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Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer.

Hepatocellular carcinomas (HCC) often recur after curvative resection. Recurrence in the remnant liver originates from intrahepatic metastasis (IM) from the primary resected tumor, and/or from multicentric (MC) occurrence. In order to achieve better survival after intrahepatic recurrence in HCC patients, we have surgically treated patients according to the recurrence pattern. In this study, we investigated the advantage of repeat surgery for MC recurrent HCC. The subjects were 176 patients who had undergone primary macroscopically complete tumor removal for HCC at our department from 1984 to 1999. Differential diagnosis of IM and MC recurrence was done by pathological analysis. Twenty-nine of the 149 patients with recurrence (19.5%) underwent a total of 31 second and third operations. Of the 29 patients, 18 had MC (14 received repeat hepatectomy and 4, microwave tissue coagulation [MTC]), 7 had IM (4 had repeat hepatectomy and 3, MTC), and, in 4 patients, pathological investigation failed to determine the mode of recurrence. The 1-, 3-, and 5-year survival rates for MC patients after the repeat operations were 100%, 69.7%, and 58.1%, respectively, and the 1-, 3-, and 5-year survival rates for the IM patients were 57.1%, 14.3%, and 14.3%, respectively. Survival after the repeat operation was significantly better in the MC group than in the IM group (P = 0.0016). Moreover, there was no significant difference between survival in the MC group after a repeat operation and survival in control patients after an initial hepatectomy (P = 0.9282). These results indicated that patients with resectable or ablative recurrent MC HCC have almost the same survival benefit after repeat operations as patients who undergo initial curative resection of HCC.

Aged↗

Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy: therapeutic efficacy on early- and late-phase recurrence.

OBJECTIVE: Our objective was to assess the efficacy and safety of radiofrequency ablation of recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare the effects on early- and late-phase recurrence. SUBJECTS AND METHODS: We studied 41 patients with 76 recurrent HCC tumors (diameter range, 2.0-6.6 cm; mean, 3.8 +/- 1.3 [SD] cm) after hepatectomy who underwent sonography-guided percutaneous radiofrequency ablation in our hospital (recurrent-HCC group). The interval between surgery and recurrence ranged from 1 to 96 months (mean, 24.5 months). These patients were divided into an early-recurrence group (20 patients with 41 recurrent HCC tumors) and a late-recurrence group (21 patients with 35 recurrent HCC tumors). Early recurrence was defined as that occurring within 1 year after surgery, and late recurrence was defined as that occurring after 1 year. Another 116 patients with 172 primary HCC tumors (diameter range, 1.2-7.0 cm; mean, 3.9 +/- 1.1 cm) treated by radiofrequency ablation were regarded as a control group. No other therapies were given before radiofrequency ablation in any group. Regular follow-up with enhanced CT was performed to evaluate the treatment results. Ablation was considered successful if no contrast enhancement was detected in the treated area on 1-month CT scans. Indexes including ablation success rate, local recurrence rate, distant recurrence rate, and survival were obtained for analysis and comparison. RESULTS: The ablation success rate, local recurrence rate, distant recurrence rate, and mean overall survival time of the recurrent-HCC group were 93.4% (71/76 tumors), 9.2% (7/76 tumors), 36.6% (15/41 patients), and 30.9 +/- 3.7 months, respectively. The incidence of distant recurrence in the early-recurrence group was significantly higher than that in the late-recurrence group (55.0% vs 19.0%, p = 0.017). The early-recurrence group had a shorter overall survival than did the late-recurrence group (mean overall survival, 16.4 +/- 2.4 vs 42.9 +/- 4.4 months, p < 0.001) or the control group (16.4 +/- 2.4 vs 45.9 +/- 2.5 months, p < 0.001). The survival time of the late-recurrence group was similar to that of the control group (42.9 +/- 4.4 vs 45.9 +/- 2.5 months, p > 0.05). Serious hemorrhage after radiofrequency ablation occurred in one patient in the late-recurrence group and was controlled with conservative treatment. CONCLUSION: Radiofrequency ablation is generally effective and safe in treating recurrent HCC after hepatectomy and is more effective in late recurrence than in early recurrence.

Adult↗

Low migraine headache recurrence with naratriptan: clinical parameters related to recurrence.

OBJECTIVE: To evaluate clinical parameters that may affect the incidence of headache recurrence or the time to headache recurrence, or both, in migraineurs treated with naratriptan, 2.5-mg tablets. BACKGROUND: The incidence of headache recurrence within 24 hours of treatment with naratriptan, 2.5-mg tablets (17%-28%), is lower than that reported for other currently available selective serotonin agonists. Identifying clinical parameters that influence headache recurrence may further reduce the incidence of headache recurrence or prolong the time to recurrence, or both, for naratriptan-treated patients. METHODS: We examined the effects of three clinical parameters (predose pain severity, headache duration prior to treatment, and relief status 4 hours post dose) on the incidence of and time to headache recurrence across four placebo-controlled naratriptan clinical trials. The impact of these parameters on headache recurrence was examined individually and in combination. RESULTS: Predose pain severity had no effect on the incidence of headache recurrence (overall 23%; moderate 22%, severe 23%). The median time to recurrence was longer for patients with moderate pain before treatment compared with patients with severe pain before treatment (14.5 hours versus 9.3 hours, respectively). Overall time to headache recurrence was 11.8 hours. Patients with headache recurrence reported a longer time until they treated the headache compared with patients without headache recurrence (median, 145 minutes versus 97.5 minutes). Patients who treated headache pain within 3 hours of onset had a lower incidence of headache recurrence (20%) than patients who treated their headache more than 3 hours after onset (28%). Patients with no pain 4 hours post dose had a lower incidence of and a longer time to headache recurrence compared with patients with mild pain 4 hours post dose (17% versus 32%; median, 17.8 hours versus 8.1 hours, respectively). The interaction of all three clinical parameters was significant in predicting headache recurrence. CONCLUSIONS: The overall incidence of headache recurrence is low after naratriptan, 2.5 mg, compared with other currently available selective serotonin agonists. Predose pain severity, time to treatment, and 4-hour relief status appear related to the incidence of or time to headache recurrence, or both. Treating less severe migraine attacks, treating earlier within an attack, and obtaining complete relief post dose may enhance the low incidence of headache recurrence and achieve longer times to recurrence with naratriptan, 2.5 mg.

Acute Disease↗

Investigation of factors related to periods to ipsilateral breast tumor recurrence after breast-conserving surgery and measures for preventing recurrence in early breast cancer.

BACKGROUND: The most important issue in breast-conserving surgery is avoidance of ipsilateral breast tumor recurrence (IBTR). We have investigated the factors related to the period between surgery and recurrence and the measures taken. SUBJECT AND METHODS: From April 1989 to December 2004, 888 cases (excluding cases who underwent neoadjuvant chemotherapy) of breast-conserving surgery were performed. IBTR occurred in 56 of these cases. We investigated the timing of these recurrences. Furthermore, the rate of recurrence before and after 1999 when postoperative adjuvant therapy (such as CEF and Taxanes) was started as standard treatment was investigated. RESULTS: The mean period to recurrence in the 56 patients that experienced IBTR was 41.3 months; early recurrence within two years occurred in 21 (37.5%) patients. On the other hand, recurrence from the fifth year onwards post-surgery occurred in 11 patients (19.6%). Of the factors related to the timing of recurrence, a significant difference was seen in tumor proliferative activity, ER (estrogen receptor) status, lymphatic invasion (ly), and whether the lesion was inside or outside the mammary gland tissue. Furthermore, patients experiencing an early recurrence including inflammatory type breast recurrence had a complicated course with distant metastases and their prognosis was poor. Therefore, there was delayed onset of recurrence in the ER positive and ly negative patients with decreased tumor proliferation. With regard to the timing of operation in relation to adjuvant therapy, there was an increase in the conservation rate for the patients in the later phase of the study (1999 onwards), and the number of significantly large and surgical margin positive patients that were at risk of a recurrence was high. However, early recurrence was significantly low, and standard therapy was found to inhibit recurrence. CONCLUSIONS: Although tumor proliferative activity, ER status and ly caused differences in timing of recurrence, standard adjuvant therapy, particularly chemotherapy for early recurrence, was effective in inhibiting recurrence.

Adult↗

Basic fibroblast growth factor expression in recurrent versus non-recurrent nasal polyposis.

Various growth factors are expressed in nasal polyps, and some of these have been suggested to play a role in polyp formation. A potential relation between growth factor expression and polyp recurrence, however, is undetermined. Basic fibroblast growth factor (bFGF) is expressed in mononuclear cells, as well as in endothelial and epithelial surface and gland cells of nasal polyps. To determine whether bFGF may play a role in the recurrence of nasal polyps, the present study aimed at a comparison of bFGF expression in recurrent versus non-recurrent polyps. Further, the expression in polyps from asthmatic patients was compared with that from non-asthmatics. Thirty patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at entry to the long-term follow-up study. Fifteen patients only had one polypectomy (no recurrence group, with a median observation time of 81 months). Fifteen patients had a median of 6.4 polypectomies (multiple recurrence group, with a median observation time of 108 months). Five of nine patients with asthma belonged to the non-recurrence group and four to the recurrence group. The polyp from the entrance polypectomy was examined for expression of bFGF by immunohistochemistry, using a polyclonal antibody. A masked semi-quantification of staining intensity was performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. bFGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of some mononuclear cells and some fibroblast-like cell profiles in the polyp stroma. Vascular endothelium was labeled occasionally. Semi-quantification of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. We conclude that the level of immunohistochemical expression of bFGF in recurrent and non-recurrent nasal polyposis is equivalent. Thus, the level of bFGF expression in the primary polyp can not predict a subsequent recurrence. The expression of bFGF is not up-regulated in patients with asthma. Further studies are needed to determine a potential role of bFGF in nasal polyposis, with special reference to different stages of polyp formation and growth.

Adolescent↗

The prognostic impact of the time interval to recurrence for the mortality in recurrent colorectal cancer.

OBJECTIVE: The risk of a cancer recurrence has been correlated with the stage of the primary tumour at the time of presentation. However, once a recurrence has developed, the primary tumour stage may not be the determining prognostic factor anymore. The objective of this study was (i) to evaluate the association between the recurrence interval and the outcome of the recurrence, and (ii) to determine whether that interval was affected by the use of adjuvant radiation and/or chemotherapy. METHOD: This retrospective study analysed 212 patients who developed recurrent colorectal cancer from 1987 to 1993. Primary parameters such as age, gender, primary tumour site and stage, and use of postoperative adjuvant treatment were correlated with the recurrence interval, the type and site of the recurrence (i.e. locoregional vs distant metastases), and the outcome. Uni- and multivariate analysis was used to compare the recurrence interval and survival between different subgroups as defined by risk factors. RESULTS: The mean time between the primary and the recurrent tumour was 25 months (range 1-252 months) with 82% of the recurrences developing within 3 years after surgery. The recurrence interval was inversely correlated with the initial tumour stage. Poor survival was associated with a short recurrence interval (less than 12 months) and a distant recurrence site. Even after adjusting for the initial tumour stage, the use of adjuvant treatment did not prolong the interval, i.e. delay the onset of recurrent cancer. CONCLUSION: The recurrence interval of colorectal cancer is a prognostic factor. However, the use of adjuvant therapy did not prolong that interval.

Adult↗

Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the South London Stroke Register.

BACKGROUND AND PURPOSE: This article examines stroke recurrence and whether the subtype of the initial stroke influences the risk and subtypes of further strokes. The proportion of recurrences attributable to conventional risk factors is quantified. METHODS: From January 1995 to August 2000, all first-in-a-lifetime strokes (n=1626) were identified and prospectively followed up in a defined multiethnic inner city population of 234 533. Twelve overlapping referral sources and face-to-face follow-up at 3 months and 1 and 3 years were used to attain complete registration of stroke recurrence. Index and recurrent stroke were classified according to the Oxford Community Stroke Project classification. RESULTS: In 2744 person-years of follow-up, 153 recurrences were observed. At 5 years, the cumulative risk of first stroke recurrence was 16.6% (95% CI, 13.5 to 20.4), and the combined risk of death or stroke recurrence was 65.3% (95% CI, 61.9 to 68.6). Ethnicity and subtype of index stroke were not associated with stroke recurrence. A change in subtype between index and recurrent stroke occurred in 45.5% (95% CI, 35.8 to 55.2) of cases and was most frequent among index lacunar strokes and primary intracerebral hemorrhages. In multivariable analyses, diabetes mellitus and atrial fibrillation were associated with both stroke recurrence and recurrence-free survival. In the stroke population, 9.1% (95% CI, -2.0 to 20.2) of recurrences were attributable to diabetes and 4.9% (95% CI, -7.3 to 17.2) to atrial fibrillation during the first year after the index stroke. CONCLUSIONS: The cause of stroke recurrence is multifactorial, and the subtypes of index and recurrent strokes are often not identical. Most recurrences remain unexplained by conventional risk factors.

Aged↗

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗

Immunohistochemical demonstration and semi-quantitation of vascular endothelial growth factor in recurrent versus non-recurrent nasal polyps.

OBJECTIVE: The expression of some growth factors in nasal polyps has been examined, although investigations addressing the reason for recurrence in some patients are lacking. Vascular endothelial growth factor (VEGF) is expressed by inflammatory cells, as well as by endothelial and epithelial cells of nasal polyps. To determine whether VEGF may play a role in the recurrence of nasal polyps, we aimed to compare VEGF expression in recurrent versus non-recurrent polyps. In addition, expression in polyps from asthmatic patients was compared with that in polyps from non-asthmatics. MATERIAL AND METHODS: A total of 30 patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at enrolment in the long-term follow-up study. Fifteen patients had only 1 polypectomy (non-recurrence group; median observation period 81 months) and 15 had a median of 6.4 polypectomies (multiple recurrence group; median observation period 108 months). Five of 10 patients with asthma belonged to the non-recurrence group and 5 to the recurrence group. The polyp obtained at the initial polypectomy was examined for expression of VEGF by immunohistochemistry, using a polyclonal antibody. A blinded semi-quantitation and comparison of the intensity of immunolabelling were performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. RESULTS: VEGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of the vessel endothelium and some stromal mono- and polymorphonuclear leukocytes. Semi-quantitation of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. CONCLUSION: Our findings indicate that the level of immunohistochemical expression of VEGF in recurrent and nonrecurrent nasal polyposis is equivalent. Thus, the level of VEGF expression cannot predict a subsequent recurrence. The expression of VEGF is not upregulated in patients with asthma. Further studies are needed to determine the role of VEGF in nasal polyposis, with special reference to different stages of polyp formation, vascularization and growth.

Adolescent↗

The hTERT-protein and Ki-67 labelling index in recurrent and non-recurrent meningiomas.

Meningiomas are considered as benign neoplasms affecting the coverings of the central nervous system and compromise approximately 20% of all intracranial tumours. However, a number of these tumours recur even after total resection. The aim of this study is to evaluate the prognostic significance for recurrence of the human telomerase catalytic subunit (hTERT) in the cells of meningiomas. The expression of hTERT-protein can be evaluated by immunohistochemical staining using a monoclonal antibody against hTERT (clone 44F42, NCL-L-hTERT). The interdependence between tumour recurrence and cell proliferation in this study is analysed by Ki-67 immunoreactivity (clone MIB-1). Archival material from 29 non-recurrent and 32 recurrent tumours has been evaluated, including specimens from World Health Organization (WHO) stages I (n = 73), II (n = 2) and III (n = 12). Although the tumours were categorized as benign meningiomas following the WHO classification, recurrence in 22 of 50 cases did not correlate with the tumour stage. For hTERT staining, the following results were found for nucleolar and total nuclear staining, respectively: non-recurrent meningiomas, 2.9% (+/- 7.7) and 3.0% (+/- 8.0); recurrent meningiomas at first resection, 16.8% (+/- 19.7) and 31.6% (+/- 30.2). Concerning the Ki-67 labelling index (LI): for the group of non-recurrent meningiomas, results were 2.1% (+/- 1.7) and for the recurrent group at first resection, 1.7% (+/- 2.0). A significant difference was seen for the hTERT staining (P < 0.001) between the non-recurrent and recurrent meningiomas, whereas no statistical significance was found for Ki-67. In conclusion hTERT-positive meningiomas had a high incidence for recurrence. Ki-67 was a good marker of cell proliferation status of the tumours, but did not correlate with recurrence; thus, hTERT alone seemed to be a potential predictor for recurrence.

Antibodies, Monoclonal↗

Clinical study on recurrence in bladder cancer patients undergoing total cystectomy--statistical analysis of factors related to recurrence.

A clinico-pathological study was performed retrospectively for 77 patients undergoing total cystectomy for primary transitional cell carcinoma of the urinary bladder between 1981 and 1995 to clarify the mode of recurrence, the risk factors which may affect recurrence following cystectomy and prognostic factors. Postoperative recurrence was recognized in 27 (35.1%) out of 77 patients and the one-, two- and three-year non-recurrent rates by the Kaplan-Meier method were 75.3, 64.9% and 63.3%, respectively. The duration from cystectomy to recurrence was 1 to 102 months with a mean of 12.1 months, and approximately 92.6% of recurrence occurred within two years. Among 27 patients with recurrence, pelvic recurrence, distant metastasis, both of them and urethral recurrence were recognized in 6 (22.2%), 18 (66.7%), 1 (3.7%) and 2 (7.4%), respectively as the first site of recurrence. The overall one-, three- and five-year cause-specific survival rates of the 77 patients were 84.7, 71.1% and 65.6%, respectively. Of the 27 patients with recurrence, 25 (92.6%) died of bladder cancer. Of the factors related to recurrence or prognosis, pathological stage, lymphatic invasion, venous invasion, type of infiltration and lymph node metastasis but not pathological grade or adjunctive chemotherapy were significant risk factors for recurrence and prognostic factors in univariate analysis. However, lymphatic invasion was the only significant risk factor for recurrence and prognosis in multivariate analysis using Cox's proportional hazard model.

Adult↗

[P53 protein expression and proliferative potential in non-recurrent and recurrent meningiomas].

Evaluation of the p53 gene protein expression and proliferative potential with MIB-1 monoclonal antibody (MBL Co.), a new marker of cellular proliferation that binds Ki67 in paraffin sections, by immunohistochemical studies were made in 10 cases of the non-recurrent meningiomas and the 8 cases (17 samples) of the recurrent meningiomas. Tissue samples were embedded in paraffin after fixation in 10% formalin, and 3-microns sections were activated by microwave heating before being immersed with p53 protein or MIB-1 monoclonal antibody. The positivity of immunostaining for p53 protein and MIB-1 was calculated as the % values of tumor cell nuclei stained to all tumor cell nuclei examined within several fields under a light microscope. The mean % value of the proliferating cell index (PCI) stained with MIB-1 monoclonal antibody was 2.1% in the non-recurrent meningiomas, and high values of 11.9% were obtained for the recurrent meningiomas. High values of PCI exceeding 3% were indicated in most of the cases of recurrent meningiomas. p53 protein was not found in the 10 cases of non-recurrent meningiomas. However, it was positive showing values of 0.5-8.5% (mean; 3.4%) in 5 of the 8 cases of recurrent meningiomas. 2 of 4 cases of recurrent meningiomas with a benign type of histology at both initial discovery and recurrence revealed p53 protein expression in the tumor tissues. 3 of 4 cases of recurrent meningiomas, which were of the benign type at the initial operation but transformed to the malignant (atypical) type on recurrence, demonstrated positive staining for p53 protein in the tumor tissues. Although positivity for p53 protein was observed in the recurrent meningiomas with high values of PCI with MIB-1, no significant correlation between the values of PCI with MIB-1 and those for the p53 protein expression was found. The p53 gene protein may be altered on tumor recurrence and/or malignant transformation in meningiomas. It is concluded that evaluations of the p53 protein expression and proliferative potential with MIB-1 are important as additional factors for the prediction of tumor recurrence in meningiomas.

Biomarkers, Tumor↗

Local recurrence after breast conservation therapy for early stage breast carcinoma: detection, treatment, and outcome in 266 patients. Dutch Study Group on Local Recurrence after Breast Conservation (BORST).

BACKGROUND: Controversy exists concerning the roles of mammography and physical examination in the detection of local recurrence after conservation therapy for breast carcinoma. In addition, the prognostic factors for and optimal treatment of patients with local recurrence are uncertain. METHODS: At eight radiotherapy institutes, two cancer institutes, and one surgical clinic in the Netherlands, regular follow-up of patients who underwent breast conservation therapy between 1980 and 1992 identified 266 patients with local recurrence in the breast. These patients exhibited no clinical signs of distant metastases at the time of diagnosis of the local recurrence. Data on the method of detection were available for 189 patients (72%). Local recurrence was diagnosed by mammography alone in 47 cases (25%). Of all patients, 85% underwent salvage mastectomy, 8% underwent local excision, 4% received systemic treatment only, and 3% remained untreated. Specimens of the primary tumor were available for review from 238 of the 266 patients (89%). RESULTS: Local recurrences detected by mammography alone were smaller than those detected by physical examination (P = 0.04). At 5 years from the date of salvage treatment, the overall survival rate for all 266 patients was 61% (95% confidence interval [CI], 55-67%), and the distant recurrence free survival rate was 47% (95% CI, 40-53%). For the 25 patients with noninvasive recurrence, these figures were 95% and 94%, respectively. Skin involvement, the extent of recurrence (< or = 10 mm vs. >10 mm), and both lymph node status and histologic grade of the primary disease were strong predictors for distant metastases in patients with invasive recurrence. CONCLUSIONS: Patients with invasive local recurrence more than 1 cm in size are at a substantial risk for distant disease. The better distant disease free survival for patients with recurrence measuring 1 cm or less may indicate that early detection can improve the treatment outcome. Recurrence with skin involvement should be considered generalized disease.

Adult↗

Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis.

PURPOSE: A retrospective analysis was performed with emphasis on the patterns of recurrence, latent period, and prognosis in patients with cervical squamous cell carcinoma of the uterus treated with definitive radiation therapy alone. Late recurrence, which was observed more than 5 years after the initial radiation therapy, was finally focused on and discussed. MATERIALS AND METHODS: Between 1976 and 1994, 256 patients with squamous cell carcinoma of the uterine cervix without hematogenous metastasis were treated with definitive radiation therapy alone. The patients were staged as follows according to the FIGO classification: 26 in Stage I, 56 in Stage II, 124 in Stage III, 28 in Stage IVa, and 22 in Stage IVb. All the patients were treated with external beam irradiation and low-dose-rate intracavitary brachytherapy. RESULTS: A total of 74 patients had recurrence. The recurrence appeared in 67 cases (90.5%) within 5 years. Metastasis to para-aortic and/or supraclavicular nodes developed later than other types of recurrence. Among patients with lymphogenous metastasis, there were more 5-year survivors after recurrence than with other types of recurrence. Patients with early recurrence, within 2 years of the initial therapy, had a worse prognosis than those with recurrence more than 2 years after treatment. Seven patients (2.7%) in all developed late recurrence more than 5 years after the treatment. The first site of recurrence was an abdominal para-aortic or supraclavicular node in all patients, excluding one patient who developed intrapelvic lymph node metastasis. Six patients had pelvic node metastasis detected with lymphangiography at the initial treatment. Median survival after late recurrence was 16.0 months. Two of 7 patients survived more than 3 years after secondary radiation therapy, and the remainder died of recurrent disease. CONCLUSION: Patients with para-aortic and/or supraclavicular node metastasis that developed late after the initial treatment are more likely to survive due to secondary radiation therapy. Careful follow-up is emphasized for long-term survivors.

Aged↗

Biochemical recurrence after definitive prostate cancer therapy. Part I: defining and localizing biochemical recurrence of prostate cancer.

PURPOSE OF REVIEW: The introduction of prostate-specific antigen into clinical practice heralded a dramatic shift in the epidemiology of prostate cancer. The diagnosis and treatment of lower stage disease in younger men with fewer competing co-morbidities has resulted in a longer period of post-treatment cancer surveillance and the potential for disease recurrence. Life-long periodic prostate-specific antigen testing for biochemical recurrence is standard of care; however, there is no single definition of biochemical recurrence that reliably predicts clinical recurrence. This review explores the complexities of biochemical recurrence, a thorough understanding of which is crucial to making appropriate treatment decisions after primary treatment. It also evaluates the array of diagnostic tests frequently employed when biochemical recurrence has occurred. RECENT FINDINGS: There is a disconnection between biochemical recurrence and progression to clinical disease. The definition of biochemical recurrence varies both by the prostate-specific antigen cut-point used and by the primary therapy employed. Furthermore, biochemical recurrence by itself appears not to be as reliable a predictor of eventual clinical recurrence as prostate-specific antigen doubling time. Current imaging modalities are rarely useful in localizing disease when biochemical recurrence is first detected. SUMMARY: The correct interpretation of biochemical recurrence is crucial to treatment decision-making. New data show that prostate-specific antigen doubling time during prostate-specific antigen recurrence may be a valid surrogate for death from the disease. The potential therefore exists for prostate-specific antigen doubling time to be accepted as a trial endpoint, which might accelerate drug approval by the United States Food and Drug Administration.

Antibodies, Monoclonal↗

Plantar fibromatosis: treatment of primary and recurrent lesions and factors associated with recurrence.

Plantar fibromatosis is a benign but often problematic foot disorder which, when surgically treated, is difficult to eradicate. The purpose of this investigation was to identify epidemiologic factors associated with disease recurrence and to determine which method of treatment most successfully eliminated recurrence. A retrospective review of surgical pathology reports and clinical histories from 1979 to 1993 was performed to identify all patients who underwent surgery for plantar fibromatosis at our institution during that time. Thirty-three feet of 30 patients were identified with a minimum 2-year follow-up. Seventeen feet underwent surgery for primary lesions, and 4 of 10 that had local excision, 1 of 3 that had wide excision, and 2 of 4 that had subtotal fasciectomy (with or without skin grafting) had recurrence. All 16 feet in patients presenting with recurrent lesions had undergone prior local excision at other institutions. When combined with patients from our institution who underwent a second procedure, 21 feet had surgery for recurrent plantar fibromatosis. Of these, three of four had further recurrence when treated with local or wide excision. In feet with recurrences treated with subtotal fasciectomy, only 4 of 17 had recurrence after the first attempt at such treatment. Average follow-up for all patients was 7.7 years, and all patients with postoperative recurrences showed evidence of disease within 14 months after surgery (mean, 6.9 months). Factors identified with an increased risk for recurrence were multiple nodules, bilateral lesions, and positive family history. In treating recurrent disease, subtotal fasciectomy was more effective than local or wide excision. This study identified factors associated with a significant likelihood of postoperative recurrence in treating plantar fibromatosis and found subtotal fasciectomy to provide the most successful treatment in eradicating disease in recurrent cases.

Adolescent↗

Intraductal papillary mucinous neoplasms of the pancreas: CT patterns of recurrence and multiobserver performance in detecting recurrent neoplasm after surgical resection.

OBJECTIVE: The purposes of our study were to describe the CT appearance of recurrent intraductal papillary mucinous neoplasms of the pancreas after surgical resection and estimate the performance of CT in detecting recurrent neoplasms. MATERIALS AND METHODS: A single unblinded reviewer characterized the presence and appearance of recurrent intraductal papillary mucinous neoplasms on 66 CT scans of 17 patients with proven recurrence, noting location and appearance of recurrent neoplasm. These results, described in this article, were summarized in tabular format and shown to three blinded observer. The observers then evaluated one postoperative CT examination from every patient at our institution who underwent surgical removal of intraductal papillary mucinous neoplasms (n = 45) for the presence or absence of local or distant recurrence. RESULTS: The unblinded reviewer found 11 cases of local recurrence. Extrapancreatic local recurrences tend to have solid components (5/6), tend to be located adjacent to the resection margin (5/6), and may exhibit vascular invasion (2/6). Intrapancreatic neoplasms are usually cystic (4/5). Nine patients had distant metastases. Prospective sensitivity for recurrent tumor ranged from 76% (13/17) to 94% (16/17). Sensitivity for local recurrence ranged from 55% (6/11) to 82% (9/11). Specificity ranged from 79% (22/28) to 96% (27/28). Interobserver agreement for predicting recurrence was moderate to substantial (kappa = 0.51-0.65). CONCLUSION: Locally recurrent intraductal papillary mucinous neoplasms of the pancreas tend to be either extrapancreatic and solid at the resection margin or intrapancreatic and cystic. CT can detect most recurrent intraductal papillary mucinous neoplasms of the pancreas with moderate to substantial interobserver agreement.

Adenocarcinoma, Mucinous↗

Prognostic implications of site of recurrence in patients with recurrent well-differentiated thyroid cancer.

OBJECTIVE: The site of treatment failure in patients with recurrent well-differentiated thyroid carcinoma (WDTC) has implications for both the mode of salvage therapy and disease-specific prognosis. The objective of this study was to evaluate the prognostic significance of the site of failure in patients with recurrent WDTC. DESIGN: Patients with recurrent thyroid cancer were identified retrospectively from 1963 to 2000. SETTING: Data were retrieved from the thyroid cancer database at the Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto (1963-2000). METHODS: Patients were placed into four different groups according to their site of recurrence: group 1, local recurrence; group 2, regional recurrence; group 3, distant recurrence; and group 4, unspecified recurrence. Patient, tumour, and treatment data were collected and compared. The Kaplan-Meier method was used to calculate survival data, and curves were compared using the log rank test. MAIN OUTCOME MEASURES: Outcome included alive, no disease; alive with disease; dead, no disease; and dead of disease. RESULTS: Seventy-three patients (21 male, 52 female; median age 44 years, range 18-84 years) were eligible for inclusion in this study. Relevant data were divided according to group 1, 22 patients; group 2, 24 patients; group 3, 13 patients; and group 4, 14 patients. The groups were comparable in terms of primary tumour and treatment factors. The actuarial disease-specific survival rate after salvage therapy was less significant in patients who developed a distant recurrence versus a local recurrence, a regional recurrence, or an unspecified recurrence (ie, 66% vs 95%, 88%, and 92%, respectively; p = .06). CONCLUSIONS: Patients with distant recurrences have a poor prognosis, with a significant reduction in the actuarial disease-specific survival rate.

Adolescent↗