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Papillomas of the upper urinary tract may be multiple, developing either simultaneously or at various times. Recurrence may occur many years after surgical treatment, even after thirty years, as in the case we report.
Recurrence of atrial fibrillation (AF) after cardioversion (CV) to sinus rhythm (SR) is determined by various clinical and echocardiographic parameters. The aim of this study was to determine the value of mitral inflow A-wave velocity, performed at 24 hours after CV in estimation of AF recurrence. The study group consisted of 187 consecutive patients with nonvalvular atrial fibrillation, who had been cardioverted to SR from 1998 to 2000. Transthoracic echocardiography was performed in all cases recruited for the study 24 hours after CV. Left atrial (LA) diameter, left ventricular ejection fraction, and mitral inflow A-wave velocity were measured. The patients were evaluated in five groups according to their recurrence time (<30 days, 31-90 days, 91-180 days, 181-365 days, and >365 days). Maintenance of SR was determined to have a negative linear correlation with age (r =-0.97, P = 0.006), LA diameter (r =-0.93, P = 0.02), and AF duration (r =-0.93, P = 0.02), while having a positive linear correlation with mitral inflow A-wave velocity (r = 0.96, P = 0.008). In the maintenance of sinus rhythm, age, LA diameter, and AF duration were not affected from the method of CV, while mitral inflow A-wave velocity was found to be affected with the method of CV. No relationship was determined between mitral inflow A-wave velocity and the maintenance of sinus rhythm in those performed electrical cardioversion, while frequency of recurrence was found to be higher in those with slow mitral inflow A-wave velocity who were performed pharmacological cardioversion (r = 0.89, P = 0.004). In conclusion, age, duration of AF, LA diameter, and the mitral inflow A-wave velocity can be used to predict the maintenance of SR after CV.
OBJECTIVE: To compare local resection of early rectal tumours by transanal endoscopic microsurgery (TEM) and the conventional posterior trans-sphincteric approach (Mason's operation). METHODS: The study group comprised 31 consecutive patients with early rectal tumours (18 villous adenomas, 13 adenocarcinomas) who underwent TEM in Kwong Wah Hospital, Hong Kong. The control group consisted of 51 patients with early rectal tumours (27 villous adenomas, 24 adenocarcinomas) who underwent Mason's operation in Peking Union Medical College Hospital, Beijing. Outcome measures included morbidity and mortality, operation time, recurrence rate and postoperative pathological staging. RESULTS: Age, sex and pathological staging were similar in the two groups. The tumour size, operation time and blood loss were similar. The median distance from the anal verge was significantly higher in the TEM group (TEM/Mason = 8.0/6.4 cm, p = 0.042). The postoperative resumption of food intake (TEM/Mason = 1/5 days, p = 0.002) and the median hospital stay (TEM/Mason = 4/10 days, p = 0.005) were significantly shorter in the TEM group. Analgesic intake was significantly less in the TEM group (TEM/Mason = 0/100 mg, p = 0.0003). There was no operation-related mortality and the resection margins were clear in both groups. Two patients (3.9%) in the Mason's group developed postoperative wound infection, and two patients (3.9%) developed faecal fistulae. There was one secondary haemorrhage in the TEM group that required injection sclerotherapy. On median follow-up of 23 months, there was no tumour recurrence in the TEM group, whereas two patients (3.9%) in the Mason's group experienced recurrence during a median follow-up of 30 months. CONCLUSION: TEM is as effective as the conventional posterior trans-sphincteric approach (Mason's operation) for local curative resection of early rectal tumours. TEM is less invasive, with shorter hospital stay and fewer complications than conventional Mason's operation.
Secondary repair of recurrent ventral hernia is difficult, and success depends on re-establishing the functional integrity of the abdominal wall. Current techniques used for closure of these defects have documented recurrence rates as high as 54 percent. The authors' 8-year experience utilizing variations of the components separation technique for autologous tissue repair of recalcitrant hernias emphasizes that recurrent or recalcitrant hernias benefit from the creation of a dynamic abdominal wall. A total of 389 patients were retrospectively identified as having abdominal wall defects, and 284 of these patients met the selection criteria. Study patients were grouped according to the type of surgical repair used. The recurrence rate was 20.7 percent over all study groups and was directly related to the extent of repair required. Group 1 patients (wide tissue undermining) had a recurrence rate of only 15 percent, while in group 2 (complete components separation), the recurrence rate was 22 percent. Group 3 patients (interpositional fascia lata graft) had a 29 percent recurrence rate. Time to recurrence was also significantly different across treatment groups, with study group 3 experiencing earlier hernia recurrence. The most frequent postoperative complication was wound infection, which was directly related to the repair performed. The relative odds of recurrence versus the risk factors of age, sex, perioperative steroid use, wound infection, defect size, and the presence of enterocutaneous fistula were studied with a logistic regression analysis. These factors did not possess statistical significance for predicting hernia recurrence. The preoperative presence of mesh was independently significant for hernia recurrence, increasing the relative odds 2.2 times (p = 0.01). Similarly, when other risk factors were controlled for, increasing the complexity of the treatment group, from study group 1 (wide tissue undermining) to study group 3 (interpositional fascia lata graft), also increased the odds of hernia recurrence 1.5-fold per group (p = 0.04). Average inpatient cost was $24,488. The length of inpatient stay ranged from 2 to 172 days (average, 12.8 days). The length of inpatient stay and costs were directly related to the extent of repair required. Using the analysis of variance test for multiple factors, the presence of an enterocutaneous fistula (p = 0.0014) or a postoperative wound infection (p = 0.008) independently increased the length of inpatient stay and hospital costs. A total of 108 successfully repaired patients were contacted by telephone and agreed to participate in a self-reported satisfaction survey. The patients noticed improvements in the appearance of their abdomen, in their postoperative emotional state, and in their ability to lift objects, arise from a chair or a bed, and exercise. These results suggest that recalcitrant hernia defects should be solved, when possible, by reconstructing a dynamic abdominal wall.
Universal Learning Networks (ULNs) are proposed and their application to chaos control is discussed. ULNs provide a generalized framework to model and control complex systems. They consist of a number of inter-connected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. Therefore, physical systems, which can be described by differential or difference equations and also their controllers, can be modeled in a unified way, and so ULNs may form a super set of neural networks and fuzzy neural networks. In order to optimize the ULNs, a generalized learning algorithm is derived, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. The derivatives are calculated by using forward or backward propagation schemes. These algorithms for calculating the derivatives are extended versions of Back Propagation Through Time (BPTT) and Real Time Recurrent Learning (RTRL) of Williams in the sense that generalized node functions, generalized network connections with multi-branch of arbitrary time delays, generalized criterion functions and higher order derivatives can be deal with. As an application of ULNs, a chaos control method using maximum Lyapunov exponent of ULNs is proposed. Maximum Lyapunov exponent of ULNs can be formulated by using higher order derivatives of ULNs, and the parameters of ULNs can be adjusted so that the maximum Lyapunov exponent approaches the target value. From the simulation results, it has been shown that a fully connected ULN with three nodes is able to display chaotic behaviors.
OBJECTIVES: This study sought to determine whether the time to first recurrence of syncope after a positive isoproteremol-tilt table test result accurately predicts the eventual frequency of syncope. BACKGROUND: Both patient care and future clinical trials involving patients with neuromediated syncope will require a simple measure that reflects the frequency of syncope. The time from tilt table testing to the first recurrence of syncope might be such a measure. METHODS: A cohort of 46 patients with syncope, in a university outpatient clinic, who had at least one syncopal spell after a positive isoproterenol-tilt table test result were followed up for up to 6.5 years (mean [+/-SD] 48 +/- 14 months). The time from tilt table testing to the first recurrence of syncope was correlated. RESULTS: A total of 40 of 46 patients had more than one recurrent spell, with a median of eight recurrent spells. The time to the first syncopal spell predicted the frequency of spells with r = -0.79 (p < 0.001), whereas the time to the second spell predicted the frequency with r = -0.92 (p < 0.001). Patients who fainted within 1 month of tilt testing had a geometric mean frequency of 1.35 spells/month (95% confidence limits 0.49, 3.74) compared with patients who fainted 1 to 24 months after testing (0.12 spells/months; 95% confidence limits 0.07 to 0.18, p < 0.001). Finally, the frequency of syncopal spells bore no relation to the duration of follow-up. CONCLUSIONS: The time to the first recurrent spell predicts the frequency of syncopal spells after a positive tilt table test result, and the instantaneous risk of syncope is constant.
Recurrent groin hernia is not uncommon in Taiwan. Subsequent surgical repairs are difficult, due to cicartrization and deterioration of the inguinal floor. In this report, the intermediate and long-term outcomes of 212 patients with recurrent groin hernias who underwent surgical repair within a 10-year period were analyzed in order to assess the effectiveness of two modified repair techniques. Patients with unilateral first-time recurrent hernia (UR; n = 87) were treated by a modified Shouldice technique using an inguinal approach. Those with bilateral or multiple recurrences (MRs; n = 125) were treated with giant prosthetic reinforcement of the visceral sac (GPRVS, Stoppa operation) using a midline preperitoneal approach. Complete exploration of the groin floor on the side of recurrence revealed a high rate of direct space defects (UR, 41.5%; MR, 65%) and multiple posterior wall defects (UR, 29.9%; MR, 30%). In the UR group, a 4 x 10-cm preperitoneal prosthetic mesh was incorporated to reinforce the repair. For MR patients, I reduced the transverse dimension of the mesh prosthesis by 2 cm compared with the original Stoppa protocol; to reduce crinkling, the average dimensions were 23 x 14 cm. Complications in the UR group included testicular atrophy (3 patients) and femoral vein thrombosis (1). Complications in the MR group were transient scrotal fluid accumulation (9 patients), fatal perioperative acute myocardial infarction (1), and failure of the peritoneum to grow over the mesh (1). The average hospital stay was 3 days in the UR group and 6 days in the MR group. The long-term follow-up (1-9 years) revealed a 5.7% re-recurrence rate with an 86.2% follow-up rate in the UR group, and a 1.9% re-recurrence rate with an 86.6% follow-up rate in the UR group. I conclude that GPRVS is an excellent treatment for URs, but the transverse dimension of the prosthetic mesh should be reduced for Taiwanese subjects. However, for first-time MRs, a modified Shouldice technique with incorporation of a preperitoneal prosthetic mesh is still recommended. The surgical dissection is less extensive and the hospital stay is shorter, while the re-recurrence rate is acceptably low.
OBJECTIVE: To evaluate responses of cats with vaccine-associated sarcomas to treatment with surgery and radiotherapy, with or without adjunctive chemotherapy. DESIGN: Retrospective study. ANIMALS: 76 cats (78 tumors). PROCEDURE: Medical records were reviewed. Factors potentially associated with survival time, time to recurrence, and time to development of metastases were evaluated. RESULTS: Following excision, electron beam radiation, and, in some cases, chemotherapy, 32 (41%) cats experienced recurrence, and 9 (12%) cats developed metastases. One- and 2-year survival rates were 86 and 44%, respectively. Median survival time from onset of disease was 730 days (range, 30 to 2,014 days). Median disease-free interval was 405 days (range, 30 to 925 days). Cats that underwent only 1 surgery prior to radiotherapy had a lower recurrence rate than did cats that underwent > 1 surgery and had a significantly longer disease-free interval. Survival time and disease-free interval decreased as time between surgery and the start of radiotherapy increased. Cats that developed metastases had significantly shorter survival times and disease-free intervals than did cats that did not develop metastases. Castrated male cats had a significantly shorter survival time than did spayed female cats. Cats with larger tumors prior to the first surgery had shorter survival times. Twenty-six cats received chemotherapy in addition to surgery and radiotherapy. Whether cats received chemotherapy was not associated with recurrence rate, metastasis rate, or survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that excision followed by electron beam irradiation may be beneficial for treatment of cats with vaccine-associated sarcomas. Extent of excision prior to radiotherapy did not seem to be associated with recurrence rate.
BACKGROUND: Gastrointestinal intolerance is observed more frequently during intraduodenal (ID) tube feeding than during intragastric (IG) feeding, possibly because it evokes a stronger gastrointestinal response and accelerates small bowel transit. We have investigated whether the accelerated small bowel transit during ID feeding results from alterations in antroduodenal motility pattern. DESIGN: The effect of IG and ID infusion of a polymeric diet (Nutrison, 125 kcal h-1) on antroduodenal motility, small bowel transit time (SBTT) and gastrointestinal hormone release was studied in nine healthy subjects. These subjects were studied on three occasions for 6 h during fasting, continuous IG or ID feeding. RESULTS: Phase III recurrence time was significantly prolonged during IG feeding compared with fasting (240 +/- 51 vs. 136 +/- 24 min; P < 0.05). None of the subjects had recurrence of phase III during ID feeding; the fed motor pattern remained present. Parameters of fed motility (mean amplitude and motility index) were not significantly different between IG and ID feeding, although the frequency of antral and duodenal contractions was lower during ID than during IG feeding. SBTT was significantly accelerated during ID compared with IG feeding and with fasting (58 +/- 8 vs. 73 +/- 9 and 83 +/- 10 min respectively; P < 0.05). Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were significantly higher during ID than during IG feeding. Peptide YY (PYY) levels were significantly higher during ID than during fasting, but not during IG feeding CONCLUSIONS: During intraduodenal feeding, a fed motility pattern is preserved, whereas during intragastric feeding transition from a fed to a fasting motor pattern is observed in over 50% of the subjects. These differences may be related to augmented hormone release during intraduodenal feeding.
PURPOSE: To study BCL10 expression in ocular adnexal lymphoma in the US population and its association with clinical outcomes. DESIGN: Institutional, retrospective study. METHODS: Immunohistochemistry was performed with antibody against BCL10 on two tissue microarray blocks that were constructed with paraffin-embedded tissues from the same cohort of 48 patients with ocular adnexal lymphomas. The main outcomes that were measured include extraorbital involvement, recurrence rate, and time to recurrence. The median length of the follow-up period was 40 months. RESULTS: Aberrant BCL10 expression (nuclear [moderate intensity] and cytoplasmic [weak to moderate intensity] staining) was observed in 10 of 33 cases (30.3%) of mucosa-associated lymphoid tissue (MALT) lymphoma, in 4 of 10 cases (40%) of follicular lymphoma (grade 1, 9 cases; grade 2, 1 case), in 0 of 2 cases of diffused large B-cell lymphoma, in 0 of 1 case of chronic lymphocytic leukemia/small lymphocytic lymphoma and in 1 of 1 case (100%) of mantle cell lymphoma. There were no differences in clinical parameters at examination (ie, average age, gender, site of occurrence, laterality, extraorbital involvement at diagnosis), recurrence rate, and time to recurrence for patients (MALT lymphoma or follicular lymphoma) with or without aberrant nuclear BCL10 expression. CONCLUSION: Aberrant BCL10 expression can occur in other types of ocular adnexal lymphomas besides MALT lymphoma. Ocular adnexal MALT lymphoma may have slightly lower frequency of aberrant BCL10 expression than gastric/pulmonary MALT lymphomas that have been reported in the literature. Furthermore, aberrant BCL10 nuclear expression in ocular adnexal lymphoma does not seem to correlate with clinical outcome. Further studies that include a larger number of cases and longer follow-up period are needed to confirm our observation.
UNLABELLED: Experience with early corticosteroid withdrawal (CSWD) in renal transplant recipients with focal segmental glomerulosclerosis (FSGS) has not been previously reported. Since corticosteroids are used to treat primary FSGS, concern exists as to whether early CSWD regimens will be associated with an increased risk of FSGS recurrence posttransplant. The purpose of the present study was to evaluate the results of early CSWD in FSGS recipients and compare these results to a historic control group of FSGS patients who underwent renal transplantation under corticosteroid-based immunosuppression. METHODS: Forty-three patients with FSGS underwent renal transplantation with early CSWD. Results in these patients were compared to FSGS patients that underwent renal transplantation with chronic corticosteroid therapy. All rejection episodes were biopsy proven with grading by Banff criteria. Statistical analyses included Student's t test and chi square tests. RESULTS: Results in 43 patients with a median follow-up of 569 days were analyzed and compared to control patients. There was no significant difference in recurrent FSGS, time to recurrence, or graft loss. CONCLUSION: CSWD does not increase risk for recurrence of FSGS. These observations indicate that ECSW can be achieved in FSGS patients, thereby affording them the benefits of steroid elimination.
In a semi-infinite geometry, a one-dimensional, M-component model of biological evolution realizes microscopically an inhomogeneous branching process for M-->infinity. This implies a size distribution exponent tau(')=7/4 for avalanches starting at a free, "dissipative" end of the evolutionary chain. A bulklike behavior with tau(')=3/2 is restored by "conservative" boundary conditions. These are such as to strictly fix to its critical, bulk value the average number of species directly involved in an evolutionary avalanche by the mutating species located at the chain end. A two-site correlation function exponent tau(')(R)=4 is also calculated exactly in the "dissipative" case, when one of the points is at the border. Together with accurate numerical determinations of the time recurrence exponent tau(')(first), these results show also that, no matter whether dissipation is present or not, boundary avalanches have the same space and time fractal dimensions as those in the bulk, and their distribution exponents obey the basic scaling laws holding there.
In this study, we compared the recurrence of metastatic brain tumors after radiosurgery versus after surgery plus radiation, and analyzed the factors associated with the recurrence of brain metastases. Twenty-eight and 35 patients with metastatic brain tumors underwent radiosurgery (52 lesions) and surgery plus radiation (46 lesions), respectively, between 1995 and 2001. The median tumor volume was 1.55 ml (range: 0.02-10.4 ml) in radiosurgery patients and 17.9 ml (range: 0.26-195 ml) in surgery plus radiation patients. The median radiosurgical tumor central and margin doses were 28.9 and 23.8 Gy (range: 20-35 and 25-15 Gy), respectively. The median total dose was 46.7 Gy (range: 30-63 Gy) in the surgery plus radiation group. The recurrence time from surgery plus radiation group (25 months) was significantly longer than that from the radiosurgery group (7.2 months) (p = 0.0199). The factors affecting the recurrence of brain metastases after radiosurgery were size, central dose of radiation and histology (colon vs. others). No factors affected the recurrence of brain metastases after surgery plus radiation. To avoid early recurrences of metastatic brain tumors, surgery plus radiation is the preferable therapeutic modality. The size and histology of brain metastases, and the dose of radiation should be considered for the effective treatment of tumors by radiosurgery.
OBJECTIVE: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-alpha (IFNalpha-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. MATERIAL AND METHODS: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNalpha-2b (8 weekly, 8 fortnightly and 6 monthly instillations). RESULTS: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A-D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1-3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). CONCLUSION: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNalpha-2b showed a better combination of efficacy and safety.
INTRODUCTION: Tuberous sclerosis is an autosomal dominant disease in which hamartomas form in multiple organs. Cutaneous changes are one of the primary characteristics of this disease. These include angiofibromas (AF), a common form of presentation that causes significant cosmetic and medical problems. The CO2 laser has been used satisfactorily in treating these lesions, but there are few studies that evaluate its long-term results. The aim of our study is to assess the long-term response of the treatment of angiofibromas. METHODS: A retrospective study was carried out on 23 patients with angiofibromas treated with CO2 laser. The patients were treated between 1991 and 2000, inclusive, with continuous or superpulsed CO2 laser. We classified the angiofibromas by size, initial treatment results and patients' ages (< 20 years and 20 years or older). RESULTS: Ages ranged from 12 to 39 years, with a median age of 22.5 years. After treatment, patients were followed up for a period of six months to 10 years. In the long-term analysis, we found that 30.1 % maintained the initial result, and 60.9 % showed different degrees of recurrence, with a mean recurrence time of 3 years. When we analyzed the long-term results by the size of the angiofibromas, initial result and patients' ages, we found no statistically significant differences among the different groups. The survival analysis of the age groups, with Kaplan-Meier curves, showed that the youngest patients (< 20 years) had earlier recurrences than the older ones (logarithmic range 4.01 and p < 0.05). CONCLUSIONS: CO2 laser treatment achieves good short-term results. On the other hand, one of the biggest problems is recurrence over the long term; this is probably due to the fact that, because of their nature, these lesions cannot be eliminated permanently. This work coincides with earlier studies which found no factors that would make it possible to predict the recurrence of the lesions. However, we can conclude that recurrence takes place at a later date in older patients, and therefore they have better cosmetic results over the long term.
Groin hernia operation is the third most frequent operation in the Czech republic. Early recurrence of the hernia after prime operation is a medical failure. The recurrences can arise after all types of operation. Incidence of recurrences, time factors of its genesis and treatment are discussed there.
Between June 1986 and August 1988, 129 patients with AIDS-related Kaposi's sarcoma were treated by cutaneous irradiation in our department. According to Mitsuyasu's staging, 25 patients (19%) were stage 1.76 (59%) stage II, no stage III was reported and 28 (22%) stage IV. Fifty four patients (42%) had previously presented with one or multiple opportunistic infections. Eighty six (66%) had previously received treatment: by interferon in 80 patients (62%) and/or Velbe in 40 (31%). Seventy six patients (59%) were treated by extensive cutaneous irradiation using 4 and/or 8 MeV electron beam energy and 53 patients (41%) by localized irradiation using 45 kV X-ray energy, 2.5 Gy/fraction, 4 times/week by split course 20 Gy then 10 Gy two weeks later. Only 111 patients were evaluable; 61% obtained complete remission and 33% partial remission after a mean period of 1.5 months (0.5-3 months). The overall tolerance was acceptable. The complications were epidermitis with some necrosis (8%), exudative epidermitis (26%) moderate epidermitis (63%) and slight reactions in 4%. The mean recurrence time was 5 1/2 months.
To determine whether transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of human hepatocellular carcinoma (HCC) we used reverse transcription-PCR to examine mRNA FHIT expression in 28 paired samples of HCC (24 in cirrhotic and 4 in noncirrhotic livers) and matched noncancerous tissue and in 10 normal livers. We also assessed loss of heterozygosity of the polymorphic D3S1300 microsatellite marker in the intron between exons 5 and 6 of the FHIT gene. Abnormal FHIT transcripts were detected in 13 cases (46.4%): 10 in the cancerous tissue only, 1 with the same pattern in both cancerous and matched noncancerous tissue, and 2 in the noncancerous tissue only. The four HCCs that arose in noncirrhotic liver all showed abnormal FHIT transcripts. No alterations were found in normal livers. Sequence analysis of abnormally sized transcripts revealed that they were generated by the fusion of exons 3 or 4 with exons 8 or 9. Among the cancerous specimens, one case showed only an abnormal sized transcript derived from the fusion of exons 4 and 9 in the absence of any normal-sized transcript, and another case showed deletion of a sequence comprised between nucleotides -35 and 399 resulting in an exon 4-9 fusion not respecting the exons' bounds. Loss of heterozygosity was found in two cases with abnormal FHIT transcripts and in only one case with normal transcript. Patients with aberrant FHIT transcripts showed a significantly higher relapse rate and shorter recurrence time (P = 0.001). This could be related to a primary genomic instability affecting particularly susceptible regions like FRA3B and could be associated with an increasing risk of recurrence without involving a causative role.