and inhibiting tumor growth by reducing mitosis. These agents are thought to be good candidates for clinically easily applicable non-toxic p53 gene activators. Our cases of advanced cancer responded well to combination treatment using chemotherapeutics and irradiation with antineoplaston A10 and AS2-1 in clinical trials being conducted in Kurume University Hospital. We describe herein the clinical cases and discuss the possible mechanism of action of this combination therapy.

[A case of lung metastasis from colon cancer treated successfully with combined chemotherapy of CPT-11 and 5'-DFUR].

The patient was a 52-year-old woman who had sigmoid colon cancer with liver metastasis and multiple lung metastases. Resection of curability B was performed, and alternating adjuvant chemotherapy consisting of hepatic artery injection of 5-FU and systemic administration of CPT-11 was performed. Lung recurrence was found and no antitumor effect of chemotherapy was observed, so the CPT-11 which had been administered every other week was given every week in a dose of 60 mg/body, half of the original dose. Moreover, 5'-DFUR was administered in a dose of 800 mg/day every day. As a result, lung metastasis tumors were reduced markedly. Adverse events such as nausea, vomiting and depilation were mitigated, and no other toxicity was observed. The patient could thus be treated extremely safely in the outpatient clinic. This was considered to be a valuable case suggestive of the significance of combination chemotherapy of CPT-11 and 5'-DFUR and the importance of appropriate administration of CPT-11.

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

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