Advantages of 70-kV CT Angiography for the Visualization of the Adamkiewicz Artery: Comparison with 120-kV Imaging.

BACKGROUND AND PURPOSE: Preprocedural identification of the Adamkiewicz artery is crucial in patients with aortic diseases. This study aimed to compare 70-kV CTA with conventional 120-kV CTA for the identification of the Adamkiewicz artery, examining differences in radiation dose and image quality. MATERIALS AND METHODS: We retrospectively analyzed 2 equal groups of 60 patients who had undergone 70-kV or 120-kV CTA to detect the Adamkiewicz artery before aortic repair. Size-specific dose estimate, the CT number of the aorta, and the contrast-to-noise ratio of the anterior spinal artery to the spinal cord were recorded. Furthermore, detectability of the Adamkiewicz artery was evaluated by using a 4-point continuity score (3, definite to 0, undetectable). RESULTS: There was significantly lower radiation exposure with 70-kV CTA than 120-kV CTA (median size-specific dose estimate, 23.1 versus 61.3 mGy, respectively; P < .001). CT number and contrast-to-noise ratio were both significantly higher in the 70-kV CTA group than the 120-kV group (999.1 HU compared with 508.7 HU, and 5.6 compared with 3.4, respectively; P < .001 for both). Detectability of the Adamkiewicz artery was not impaired in the 70-kV CTA group (90.0% versus 83.3% in the 120-kV group, P = .28). Moreover, the Adamkiewicz artery was detected with greater confidence with 70-kV CTA, reflected by a significantly superior continuity score (median, 3) compared with 120-kV CTA (median, 2; P = .001). CONCLUSIONS: Seventy-kilovolt CTA has substantial advantages for the identification of the Adamkiewicz artery before aortic repair, with a significantly lower radiation exposure and superior image quality than 120-kV CTA.

Enhanced efficacy of herpes simplex virus mutant HF10 combined with paclitaxel in peritoneal cancer dissemination models.

BACKGROUND/AIMS: Oncolytic viral therapy is used worldwide. Many genetically engineered viruses have been evaluated for their potential as a new therapeutic agent for cancer. HF10, herpes simplex virus (HSV) type-1 clone, has remarkable anti-tumor effects, based on our previous research. In this study, we investigated the ability of HF10 to infect and lyse murine colon cancer cells, CT26, in vitro, and tested its efficacy in an immuno-competent animal model of colorectal cancer. Further, we attempted to evaluate HF10/paclitaxel combination therapy. METHODOLOGY: In vitro, viral replication and cytotoxicity of HF10 against CT26 was observed. In vivo, BALB/c mice harboring carcinomatous peritonitis of CT26 cells were treated with HF10, paclitaxel or HF10 combined with paclitaxel. RESULTS: HF10 is effective for peritoneal dissemination without ascites. The combination of HF10 and paclitaxel prolonged survival of mice bearing carcinomatous dissemination of CT26 compared with the controls, HF10 alone and paclitaxel alone. Paclitaxel did not suppress viral replication and cytotoxicity of HF10. CONCLUSIONS: These results indicate that the combination of HF10 and paclitaxel had a remarkable effect as a cancer therapy and this method is applicable to almost all advanced cancers. This new combination therapy is a potentially epoch-making cancer therapy.

Oncolytic virus therapy--foreword.

We are very pleased and proud to be able to publish this special issue of Current Cancer Drug Targets devoted to oncolytic virus therapy covering basic and clinical research on adenovirus, vaccinia virus, herpes virus, and Newcastle disease virus. In these papers, we welcome the world's top authorities in the field who have generously contributed their latest review articles for exclusive publication in this special issue. Moreover, this issue also includes a range of opinion from government drug organizations. Here we simply wish to bring together the newest knowledge and experience in the field of cutting-edge oncolytic virus therapy for researchers and every kind of cancer therapist. The Foreword presents a historical perspective on the development of oncolytic virus together with the encouraging results of recent clinical trials (e.g., H101 has been tested in clinical trial of nearly 250 patients and approved for human use by the Chinese FDA, while PV701 has been tried in over 110 patients, as described in our special issue).

Clinical experiment of mutant herpes simplex virus HF10 therapy for cancer.

We reviewed our clinical trial using mutant herpes simplex virus "HF10". We have evaluated the safety and effect of HF10 against recurrent breast cancer since 2003 and also applied HF10 to non-resectable pancreatic cancer since 2005. An oncolytic herpes simplex virus type 1, mutant HF10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immunocompetent mouse models. From long time before clinical trial, we have found that the mutant virus can have remarkable potential to effectively treat cancer in experimental studies using animals, and that all of the surviving mice acquire resistance to rechallenge of the tumor cells. A number of studies have shown that HF10 is effective and safe for use in localized or peritoneally disseminated malignant tumors of non-neuronal origin in animals. Pilot studies using HF10 have been initiated in patients with metastatic breast cancer. For each patient, 0.5 ml HF10 diluents at various doses were injected into test nodule, and 0.5 ml sterile saline was injected into a second nodule. All patients were monitored for local and systemic adverse effects, and the nodules were excised 14 days after viral injection for histopathological studies. All patients tolerated the clinical trial well. While no adverse effects occurred, there was cancer cell death and 30-100% regression histopathologically in recurrent breast cancer. As mentioned above, intratumoral injection of mutant herpes simplex virus HF10 for recurrent metastatic breast cancer was safe and effective. Also a trial for non-resectable pancreatic cancer being carried out on the basis of the above result has proved to be innocuous and has been in progress to assess the clinical benefit and enhance the potentiality of HF10 against cancer.

The useful combination of a higher frequency miniprobe and endoscopic submucosal dissection for the treatment of T1 esophageal cancer.

BACKGROUND: There are few published data on the discrimination ability of endoscopic ultrasonography (EUS) among each subdivision of T1 cancer, and overdiagnosis is an unsolved problem that eventually causes overtreatment. The purpose of this study was to verify whether our treatment strategy incorporating EUS realizes a tailored patient management of T1 esophageal cancer. METHODS: This study comprised 20 esophageal cancer patients undergoing 12- to 20-MHz miniprobes for T staging and a 7.5-MHz dedicated echoendoscope for N staging. Initial therapy constituted endoscopic submucosal dissection (ESD) for endosonographically node-negative, mucosal, or slight submucosal cancers and a primary esophagectomy with three-field lymphadenectomy for deeper cancers. If the ESD specimen revealed no cancer involvement of the muscularis mucosa, the patients entered a follow-up program; otherwise, they were advised to undergo a subsequent esophagectomy and three-field lymphadenectomy. RESULTS: Perfect discrimination accuracy was achieved among T1, T2, and T3 cancers. Whether cancer depth was up to the slight submucosal layer or deeper was correctly differentiated in 12 of 14 T1 cancers (86%). EUS categorized all patients correctly into candidates for either ESD or surgery. The pathological cancer depth of the resected specimens revealed that no patients experienced unnecessary overtreatment. CONCLUSIONS: A higher frequency miniprobe is useful for the detailed evaluation of cancer depth, contributing to decision making for treatment options of T1 esophageal cancer. A miniprobe and echoendoscope in combination with ESD provide an appropriately tailored management plan on an individual basis, avoiding unnecessary treatment or indicating radical surgery.

A seasonal variation in the onset of postoperative adhesive small bowel obstruction is related to changes in the climate.

BACKGROUND: Postoperative small bowel obstruction following abdominal procedures is more common in patients who have undergone laparotomy. However, little is known about the influence of climate on the incidence of postoperative small bowel obstruction. METHODS: To evaluate whether seasonal climatic variations are a risk factor for postoperative small bowel obstruction, hospital-based, retrospective case series was designed from medical records of 230 patients suffering from postoperative small bowel obstruction admitted to the Tokyo University Branch Hospital. Detailed analysis of weather charts from the Japanese Meteorological Agency and review of medical records for selected patients who were diagnosed with postoperative small bowel obstruction. The obstruction was diagnosed by abdominal X-ray imaging, clinical examination, and patient interviews. RESULTS: A total of 233 patients diagnosed with postoperative small bowel obstruction were identified. Analysis of the medical records of these 233 patients revealed that the variables associated with an increased risk of postoperative small bowel obstruction included low ambient temperatures of 5-10 degrees C, an increase in air humidity by 40-50% and air pressure of 1010-1015 hPa. CONCLUSION: The typical winter weather in Tokyo is characterised by low temperatures, low humidity and moderate air pressure. These winter climate conditions could be correlated with an increased incidence of postoperative small bowel obstruction in Tokyo during our period.

Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer.

BACKGROUND: No reports have, to date, focused on the relationship between preoperative determination of the depth of invasion and lymph node metastasis. The present study, under the leadership of the Japanese Gastric Cancer Association, was designed to form a basis for decision making in limited treatment for early gastric cancer (EGC). METHODS: From eight major hospitals in Japan, 2672 gastric cancers whose preoperative depth of invasion was mucosal(M-cancer), and 6209 EGCs, consisting of 3584 mucosal(m-) and 2625 submucosal(sm-) cancers, were collected by questionnaire. All registered patients underwent gastrectomy with D1 or more extensive lymphadenectomy between 1985 and 1998. RESULTS: The accuracy of preoperative diagnosis of depth of invasion of M-cancers was 80.2% (2144/2672). However, of the total of 2432 M-cancers in which no nodal involvement was observed intraoperatively (N0), histological examination of the resected specimens confirmed that lymph node metastasis was absent in 2353 (96.8%). The frequencies of lymph node metastasis in early gastric, m-, and sm-cancers were 8.9%, 2.5%, and 17.6%, respectively. Node involvement was associated with a higher frequency of undifferentiated than differentiated histology, as well as with greater tumor size. The incidences of lymph node metastasis in m-cancers with a diameter of less than 4 cm, and in sm-cancers with a diameter below 1 cm were 1.3% (37/2837) and 4.9% (4/82), respectively. These metastases rarely extended beyond the first tier. CONCLUSION: N0 and M-cancers, m-cancers less than 4 cm in diameter, and sm-cancers no larger than 1 cm in diameter may be appropriate indications for limited surgery.

A rare case of alpha-fetoprotein-producing early gastric cancer.

Most of the alpha-fetoprotein-producing gastric cancer is advanced at the time of presentation, and alpha-fetoprotein-producing early gastric cancer is extremely rare. Alpha-fetoprotein-producing early gastric cancer was confirmed by immunohistochemistry and serum analysis of alpha-fetoprotein concentration. Alpha-fetoprotein carbohydrate chain microheterogeneity was further evaluated by lectin binding specificity. A 71-year-old-male patient underwent total gastrectomy due to a depressed type of gastric cancer in the upper third of the stomach. There was no evidence of synchronous liver metastasis and hepatitis. Histological examination revealed that the tumor invasion was limited to the submucosal layer, and that the tumor consisted of both well-differentiated, papillo-tubular growth areas and trabecular and medullary growth areas resembling hepatoid carcinoma. Immunohistochemically, alpha-fetoprotein and cytokeratin localization were confirmed in the cancer cells, whereas simultaneous localization of carcinoembryonic antigen, carbohydrate antigen 19-9, and human chorionic gonadotropin could not be observed. The elevated preoperative serum alpha-fetoprotein concentration (113 ng/mL) promptly decreased to and remained within normal levels postoperatively (3.6 ng/mL). The predominance of a strong-bound fraction with lectin, which was demonstrated by lens culinalis agglutinin affinity chromatography, suggests that the alpha-fetoprotein carbohydrate chain species in the present case was a hepatic type. The patient received adjuvant intravenous chemotherapy consisting of 5-fluorouracil and cisplatin, and has been further supported by oral 5-fluorouracil administration. The patient has been disease free for 15 months following surgery. We report here a rare case of alpha-fetoprotein producing early gastric cancer. The alpha-fetoprotein carbohydrate phenotype analysis helps to consider the primary differentiation of alpha-fetoprotein-producing gastric cancer.

A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis.

Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse collection of intraperitoneal gelatinous fluid is associated with gelatinous implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic metastasis is extremely rare. In addition, an inguinal mass as an initial presentation is also relatively rare. This is a case report of a PMP patient who had splenic metastasis and showed an inguinal tumor as an initial presentation. A 59-year-old female patient, who had undergone bilateral oophorectomy because of a ruptured ovarian mucinous tumor of boderline malignancy 12 years previously, presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed tomography revealed a low density mass in the pelvic cavity and in the inguinal lesion, as well as in the spleen without any diseases around the organ. The preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and appendectomy, as well as left inguinal herniorrhaphy. Histological examinations revealed a splenic metastasis of PMP originating from the ovarian low-grade mucinous tumor. She received postoperative intraperitoneal lavage as well as chemotherapy, and has survived for over 7 years postoperatively without any evidence of recurrence, as confirmed by repeated follow-up CT examinations and CEA determination. Splenic metastasis of PMP is extremely rare; this represents only the third reported case of its kind in the literature. Furthermore, it should be noted that an inguinal tumor can sometimes be an initial presentation of PMP.

Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells.

Antigen capturing in the skin and antigen trafficking into regional lymph nodes (LN) initiate immune responses. In this study, employing melanin granule (MG) as an easily traceable antigen in two mouse strains that carried steel factor or hepatocyte growth factor transgenes and had melanocytosis in the epidermis or in the dermis respectively, we investigated the mechanism of antigen trafficking from the skin. MG captured in the epidermis or dermis accumulated in the regional LN, but not other tissues. Only in alymphoplastic mice did MG-laden cells pass through the lymphatics and reached many tissues. Since inflammatory regions were not observed in the skin of either type of transgenic mouse, our developmental system enables us to investigate constitutive capturing and trafficking of insoluble antigens in the steady state. Both dendritic cells and macrophages were laden with MG in the regional LN. To determine which cells traffic antigens to the LN, we prepared double mutants that carried the transgenes and lacked transforming growth factor (TGF)-beta1, since mice lacking TGF-beta1 are reported to be deficient of Langerhans cells. Few MG were observed in the regional LN of these double-mutant mice. We also showed that signaling via macrophage colony stimulating factor receptor or Flt3/Flk2 is not essential for development of the cells for this antigen trafficking. These results indicate that antigens in the epidermis and dermis in the steady state are trafficked into regional LN only by TGF-beta1-dependent cells, which may be a dendritic cell lineage.

Results of local resection with regional lymphadenectomy for early gastric cancer.

BACKGROUND: In 1999, the authors reported preliminary results of local resection with regional lymphadenectomy(LR) for early gastric cancer. METHODS: Twenty-four patients underwent LR until May 2000. Laparoscopic techniques were recently applied. The dissected area for lymphadenectomy depended on the lymphatic flow from the tumor. Local gastric resection was performed with a 2 cm cancer-free margin. Among the 24 patients, 14 who had been followed up for more than 1 year were eligible for the nutritional study, and the nutritional parameters were compared with those for patients undergoing pylorus-preserving gastrectomy (PPG). RESULTS: Twenty-two patients not receiving additional gastrectomy needed no restriction of food intake and had neither postgastrectomy symptoms nor recurrence. All nutritional parameters remained stable between the preoperative and the subsequent period. Nutritional superiority of LR over PPG was observed. CONCLUSIONS: For selected patients with early gastric cancer, LR can be a treatment of choice to provide a good quality of life.

Wider indications for the local resection of gastric cancer by adjacent lymphadenectomy.

BACKGROUND AND OBJECTIVES: A variety of minimal invasive treatment strategies for early gastric cancer without reducing the curability have been introduced, however, the indications for the local resection of early gastric cancer have not been precisely established. METHODS: Two approaches are adopted in this study to elucidate indications for local resection. One is a retrospective review of surgically resected, postoperatively histologically proven early gastric cancers between 1976 and 1996 (611 patients), and the other is the patient selection from those who underwent modified D(1) lymphadenectomy in a prospective manner between 1987 and 1996, based on the preoperative and intraoperative diagnoses of mucosal, node negative, nonpalpable gastric cancer (125 patients). In these approaches, patterns of nodal involvement in association with clinicopathological characteristics of gastric cancer were investigated. RESULTS: The depressed with ulceration type and histologically high grade type were predominant characteristics of mucosal, node positive gastric cancer patients. Of these patients, after the exclusion of those who were diagnosed to have submucosal or advanced cancer preoperatively or who had palpable cancer intraoperatively, the gastric cancer < or =4 cm in maximum diameter had positive nodes confined to only one station adjacent to the cancer without simultaneous nodal involvement in the other stations. CONCLUSIONS: Local resection can be performed for gastric cancers < or = 4 cm in maximum diameter that meet our criteria for modified D(1) lymphadenectomy, in association with the frozen section confirmation of cancer negative in the simultaneously dissected lymph nodes in the stations adjacent to the cancer. The adjacent lymphadenectomy and frozen section examination make the application of local resection possible for a wider segment of patients.

Increased angiogenin expression in gastric cancer correlated with cancer progression.

PURPOSE: The purpose of this study is to elucidate the expression of angiogenin and its previously undemonstrated clinical significance in gastric cancer (GC). METHODS: Angiogenin expression was examined immunohistochemically in 21 GC tissues and 21 corresponding normal gastric tissues. The serum concentration was determined by enzyme-linked immunosorbent assay (ELISA) in GC patients preoperatively (n = 48) and postoperatively (n = 41), in nonneoplastic patients preoperatively (n = 23) and postoperatively (n = 19), and in 32 healthy volunteers. The amount of angiogenin in the tissue of 21 GC patients was also determined by ELISA. RESULTS: Angiogenin expression was observed in GC cells as well as in some fundic glandular cells and some inflammatory cells. The mean serum concentration in GC patients (407.8 +/- 105.2 ng/ml) was significantly higher than that in the nonneoplastic patients (345.7 +/- 58.3 ng/ml; P < 0.003) and in the healthy volunteers (333.0 +/- 59.3 ng/ml; P < 0.0002). The mean serum angiogenin concentrations were progressively higher in the order T1 + T2 (P < 0.04) < T3 + T4 (P < 0.0001) < recurrent GC (P < 0.05) subgroups, in the order node-negative (P < 0.05) < node-positive (P < 0.0002) subgroups, and in the order stage I +II (P < 0.02) < stage III and over (P < 0.0005) subgroups as compared with those in the healthy volunteers. These elevated serum angiogenin concentrations in each subgroup were significantly (P < 0.0003) reduced after cancer resection. The amounts of angiogenin in GC tissues correlated significantly with the serum angiogenin concentration (P < 0.01). CONCLUSIONS: These results suggest that angiogenin expression is increased in GC and that the increased serum concentration in GC patients correlates with cancer progression.

Feasibility of daily concurrent chemoradiation therapy as nonsurgical management for esophageal cancer: our experience and theoretical background.

BACKGROUND AND OBJECTIVES: Many combination patterns of chemotherapy and radiotherapy (chemoradiation therapy; CRT) for the treatment of esophageal cancer indicate that the optimal doses of chemotherapeutic agents and of chemotherapy and radiotherapy regimens remain unclear. The feasibility and promising outcome of our newly developed definitive CRT for nonsurgical management of esophageal cancer, essentially based on the theoretical backgrounds of the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, is investigated. METHODS: Six nonoperated esophageal cancer patients were treated by daily concurrent CRT, which consisted of continuous 5-fluorouracil administration with leucovorin, combined with a low dose of daily cisplatin administration before each fraction of radiation. Response to CRT and toxicities and survivals were evaluated. RESULTS: Complete and partial responses were seen in 2 patients each. Histologic examination of the biopsy specimens in the primary site showed no cancer cells in 4 patients; 1 of them survived for 31 months after CRT. The other 2 patients showed good-quality survival, having dramatic relief from dysphagia. There were no treatment-related deaths. CONCLUSIONS: The daily concurrent CRT is rational and promising and compares well with other series of definitive CRT. The CRT based on the theoretical background is feasible as a nonsurgical management option for esophageal cancer patients.

The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli.

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II-peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II-peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor alpha, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II-HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC-peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II-peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II-peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.

Prospectively performed modified D1 lymphadenectomy for clinically diagnosed mucosal, node negative gastric cancer: findings over the past decade.

Based on retrospective analyses demonstrating the low probabilities of both lymph node metastasis and recurrence of curatively resected mucosal gastric cancer, we have established criteria for modified D1 lymphadenectomy (lymphadenectomy in the perigastric region as well as along the left gastric artery) and performed this in a prospective manner. In this study, we evaluate our treatment strategy by reviewing the patients prospectively undergoing modified D1 lymphadenectomy. The clinicopathological characteristics and survival data of 138 patients who underwent modified D1 lymphadenectomy between 1987--when we first introduced endoscopic ultrasonography--and 1996 were analyzed. The criteria for modified D1 lymphadenectomy were mucosal, node negative gastric cancer by pre-operative and intra-operative examinations. Depth of invasion was correctly diagnosed in 80% of the patients. Among the resultant submucosal gastric cancer patients, the incidence of slight submucosal invasion was increased in the second half-period (78%) as compared with that in the first half-period (44%). Nodal involvement was observed in 4 patients (2.9%); all of them exhibited the depressed type with ulceration and a histologically high grade of gastric cancer. Because their metastasized lymph nodes were all confined to the perigastric region, surgical treatment resulted in no residual cancer macroscopically. No patients succumbed to gastric cancer within the median and mean follow-up periods of over 6 years. These results suggest that our modified D1 lymphadenectomy is an effective option for the pre-operatively and intra-operatively diagnosed mucosal, node negative gastric cancer which meets our criteria.

A case of complete response to esophageal cancer by a novel concurrent chemoradiation therapy.

BACKGROUND/AIMS: A combination of chemotherapy and radiotherapy (chemoradiation therapy) has recently been developed for the treatment of non-operable esophageal cancer patients. Chemoradiation therapy is based on the concept of biochemical modulation effects and radiosensitizing effects of chemotherapeutic agents. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens have not been precisely established. METHODOLOGY: Based on our recent experience of an effective chemoradiation therapy protocol which consisted of 5-fluorouracil (5-FU) combined with daily concurrent cisplatin and radiation, in addition to the recent knowledge on the biochemical modulation between 5-FU and cisplatin or between leucovorin and 5-FU, we have developed a complete daily concurrent chemoradiation therapy for non-operated esophageal cancer as a treatment modality with curative intent. RESULTS: We report here a novel intensive concurrent chemoradiation protocol by which complete response could be achieved. A low dose of 5-FU (250 mg/body/day) was continuously infused over 24 hours followed by leucovorin (30 mg/body), and a low dose of daily cisplatin (5 mg/body) was administered 1 hour before radiotherapy (2 Gy/day). The administration schedule was 5 consecutive days, followed by a 2-day withdrawal, and then repeated weekly for 4 weeks. CONCLUSIONS: Our completely daily concurrent chemoradiation therapy is rational, effective, and safe, because an endoscopically and pathologically complete response without severe side effects was able to be achieved and this has continued for at least 6 months after chemoradiation therapy. Therefore, we believe that our completely daily concurrent chemoradiation therapy can be recommended for non-operated esophageal cancer patients.

Dual roles of peptic ulcer in the carcinogenesis or extension of early gastric cancer.

BACKGROUND: Early gastric cancer (EGC) often coexists with peptic ulcer. In this study we investigated the roles of peptic ulcer in the carcinogenesis and extension of gastric cancer. METHODS: The clinicopathological characteristics of EGC and peptic ulcer and their relationship, as well as that of the background intestinal metaplasia, were compared among the following three groups: patients with peptic ulcer only inside the EGC (Contained group, 53 patients); patients with peptic ulcer only outside the EGC (Separate group, 26 patients); and patients of EGC with no peptic ulcer (Absent group, 43 patients). RESULTS: In the Separate group, a male preponderance was observed (P = .006), and all EGCs developed in the middle or lower third of the stomach (P = .06). Most of the EGCs were an intestinal type of cancer with severe background intestinal metaplasia. Topographically, 88% of the peptic ulcers in the Separate group developed proximal to the EGC. On the other hand, in the Contained group, most EGCs developed in the middle third of the stomach with an intestinal/diffuse type ratio of 1:1. Peptic ulcers inside the EGC were significantly more shallow than those that developed outside the EGC (P = 0.008). Although the incidences of submucosal cancer were nearly the same among the three groups, the maximum cancer diameter tended to be increased in the Contained group compared to that in the Absent group, and the incidence of lymph node involvement tended to be higher in the Contained group (8%) as compared with the other two groups (4%-5%). CONCLUSIONS: These results suggest that peptic ulcer outside the EGC contributes to the development of the intestinal type of EGC, with the background of more severe intestinal metaplasia during the peptic ulcer healing processes, whereas peptic ulcer inside the EGC develops secondary to EGC and favors cancer extension and metastasis. Peptic ulcer associated with EGC can be considered to exert different biological roles in the carcinogenesis or extension of ECG according to the location of the peptic ulcer.

Increased serum angiogenin concentration in colorectal cancer is correlated with cancer progression.

We have previously demonstrated that the increased expression of angiogenin (ANG) in pancreatic cancer is related to cancer aggressiveness; however, the relationship between ANG expression and its clinical relevance in colorectal cancer has not been demonstrated. We therefore investigated the correlation between serum ANG (sANG) concentration and colorectal cancer progression or the changes in sANG concentrations before and after cancer resection. To determination sANG concentration by ELISA, sera were obtained from colorectal cancer patients (the cancer group) preoperatively (n = 34) and postoperatively (n = 25), from hernia patients (the nonneoplastic group) preoperatively (n = 9) and postoperatively (n = 4), and from 23 healthy volunteers. The amount of ANG in the colorectal cancer tissues (n = 19) was determined by the same method. Before surgery, the mean sANG concentration in the cancer group (411.8 +/- 106.3 ng/ml) was significantly higher than that in both the nonneoplastic group (344.0 +/- 60.7 ng/ml; P = 0.04) and in the healthy volunteers (321.7 +/- 59.7 ng/ml; P = 0.0001). The degree of elevation of sANG concentration in the cancer group was more significant in the more progressed subgroups as compared with that in the normal group (versus T(is) + T1 + T2 cancer, P = 0.01; versus T3 + T4 cancer, P = 0.002; versus stage 0 + I cancer, P = 0.02; versus >stage III cancer, P = 0.001; versus Dukes' A cancer, P = 0.02; versus Dukes' C cancer, P = 0.006). After cancer resection, the mean sANG concentrations in each subgroup decreased to the same levels as those of the normal group; the degrees of reduction were more significant in the more progressed subgroups. The tissue ANG amount correlated significantly with sANG concentration (P = 0.007). These results suggest that the increased concentration of sANG that is derived from colorectal cancer correlates with cancer progression.