Concurrent chemoradiation for patients with squamous cell carcinoma of the cervical esophagus.

Little is known concerning the role of concurrent chemoradiation (CCRT) in the management of carcinoma of the cervical esophagus. We retrospectively evaluated our treatment approach for patients with cervical esophageal cancer with special emphasis on CCRT with or without surgery. Medical records of 21 consecutive patients with cervical esophageal carcinoma treated mainly with CCRT (1997-2004) were reviewed, and factors that influenced patient survival were analyzed retrospectively. Nineteen received CCRT with cisplatin/5-fluorouracil and five underwent curative surgery. Two patients who were deemed unfit for CCRT received radiation therapy alone. All had three-dimensional treatment planning (median total dose, 40 Gy with surgery, 64 Gy without surgery). Of the 19 patients who received CCRT, 11 patients including five who underwent curative surgery achieved initial local control. Neither of the two patients who received radiation therapy alone achieved local control. Among 19 patients who underwent CCRT, 9/11 with T1-3 grade tumors achieved initial local control, but only 2/8 patients with T4 tumors (P = 0.011, chi(2) test) achieved initial local control. No patient without initial local control survived > 20 months compared with 2-year and 5-year survival rates of 60% and 40% in those who achieved initial local control (P = 0.038). No patient with T4 tumors survived > 18 months, whereas 2- and 5-year survival rates were 62% and 41%, respectively, in those with T1-3 tumors (P = 0.006). The significant effect of T-classification on survival was maintained when analyzed among 19 patients who received CCRT. CCRT shows promise for cervical esophageal carcinoma. T-classification and initial local control had significant impact on survival.

Development of less invasive surgical procedures for thoracic esophageal cancer.

In order to minimize the invasiveness of the operative procedure for thoracic esophageal cancer, several procedures have been introduced since January 1997. They included: (i) perioperative use of steroids; (ii) muscle-sparing thoracotomy without costectomy; (iii) preparation of the gastric tube with preservation of sufficient blood supply; (iv) reconstruction of the alimentary tract via posterior-mediastinal route; and (v) formation of anastomosis between the remaining esophagus and the gastric tube at a location between the gastroepiploic arteries of the gastric greater curvature. Twenty-one patients who did not receive preoperative chemoradiotherapy underwent the newly developed procedure, and were compared with those receiving the original procedure. Hospital mortality was zero, and postoperative systemic inflammatory response syndrome was suppressed. The mean postoperative hospital stay was 21.5 days, and the actuarial 3-year survival rate was 76.2%. From the comparison with those receiving the original procedure, it can be concluded that the newly developed procedures were effective in minimizing surgical invasiveness and were sufficiently curative in terms of cancer treatment.

Prognostic value of preoperative serum immunosuppressive acidic protein in patients with esophageal squamous cell carcinoma.

Immunosuppressive acidic protein (IAP) is a potent biological marker of immunological surveillance in patients with malignant tumors. The aim of this study was to analyze the clinicopathologic significance of IAP in patients with esophageal carcinoma. Preoperative serum IAP concentration was measured by enzyme-linked immunosorbent assay in 115 patients with primary esophageal squamous cell carcinomas. The associations between clinicopathologic factors, C-reactive protein (CRP) values and IAP concentration were determined. Prognostic values were determined by multivariate analysis using Cox's proportional hazards model. The IAP concentration is significantly higher in patients with stage II-IV cancers than in those with stage I cancer. Significant differences in IAP concentration were observed depending upon tumor size, tumor depth, lymph node status and CRP values. A high IAP concentration, more than 500 micro g/mL, was an independent prognostic factor. Thus, a high IAP concentration is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma.

The ability to predict patients' responses to chemoradiotherapy by analyzing pre-treatment biopsy specimens would be valuable for managing oesophageal squamous-cell cancer. To this end, the expression of p53, thymidine phosphorylase and vascular endothelial cell growth factor was analyzed by immunohistochemistry in 52 patients with oesophageal squamous-cell cancer prior to chemoradiotherapy. Treatment consisted of radiotherapy (40 Gy) and 5 day-infusion of 5-Fluorouracil (500 mg m(-2) per day) combined with cisplatin (10 mg m(-2) per day). Following treatment, imaging and endoscopic reassessment was performed to establish treatment response. Thirty-one patients underwent radical surgery and 21 patients were treated with an additional 20 Gy of radiotherapy. Of the tumours studied, 58% were p53-positive, 40% thymidine phosphorylase-positive and 44% vascular endothelial cell growth factor-positive. A clinical response was observed in 36 patients (69%) and was negatively associated with thymidine phosphorylase expression (P=0.02) and vascular endothelial cell growth factor expression (P<0.001). However, the 5-year survival rate was significantly lower only in patients with vascular endothelial cell growth factor-positive tumours (P=0.037). Multivariate analysis identified vascular endothelial cell growth factor as a significant independent prognostic factor (P=0.0147). These results suggest that expression of angiogenic factors has predictive value for the treatment response and outcome of patients with oesophageal cancer.

Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S-VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S-VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma. METHODS: Pretreatment S-VEGF was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96 patients with esophageal squamous cell carcinoma (82 patients with primary tumors and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients followed by response evaluation. RESULTS: S-VEGF was found to be significantly elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant differences were observed when S-VEGF was categorized by tumor size (P = 0.0002), tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis (P = 0.028), and International Union Against Cancer TNM stage (P < 0.0001). The patients who achieved a partial or complete response to chemoradiotherapy showed significantly less S-VEGF than those patients who were nonresponders (P = 0.018). A high (> 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001). Multivariate analysis found S-VEGF to be a significant and independent prognostic factor (P < 0.001). CONCLUSIONS: In the current study, a high S-VEGF was found to be associated with tumor progression, poor treatment response, and poor survival in patients with squamous cell carcinoma of the esophagus.

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer.

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer.

Chemoradiation for patients with esophageal cancer aged 80 and older.

BACKGROUND: The objectives of this study were to evaluate the efficacy and toxicity of concurrent chemoradiation in patients with esophageal cancer aged 80 and older. PATIENTS AND METHODS: Seven patients with esophageal cancer, aged 80 or more were treated with chemoradiation. Five received a systemic combination of cisplatin and 5-fluorouracil while 2 received daily 5-fluorouracil, concurrent with radiotherapy. The total doses of radiotherapy ranged from 50 to 65 Gy. RESULTS: Complete response was obtained in 3 patients, and partial response and no change in 2 cases each. Esophageal passage improved in 4 patients. The treatment was well-tolerated. There was no death attributable to any adverse treatment effects. None of the patients experienced grade 3 or worse acute toxicities. CONCLUSION: This study demonstrated that advanced age per se is not a sufficient reason to exclude elderly patients from aggressive treatment.

Clinical benefits of steroid therapy on surgical stress in patients with esophageal cancer.

BACKGROUND: Despite improvements in surgical techniques and perioperative care, severe complications lead to long hospital stays for some esophageal cancer patients. The purpose of this study was to evaluate the safety and effectiveness of perioperative steroid therapy on the postoperative clinical course. METHODS: Fifty-seven patients operated for esophageal cancer in 1997 and 1998 were treated with perioperative steroid therapy. Fifty consecutive patients operated in 1995 and 1996 served as a control group. In the steroid group, each patient was given 250 mg of methylprednisolone intravenously before operation followed by 125 mg on postoperative days 1 and 2. Serum interleukin-6, polymorphonuclear cell elastase, and C-reactive protein levels, and the postoperative clinical course were compared between the groups. RESULTS: Morbidity rates including hyperbilirubinemia, anastomotic leakage, and liver dysfunction were significantly lower in the steroid group than in the control group. Days until extubation and hospital stay were significantly shorter for the steroid group. Inflammatory mediators, body temperature, heart rate, and respiratory index after the surgical procedure were significantly lower in the steroid group. Adverse effects possibly caused by steroid therapy were not observed. CONCLUSIONS: Perioperative steroid therapy was safe and effective for the inhibition of inflammatory mediators and the improvement of the postoperative clinical course of patients with esophageal cancer.

Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma.

BACKGROUND: Patients with superficial (mucosal or submucosal) esophageal carcinoma (SEC) have significantly better survival rates than patients with advanced carcinoma. Some patients with advanced esophageal carcinoma have been reported to test positive for serum p53 antibodies (Abs). Because very few patients with superficial carcinoma have been examined, the aim of this study was to evaluate the clinical significance of serum p53-Abs in patients with superficial esophageal squamous cell carcinoma (SESCC). METHODS: Thirty-five consecutive patients with SESCC were studied for serum p53-Abs by enzyme-linked immunoabsorbent assay before and after treatment. The clinicopathologic features of p53 seropositive and p53 negative patients were compared. The relation between the presence of serum p53-Abs and p53 immunoreactivity of the resected specimens was examined. Three tumor markers (squamous cell carcinoma antigen [SCC-Ag], CYFRA21-1, and carcinoembryonic antigen [CEA]) were assessed to compare their sensitivities with serum p53-Abs. RESULTS: Fourteen of 35 patients (40%) were p53 seropositive. Relatively few patients tested positive for the other tumor markers: CEA, 11.4%; SCC-Ag, 14.3%; CYFRA21-1, 5.7%. There were no significant correlations between clinicopathologic features and p53 seropositivity except for tumor location. A strong correlation between p53 immunostaining and the presence of serum p53-Abs was observed (P = 0.003). Of the 14 patients with seropositive results, 12 turned seronegative after resection, and the other 2 experienced disease recurrence. CONCLUSIONS: Surveillance of serum p53-Abs is superior to the three tumor markers for detecting SESCC. This serum marker is also useful for the detection of p53 protein overexpression and for the monitoring of residual tumor cells.

Hemoperitoneum secondary to exophytic leiomyoma: report of a case.

We report herein the case of a 63-year-old male with hemoperitoneum secondary to exogastric leiomyoma. The patient had been receiving anticoagulation therapy for a cerebral embolism and complained of sudden, severe abdominal pain. A sonogram and computed tomography scan showed an exogastric mass and massive ascites. A peritoneal puncture proved the presence of an intraperitoneal hemorrhage. An emergency laparotomy revealed a pedunculated bleeding tumor, thus confirming the preoperative diagnosis of a ruptured exogastric tumor. A microscopic analysis of the excised tumor demonstrated gastric leiomyoma. Other authors have reported hemoperitoneum secondary to gastric myogenic tumors, but no cases of leiomyomas could be found in the literature.

Diffuse schwannoma involving the entire large bowel with huge extramural development: report of a case.

Schwannoma of the large bowel is a rare clinical entity, which has reportedly been recognized to arise from one place with a submucosal tumor morphology. We present herein the unique case of a 25-year-old woman who suffered from a schwannoma diffusely involving the entire large intestine. The patient complained of abdominal distension and imaging studies revealed a giant tumor occupying the whole abdomen, but no confirmed preoperative diagnosis could be made. A laparotomy proved the huge tumor detected preoperatively to be the markedly wall-thickened entire large bowel itself due to the diffuse extramural development of a neoplasm, but no other organs were involved. Biopsy specimens from the tumor were histologically diagnosed as benign schwannoma. However, because of the possibility of malignancy, we later performed a total proctocolectomy followed by an ileal J-pouch-anal canal anastomosis. The final pathological diagnosis was also that of a benign schwannoma originating from the large intestine. The patient remains well without recurrence 15 months after surgery. To the best of our knowledge, no such case of a schwannoma in the entire large bowel has yet been reported in the literature, and the pathogenesis of its occurrence remains unknown.

Acidic fibroblast growth factor is progressively increased in the development of oesophageal glandular dysplasia and adenocarcinoma.

AIMS: To determine by immunohistochemistry and amplification of cDNA the relationship between fibroblast growth factor (FGF) expression and progressive changes in Barrett's oesophagus associated with oesophageal adenocarcinoma (OA). The FGFs are potent mitogens that possess angiogenic properties and the capability to regulate growth and differentiation of various cell types. They have also been implicated in the development and progression of numerous solid tumours, including some carcinomas of the aerodigestive tract, such as nasopharyngeal carcinoma and pancreatic adenocarcinoma. MATERIAL AND RESULTS: We studied the expression of the two prototypic FGFs, acidic FGF (FGF-1) and basic FGF (FGF-2), in OA and OA precursor lesions, including intestinal metaplasia (IM), low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Fresh tissue from 10 OAs and four associated HGDs was available for the determination of FGF-1 and FGF-2 mRNA expression accomplished by the PCR amplification of cDNA. Using immunohistochemistry, we studied the expression of the FGF-1 and FGF-2 proteins in archival, paraffin-embedded tissue that was available from 17 oesophageal resection specimens that included OAs and OA precursor lesions. As compared to gastric fundic mucosal controls, OAs and HGDs showed significantly enhanced expression of FGF-1 mRNA and protein. IMs and LGDs showed significantly lesser degrees of FGF-1 immunoreactivity that were not increased over controls. In contrast, both the overall percentage of FGF-2-reactive OAs and the overall FGF-2 protein expression, assessed using an immunoreactivity score, are comparable to FGF-2 expression in controls. CONCLUSIONS: It appears that FGF-2 is ubiquitously expressed in OA and in normal oesophageal and gastric mucosa while significant FGF-1 expression is essentially restricted to HGD and OA. Our data also suggest that FGF-1 is sequentially upregulated in the progression from metaplasia to dysplasia and adenocarcinoma.

Metastatic malignant meningioma of the liver with hypoglycemia: report of a case.

We herein present the case of a 68-year-old male who suffered an episode of hypoglycemic shock 2 years after undergoing total removal of a bifrontal parasagittal malignant meningioma. Imaging studies revealed three giant hypervascular tumors with a cystic portion in the right lobe, but no confirmed preoperative diagnosis could be made. At laparotomy, liver tumors were found in the medial segment of the left lobe as well as in the right lobe, and thus an extended right lobectomy was performed. All the resected tumors were histologically diagnosed as metastatic malignant meningiomas of the liver. Despite subsequent transarterial chemoembolization for a recurrence in the residual liver, the patient died 11 months after surgery. To the best of our knowledge, only one other case of a hepatectomy for liver metastases from an intracranial malignant meningioma has been reported in the literature, but there has never been any report of surgical treatment for a metastatic meningeal tumor in the liver associated with hypoglycemia. Although our surgical treatment provided effective palliation, the prognostic significance of a surgical strategy for such patients has yet to be established.

Rapid Intraoperative Scrape Cytology Assessment of Surgical Margins in Breast Conservation Surgery.

Rapid intraoperative scrape cytologic examination for diagnosing surgical margin involvement of specimens obtained by breast conservation surgery was evaluated. Four surgical margins(nipple side, two lateral sides and distal side)of the removed breast tissue were cytologically examined and histologically compared following segmentectomy in 50 breast cancer patients(200 margins). Intraductal carcinoma had a tendency to spread most extensively to the nipple, compared with other margins. The margin positive rate of tumors with ductal spread(DS)of over 20mm was significantly higher than in tumors with a DS under 20 mm(52.2% vs 7.4%)(P < 0.001). of 50 canditates 10 patients underwent total mastectomy due to positive margins on repeat cytologic examination after re-excision. Four of the 10 patients had an extensive intraductal component on microscopy. The sensitivity, specificity and accuracy of cytology were 96.4 %, 90.7% and 91.5%, respectively.Scrape cytology is useful to determine surgical margin involvement after segmentectomy for breast cancer, although overestimation of involvement will tend to result.

Occult Breast Cancer: A Case Report and Review of the Literature.

We report a case of a 44-yar-old woman with occult breast cancer presenting as an axillary mass in whom sonography was able to detecct an involved internal mammary node also, thus helping to establish a diagnosis of breast cancer. The patient underwent extended radical mastectomy, including internal mammary lymphadenectomy. Microscopy of the removed specimen failed to find a primary breast cancer lesion. Metastatic cancer was seen in the palpable axillary node, another resected axillary node and a removed internal mammary node. The estrogen and progesterone receptor analysis of the axillary node were negative. Since occult breast cancer was found highly potential for metastasizing to the infraclavicular or internal mammary nodes, it is reasonable to treat such patients in the same way as those with palpable breast cancer, with adjuvant chemotherapy.

The mutational status of p53 protein in gastric and esophageal adenocarcinoma cell lines predicts sensitivity to chemotherapeutic agents.

Resistance to chemotherapy remains a serious problem in the successful treatment of gastric and esophageal cancers. DNA-damaging agents alter levels of p53 protein in several cell types and it has been speculated that regulation of p53 can be involved in the resistance or sensitivity of cancer cells to some chemotherapeutic drugs, depending on whether cells have mutant or wild-type p53; however, little is known about the relationship of p53 to drug sensitivity in gastric/esophageal cancers. Here we have examined human gastric/esophageal adenocarcinoma cell lines for p53 mutational status, chemosensitivity to 5-fluorouracil, mitomycin C, and cis-dichlorodiammineplatinum(II), alteration in p53 levels following exposure of cells to these drugs, and the mechanisms involved in regulating p53 levels. Our results indicate that wild-type p53 protein levels increase after treatment with each of these drugs via either post-translational and/or translational mechanisms and that this increase in wild-type p53 appears to be required for effective chemotherapeutic growth control of gastric/esophageal adenocarcinoma cells. In contrast, gastric/esophageal cancer cells expressing either mutated p53 protein or no p53 protein are more resistant to the growth-inhibitory effects of these drugs, despite the fact that drug exposure can also increase mutant p53 levels by a translational mechanism. Thus, these data indicate that the mutational status of p53 is predictive of chemosensitivity of gastric and esophageal adenocarcinomas, and suggest a mechanism in which p53 protein contributes to the cellular response to chemotherapy.

[A clinical evaluation of reconstruction methods after pancreatoduodenectomy from a view of fat digestion and absorption].

The purpose of this study was to evaluate the reconstruction methods of modified Imanaga procedure and modified Child procedure from a point of fat digestion and absorption in patients who received pancreatoduodenectomy by using 13C-labelled medium chain fat. The 13CO2 abundances were elevated rapidly after oral ingestion of 13C-octanoic acid and 13C-trioctanoin in modified Imanaga procedure group. The peak 13CO2 abundances appeared earlier in modified Imanaga procedure group than in modified Child procedure group. No significant difference was seen between two groups in the percent recovery of 13CO2 in the breath after oral loading of 13C-octanoic acid. But modified Imanaga procedure group showed significantly higher recovery rate of 13CO2 of 13C-trioctanoin when compared to modified Child procedure group. These results suggest that modified Imanaga procedure would have a benefit for fat digestion and absorption after pancreatoduodenectomy.

Ribose-transfer activity from uridine to 5-fluorouracil in Ehrlich ascites tumor cells.

Anabolism of 5-fluorouracil (5-FU) in the presence of uracil was examined using the cell-free extract of Ehrlich ascites tumor cells. FU-nucleoside formation from 5-FU with ribose 1-phosphate (R-1-P) or 2'-deoxyribose 1-phosphate was not readily inhibited even by the addition of uracil at 100 times higher concentration than 5-FU. FU-nucleotide formation from 5-FU with R-1-P and adenosine 5'-triphosphate or with 5-phosphoribosyl 1-pyrophosphate was slightly reduced as the concentration of uracil was increased. It was also found that 5-fluorouridine (5-FUR) was produced by "nucleoside N-ribosyltransferase," transferring a ribose moiety from uridine (UR) to 5-FU directly. This activity might play a role in the preferential formation of 5-FUR. However, 5-fluoro-2'-deoxyuridine was not produced by directly transferring a deoxyribose moiety. On the basis of several column chromatographies and characterization of kinetics, pH dependency, and response to inhibitors, the enzyme protein of the ribosyltransferase could not be distinguished from that of the phosphorylase.

[Effect of high dose etoposide, adriamycin, cisplatin (EAP) therapy with autologous bone marrow transplantation in gastric cancer].

A clinical usefulness of high dose EAP therapy with autologous bone marrow transplantation for gastric cancer was investigated. Three patients with advanced gastric cancer (one recurrent and 2 inoperable) with measurable lesions were treated with high dose EAP therapy consisting of VP-16 1200 mg/m2, ADM 80 mg/m2 and CDDP 80-120 mg/m2, and then 1 x 10(7)/kg of cryopreserved autologous bone marrow cells were transfused intravenously. All patients were recovered from aplastic period without any severe complications. Measurable lesions, namely, stenosis of prepyloris lesion, lymph node metastasis and invasion into pancreas in 3 patients with gastric cancer were reduced or diminished. It seemed that high dose EAP therapy with autologous bone marrow transplantation was safe and an useful strategy, especially for advanced gastric cancer.