Technical skills simulation in transplant surgery: a systematic review.

Purpose:  Transplant surgery is a demanding field in which the technical skills of the surgeon correlates with patient outcomes. As such, there is potential for simulation-based training to play an important role in technical skill acquisition. This study provides a systematic assessment of the current literature regarding the use of simulation to improve surgeon technical skills in transplantation. Methods:  Data were collected by performing an electronic search of the PubMed and Scopus database for articles describing simulation in transplant surgery. The abstracts were screened using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Three reviewers analyzed 172 abstracts and agreed upon articles that met the inclusion criteria for the systematic review. Results:  Simulators can be categorized into virtual reality simulators, cadaveric models, animal models (animate or inanimate) and synthetic physical models. No virtual reality simulators in transplant surgery are described in the literature. Three cadaveric models, seven animal models and eight synthetic physical models specific to transplant surgery are described. A total of 18 publications focusing on technical skills simulation in kidney, liver, lung, pancreas, and cardiac transplantation were found with the majority focusing on kidney transplantation. Conclusions:  This systematic review identifies currently reported simulation models in transplant surgery. This will serve as a reference for general surgery and transplant surgery professionals interested in using simulation to enhance their technical skills.

Fatal anaphylactic sting reaction in a patient with mastocytosis.

We report on a 33-year-old female patient with indolent systemic mastocytosis and urticaria pigmentosa who died of an anaphylactic reaction after a yellow jacket sting. As she had no history of previous anaphylactic sting reaction, there was no testing performed in order to detect hymenoptera venom sensitization. But even if a sensitization had been diagnosed, no venom immunotherapy (VIT) would have been recommended. It is almost certain that VIT would have saved her life and it is most likely that VIT is indicated in some patients with mastocytosis with no history of anaphylactic sting reaction. However, no criteria have been established in order to allow a selection of mastocytosis patients eligible for such a 'prophylactic' VIT.

Mediation of cytotoxic immune responses against human tumor-associated antigens by xenogeneic immune RNA.

Xenogeneic immune RNA (I-RNA), extracted from the lymphoid organs of sheep or guinea pigs immunized with human tumor cells, mediated in vitro cytotoxic immune responses that were directed specifically against tumor-associated antigens of human tumor target cells. Normal human peripheral blood lymphocytes from healthy donors became markedly more cytotoxic for human tumor target cells after being incubated with I-RNA extracted from the lymphoid organs of animals that had been immunized with that particular tumor. Gastric carcinoma, malignant melanoma, and carcinoma of the breast were studied. Lymphocytes incubated with RNA from animals immunized with only complete Freund's adjuvant evidenced no increased cytotoxic activity. RNA extracted from the lymphoid organs of animals immunized with normal skin fibroblasts that were autologous to the immunizing tumor, when incubated with normal allogeneic lymphocytes, also mediated cytotoxic immune reactions against tumor target cells. These immune responses probably were directed principally against normal transplantation antigens. However, when lymphocytes that were autologous to the immunizing tumor and/or the tumor target cells were incubated with RNA from animals immunized with autologous normal fibroblasts, cytotoxicity did not increase. Only I-RNA extracted from donor animals specifically immunized with tumor cells mediated cytotoxic antitumor immune responses when incubated with autologous lymphocytes.

Mediation of cytotoxic immune responses against human tumor-associated antigens by allogeneic immune RNA.

Allogeneic immune RNA (I-RNA), extracted from the peripheral blood lymphocytes of patients putatively cured of cancer, mediated cytotoxic immune reactions that apparently were directed specifically against human tumor-associated antigens. I-RNA was extracted from the peripheral blood lymphocytes of patients with various types of cancer. Patients selected had not been previously sensitized to HL-A or other normal transplantation antigens or to blood group antigens. Normal human peripheral blood lymphocytes were incubated with these allogeneic I-RNA preparations and tested for cytotoxicity against human target cells in vitro. Allogeneic I-RNA mediated cytotoxic immune reactions only against tumor target cells of the same histologic type as the I-RNA donor. I-RNA's extracted from peripheral blood lymphocytes of melanoma patients mediated cytotoxic immune reactions only against melanoma cells. Similarly, only I-RNA's extracted from the lymphocytes of patients with colon cancer mediated cytotoxic immune reactions against colon carcinoma cells, and only I-RNA's from the lymphocytes of breast cancer patients mediated immune reactions against breast cancer target cells. Allogeneic I-RNA extracted from peripheral blood lymphocytes of cancer patients possibly mediated specific cytotoxic immune reactions that were directed against common tumor-associated antigens shared by human tumors of similar histologic type.

Production of antisera with specificity for malignant melanoma and human fetal skin.

Complement-dependent cytotoxic antibodies to common cell surface antigens of cultured melanoma cells were produced in guinea pigs. At appropriate dilution, melanoma antisera were cytotoxic only to melanoma target cells. Following absorption with pooled lymphoid cells, additional absorption with melanoma cells but not absorption with fibroblasts or carcinoma cells was found to remove all cytotoxic activity from melanoma antisera. Absorption with human fetal skin cells but not with autologous fetal visceral cells was found to remove cytotoxicity from melanoma antisera. Tissue type-specific antigens may be shared by human malignant melanomas and fetal skin of black racial origin (at 16 to 18 weeks of gestation). The methods may be useful in the production of xenogeneic antisera with "operational monospecificity" for common melanoma-specific antigens. Sera from 47 patients with malignant melanoma failed to evidence specific cytotoxicity for melanoma target cells.

Leukocyte and lymphoid cell counts in myasthenia gravis.

Serial leukocyte counts and lymphoid cell counts were compared before and after thymectomy via sternal-splitting incision in 50 patients with myasthenia gravis. Leukocyte counts and lymphoid cell counts of the thymectomized patients also were compared to those of 30 non-thymectomized myasthenic patients and 150 non-myasthenic patient controls. While mean leukocyte counts did not change significantly before and 5.5 plus or minus 5 years after thymectomy, mean lymphoid cell counts were slightly lower during this observation period post-thymectomy (t equals 1.918, p equals 0.03). Lower lymphoid cell counts appeared to correlate with a favorable response of myasthenia gravis in patients with thymic hyperplasia and mainly involuted thymus.

A new micromethod for the detection of HL-A antigens on cultured human tumor cells.

A rapid microcytotoxicity assay for the detection of HL-A antigens on tissue culture cells derived from human solid tumors is described. Tumor cells were prelabeled with 125Iododeoxyuridine. Isotopically labeled tumor cells were reacted with up to 37 highly selected HL-A antisera and diluted rabbit complement. Results of the HL-A typing of nine human tumor cell lines are reported. Three melanoma cell lines showed individually distinct HL-A profiles at the first HL-A locus which agreed with the antigenic pattern of the tumor donor's autologous lymphocytes. Less reactivity was noted with HL-A antisera defining second locus specificities on the three melanoma cell lines, whereas some other cell lines showed more HL-A reactions than required to present a "full house". This method obviates the necessity for visually enumerating residual tumor target cells.

Detection of impaired mitogen responses in autologous whole blood of cancer patients using an optimized method of lymphocyte stimulation.

Mitogenic lymphocyte stimulation with six concentrations of phytohemagglutinin (PHA) was compared in 60 patients with advanced or metastatic cancer and 30 age- and sex-matched healthy controls using an optimized whole blood method. Since the method is simple and the number of technical variables relatively small, a "normal" range of PHA responsiveness expressed in absolute cpm, could be established. It is thus possible to directly compare results from different laboratories. A markedly reduced lymphocyte stimulation was found in cancer patients compared to controls, although leukocyte and lymphocyte counts were almost "normal". The implications of this finding are discussed with regard to immunosuppression by the tumor and previous chemotherapy.

The phylogenetic diversity of thermophilic members of the genus Bacillus as revealed by 16S rDNA analysis.

Sixteen thermophilic strains of the genus Bacillus, representing eight validly described and six invalidly described species, as well as one unassigned strain, were investigated by comparative 16S rDNA analyses and the sequences compared to the existing database for the genera Bacillus and Alicyclobacillus. The majority of strains were found to cluster in two groups represented by B. stearothermophilus and B. pallidus. Bacillus smithii, B. thermocloacae, and B. thermoruber are phylogenetically well separated and cluster within the radiation of mesophilic bacilli. The as yet undescribed taxon 'B. flavothermus' warrants species status. B. schlegelii and B. tusciae group peripherally with members of Alicyclobacillus and may be reclassified when more phenotypic data support their phylogenetic position.

Comparison of ftorafur with 5-fluorouracil in combination chemotherapy of advanced gastrointestinal carcinoma.

The aim of the study was to compare the combination 5-FU-carmustine with ftorafur-carmustine in the treatment of advanced gastrointestinal cancer. To this end, a prospective, multicenter, randomized trial was initiated. Part I of this trial showed that similar response rates can be obtained with 5-FU-carmustine and ftorafur-carmustine in 109 patients (32.7% versus 26.3%). However, median survival was better in patients treated with 5-FU-carmustine (307 days versus 163 days). Part II of the trial revealed that neither a higher dosage of ftorafur (2 g/m2/day X 5 days) nor the addition of vincristine to both regimens changed the previously obtained results significantly. Again, median survival was found to be better in patients treated with 5-FU combination chemotherapy (304 days versus 144 days). Both the 5-FU and the ftorafur combination were tolerated reasonably well. The results suggest that combination chemotherapy including 5-FU is superior to ftorafur at the applied dosages in terms of survival.

Immunotherapy of cancer with "immune" RNA. A preliminary report.

A phase I clinical trial of immunotherapy with "Immune" RNA was undertaken fifteen months ago. Twenty-six cancer patients were treated with RNA extracted from the lymphoid organs of sheep immunized with either autologous tumor cells or allogeneic tumor cells of the same histologic type. Eighteen patients had gross disease and eight had minimum residual disease. RNA was administered weekly, intradermally, at doses up to 9 mg/week without any significant local or systemic toxicity. Four patients improved, thirteen achieved stability of disease or possible improvement, seven were treatment failures, and two are indeterminate. Lymphocyte-mediated cytotoxicity to allogeneic tumor target cells of the same histologic type were monitored in eleven patients. In seven patients, cytotoxicity increased after "Immune" RNA therapy; no change was observed in three patients; a decrease was noted in one patient. There appeared to be a possible correlation between cytotoxicity assessed in vitro and clinical response. There is some evidence that these responses may be specific for the particular tumor used to immunize the RNA donor.

Combination of Bolus 5-Fluorouracil, Folinic Acid and Mitomycin C in Advanced Gastric Cancer: Results of a Phase II Trial.

BACKGROUND: Gastric carcinoma still is a worldwide major cause of cancer death. Although various chemotherapy schedules yielded high response rates, median survival rarely exceeds 8-10 months. Many regimens are inevitably associated with significant toxicity which jeopardizes their value as palliative treatment, especially in patients with reduced performances status. Therefore, we initiated a phase II study for the treatment of advanced gastric carcinoma using a bolus regimen with mitomycin C (MMC), 5-fluorouracil (5-FU) and folinic acid (FA), allowing the enrollment of elderly patients or those with reduced performance status (WHO grade 2). PATIENTS AND METHODS: Between 1996 and 1998 we recruited a total of 58 patients with advanced gastric cancer to receive bolus MMC 3 mg/m(2), 5-FU 450 mg/m(2), and FA 100 mg/m(2) on days 1-3. Treatment was repeated on day 22. 53 patients met the inclusion criteria: male n = 36, female n =17; median age 65 (range 26-81); mean WHO status 1 (range 0-2). RESULTS: Out of 53 patients 50 were evaluable for response, all 58 patients who received therapy were evaluable for toxicity. Eleven patients (22%) achieved partial remission (95% CI: 11.5 -36.0%), 24 (48%) no change and 15 (30%) were progressive. Median overall survival was 11.5 months, the median time to progression 6.0 months. Out of 290 treatment cycles the worst toxicities observed (WHO 2/3/4) were as follows: anemia 13/3/1, leukopenia 19/1/1, thrombopenia 11/3/0, nausea/emesis 11/2/0, infections 2/1/0, diarrhea 14/2/0, and stomatitis 6/1/1. One patient developed hemolytic-uremic syndrome. CONCLUSIONS: The tumor control rate (PR + NC) of 70% was comparable to established chemotherapy regimens, while median overall survival was promising. Toxicity was mild, allowing the treatment especially for elderly patients and on outpatient basis. Copyright 2000 S. Karger GmbH, Freiburg

[Immunodiagnostic aspects of breast cancer. The phenomenon of leukocyte adherence inhibition]. / Aspetti immunodiagnostici del carcinoma mammario. Il fenomeno dell'inibizione dell'adesività leucocitaria.

In 39 patients with breast cancer and in 38 female controls the leucocyte adherence was tested in glass tubes in the presence of a series of extracts of breast cancer and control tissues. It was shown that the adherence of leucocytes of patients with operable carcinoma of the breast (stage I/II) is selectively inhibited by extracts from breast cancer tissues. Leucocyte adherence inhibition tests could thus become important for immunodiagnostics.

A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling.

A transcript of unknown function, regulated by fasting and feeding, was identified by microarray analysis. The transcript is up-regulated in the fasting state. An 1168-bp cDNA was cloned from rat hypothalamus and sequenced. This sequence is consistent with adipogenesis down-regulating transcript 3 (AGD3) (also known as human OCC-1) mRNA. A protein sequence identical to AGD3 was determined by mass spectrometry. In the rat brain, AGD3 mRNA is distributed in the arcuate nucleus, ventromedial hypothalamus, amygdaloid nuclei, hippocampus, and somatic cortex. Double in situ hybridisation showed that AGD3 mRNA is co-localised with pro-opiomelanocortin and neuropeptide Y in arcuate nucleus neurones. AGD3 binds with insulin receptor substrate 4 and increases insulin-stimulated phospho-Akt and regulates AMP-activated protein kinase and mammalian target of rapamycin downstream target S6 kinase phosphorylation.