Donor-derived tuberculosis in an anesthetist after short-term exposure : An old demon transplanted from the past to the present.

We report a case of a 27-year-old anesthetist who acquired tuberculosis (TB) while performing general anesthesia in a renal transplant (RTX) patient who had donor-derived contagious TB. The anesthetist developed pleural TB 6 months after exposure. Contact investigations (CIs) did not include health care workers (HCWs) of the Department of Anesthesiology, thereby missing the opportunity for the early diagnosis and treatment of TB. Genomic fingerprinting revealed identical Mycobacterium tuberculosis (MT) isolates in the anesthetist and in the RTX patient. The recipient had acquired disseminated TB from the harvested renal graft. The donor (liver and kidneys), a 67-year-old immigrant, had died from brain death by cerebral herniation after a stroke. She had been treated for tuberculosis with a pneumectomy 40 years ago. Since that time, she had been suffering from latent tuberculous infection (TBI), but had been considered to have been cured.

Donor-derived tuberculosis after solid organ transplantation in two patients and a staff member.

Because of global mobility and migration resulting in a growing diversity of the donor pool, the risk for donor-derived tuberculosis in solid organ transplant recipients becomes more and more relevant, even in countries with a low overall tuberculosis incidence. Here, we describe a case series of donor-derived tuberculosis in 2 of 3 solid organ transplant recipients and one medical staff member in Germany resulting in the death of one recipient. This case series highlights the relevance of this topic to clinicians. It advocates for a better communication between organ procurement organizations and transplant centers regarding donor information and transplant recipient outcome. Furthermore, it underpins the necessity for a standardized critical incident reporting system in the german transplant system to improve short- and long-term recipient's safety, health and survival.

Limited surgery for benign tumours of the pancreas: a systematic review.

BACKGROUND: Limited surgical procedures for benign cystic neoplasms and endocrine tumours of the pancreas have the potential advantage of pancreatic tissue sparing compared to standard oncological resections. METHODS: Searching PubMed/MedLine, Embase and Cochrane Library identified 86 full papers: 25 reporting on enucleation (EN), 38 on central pancreatectomy (CP) and 23 on duodenum-preserving total/partial pancreatic head resection (DPPHRt/p). The results are based on analysis of data of 838, 912 and 431 patients for EN, CP and DPPHRt/s, respectively. RESULTS: The indication for EN for cystic neoplasms and neuro-endocrine tumours to EN was 20.5 and 73 %; for CP 62.9 and 31 %; and for DPPHRt/p 69.6 and 10.2%, respectively. The estimated mean tumour sizes were in EN-group 2.4 cm, in CP-group 2.9 cm and in DPPHRt/p-group 3.1 cm (DPPHRt/p vs EN, p = 0.035). Postoperative severe complications developed after EN, CP and DPPHRt/p in 9.6, 16.8 and 11.5% of patients; pancreatic fistula in 36.7, 35.2 and 20.1%; and reoperation was required in 4.7, 6.5 and 1.8 %, respectively. Hospital mortality after EN was 0.95 %; after CP 0.72%; and after DPPHRt/p 0.49%. Compared to EN and CP, DPPHRt/p exhibited significant lower frequency of reoperation (p = 0.029, p < 0.001) and lower rate of fistula (p < 0.001; p = 0.001). CONCLUSION: EN, CP and DPPHRt/p applied for benign tumours are associated with low surgery-related early postoperative morbidity, a very low hospital mortality and the advantages of conservation of pancreatic functions. However, the level of evidence for EN and CP compared to standard oncological resections appears presently low. There is a high level of evidence from prospective controlled trials regarding the significant maintenance of exocrine and endocrine pancreatic functions after DPPHRt/p compared to pancreato-duodenectomy.

Management of urologic complications in renal transplantation: a single-center experience.

INTRODUCTION: Ureterovesical complications subsequent to renal transplantation are associated with a high morbidity leading to graft loss or even death. In the present study, the management of these complications by using interventional and surgical procedures (native pyeloureterostomy [NPUS]/ureteroureterostomy [NUU] vs ureteroneocystostomy [UNC]) was evaluated retrospectively. PATIENTS AND METHODS: Between 1994 and 2012, a total of 780 kidney transplantations (690 deceased and 90 living donors) were performed at our institution. Demographic, clinical, and laboratory data from patients with urologic complications were analyzed and compared. RESULTS: Fifty patients (6.4%) exhibited ureterovesical complications, and 18 patients (36%) were operated on immediately. In 32 (64%) of 50 patients, an interventional procedure was initially performed, with 21 patients (66%) undergoing operation due to therapy failure. NPUS/NUU and UNC were performed in 26 (66.6%) and 13 (33.3%) patients, respectively. Indications for an operation were ureteral stenosis in 12 patients (30.8%), ureteral necrosis and urine leakage in 19 patients (48.7%), and symptomatic vesicoureteral reflux in 8 patients (20.5%). Long-term results were comparable between all groups. CONCLUSIONS: Surgical revision of ureteral complications should be the standard therapy. NPUS/NUU, UNC, and the successful interventional procedures did not differ significantly in terms of long-term results.

Transgastric appendicectomy.

BACKGROUND: Experimental studies and small anecdotal reports have documented the potential and feasibility of transgastric appendicectomy. This paper reports the results of the new technique in a selected group of patients. METHODS: From April 2010 transgastric appendicectomy was offered to all patients with acute appendicitis, but without generalized peritonitis or local contraindications. RESULTS: Of 111 eligible patients 15 agreed to undergo the transgastric operation. After conversion of the first case to laparoscopy because of severe inflammation and adhesions, the following 14 consecutive transgastric procedures were completed. Two patients with initial peritonitis required laparoscopic lavage 4 days after transgastric appendicectomy, but no leaks were detected at the appendiceal stump or stomach. CONCLUSION: These preliminary results have shown the feasibility of this innovative procedure. Additional studies, however, are required to demonstrate the specific advantages and disadvantages of this approach, and define its role in clinical surgery.

[Pancreatic surgery in a regional hospital]. / Pankreaschirurgie an einem Krankenhaus der Grund- und Regelversorgung.

BACKGROUND: Recently it was shown that in several surgical procedures the case load of an institution correlated in direct proportion with the outcome. Therefore, the German authorities with effect from January 1, 2008 have defined the minimum case load per year of an institution for selected surgical procedures in order to increase the medical quality and improve the outcome. Until now, however, there is no experience in establishing a medical centre for pancreatic surgery according to these regulations. The aim of this study was, therefore, to describe the possibilities and the prerequisites necessary to establish a new pancreatic centre according to the requirements of the German official regulations. PATIENTS AND METHODS: In a prospective clinical study, the data of 269 patients who underwent a resective surgical procedure for pancreatic diseases between May 1998 and August 2007 were analysed. All included patients underwent a defined surgical procedure for malignant and benign lesions of the pancreatic gland. Indication for operation, operative procedure, postoperative morbidity and mortality were analysed in this study. RESULTS: After the year 2000, the annual case load of pancreatic resections per year amounted to over 30 patients. In most cases (n = 127) the indication for operation was a malignant disease of the pancreatic head, in 94 cases the patients were operated for chronic pancreatitis with a benign tumour of the pancreatic head. In most cases (n = 106) a pylorus-preserving partial duodenopancreatectomy was performed followed by the duodeno-preserving pancreatic head resection (Beger procedure, n = 55). The overall complication rate amounted to 30.2 %, overall mortality 0.7 %. Two patients died on the 37 (th) and 44 (th) day postoperatively. CONCLUSIONS: The establishment of a medical centre for pancreatic surgery is possible according to the regulations of the German authorities. Nevertheless, there are multiple factors influencing medical quality apart from the case load of a hospital. These are a well-functioning intensive care unit and the possibility for radiological and/or gastroenterological interventions 24 hours a day. Most important is the personal motivation of the doctors and nurses in successfully supporting such a programme. So far the prospective implication on health care or medical education cannot be finally anticipated. The different independent factors of medical quality concerning pancreatic surgery have still to be identified and should reasonably influence any governmental or institutional regulations.

Subjective perception of cognition is related to mood and not performance.

OBJECTIVE: Clinicians monitor cognitive effects of drugs primarily by asking patients to describe their side effects. We examined the relationship of subjective perception of cognition to mood and objective cognitive performance in healthy volunteers and neurological patients. METHODS: Three separate experiments used healthy adults treated with lamotrigine (LTG) and topiramate (TPM), adults with epilepsy on LTG or TPM, and patients with idiopathic Parkinson's disease. Correlations were calculated for change scores on and off drugs in the first two experiments and for the single assessment in Experiment 3. RESULTS: Across all three experiments, significant correlations were more frequent (chi(2)=259, P < or = 0.000) for mood versus subjective cognitive perception (59%) compared with subjective versus objective cognition (2%) and mood versus objective cognitive performance (2%). CONCLUSIONS: Subjective perception of cognitive effects is related more to mood than objective performance. Clinicians should be aware of this relationship when assessing patients' cognitive complaints.

["Fast-track" and elective, laparoscopic colo-rectal surgery]. / "Fast-track" und elektive laparoskopische Eingriffe am Kolorektum.

UNLABELLED: The aim of this prospective clinical evaluation was to investigate the influence of "Fast-track"-treatment in patients undergoing laparoscopic colorectal operations and its effect on morbidity, hospital stay and recovery. PATIENTS AND METHODS: Bowel cleaning under enteral hypercaloric nutrition (Biosorb Energie, Fa. Nutricia, Germany) was achieved with Fleet (Ferring Arzneimittel, Germany) one day prior to surgery. A peridural catheter was placed preoperatively. Intraoperative electrolyte substitution should not exceed 12 ml/kg KG/h. In case of decreasing intraoperative blood pressure hydroxyethylstarch 6% was substituted. The nasogastric tube was removed immediately after the operation, the urinary catheter was removed on the first postoperative day. The patients stayed on the intermediate care department for one night and started already there with oral feeding and mobilisation (for 2 h). The following days mobilisation increased to 4 h daily under normal enteral nutrition without infusions. RESULTS: Between June 2003 and January 2006, 147 patients undergoing elective colorectal surgery were included in this study. Diverticulitis (n = 114), malignant tumors of the sigmoid colon (n = 6) or rectal cancer (n = 13), colonic adenomas (n = 5), stenotic Crohn's disease (n = 4) and small bowel carcinoid (n = 1), rectal prolaps (n = 1) and elongated colon sigmoideum (n = 4) were indications for surgical treatment. Laparoscopic sigmoid resection (n = 117), left hemicolectomy (n = 11), ileocecal resection (n = 8), anterior resection with total mesorectal excision (n = 9), abdomino-perineal exstirpation (n = 1) and anterior-segmental resection of the rectum (n = 1) were performed. Drainages were removed on the 2nd, peridural catheter on the 3rd postoperative day. Defecation occurred in all patients until the 2 (nd) postop. day. Early postoperative complication rate was 15% (22/147 patients) without mortality. 8 patients (5%) with anastomotic leakage were reoperated. The mean hospital stay was 6 days. The re-admission rate was 3% (4/147 patients) and included one patient with anastomotic leakage. CONCLUSION: "Fast-track"-treatment in combination with minimal-invasive surgery is a safe and comfortable perioperative treatment for patients with elective colorectal operations.

Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model.

PURPOSE: We describe the technique of fluorescence image guided optical coherence tomography (FG-OCT). We examined its ability to enhance specificity and sensitivity for the noninvasive diagnosis of early bladder cancer. MATERIALS AND METHODS: Transitional cell carcinoma was developed in 54 Fisher 344 female rats by intravesical methyl-nitroso-urea instillations. Two or three rats were diagnosed sequentially by 5-ALA (5-aminolevulinic acid hydrochloride) induced fluorescence imaging, cross-sectional OCT and histological microscopy weekly during weeks 11 to 33 following initial methyl-nitroso-urea instillation to track the course of carcinogenesis. RESULTS: The specificity of fluorescence detection was significantly enhanced by FG-OCT (53% and 93%, respectively, p <0.0001). The sensitivity of fluorescence detection and FG-OCT was 79% and 100%, respectively. CONCLUSIONS: FG-OCT cystoscopy has the potential to diagnose early bladder cancer with high sensitivity and specificity with drastically decreased imaging time compared to that of white light guided OCT cystoscopy.

Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers.

BACKGROUND: The relative cognitive and behavioral effects of lamotrigine (LTG) and topiramate (TPM) are unclear. METHODS: The authors directly compared the cognitive and behavioral effects of LTG and TPM in 47 healthy adults using a double-blind, randomized crossover design with two 12-week treatment periods. During each treatment condition, subjects were titrated to receive either LTG or TPM at a target dose of 300 mg/day for each. Neuropsychological evaluation included 17 measures yielding 41 variables of cognitive function and subjective behavioral effects. Subjects were tested at the end of each antiepileptic drug (AED) treatment period and during two drug-free conditions (pretreatment baseline and 1 month following final AED withdrawal). RESULTS: Direct comparison of the two AEDs revealed significantly better performance on 33 (80%) variables for LTG, but none for TPM. Even after adjustment for blood levels, performance was better on 19 (46%) variables for LTG, but none for TPM. Differences spanned both objective cognitive and subjective behavioral measures. Comparison of TPM to the non-drug average revealed significantly better performance for non-drug average on 36 (88%) variables, but none for TPM. Comparison of LTG to non-drug average revealed better performance on 7 (17%) variables for non-drug average and 4 (10%) variables for LTG. CONCLUSIONS: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages employed may not have been equivalent in efficacy. Future studies are needed to delineate the cognitive and behavioral effects of TPM at lower dosages.

The influence of oxygenated water on the immune status, liver enzymes, and the generation of oxygen radicals: a prospective, randomised, blinded clinical study.

BACKGROUND & AIMS: Oxygenated water with an oxygen concentration of 30-120 mg/l water is believed to improve the immune status, without any toxicological effects. The purpose of this clinical study was to assess the effects of long-term drinking of oxygenated water on the immune status. METHODS: In this prospective, double-blinded, randomised study 24 volunteers of either sex (age 18-63 years) drank daily 3 times 500 ml either oxygenated (Verum-group: n=12) or normal mineral water (Placebo-group: n=12) for 28 days. On day 1 and day 28 standard laboratory tests, IgG, IgA and IgM, lymphocyte subpopulations and functional analysis of T-cells by flow cytometry, were done. Furthermore, the oxygen radicals were determined by the detection of the ascorbyl radicals. RESULTS: Drinking of normal or oxygenated water had no effect on whole blood count or the liver enzymes. Interestingly the volunteers in the Verum-group showed a significant increase in ascorbyl radicals after drinking oxygenated water for 14 and 21 days. CD4+ and CD4+CD45RA+ lymphocytes as well as lymphocyte activation marker (CD69) and soluble IL-2 receptor increased in both groups, in contrast T-helper2 cells and IgG decreased during the study. The only differences between the two groups were a significant decrease of NK-cells form 13.42%+ or -5.04 to 10.83%+ or -4.82 (P<.002) and an increase of the Th1/Th2-ratio from 2.77%+ or -1.07 to 6.68%+ or -5.33 (P<.03) in the Verum-group. CONCLUSION: Long-term consumption of oxygenated water has no apparent harmful effect on the liver, blood and the immune system. Moreover it leads to a transient moderate increase of oxygen radicals in the blood. An interesting observation is the increase of the Th1/Th2-ratio in the Verum group, whereas in both groups T-cell activation after mitogen stimulation, the soluble IL-2 receptor, the CD4+ and the naive CD4+CD45RA+ cells increased.

Regional celiac artery infusion in the adjuvant treatment of pancreatic cancer.

UNLABELLED: We performed adjuvant celiac artery infusion in pancreatic cancer, to find out whether this treatment prolongs survival and changes the biology of the disease after resection, especially by reducing liver metastasis. PATIENTS AND METHODS: Thirty-one patients received cyclic celiac artery infusions (CAI) after resection of their pancreatic cancer (27 ductal, 4 cystadenocarcinoma). The treatment consisted of 6 cycles (1 cycle = 5 days treatment) intra-arterial infusion using Seldingers technique with mitoxantrone A (Novantron) 10 mg/m2 d1, 5-fluorouracil + folinic acid 600 mg/m2 + 170 mg/m2 d2-d4 and cis-platinum 60 mg/m2 d5. Four to 5-week intervals between each cycle of chemotherapy were scheduled. The patients were monitored for toxicity, development of disease progression and survival. RESULTS: The median survival time was 21 months. During an observation period of 19 months, 70% of the patients developed disease progression. In 50% of cases the progression was local, in 40% intraperitoneal while in 15% liver metastases developed. The median survival time of the CAI (celiac artery infusion)-treated patient group compared favorably to the median survival of 9.3 months in a matched historical control group, being significantly longer (p < 0.0003). CONCLUSION: Adjuvant celiac artery infusion seemed to prolong median survival and the occurrence of liver metastases appeared to be delayed or reduced.

The generation of oxygen radicals after drinking of oxygenated water.

UNLABELLED: It has been speculated whether ingestion of oxygenated water can lead to an enhanced generation of oxygen radicals. The purpose of three prospective randomized blinded clinical studies was therefore to measure if, when and at which oxygen content in the water,drinking of oxygenated water induces the generation of radicals. Moreover in the fourth prospective,randomized, blinded study possible longterm effects of drinking oxygenated water were examined. METHODS: Altogether 66 volunteers were drinking 300 ml oxygenated or tap water within 15 minutes. Before drinking, altogether 15 ml of blood from the antecubital vein was collected for determination of ascorbyl radicals with ESR, routine laboratory data (hemoglobin, erythrocytes, hematocrit, leukocytes, thrombocytes, uric acid) and the vitamins A,C,E by HPLC. After drinking the ascorbyl radical measurements were repeated from blood of the antecubital vein. In the longterm study ( fourth study) the volunteers had to undergo the same procedure, as described above, at day 1 and day 21. In the meantime they were drinking per day three times 300 ml either oxygenated water or tap water. RESULTS: All subjects exhibited normal vitamin levels in all three studies. Concommitantly in the fourth study there was no statistically relevant alteration of vitamin concentrations during the observation period of three weeks in the verum and placebo-group. 30 minutes after drinking oxygenated water the concentration of ascorbyl radicals increased significantly by median 42 % from median 48 to 65 nmol/l. This increase of ascorbyl radicals after 30 minutes was reproducible in all studies. The levels of ascorbyl radicals remained elevated for 60 minutes after drinking and returned to normal after 120 minutes. This increase was independent of the oxygen concentration in the water, beginning at 30 mg oxygen/l. Water containing 15 mg oxygen/l did not lead to an enhanced radical formation. Longterm consumption of oxygenated water attenuated the ascorbyl radical increase normally observed, thus the initial increase of ascorbyl radicals at day 1 could not be observed after day 21, if the subjects were drinking oxygenated water regularly during the observation period. CONCLUSION: Drinking of oxygenated water possibly leads to a time-limited, yet very moderate, systemic generation of radicals. Regular consumption of oxygenated water over a longer period of time seems to attenuate this effect. The mechanisms leading to this effect and adaptation are unknown.

Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors.

Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding regions have been reported in cancer. The mechanisms that generate such mutations and the importance of mtDNA mutations in tumor development are still not clear. Here we present the identification of a specific and highly polymorphic homopolymeric C stretch (D310), located within the displacement (D) loop, as a mutational hotspot in primary tumors. Twenty-two % of the 247 primary tumors analyzed harbored somatic deletions/insertions at this mononucleotide repeat. Moreover, these alterations were also present in head and neck preneoplastic lesions. We further characterized the D310 variants that appeared in the lung and head and neck tumors. Most of the somatic alterations found in tumors showed deletion/insertions of 1- or 2-bp generating D310 variants identical to constitutive polymorphisms described previously. Sequencing analysis of individual clones from lymphocytes revealed that patients with D310 mutations in the tumors had statistically significant higher levels of D310 heteroplasmy (more than one length variant) in the lymphocyte mtDNA as compared with the patients without D310 mutations in the tumor mtDNA. On the basis of our observations, we propose a model in which D310 alterations are already present in normal cells and achieve homoplasmy in the tumor through a restriction/amplification event attributable to random genetic drift and clonal expansion.

Molecular detection of prostate cancer in urine by GSTP1 hypermethylation.

Novel approaches for the early detection and management of prostate cancer are urgently needed. Clonal genetic alterations have been used as targets for the detection of neoplastic cells in bodily fluids from many cancer types. A similar strategy for molecular diagnosis of prostate cancer requires a common and/or early genetic alteration as a specific target for neoplastic prostate cells. Hypermethylation of regulatory sequences at the glutathione S-transferase pi (GSTP1) gene locus is found in the majority (>90%) of primary prostate carcinomas, but not in normal prostatic tissue or other normal tissues. We hypothesized that urine from prostate cancer patients might contain shed neoplastic cells or debris amenable to DNA analysis. Matched specimens of primary tumor, peripheral blood lymphocytes (normal control), and simple voided urine were collected from 28 patients with prostate cancer of a clinical stage amenable to cure. Genomic DNA was isolated from the samples, and the methylation status of GSTP1 was examined in a blinded manner using methylation-specific PCR. Decoding of the results revealed that 22 of 28 (79%) prostate tumors were positive for GSTP1 methylation. In 6 of 22 (27%) cases, the corresponding urine-sediment DNA was positive for GSTP1 methylation, indicating the presence of neoplastic DNA in the urine. Furthermore, there was no case where urine-sediment DNA harbored methylation when the corresponding tumor was negative. Although we only detected GSTP1 methylation in under one-third of voided urine samples, we have demonstrated that molecular diagnosis of prostate neoplasia in urine is feasible. Larger studies focusing on carcinoma size, location in the prostate, and urine collection techniques, as well as more sensitive technology, may lead to the useful application of GSTP1 hypermethylation in prostate cancer diagnosis and management.

Renal artery pseudoaneurysm occurring after partial nephrectomy.

Retroperitoneal hemorrhage resulting from intrarenal pseudoaneurysm formation has been reported after percutaneous renal surgery. However, although hemorrhage is a well-recognized complication of partial nephrectomy, hemorrhage caused by an intrarenal pseudoaneurysm after open partial nephrectomy is rare. We report a case of retroperitoneal hematoma associated with a renal artery pseudoaneurysm occurring in a 56-year-old woman 2.5 weeks after she underwent left partial nephrectomy for renal cell carcinoma. The pseudoaneurysmal branch was successfully identified and selectively embolized using percutaneous renal arterial angiography.

Clinical significance of denuded urothelium in bladder biopsy.

PURPOSE: Although to our knowledge the significance of denuded urothelium in bladder biopsies has not been studied previously, it is thought to be a problem because benign urothelial cells are cohesive and not expected to shed into the urine. We correlated the pertinent clinical features of patients with denuded bladder biopsies and/or specific pathological features of denuded bladder biopsy specimens with patient outcome in regard to bladder lesions to help predict the subsequent likelihood of diagnosing bladder carcinoma in a patient with a nondiagnostic denuded biopsy. MATERIALS AND METHODS: We studied 51 denuded bladder biopsies from 44 patients in which the average extent of epithelial denudation was 90%. RESULTS: Of the 27 male (69%) and 17 female (31%) patients 22 to 86 years old (mean age 62) 34% had no history of bladder neoplasms. In remainder there were flat carcinoma in situ with or without other tumors (26%), high (20%) and low (14%) grade papillary tumors without carcinoma in situ and miscellaneous conditions (6%). Overall 31% of patients were diagnosed with carcinoma in situ within 24 months (median 5.5) after the denuded specimen was obtained. Parameters that did not correlate with the subsequent diagnosis of carcinoma in situ included cystoscopic impression, history of intravesical chemotherapy, sex, age, tissue inflammation, percent of tissue fragments with any denudation, number of denuded tissue fragments and percent of overall denuded epithelium. A history of carcinoma in situ before denuded biopsy predicted a diagnosis of carcinoma in situ within 24 months after denuded biopsy in 54% of patients in contrast to 19% of those without a history of carcinoma in situ (p = 0.03). Factoring in a history of other bladder tumor types in various combinations did not predict carcinoma in situ after denuded biopsy. The other predictive factor was cold cup biopsy. Carcinoma in situ developed within 24 months in 45% of patients in whom the denuded specimen was obtained by cold cup biopsy in contrast to none who underwent hot wire loop biopsy (p = 0.007). Cold cup biopsy and a history of carcinoma in situ were independently predictive. Carcinoma in situ developed within 24 months in 75% of patients with a history of that condition and a subsequent cold cup biopsy showing denuded epithelium. However, only 29% of those who underwent cold cup biopsy and had no history of carcinoma in situ were diagnosed with carcinoma in situ. CONCLUSIONS: In bladder biopsies obtained by a hot wire loop denudation most likely results from thermal injury when there is a low risk of subsequent carcinoma in situ. When the denuded biopsy sample was obtained by cold cup biopsy, particularly when associated with a history of carcinoma in situ, most cases represent neoplastic cell denudation and a high risk for subsequent carcinoma in situ.