Erratum to "The influence of ecological factors on cnidarian venoms" [Toxicon: X 9-10C (2021) 100067].

[This corrects the article DOI: 10.1016/j.toxcx.2021.100067.].

Inducing metamorphosis in the irukandji jellyfish Carukia barnesi.

Here we utilize chemical ecology as a tool to manipulate the biological system of a small, but highly venomous to humans, cubozoan jellyfish, Carukia barnesi. We trialled a range of chemical reagents including indole compounds, 9-cis-retinoic acid and lugols solution to induce metamorphosis between the polyp and medusa life stages. An optimum method was determined resulting in a 90% metamorphosis rate to healthy medusa by exposing the polyps to 1 µM of 5-methoxy-2-methylindole for 24 h. Of note is that chemical exposure time significantly impacts health and metamorphosis rates in this species. We also present a theoretical mechanism for the chemical/biological interactions occurring during metamorphosis. This is a significant methodological advancement which now enables rearing of this animal en mass in aquaria-a world first for this species-which will subsequently supply and facilitate venom research into this understudied jellyfish.

The influence of ecological factors on cnidarian venoms.

Venom research is often focussed on medical relevance, novel compounds and venom evolution, whilst studying the relationship between a venom and its environment - venom ecology - has been conducted to a lesser extent. Given the projected environmental changes envisioned to occur with global warming, it is pertinent now more than ever, to highlight this topic. Here we review literature examining the influence of ecological factors such as environmental temperature, salinity, ontogeny, geographic location and diet on cnidarian venoms. This review provides an exclusive focus on the cnidarian phylum and encompasses all available published, peer-reviewed literature to our knowledge regarding the ecological factors influencing venom. We find a startling lack of research into the effects of both environmental and biological factors on venoms, with very few to no studies available per category. Importantly, research does exist that suggest these ecological processes may influence other marine or terrestrial venoms, thus we recommend future research is needed to explore this concept in cnidarians.

Effect of Biomechanical Environment on Degeneration of Meckel's Cartilage.

During orofacial tissue development, the anterior and posterior regions of the Meckel's cartilage undergo mineralization, while the middle region undergoes degeneration. Despite the interesting and particular phenomena, the mechanisms that regulate the different fates of Meckel's cartilage, including the effects of biomechanical cues, are still unclear. Therefore, the purpose of this study was to systematically investigate the course of Meckel's cartilage during embryonic development from a biomechanical perspective. Histomorphological and biomechanical (stiffness) changes in the Meckel's cartilage were analyzed from embryonic day 12 to postnatal day 0. The results revealed remarkable changes in the morphology and size of chondrocytes, as well as the occurrence of chondrocyte burst in the vicinity of the mineralization site, an often-seen phenomenon preceding endochondral ossification. To understand the effect of biomechanical cues on Meckel's cartilage fate, a mechanically tuned 3-dimensional hydrogel culture system was used. At the anterior region, a moderately soft environment (10-kPa hydrogel) promoted chondrocyte burst and ossification. On the contrary, at the middle region, a more rigid environment (40-kPa hydrogel) enhanced cartilage degradation by inducing a higher expression of MMP-1 and MMP-13. These results indicate that differences in the biomechanical properties of the surrounding environment are essential factors that distinctly guide the mineralization and degradation of Meckel's cartilage and would be valuable tools for modulating in vitro cartilage and bone tissue engineering.

Altered mucosa-associated microbiota in the ileum and colon of neonatal calves in response to delayed first colostrum feeding.

The present study investigated whether delaying the first feeding of colostrum affected ileum and colon mucosa-associated microbiota in calves. Twenty-seven male Holstein calves were randomly assigned to 1 of 3 groups, fed colostrum at 45 min, 6 h, and 12 h after birth, respectively. Ileum and colon mucosa were collected at 51 h after birth, and their associated microbial profiles were assessed using amplicon sequencing. Both ileum and colon mucosa-associated microbiota were predominated by genus Escherichia-Shigella. The negative correlation between the molar proportion of short-chain fatty acids (SCFA) and ileum mucosa-associated opportunistic pathogens, and the positive correlation between the molar proportion of SCFA and colon mucosa-associated beneficial bacteria, suggest that SCFA might play an important role in maintaining the gut health of 2-d-old calves. A higher relative abundance of ileum mucosa-associated Enterococcus and Streptococcus was detected when the first colostrum feeding was delayed for 12 h. The relative abundance of colon mucosa-associated Lactobacillus tended to be lower in calves fed colostrum 12 h than those under the other 2 treatments, whereas that of Faecalibacterium tended to be lower in calves fed colostrum immediately after birth than those fed colostrum 6 and 12 h after birth, respectively. Our findings suggest that delayed first colostrum feeding affects the establishment of ileum and colon mucosa-associated bacteria, which may have long-term effects on gut health of calves.

Effects of dry period length on metabolic status, fertility, udder health, and colostrum production in 2 cow breeds.

Shortening the dry period improves postpartum energy balance, which has potential positive effects on metabolic health. This concept has been mainly studied in Holstein cows. The aim of this study was to assess the effect of a short dry period of 4 wk, compared with a standard dry period of 8 wk, on the metabolic status, progesterone profiles, health, and colostrum quality of dairy cows of 2 breeds, Swedish Red (SR) and Swedish Holstein (SH), not treated with antibiotics at dry off. The IgG uptake in calves was also studied to reflect the colostrum quality when shortening the dry period. Cows of both SH and SR were blocked by breed and parity and then randomly allocated to a short dry period of 4 wk (4W, n = 43) or a conventional dry period of 8 wk (8W, n = 34). Blood samples were collected wk -8, -4, -2, -1 and 1, 2, 3, 4, 6, 9, and 12 relative to calving. Prepartum, cows with a 4-wk dry period had higher concentrations of nonesterified fatty acids and lower concentrations of insulin-like growth factor-1 and insulin than 8W cows. Postpartum, plasma concentration of nonesterified fatty acids was lower, whereas plasma insulin and insulin-like growth factor-1 tended to be higher for 4W cows than for 8W cows. Plasma concentration of ß-hydroxybutyrate did not differ between dry period lengths. Swedish Holstein cows with a 4W dry period responded with a lower concentration of insulin prepartum than SR and SH on an 8W dry period. The dry period length had no effect on the proportion of disturbed progesterone profiles; disturbed progesterone profiles occurred in 30% of the 4W cows and 47% of the 8W cows. In this trial, only 48.8% of the SR cows had a normal progesterone profile, which differed from the SH where 76.5% had a normal profile. Fertility-related diseases (endometritis, pyometra, anestrus, ovarian cyst) did not differ between the 2 dry period groups: 21% in the 8W group versus 12% in the 4W group, whereas mastitis tended to be more common: 26% of the 4W cows versus 9% of the 8W cows. A short dry period resulted in less colostrum but with a higher content of protein and somatic cell count. Calves were fed colostrum from their dam, and the IgG and total protein in plasma did not differ between calves to mothers with different a dry period length. Shortening the dry period could improve metabolic status in cows of both SH and SR breed postpartum, without compromising the colostrum quality. Health and progesterone profiles were not affected by the dry period length for SH or SR in this study.

Effects of dry period length on milk production and energy balance in two cow breeds.

Shortening the dry period (DP) has been proposed as a strategy to improve energy balance (EB) in cows in early lactation. This study evaluated the effects of shortening the DP on milk yield (MY), EB and residual feed intake (RFI) in two breeds; Swedish Red (SR) and Swedish Holstein (SH). Cows were blocked by breed and parity and then randomly assigned to one of two treatments; short DP of 4 weeks (4W, n=43) or conventional DP of 8 weeks (8W, n=34). Cows were kept and fed under the same conditions, except for the 4 weeks when the 4W group were still lactating prepartum and thus kept with the lactating cows. Milk yield and BW were recorded and body condition score (BCS) was rated from 10 weeks prepartum to 12 weeks postpartum. Dry matter intake (DMI) was recorded for lactating cows postpartum. Milk yield was reduced by 6.75 kg/day during the first 12 weeks postpartum (P<0.001) for the 4W cows compared with 8W cows, but there was no significant difference in total MY (3724 kg compared with 3684 kg, P=0.7) when the milk produced prepartum was included. Protein content was higher in 4W cows (3.42%) than in 8W cows (3.27%) (P<0.001) postpartum. In the 8W group, cows lost more BCS after calving (P<0.05). Cows of SR breed had higher BCS than cows of SH breed (SR=3.7, SH=3.2, P<0.001), but no differences in BW were found between breed and treatment. Energy balance was improved for cows in the 4W group (P<0.001), while feed efficiency, expressed as RFI, was reduced for 4W cows than for 8W cows (5.91 compared with -5.39, P<0.01). Shortening the DP resulted in improved EB postpartum with no difference between the breeds and no milk losses when including the milk produced prepartum.

Mesenchymal stem/progenitor cell isolation from tooth extraction sockets.

Bone marrow-derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach. It is well known that stem cells migrate from surrounding tissues and play important roles in wound healing. We thus hypothesized that stem/progenitor cells could be isolated from granulation tissue in the dental socket, and we subsequently collected granulation tissue from dog dental socket 3 d after tooth extraction. After enzyme digestion of the collected tissue, the cells forming colonies constituted the dental socket-derived stem/progenitor cells (dDSCs). Next, dDSCs were compared with dog BMSCs (dBMSCs) for phenotype characterization. A flow cytometric analysis showed that dDSCs were positive for CD44, CD90, and CD271 but negative for CD34 and CD45, similar to dBMSCs. dDSCs also exhibited osteogenic, adipogenic, and chondrogenic differentiation ability, similar to dBMSCs, with a higher capacity for colony formation, proliferation, and motility than dBMSCs. In addition, an in vivo ectopic bone formation assay showed that dDSCs and dBMSCs both induced hard tissue formation, although only dDSCs formed a fibrous tissue-like structure connected to the newly formed bone. Finally, we tested the ability of dDSCs to regenerate periodontal tissue in a one-wall defect model. The defects in the dDSC-transplanted group (ß-TCP/PGA/dDSCs) were regenerated with cementum-like and periodontal ligament-like tissues and alveolar bone, whereas only bony tissue was observed in the control group (ß-TCP/PGA). In conclusion, we identified and characterized a population of stem/progenitor cells in granulation tissue obtained from the dental socket that exhibited several characteristics similar to those of BMSCs. Dental sockets could therefore be a novel source for isolating stem/progenitor cells from bone.

Stress analysis in human temporomandibular joint affected by anterior disc displacement during prolonged clenching.

Parafunctional habits, such as prolonged clenching and bruxism, have been associated with dysfunctional overloading in the temporomandibular joint (TMJ). In this study, stress distributions in the TMJ were analysed during prolonged clenching, using three-dimensional finite element (FE) models of the TMJ with and without disc displacement. The aim of this study was to investigate stress distribution of the cartilaginous tissues in the TMJ with and without disc displacement. Finite element models were developed on the basis of magnetic resonance images from two subjects with and without anterior disc displacement. Condylar movements recorded during a 5-min clenching were used as the loading condition for stress analysis. In the asymptomatic model, the highest von Mises stresses were located in the lateral area (4·91 MPa) of the disc surfaces, and after 5-min clenching, the higher stresses were still located at the lateral area (3·65 MPa). In all the cartilaginous tissues, 30-50% of stress reduction occurred during 5-min clenching. In contrast, the von Mises stress in the cartilaginous tissues of the symptomatic model with disc displacement was markedly lower, compared with the asymptomatic model. However, in the condylar cartilage, stress relaxation during clenching was not recognised. Furthermore, relatively high stresses were observed in the retrodiscal tissues throughout clenching. The present results indicate that disc position could be involved in the stress distribution of the TMJ components during prolonged clenching.

A novel vibratory stimulation-based occlusal splint for alleviation of TMD painful symptoms: a pilot study.

This pilot study introduces a novel vibratory stimulation-based occlusal splint (VibOS) for management of pain related to temporomandibular disorders (TMD). The study sample consisted of 10 patients (mean age: 40·5 ± 13·7 years, male/female: 3/7) who were using stabilisation splints for more than 2 months prior to the study onset and still complained of pain. Patients utilised the active and inactive VibOS during 15 days in a crossover designed clinical trial. The analysed variables were self-reported VAS pain levels and number of painful sites to palpation (PSP). Statistical analysis was performed with repeated measures anova. At baseline, mean VAS pain levels for group I and II were 45·6 ± 21·0 mm and 37·4 ± 16·3 mm, respectively. Comparison between these baseline values showed no statistical difference (P > 0·05, unpaired t-test). In group I, the inactive VibOS caused a slight increase in VAS pain levels, whereas the active VibOS promoted a significant decrease in VAS pain levels and PSP (P < 0·01). In group II, which received the active VibOS first, a significant decrease in VAS levels (P < 0·05) and in PSP (P < 0·01) was observed. No significant decrease in VAS pain levels or PSP (P > 0·05) was observed with the use of the inactive VibOS. In conclusion, this study demonstrated a good tendency of this novel VibOS in the alleviation of painful symptoms related to TMD after a 15-day management period compared to control VibOS.

Identification of risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases.

This retrospective study identified the risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases. The study group included a total of 182 patients who were installed 219 suprastructures at the Fixed Prosthodontic Clinic of Okayama University Dental Hospital between February 1990 and March 2005 and were subdivided in two subgroups: 120 patients (149 facing suprastructures) were included in the subgroup to investigate the risk factors of fracture of veneering materials, and 81 patients (92 suprastructures) were included in the subgroup to identify the risk factors of abutment screw loosening. Each patient was followed up from the day of suprastructure installation until March, 2005. A Cox proportional hazards regression model was used to identify the risk factors related to technical complications, and eight factors were regarded as candidate risk factors. Screw retention was the significant risk factor for fracture of veneering materials, whereas connection of suprastructures with natural tooth was the significant risk factor for screw loosening. It was suggested that screw retention was a significant risk factor for the fracture of veneering materials, and connection of suprastructures with natural tooth was a significant risk factor for screw loosening. Future studies, involving dynamic factors (e.g. bruxism) as predictors as well, are more helpful to discuss the risk factor of fracture of veneering materials and screw loosening.

Occlusal dysesthesia: a qualitative systematic review of the epidemiology, aetiology and management.

Occlusal dysesthesia refers to a persistent complaint of uncomfortable bite sensation with no obvious occlusal discrepancy. This systematic review aimed to draw a picture of such patients, to present an agreement of previously reported diagnostic criteria and to analyse the evidence level of the recommended management approaches. An electronic search for all relevant reports on occlusal dysesthesia was thoroughly performed based on previous nomenclatures (e.g. phantom bite, occlusal hyperawareness) in PubMed and The Cochrane Library in July, 2011. A total of 84 reports were matched, among which only 11 studies were included after a two-step (abstract and detailed full-text revision) screening process. Additionally, a thorough manual review of reference lists of the included reports enabled the inclusion of two additional studies. Data analysis revealed that 37 occlusal dysesthesia patients presented a mean age of 51.7 ± 10.6 years and were predominantly women (male/female: 1/5.1) with symptom duration of more than 6 years (average: 6.3 ± 7.5 years) and with concomitant psychological disturbances (e.g. mood disorders, somatoform disorders, personality disorders). Only four authors presented diagnostic criteria for occlusal dysesthesia, which served as the basis for an agreement in the diagnostic criteria. Treatment approaches included psychotherapy, cognitive/behaviour therapy, splint therapy and prescription of anti-depressants or anti-anxiety drugs. Classification of evidence level of management approaches, however, revealed that most of them were expert opinions with single- or multiple-case report(s). Future studies are necessary for a deeper understanding of the mechanisms behind the occlusal dysesthesia symptoms, and consequently, for improvements in evidence-based management approaches.

Response shift in oral health-related quality of life measurement in patients with partial edentulism.

The purposes of this study were to determine whether a response shift was observable after partial denture treatment and to identify the predictors that influenced the response shift magnitude and direction. A total of 173 consecutive patients with no more than eight missing teeth who received implant-supported, fixed or removable partial dentures at Okayama University Dental Hospital were asked to complete a full-version Oral Health-Related Quality of Life (OHRQoL) questionnaire before (pre-test) and after treatment (post-test). Additionally, a short form (then-test) consisting of seven questions selected from the full version had its reliability verified and was utilised to retrospectively assess the pre-treatment OHRQoL status. The difference between the summary scores of the then-test and the pre-test determined the response shift magnitude and direction. The then-test mean score (22·9 ± 6·6) was significantly lower (worse OHRQoL) than that of the pre-test (26·4 ± 5·2). The response shift effect size was of moderate magnitude and negative direction (d = -0·78). A multiple regression analysis showed that age (younger patients) (P < 0·01), number of replaced teeth (fewer) (P < 0·01) and pre-test scores (lower) (P < 0·01) were the significant predictors for response shift. In conclusion, a response shift phenomenon with negative and moderate effect size was observed after partial denture treatment. The significant predictor variables were young age, fewer numbers of replaced teeth and lower pre-test scores.

Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling.

The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene had been isolated as an antagonist to RAS signaling; however, the mechanism of its action is not clear. In this study, the effect of loss of RECK function was assessed in various ways and cell systems. Successive cell cultivation of mouse embryonic fibroblasts (MEFs) according to 3T3 protocol revealed that the germline knockout of RECK confers accelerated cell proliferation and early escape from cellular senescence associated with downregulation of p19(Arf), Trp53 and p21(Cdkn1a). In contrast, short hairpin RNA-mediated depletion of RECK induced irreversible growth arrest along with several features of the Arf, Trp53 and Cdkn1a-dependent cellular senescence. Within 2 days of RECK depletion, we observed a transient increase in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation associated with an upregulated expression of cyclin D1, p19(Arf), Trp53, p21(Cdkn1a) and Sprouty 2. On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence. In addition, we observed that epidermal growth factor receptor (EGFR) activity was transiently upregulated by RECK depletion in MEFs, and continuously downregulated by RECK overexpression in colon cancer cells. These findings indicate that RECK is a novel modulator of EGFR signaling.

Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent inactivation of the RB1/p16 and p53 pathways.

BACKGROUND: Aberrant methylation of CpG islands in the promoter regions of cancer-related genes has been demonstrated in many human tumours. However, the methylation profile of these regions in cutaneous squamous cell carcinomas (SCCs) has not been well studied. OBJECTIVES: To examine epigenetic abnormalities of a wide range of cancer-related genes in SCCs. METHODS: We investigated the methylation status of 11 candidate cancer-related genes (CDH1, p16(INK4a), p14(ARF), DAPK1, MGMT, RB1, RASSF1, p15(INK4b), PTEN, PRDM2 and p53) in 20 cases of SCC by methylation-specific polymerase chain reaction, and comparatively examined the protein production of E-cadherin (CDH1), p16, RB1, p14, BMI1 and cyclin A by immunohistochemical analysis. RESULTS: The frequency of cancer-related gene methylation in SCCs was: CDH1 (95%), p16 (20%), p14 (15%), DAPK1 (15%), MGMT (15%), RB1 (5%), RASSF1 (5%), p15 (0%), PTEN (0%), PRDM2 (0%) and p53 (0%). Almost all cases with hypermethylation of CDH1, p16, RB1 and p14 showed no obvious production of each protein, suggesting that promoter hypermethylation of these genes contributes to the loss of protein production. The results of methylation analysis, in combination with the results of our previous mutation analysis of CDKN2A locus and p53, revealed that 70% of SCCs have alterations in the RB1/p16 or p53 pathway. CONCLUSIONS: Our findings indicate that the promoter hypermethylation of cancer-related genes, especially CDH1, is frequently shown in SCCs, and dysregulation of the RB1/p16 and/or p53 pathway through either genetic or epigenetic mechanisms, except for epigenetic abnormalities of p53 itself, should contribute to the carcinogenesis of SCCs.

Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b.

The Ets transcription factor PU.1 is a hematopoietic master regulator essential for the development of myeloid and B-cell lineages. As we previously reported, PU.1 sometimes represses transcription on forming a complex with mSin3A-histone deacetyl transferase-MeCP2. Here, we show an interaction between PU.1 and DNA methyltransferases, DNA methyltransferase (Dnmt)3a and Dnmt3b (Dnmt3s). Glutathione-S-transferase pulldown assay revealed that PU.1 directly interacted with the ATRX domain of Dnmt3s through the ETS domain. Dnmt3s repressed the transcriptional activity of PU.1 on a reporter construct with trimerized PU.1-binding sites. The repression was recovered by addition of 5-aza-deoxycitidine, a DNA methyltransferase inhibitor, but not trichostatin A, a histone deacetylase inhibitor. Bisulfite sequence analysis revealed that several CpG sites in the promoter region neighboring the PU.1-binding sites were methylated when Dnmt3s were coexpressed with PU.1. We also showed that the CpG sites in the p16(INK4A) promoter were methylated by overexpression of PU.1 in NIH3T3 cells, accompanied by a downregulation of p16(INK4A) gene expression. These results suggest that PU.1 may downregulate its target genes through an epigenetic modification such as DNA methylation.

Celecoxib reduces narcotic use and pain following augmentation mammaplasty.

BACKGROUND: Narcotics have traditionally been used to control pain after augmentation mammaplasty, but they have adverse side effects, including addiction potential, clouded sensorium, nausea, and respiratory depression. Alternative strategies for managing postoperative pain are expensive, cumbersome, and also have their own risks. While long-term use of celecoxib has been associated with an increased risk of serious adverse cardiovascular effects, no problems have been reported with short-term use. OBJECTIVE: The purpose of this study was to determine whether the addition of celecoxib, a selective nonsteroidal anti-inflammatory, to an analgesic regimen reduced narcotic use and pain following augmentation mammaplasty. METHODS: One hundred patients underwent submuscular augmentation mammaplasty with smooth saline-filled mammary prostheses using an intravenous sedation technique. Group A (N = 50) used hydrocodone to manage postoperative pain. Group B (N = 50) used celecoxib 400 mg 1 to 2 hours before surgery and then daily in addition to hydrocodone postoperatively. Narcotic use, incidence of nausea, and complications were recorded. Pain was assessed daily with a Likert pain scale from 0 (no pain) to 10 (severe pain). RESULTS: Group A used 110 +/- 34 mg hydrocodone during the immediate 7-day postoperative period and reported an average pain scale score of 5.1. Group B, which used celecoxib, used 34 +/- 22 mg hydrocodone during the same period with an average pain scale score of 3.3. These differences were statistically significant (P < .05). Group B experienced 53% less nausea than Group A. There were no significant differences between the groups regarding age, implant size, or complications. CONCLUSIONS: Perioperative celecoxib administration in patients undergoing augmentation mammaplasty significantly reduced postoperative narcotic use, pain, and nausea. Its use should facilitate the patient's ability to resume everyday activities following surgery.

Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12.

BACKGROUND: Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy. MATERIALS AND METHODS: Patients' DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg(-1) of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated. RESULTS: The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses. CONCLUSIONS: Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.

Newly developed 3D endoscopic system: preliminary experience.

Although there have been earlier reports on the use of three-dimensional endoscopic systems in the gastrointestinal tract, real-time three-dimensional imaging has not previously been described. This paper presents experience in three cases with a novel endoscopic system for three-dimensional observation in clinical situations. Case 1 was a hyperplastic gastric polyp, the shape of which was considerably enhanced in comparison with two-dimensional endoscopic viewing. Case 2 was an advanced esophageal cancer, in which the sense of depth was improved in the esophagus. Case 3 was a depressed early gastric cancer, the shape of which was also enhanced. Between July 2001 and March 2002, three experienced endoscopists also used this new system in a further 34 patients. A three-dimensional endoscopic environment was visible with the system in all patients, and all of the endoscopists were able to obtain visual information regarding spatial depth. This experience suggests that the three-dimensional video-endoscopic system used here can be of value in gastrointestinal endoscopy.

A squamous cell carcinoma of the gastric cardia showing submucosal progression.

We report a case of squamous cell carcinoma (SCC) of the gastric cardia showing submucosal progression with direct invasion of the liver. A 71-year-old man was admitted with dysphagia. Esophagogastroscopy showed a protruding tumor covered with normal gastric mucosa in the anterior wall of the gastric cardia, although no abnormal findings were detected in the esophagus, including the esophagogastric junction. Serum SCC-related antigen level was elevated (6.6 ng/ml; normal level, less than 2.5 ng/ml). Endoscopic biopsy specimens taken from this tumor did not show malignant cells. Based on these findings, the preoperative diagnosis was a submucosal tumor of the stomach. Laparotomy was done; however, the tumor was not resected because it had direct invasion to the left lateral segment of the liver and adjacent tissues. As the tumor showed continuous bleeding from the stomach after surgery, total gastrectomy, combined with transhiatal lower esophagectomy, left lateral segmentectomy of the liver, splenectomy, and distal pancreatectomy was performed. Because histologic findings showed poorly or moderately differentiated SCC with direct invasion of the liver, the final diagnosis was SCC of the gastric cardia showing submucosal progression with hepatic invasion. Such a case of SCC of the gastric cardia showing submucosal progression is rare, and accurate preoperative diagnosis was very difficult. However, it may be important to consider SCC of the gastric cardia in such a situation.