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.

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.

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.

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.

Increased angiogenin expression in pancreatic cancer is related to cancer aggressiveness.

We have investigated the expression of angiogenin (ANG) in pancreatic cancer and the relevance of ANG expression to the progression of pancreatic cancer. In comparison to normal pancreas, increased ANG mRNA expression was observed in 80.0% of the cases of pancreatic cancer by in situ hybridization, and increased ANG protein expression was observed in 86.7% of the cases of pancreatic cancer using Western blot analysis. The mean serum ANG concentration of pancreatic cancer patients (566.6 +/- 191.9 ng/ml) was significantly higher (P < 2.0 x 10(-8)) than that of healthy volunteers (359.0 +/-t 59.9 ng/ml). Increased ANG mRNA expression as well as elevated serum ANG concentration correlated with poor prognosis. These findings suggest that ANG expression is up-regulated in pancreatic cancer patients and that ANG contributes to the aggressiveness of pancreatic cancer.

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.

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 pylorus-preserving gastrectomy with a wider scope of lymphadenectomy.

OBJECTIVE: To demonstrate the feasibility and safety of pylorus-preserving gastrectomy (PPG) accompanied by complete suprapyloric and infrapyloric lymph node dissection. DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Fifteen patients underwent PPG, and 28 patients underwent conventional distal gastrectomy (CDG) with Billroth I anastomosis. All patients had early gastric cancer, with either limited invasion in the mucosal layer or invasion into the submucosal layer. INTERVENTIONS: In the PPG procedure, the distal part of the stomach was resected while retaining a 1.5-cm pyloric cuff. The right gastroepiploic artery, the right gastric artery, and hepatic and pyloric branches of the vagus nerve were divided, and the infrapyloric artery was preserved. A modified D1 or D2 lymphadenectomy accompanied the PPG. MAIN OUTCOME MEASURES: Patients undergoing the PPG and CDG procedures were assessed 1 year after their surgical procedure. Changes in body weight, serum total protein levels, and serum albumin levels, the incidence of dumping syndromes, and endoscopic findings in the gastric remnant were compared between the 2 groups. RESULTS: Weight loss was significantly less in the PPG group than in the CDG group (P=.02). The incidences of early dumping syndromes, especially vasomotor symptoms, were significantly lower in the PPG group than in the CDG group (P=.03 and P=.02, respectively). The pyloric sphincter function was preserved, and there was no anastomotic leakage in the PPG group. CONCLUSIONS: The PPG procedure with complete D2 lymphadenectomy can be performed safely with a low incidence of major complications and a better postoperative outcome than the CDG procedure. The PPG procedure can be recommended for the treatment of early gastric cancer with broader indications.

Overexpression of intercellular adhesion molecule-1 (ICAM-1) in pancreatic adenocarcinoma in comparison with normal pancreas.

To elucidate the role of intercellular adhesion molecules (ICAMs), which has not been well understood in pancreas, we investigated the localization and expression of ICAM-1 by immunohistochemistry and in situ hybridization (ISH) in pancreatic adenocarcinoma and in normal pancreas. The localizations of ICAM-2 and ICAM-3 were also investigated by immunohistochemistry. In normal pancreas, acinar cells, duct epithelial cells, and Langerhans islet cells failed to stain with anti-ICAM-1, anti-ICAM-2, and anti-ICAM-3 antibodies. These cells showed no expression of ICAM-1 mRNA. On the other hand, various percentages of carcinoma cells were stained with anti-ICAM-1 antibody, while no carcinoma cells were stained with anti-ICAM-2 and anti-ICAM-3 antibodies. ICAM-1 mRNA expression was also observed in carcinoma cells, and ICAM-1 mRNA expression was associated with localization of the ICAM-1 protein. These results suggest that ICAM-1 expression is up-regulated in pancreatic adenocarcinoma cells and that ICAM-1 is involved in malignant processes in pancreas.

Increased angiogenin expression in obstructive chronic pancreatitis surrounding pancreatic cancer but not in pure chronic pancreatitis.

We previously demonstrated the increased expression of angiogenin (ANG) in pancreatic cancer and its relation to cancer aggressiveness; however, the expression patterns and the roles of angiogenin in chronic pancreatitis are still unknown. We investigated the expression of ANG both in the tissues and in the sera of chronic pancreatitis patients (pure chronic pancreatitis) by using in situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay. In situ hybridization revealed no detectable ANG messenger RNA (mRNA) signals in all tissues of pure chronic pancreatitis and normal pancreas. Only a small amount of protein band expression was obtained in all of the protein lysates of pure chronic pancreatitis and normal pancreas. Accordingly, there was no significant difference between the mean serum ANG concentration of chronic pancreatitis patients (352.1+/-72.5 ng/ml) and that of healthy volunteers (357.6+/-45.2 ng/ml). By contrast, acinar cells and interstitial fibroblasts in the tissues surrounding pancreatic cancer showed increased ANG mRNA expression. Strong protein band expression was obtained in the protein lysates of pancreatic cancer surrounding tissue, and mean serum ANG concentration was increased in pancreatic cancer patients. These findings suggest that ANG expression is increased in pancreatic cancer surrounding tissue but is not increased in pure chronic pancreatitis, and that ANG is potentially involved in the pancreatic cancer microenvironment rather than the establishment of pure chronic pancreatitis.

A rare case of gastric cancer in an acromegalic patient.

Although it has been demonstrated that acromegalic patients have an increased risk of neoplasms, especially colon neoplasms, gastric cancer with acromegaly is very rare--only five cases have been reported to date in Japan. We report here a rare case of gastric cancer with acromegaly in a 58-year-old woman, whose acromegalic change began at age 44. This patient showed typical clinical features of acromegaly, with increased concentrations of blood growth hormone (GH) and insulin-like growth factor I (IGF-I); she had four types of neoplasms; gastric cancer, colon tubular adenoma with moderate atypia, pancreatic mucinous cystadenoma, and subcutaneous lipoma. The gastric cancer was macroscopically 0-IIc type, 3.0 x 2.5 cm in size, and histologically diagnosed as a poorly differentiated adenocarcinoma with limited invasion of the mucosal layer. The previously documented stimulatory effects of GH and/or IGF-I on tumorigenesis and cell proliferation may have been responsible for the development of the multiple neoplasms in our patient.

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.

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.

Basal expression and cytokine induction of intercellular adhesion molecule-1 in human pancreatic cancer cell lines.

Although expression of intercellular adhesion molecule-1 (ICAM-1) expression has been demonstrated in many human malignancies, very little is known about the ICAM-1 expression in human pancreatic cancer. We have examined ICAM-1 expression in pancreatic cancer cell lines and the induction of ICAM-1 in these cells by flow cytometry. The degree of baseline ICAM-1 expression was most significant in Panc-1, followed by PMH-2, Capan-2, Bx-PC-3, Capan-1, and PMH-3 in that order. PaCa-2 and AsPC-1 showed very low levels of baseline ICAM-1 expression. After tumor necrosis factor alpha and interferon gamma stimulation, five cell lines exhibited distinct ICAM-1 induction. The degree of induction was remarkable in AsPC-1 (32-fold), and moderate in PMH-3 (6.5-fold), PaCa-2 (3.2-fold), Capan-1 (1.6-fold), and BxPC-3 (1.5-fold). The ICAM-1 expression levels of PMH-2 and Capan-2 after stimulation were nearly the same as those before stimulation (1.2-fold and 1.1-fold, respectively). These results suggest that ICAM-1 is overexpressed and inducible by tumor necrosis factor alpha and interferon gamma in pancreatic cancer cell lines.

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.

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.

Results of subtotal gastrectomy with complete dissection of the N2 lymph nodes preserving the spleen and pancreas in surgery for gastric cancer.

In radical resection for gastric cancer, dissection of the N2 lymph nodes is recommended, and total gastrectomy with splenectomy and distal pancreatectomy is sometimes necessary, even if the cancer is located in the middle part of the stomach. However, splenectomy affects the immunological status, and distal pancreatectomy induces diabetes mellitus. In 22 patients with macroscopic Stage II gastric cancer located in the middle part of the corpus, we performed a complete N2 lymph node dissection without splenectomy or pancreatectomy and preserving the short and splenic vessels. Of the 22 cases, 6 had early gastric cancer and 16 advanced cancer. Twenty cases underwent subtotal gastrectomy and 2 cases total gastrectomy. The average number of lymph nodes dissected was 39 (13-82), and 8 patients (36%) showed positive lymph node metastasis (N1(+) 2 cases, N2(+) 6 cases). Postoperative complications were observed in 4 patients (18%), one of whom died of an intraabdominal abscess; the others are alive with no recurrence. This operation is safe and rational, and is recommended mainly in patients with mid-stage gastric cancer located in the middle part of the corpus.

Expression and alteration of p53 and p21(waf1/cip1) influence the sensitivity of chemoradiation therapy for esophageal cancer.

BACKGROUND/AIMS: In vitro analyses have been demonstrated that wild type p53 and p21(waf1/cip1) proteins regulate cellular proliferation and sensitivity of anticancer agents, however, the roles of p53 and p21(waf1/cip1) expression on the response to the chemoradiation therapy for human esophageal squamous cell cancer have not been investigated. METHODOLOGY: With an immunohistochemical method using specimens before and after the chemoradiation therapy, we investigate in this report the influence of the p53 and p21(waf1/cip1) expression on the chemoradiation therapy response or alteration of these protein expressions by chemoradiation therapy in thirteen esophageal squamous cell cancer patients who received our recently developed chemoradiation therapy. RESULTS: In the biopsy specimens before the chemoradiation therapy, 82% of the responders and 71% of patients with down T-classification had either a p53-/p21+ or p53+/p21+ phenotype. Eighty two percent and 46% of the cases with these two phenotypes showed complete or partial response and down T-classification, respectively. After the chemoradiation therapy, 73% of the responders and 71% of the patients with down T-classification had either a p53-/p21+ or p53+/p21+ phenotype. Eighty eight percent and 56% of the cases with these two phenotypes showed complete or partial response and down T-classification, respectively. Comparative analysis before and after the chemoradiation therapy revealed that four patients had an alteration of p53 and p21(waf1/cip1) expression in association with the therapeutic response. CONCLUSIONS: These results suggest that wild type p53 or p21(waf1/cip1) expression relates with and can be altered by the chemoradiation therapy, which could influence the therapeutic efficacy.

A rare case of primary malignant mesothelioma originating from the rectovaginal tissue.

A 35 year-old female patient with pelvic malignant mesothelioma is described. The patient underwent total pelvic exenteration due to a pelvic tumor. Macroscopically, the resected tumor was located in the rectovaginal lesion with invasion into the rectal and vaginal wall, and around the internal urethral ostium. Light microscopically, the tumor predominantly consisted of sheets of plump round cells with acidophilic cytoplasm, and focally of tumor cells showing papillary growth pattern. The tumor cells showed remarkable cellular pleomorphism, and were both alcian blue and periodic acid-Schiff stain negative. Electron microscopically, these tumor cells had numerous long bush-like microvilli on their surface with increased length/width ratios. Positive staining with epithelial membrane antigen, cytokeratin, and vimentin, and negative staining with the carcinoembryonic antigen and S-100 protein were observed immunohistochemically. Based on these histological and immunohistochemical estimations, the tumor was diagnosed as a primary malignant mesothelioma originating from the rectovaginal tissue. Review of the literature confirmed the rarity of pelvic malignant mesothelioma. The possibilities of the pathogenesis of the tumor include the tumor's arising from the peritoneal remnant in the rectovaginal tissues, or from the epithelium of the secondary Mullerian system, which shares the same ancestry with the peritoneum.

Digoxin-like immunoreactive substance in urine of patients with mucocutaneous lymph node syndrome (MCLS).

Levels of digoxin-like immunoreactive substance (DLIS) and dehydroepiandrosterone sulfate (DHEA) in urine from patients with mucocutaneous lymph node syndrome (MCLS) were measured by radioimmunoassay. Because DLIS of stored samples was often below the level of detection by conventional immunoassay, the authors used 80% ammonium sulfate and extraction with phosphate buffer and then 80% hot ethanol. To study the origin of raised levels of DLIS in urine, the synthesis of DLIS by cultured human umbilical vein endothelial cells (HUVEC) was tested in vitro. The correlation between DLIS and DHEA levels was not significant. Mean levels of urinary DLIS corrected for creatinine in the patients with MCLS were significantly higher than in both normal and diseased controls. The culture medium of HUVEC was found to contain DLIS activity. These results show that MCLS should be added to the clinical states associated with an increased urinary concentration of DLIS and that the endothelial cells are one source of DLIS in man.