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PubMed1999

[125 reinterventions for recurrent popliteal varicose veins after excision of the short saphenous vein. Anatomical and physiological hypotheses of the mechanism of recurrence].

Recurrence of popliteal varicose veins has long been attributed to insufficient excision of an incompetent short saphenous vein. Indeed, recurrence is still frequent after surgery of the short saphenous. In order to assess the risk of insufficient excision and study the mechanism of recurrence, we reviewed 125 popliteal procedures for recurrence after excision of an incompetent short saphenous vein. Among this series, 48 were personal procedures and among these, 43 had been performed without preoperative ultrasound explorations prior to 1991. Recurrences were classified into five categories (table I) according to the anatomic presentation at reoperation. Type 1) 17 patients had an intact short saphenous (13.6%) with either an inadequate incision or a simple recanalized suture. Type 2) 53 patients had a long stump (42.4%) with new superficial varicose communications. Type 3) 4 patients had a small residual and incompetent short saphenous trunk (3.2%), 20 patients had both a long stump and an incompetent residual trunk (16%). Type 4) 29 patients had incompetent popliteal perforating veins (23.2%). Type 5) 2 patients developed recurrence on a new varicose communication which followed the posterior nerves of the thigh. Among our personal series, 43 reoperations for recurrence were performed without preoperative duplex Doppler exploration. Among them, excision was insufficient in 38 (table II). The 5 patients reoperated after preoperative ultrasound exploration had a popliteal perforating vein. Recurrence with a popliteal perforator was significantly more frequent in men than in women (table III). The delay to reoperation for popliteal recurrence after surgery of the short saphenous (50% at 6 years) was significantly shorter than the delay to reoperation for inguinal recurrence after surgery of the greater saphenous (50% at 12 years) (table V). Insufficient excision was observed in 75.2% of the cases, but 23.2% of the recurrences were due to the development of an incompetent popliteal perforating veins. These perforating veins were residual stumps of the short saphenous with complex pathways, unrecognized perforating veins associated with the short saphenous at the first operation, or a new popliteal incompetence. Ces perforantes de la fosse poplitée pourraient être des moignons résiduels de petites saphènes à trajet complexe, des perforantes méconnues associées à la petite saphène developing in several perforating vessels described in the popliteal fossa. The lack of preoperative ultrasound data made it difficult to interpret these recurrences. The development of perforating veins in the popliteal fossa is a type of recurrence which is probably the expression of particular hemodynamic phenomena in the popliteal venous circulation. These phenomena probably involve the flexion of the popliteal vein, the contraction of the calf muscles, and also popliteal valvular incompetence frequently demonstrated in patients who develop short saphenous vein insufficiency.

Female↗

PubMed1988

Metastatic pattern in recurrent breast cancer. Special reference to intrathoracic recurrences.

The anatomical and temporal patterns of recurrence were studied in 401 patients with first recurrence of breast cancer. All patients underwent the same scheduled investigation program: history, physical examination, blood tests, bone scanning, bilateral iliac crest biopsy, radiologic bone survey, chest x-rays, and ultrasound scanning of the liver. The current article focuses on the diagnosis of intrathoracic (ITH) recurrence. Most patients recurred in a single site and 50% of the recurrences were diagnosed within the first 2 years from initial diagnosis. Chest x-ray revealed ITH recurrence in 27% (109 patients), and in 8% the lung, pleura, and/or mediastinum were the only signs of recurrence. Generally, the status of primary demographic, clinical, and pathoanatomical characteristics were not predictive as to the development of ITH recurrence, although patients with pleural recurrences often had centrally located primary tumors, locally advanced disease, and often received adjuvant radiotherapy. Clinical symptoms and signs of ITH recurrence were present in only one third of the patients, and the diagnostic specificity and sensitivity of serum lactate dehydrogenase were only 33% and 85%, respectively. Since ITH recurrences often are silent, and since recurrence in this site may have both prognostic and therapeutical implications, routine chest x-ray is indicated in all patients with first recurrence of breast cancer.

Breast Neoplasms↗

PubMed1996

Clinical and histopathological analysis of proliferative potentials of recurrent and non-recurrent meningiomas.

Proliferative potentials of meningiomas from 127 patients were examined immunohistochemically using the anti-Ki-67 monoclonal antibody, MIB-1, on paraffin sections, and the correlation among MIB-1 staining index (SI), histopathological finding, and clinical course of the disease was analyzed retrospectively. The mean MIB-1 SI of 50 male patients with meningioma was 5.5%, whereas that of 77 female patients was 2.7%. Higher MIB-1 SI were observed for younger patients. These age- and sex-related differences in MIB-1 SI were statistically significant. The patients were assigned to one of three groups: those with non-recurrent meningioma (n = 73); those with recurrent meningioma in whom the specimens obtained during the initial surgery were used to calculate the MIB-1 SI (n = 21); and those with recurrent meningioma for whom the specimens obtained during the surgery for recurrent tumors were used to calculate the MIB-1 SI (n = 33). The mean MIB-1 SI in these patients were 1.6%, 3.6%, and 8.8%, respectively, and there were statistically significant differences among these three groups. Statistical analyses reveal that meningiomas with a MIB-1 SI of 3% or more have a significantly high tendency for recurrence during the clinical courses, especially within the first 10-year follow-up periods. Moreover, there is statistically significant correlation between MIB-1 SI and recurrence in each Simpson's grade. The time interval to the next recurrence for recurrent meningiomas is associated with the proliferative potential represented by the MIB-1 SI, and a correlation equation has been proposed to predict the date of the next recurrence. Analyses on cellularity of meningiomas revealed no statistically significant difference in cellularity between non-recurrent and recurrent meningiomas. There was no statistically significant relationship between cellularity and MIB-1 SI of meningiomas. In conclusion, examination on proliferative potentials of meningiomas using MIB-1 SI is very important for biological and histopathological analyses and the prediction of future recurrence.

Adult↗

PubMed1994

Recurrence of primary intracranial germinomas after complete response with radiotherapy: recurrence patterns and therapy.

Nine germinoma patients are described who developed a recurrence after a complete response to radiation without adjuvant chemotherapy. Extraembryonic tumors producing alpha-fetoprotein and human chorionic gonadotropin were excluded from this study. Four patterns of recurrence are described with respect to mechanism and appropriate treatment. Type I germinoma recurrence, characterized by intracranial recurrence caused by an inadequate initial irradiation field was treated by total craniospinal irradiation. Type II recurrence, characterized by a benign teratoma caused by late growth of the teratoma component was treated by surgery alone. All patients with these patterns of recurrence are still alive. Type III local recurrence is characterized by human chorionic gonadotropin- or alpha-fetoprotein-producing tumors of extraembryonic origin. This pattern of recurrence should be treated by chemotherapy or radiosurgery, because all these patients died. Type IV germinoma recurrence consists of extraneural metastasis without evidence of intracranial recurrence. Two of these patients were treated with chemotherapy. In summary, four patients died after recurrence, whereas the remaining five patients survived. The classification of germinoma recurrence patterns should facilitate the selection of the most appropriate treatment. However, it has been difficult to identify the precise histopathology by biopsy or partial resection alone. Furthermore, chemotherapy is indicated in treating germinomas that have a ventriculoperitoneal shunt because of the risk of extraneural metastases.

Adolescent↗

PubMed2003

Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery?

OBJECTIVE: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. METHODS AND MATERIALS: A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. RESULTS: Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. CONCLUSION: There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.

Adenocarcinoma↗

PubMedDate not supplied

Usefulness of proton pump inhibitor (PPI) maintenance therapy for patients with H. pylori-negative recurrent peptic ulcer after eradication therapy for H. pylori: pathophysiological characteristics of H. pylori-negative recurrent ulcer scars and beyond acid suppression by PPI.

BACKGROUND/AIMS: Problems after Helicobacter pylori (Hp) eradication therapy include recurrence of Hp-negative peptic ulcers. We investigated the pathophysiological characteristics of Hp-negative recurrent ulcer scars, and performed proton pump inhibitor (PPI) maintenance therapy as a new therapy for prevention of recurrence in patients with Hp-negative recurrence after Hp eradication and investigated its usefulness. METHODOLOGY: The subjects were 21 patients with Hp-negative recurrent peptic ulcers after Hp eradication (gastric ulcer: 19, duodenal ulcer: 2) and 25 patients with non-recurrent ulcers (gastric ulcer: 20, duodenal ulcer: 5). The mucosa from the ulcer scar lesion was endoscopically obtained from patients, and HE staining, CD68 immunohistochemical staining, and investigation of the mucosal expression levels of TNF-alpha and IFN-gamma were performed by ELISA. Patients with recurrence after eradication were divided into two groups at the time of ulcer scar after the first treatment, and received maintenance therapy: the intermittent treatment group that received lansoprazole (LPZ), 30 mg/day, on two days on weekends (gastric ulcer: 9, duodenal ulcer: 1) and the ranitidine (RAN) 150 mg/day daily treatment group (gastric ulcer: 8, duodenal ulcer: 1). RESULTS: Infiltration of CD68-positive inflammatory cells was observed in the lamina propria mucosae over the epithelial layer in ulcer scars of the Hp-negative recurrent ulcer group compared with the non-recurrent ulcer group, and TNF-alpha and IFN-gamma significantly increased (27.22+/-6.23 pg/mg, 52.12+/-5.41 pg/mg vs. 4.23+/-2.14 pg/mg, 7.11+/-3.06 pg/mg, P<0.001). In the RAN maintenance therapy group, the ulcer recurred within 10 months in all patients, while the ulcer recurred in only one patient in the intermittent LPZ treatment group. CONCLUSIONS: These results suggested that the pathophysiological characteristic of Hp-negative recurrent ulcer scar lesions after eradication was infiltration of inflammatory cells, mainly monocytes/macrophages, in the lamina propria mucosae over the epithelial layer, and this may be a key factor in ulcer recurrence. Furthermore, intermittent PPI therapy using LPZ may be a useful maintenance therapy for prevention of recurrence in these cases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2005

Comparison of amniotic membrane graft alone or combined with intraoperative mitomycin C to prevent recurrence after excision of recurrent pterygia.

PURPOSE: Without effective adjunctive therapy, the recurrence rate after excision of recurrent pterygia is high. In an effort to determine a way to better reduce the recurrence of pterygia, we compared the efficacy and safety of amniotic membrane graft (AMG) alone and AMG combined with intraoperative mitomycin C after excision of recurrent pterygia. METHODS: Patients with recurrent pterygia were randomly assigned to receive excision of pterygia followed by AMG alone or AMG combined with intraoperative 0.025% mitomycin C for 3 minutes (AMG-mitomycin C). Patients who could be followed up for more than 12 months were entered for data analysis. Conjunctival (potential) and corneal (true) recurrence of pterygia and other complications were recorded. RESULTS: The group receiving AMG alone was made up of 48 eyes in 48 patients, and the group receiving AMG-mitomycin C consisted of 47 eyes in 46 patients. No significant difference was found in age distribution, sex distribution, or duration of follow-up between the 2 groups. Regarding the recurrence rates of each group, 6 conjunctival (12.5%) and 6 corneal (12.5%) recurrences developed in the AMG group, and 4 conjunctival (8.5%) and 6 corneal (12.8%) recurrences developed in the AMG-mitomycin C group. No significant difference was found in the conjunctival and corneal recurrence rate between the 2 groups (P=0.623 and 0.966, respectively; log rank test), and no major complications developed in either group. CONCLUSIONS: AMG alone can be considered an effective alternative adjunctive treatment of recurrent pterygia. The addition of intraoperative mitomycin C did not further reduce the recurrence rate.

Adult↗

PubMed2003

Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease.

BACKGROUND: Despite increasingly radical surgery for esophageal carcinoma, a large number of patients still experience recurrent disease soon after operation. The current study was undertaken to evaluate the pattern of recurrence after curative esophagectomy for cancer of the thoracic esophagus and to identify factors predictive of recurrent disease. METHODS: A total of 439 consecutive patients discharged from the authors' institution following R0 resection between January 1982 and July 2002 were followed for evidence of recurrence over a mean interval of 37.3 (range, 1-207) months. RESULTS: Overall 1-, 3- and 5-years survival rates were 91%, 54%, and 41%, respectively. Some 230 patients (52.4%) developed proven recurrence, of whom 24 were alive and 206 were dead at the time of writing. The median time to recurrence was 12.0 (range, 6-96) months, with a median survival thereafter of 7.0 (range, 0-83) months. The pattern of recurrence was local in 12.1%, regional in 20.5% (cervical 3.6%, mediastinal 14.8%, and abdominal 2.1%), and distant in 19.8%, respectively. The overall pattern of dissemination was significantly different according to the histologic subtype (P = 0.021). One hundred five (45.7%) of all recurrences occurred within 12 months of surgery, with local, regional, and distant recurrence occurring at a median of 14.0 (range, 6-77), 13.5 (range, 6-73), and 11.0 (range, 6-96) months, respectively; A factor predictive of recurrent disease was histologic tumor depth invasion (P = 0.001). CONCLUSIONS: Depth of tumor invasion should be used to identify patients who will have recurrence within 12 months of operation, so that these patients may be either entered into trials of multimodality treatment or offered nonsurgical palliation.

Adult↗

PubMed1986

Facial nerve sacrifice and tumor recurrence in primary and recurrent benign parotid tumors.

Three hundred eight patients underwent parotidectomy for a benign parotid tumor between 1948 and 1979. Two hundred seventy-four had operation for primary tumor, and 34, for recurrent tumor. Ninety-eight percent of those with primary tumors had superficial or total parotidectomy, and 2 percent had local excision with a wide margin of normal tissue. In those with recurrent tumor, 91 percent had superficial or total parotidectomy and 9 percent had local excision with a wide margin of normal tissue. There were nine recurrences in the primary group (3.2 percent) and 10 in the recurrent group (29 percent), at an average follow-up of 10 and 13 years, respectively. The time to recurrence in the primary group was between 5 and 20 years, whereas, second recurrences in the recurrent group generally took place within 5 years. Seven patients in the primary group (2.5 percent) and 9 in the recurrent group (26 percent) had sacrifice of the facial nerve. Most facial nerve sacrifices in the primary group were minor, involving a branch of the nerve only. Facial nerve sacrifice in the recurrent group, however, usually involved division of the nerve or the nerve trunk. These findings demonstrate that the major morbidity associated with managing benign parotid tumors occurs in dealing with recurrent tumors. Recurrence is uncommon if superficial or total parotidectomy is performed for a primary tumor.

Adenolymphoma↗

PubMed1999

Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Dutch Study Group on local Recurrence after Breast Conservation (BORST)

The purpose of this study was to determine which histological factors are associated with an increased risk for local recurrence in the breast after breast-conserving therapy for early breast cancer (TNM stage I and II) and whether risk patterns vary according to menopausal status and type of local recurrence. Through complete follow-up of the patients of eight regional radiation oncology departments, two cancer institutes and one surgical clinic in The Netherlands, 360 patients were identified with local recurrence in the breast after having received breast-conserving therapy (local tumour excision, axillary dissection and irradiation of the whole breast and a boost to the tumour bed) during the 1980s. For each case, two controls with a follow-up of similar duration without local recurrence were randomly selected. Histological slides of the primary tumour were reviewed. Among premenopausal patients the risk of recurrence for those younger than 35 years was significantly higher than that for premenopausal patients of 45 years or older (relative risk (RR) 2.9; 95% confidence interval (95% CI) 1.3-6.6, P < 0.05). The risk of recurrence at or near the site of the primary tumour was most significantly increased for patients with high grade extensive intraductal component (EIC) adjacent to the primary tumour (RR 4.1; 95% CI 1.7-9.8, P < 0.01). Microscopic margin involvement was an important risk indicator for diffuse recurrence and recurrence in the skin of the breast, especially in the presence of vascular invasion (RR 25; 95% CI 4.0-150, P < 0.001). To prevent local recurrence at or near the site of the primary tumour, local excision with a 1-2 cm margin of healthy tissue and a 15 Gy boost seemed adequate local treatment for patients with well differentiated EIC. In contrast, a wider surgical margin, a higher boost dose or mastectomy should be considered for patients with poorly differentiated EIC. Microscopic margin involvement in the presence of vascular invasion significantly increases the risk of diffuse recurrence or recurrence in the skin.

Adult↗

PubMed1995

IgA serology in recurrent and non-recurrent IgA nephropathy after renal transplantation.

BACKGROUND: This study investigated whether abnormal circulation of macromolecular IgA and IgA with altered glycosylation or electrical charge plays a role in the recurrence of IgA nephropathy (IgAN) after transplantation. STUDY DESIGN: A total of 92 renal transplant patients were enrolled; 52 IgAN patients and 40 with other non-IgAN. The IgAN group included 10 patients showing IgA mesangial deposits in the grafted kidneys (recurrent group) and 10 who did not (immunohistochemically proven non-recurrent group). In addition another 22 IgAN transplant patients were clinically free of recurrent disease. METHODS: The analyses included macromolecular IgA (IgAIC) detected by the conglutinin assay (K), heavy IgA precipitated in 2.5% polyethylene glycol (PEG), IgA-fibronectin aggregates (IgA/F Aggr), mixed IgA/IgGIC, IgA binding to mesangial matrix components (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine) and IgA with altered glycosylation (Jacalin-binding assay). RESULTS: After transplantation, IgAN patients displayed significantly higher mean levels for each variable measured than non-IgAN (ANOVA, P < 0.05). By stepwise regression analysis, the binding of IgA to fibronectin had the highest coefficient. By comparing data in recurrent and clinically non-recurrent IgAN, we observed that two groups could be distinguished by the results of the two assays for macromolecular IgA (conglutinin IgAIC and IgA-fibronectin aggregates) and IgA with increased affinity for type IV collagen (P < 0.05). When the selected group of immunohistochemically proven non-recurrent IgAN was compared to the recurrent one, a statistically significant difference was found only for the binding of IgA to type IV collagen (P < 0.05). Data from this test were significantly related with proteinuria (P < 0.05) and microscopic haematuria (P < 0.04). CONCLUSIONS: Even though the IgA serology of renal transplant IgAN patients shows peculiar features and recurrent and non-recurrent IgAN differ in many aspects, the prevalence of positive data in the two groups had no predictive value. This suggests that the recurrence of IgAN is modulated by factors affecting the interaction between circulating abnormal IgA and mesangial cells and/or matrix.

Analysis of Variance↗

PubMed1998

The first unprovoked, untreated seizure in childhood: a hospital based study of the accuracy of the diagnosis, rate of recurrence, and long term outcome after recurrence. Dutch study of epilepsy in childhood.

OBJECTIVE: To assess the accuracy of the diagnosis of a first unprovoked seizure in childhood, the recurrence rate within two years, the risk factors for recurrence, and the long term outcome two years after recurrence. METHODS: One hundred and fifty six children aged 1 month to 16 years after a first seizure, and 51 children with a single disputable event were followed up. The diagnosis of a seizure was confirmed by a panel of three child neurologists on the basis of predescribed diagnostic criteria. None of the children was treated after the first episode. RESULTS: Five children with a disputable event developed epileptic seizures during follow up. The diagnosis did not have to be revised in any of the 156 children with a first seizure. The overall recurrence rate after two years was 54%. Significant risk factors were an epileptiform EEG (recurrence rate 71%) and remote symptomatic aetiology and/or mental retardation (recurrence rate 74%). For the 85 children with one or more recurrences, terminal remission irrespective of treatment two years after the first recurrence was >12 months in 50 (59%), <six months in 22 (26%), and six to 12 months in 11 (13%) and unknown in two (2%). Taking the no recurrence and recurrence groups together, a terminal remission of at least 12 months was present in 121 out of the 156 children (78%). CONCLUSIONS: The diagnosis of a first seizure can be made accurately with the help of strict diagnostic criteria. The use of these criteria may have contributed to the rather high risk of recurrence in this series. However, the overall prognosis for a child presenting with a single seizure is excellent, even if treatment with antiepileptic drugs is not immediately instituted.

Adolescent↗

PubMedDate not supplied

Impact of intravesical chemotherapy on recurrence rate of recurrent superficial transitional cell carcinoma of the bladder: results of a meta-analysis.

BACKGROUND: The impact of in tranvesical chemotherapy on preventing recurrence of superficial transitional cell carcinoma of the bladder is controversial. The objective of this report is to present a meta-analysis of the available clinical trial data to quantify the effect of intravesical chemotherapy on tumor recurrence following trans-urethral resection (TURB) in patients with recurrent superficial bladder cancer. METHODS: A prospective study protocol outlining a meta-analysis was developed followed by a thorough search of the existing published literature using strict eligibility criteria. Eight randomized trials were found which met protocol specifications. These studies contained data on 1,609 patients which were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients with tumor recurrence at one, two and three years post-TURB. RESULTS: Combining all 8 studies using 1 year recurrence as the outcome measure yielded a Peto odds ratio (ORp) of 0.62, demonstrating a 38% reduction in one year recurrence among patients treated with intravesical chemotherapy versus TURB alone. Using 2 and 3 year recurrence as the outcome measure yielded ORp's of 0.46 and 0.35 respectively, favoring TURB + intravesical chemotherapy versus TURB alone. A statistical test for heterogeneity (Q) showed the 2 and 3 year outcome data to be heterogeneous (i.e. the studies are not measuring an effect of the same magnitude). Sensitivity analyses showed that drug type appeared to account for the observed heterogeneity with a stratified analysis demonstrating that adriamycin is less effective in reducing subsequent tumor recurrences than all other drugs studied. CONCLUSION: Intravesical chemotherapy appears to have a major impact on decreasing the chance of recurrence of recurrent superficial bladder cancer. Three year recurrence is decreased by as much as 70% when compared with TURB alone. These data are in contrast to prior analyses suggesting only modest efficacy of such treatment in this clinical setting.

Administration, Intravesical↗

PubMed2002

Recurrent and non-recurrent pigmented villonodular synovitis 1.

Pigmented villonodular synovitis (PVNS) is a benign intra-articular lesion. Patients are at risk for local recurrence. Factors that predict recurrence are not established. Two groups of patients were retrieved from our files. One consisted of 25 patients who had one or more recurrences within 5 years after primary surgery. The second group contained 18 historical controls free of recurrence for at least 5 years after primary surgery. Patient medical records and surgical notes were reviewed. We compared proliferative activity and DNA ploidy using digital image analysis, and other clinicopathologic features between the 2 groups of patients. The location of PVNS was significantly different between the two groups (p=0.03). In the recurrence group, there were 7 (28%) cases with disease in the knee. However, none of the controls had disease in the knee. Among recurrent cases, tumors in the knee were, on average, larger than tumors in the small joints. The size of all recurrent tumors was not significantly different than non-recurrent tumors (median of 1.8 cm versus 1.3 cm, respectively; p=0.06). There were no significant differences in age, sex, completeness of surgical removal, MIB-I index, DNA ploidy, or the percent of tumor nuclei in the diploid, S-phase, tetraploid, or hypertetraploid DNA histogram categories between the two groups. Our results indicate that recurrent PVNS tumors were more likely to be located in the knee, which may be related to larger tumor size. Patient age, sex, completeness of surgical removal, DNA ploidy, and MIB-I proliferation were not significantly different between recurrent and non-recurrent lesions.

Adolescent↗

PubMed2026

Transcriptome-based high-frequency recurrence index predicts frequent recurrence in non-muscle-invasive bladder cancer after Bacillus Calmette-Guérin therapy.

BACKGROUND: High-frequency recurrence (HfR, ≥ 2 recurrences) in non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical burden. Current risk models, such as the European Organization for Research and Treatment of Cancer (EORTC), the European Association of Urology (EAU), and the UROMOL classification, offer limited predictive accuracy for identifying patients at risk for frequent recurrence despite appropriate treatment. METHODS: A 75-gene high-frequency recurrence index (HfRI) was constructed by selecting recurrence-associated genes using differential expression and Cox regression analyses. The HfRI was computed as a weighted sum of normalized gene expression values. The model was trained on a discovery cohort and validated in multiple cohorts (n = 1379) using machine-learning approaches. Clinical relevance was assessed using recurrence-free survival (RFS) and Cox models, and predictive performance was compared with that of the EORTC, EAU, and UROMOL classifications using the area under the curve (AUC) and the concordance index (c-index). RESULTS: The HfRI robustly stratified patients into high-risk and low-risk groups across six independent NMIBC cohorts. Patients classified as HfRI-high had a significantly greater likelihood of experiencing ≥ 2 recurrences (χ2, p = 0.001) and showed markedly reduced RFS (log-rank test, p < 0.001). The adverse prognostic effect of the HfRI persisted even among patients treated with BCG therapy (log-rank test, p = 0.02). Multivariate analysis revealed that the HfRI was an independent predictor of HfR (HR = 2.82, 95% CI = 1.89-4.20, p < 0.001). Compared with established clinical risk classifiers, the HfRI demonstrated superior predictive performance (AUC = 0.736, c-index = 0.673) in terms of the EORTC (AUC = 0.594), EAU (AUC = 0.557) risk groups, and UROMOL2021 (AUC = 0.596) classification. Pathway analysis revealed that HfRI-high tumors were characterized by upregulation of cell cycle progression and DNA replication pathways, accompanied by suppression of immune signaling pathways. These biological features provide a mechanistic explanation for the reduced responsiveness to intravesical BCG therapy, underscoring the role of HfRI not only as a predictor of recurrence risk but also as a biomarker capable of identifying patients unlikely to benefit from standard BCG treatment. CONCLUSIONS: HfRI represents a robust, transcriptome-based tool for predicting frequent recurrence in NMIBC patients. The HfRI supports earlier identification of patients at risk of high-frequency recurrence, thereby supporting personalized treatment strategies.

Humans↗

PubMed1991

Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism.

Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity.

Adenoma↗

PubMed2005

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence.

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.

Adult↗

PubMed1997

The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study.

Orthotopic liver transplantation (OLTx) in the presence of hepatocellular carcinoma (HCC) has been complicated by high recurrence rates. The ability to determine the risk and timing of HCC recurrence on an individual basis would greatly aid in the candidate selection process resulting in a more efficient use of donated organs and allow the individualization and better evaluation of adjuvant chemotherapy. The 214 patients who underwent OLTx in the presence of HCC were analyzed. From the 178 patients who survived more than 150 days, 71 (40%) have suffered HCC recurrence. Based on five risk factors, that is, gender, tumor number, lobar tumor distribution, tumor size, grade of vascular invasion, artificial neural network models predicting the likelihood of HCC recurrence within 1, 2, and 3 consecutive years after transplantation were developed. Based on model predictions, those combinations of risk factors that should/should not lead to recurrence were generated, allowing stratification of patients into the following three groups: 1) patients who should not suffer HCC recurrence and who should not need adjuvant therapy, 2) patients who will suffer recurrence and for whom postoperative chemotherapy significantly prolonged survival (but did not prevent recurrence), and 3) patients who may or may not suffer HCC recurrence and whose recurrence may be prevented by adjuvant chemotherapy. The outcome of OLTx for patients with HCC can be prognosticated based on a number of clinical variables. If verified through multicenter trials, these models could be made available to transplantation programs performing OLTx in the presence of HCC.

Adolescent↗