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PubMed1991

Prognosis following local recurrence in the conservatively treated breast cancer patient.

At Yale-New Haven Hospital conservative treatment of early stage breast carcinoma with lumpectomy and radiation therapy has been used with increasing frequency since the 1960s. We have reviewed our experience with specific reference to prognosis following local recurrence. Between January 1962 and December 1984 a total of 433 patients were treated with conservative surgery and radiation therapy using standard techniques. As of December 1989, with minimum evaluable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 ipsilateral breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Extent of disease at the time of local recurrence was clinically categorized as localized (less than 3 cm without dermal involvement) or diffuse (greater than 3 cm and/or with dermal involvement). Seventy-two percent of the recurrences were at or near the original tumor site whereas 28% recurred elsewhere in the breast. At a median follow-up post recurrence of 5.0 years (range 0.3-16.9 years), the 5-year actuarial survival for breast recurrences was 59% and the 5-year disease-free survival was 65%. A number of clinical and pathological features at the time of original diagnosis as well as at the time of local recurrence were tested as possible prognostic indicators for survival following local recurrence. By univariate analysis, significant factors associated with survival following local recurrence included extent of local disease at the time of recurrence (p less than .01), time to local recurrence (p less than .03), with later recurrences doing better, and site of local recurrence (p less than .01), with recurrences elsewhere in the breast doing better. We conclude from this large single institutional experience with a median follow-up post-recurrence of over 5 years that patients experiencing a local recurrence in the conservatively treated breast have a relatively favorable prognosis. The prognostic factors correlating with survival and implications regarding adjuvant systemic therapy at the time of local recurrence are discussed.

Adult↗

PubMed2000

The recurrence pattern of esophageal carcinoma after transhiatal resection.

BACKGROUND: There is much controversy about the optimal resection for carcinoma of the esophagus. Little is known about the pattern of recurrence after transhiatal resection for esophageal carcinoma. STUDY DESIGN: We retrospectively reviewed the charts of 149 patients who underwent transhiatal esophagectomy for carcinoma of the mid or distal esophagus or gastroesophageal junction between June 1993 and June 1997. Recurrence was classified as locoregional or distant recurrence. Nine patients with macroscopically evident tumor left after resection and three patients (2.0%) who died in the hospital were excluded from the analysis. This left 137 patients; 105 men and 32 women with a median age 65 years (range 37 to 84 years). RESULTS: There were 95 adenocarcinomas (69.3%) and 42 squamous cell carcinomas (30.7%). Overall the median followup was 24.0 months (range 1.4 to 69.2 months). For patients alive at the end offollowup without recurrence, the median followup was 36.5 months (range 23.6 to 69.2 months). Seven patients died of other causes. The median interval between operation and recurrence was 11 months (range 1.4 to 62.5 months) for patients who had recurrence, with no significant difference in interval between locoregional and systemic recurrence. Seventy-two of the 137 patients (52.6%) developed recurrent disease. Thirty-two patients (23.4%) developed locoregional recurrence only, 21 patients (15.3%) developed systemic recurrence only, and 19 patients (13.9%) had a combination of both. In only 8.0% of all patients was there recurrence in the cervical lymph nodes. The most frequent sites of distant recurrence were liver (37.5%), bone (25.0%), and lung (17.5%). Recurrence was related to postoperative lymph node status (p<0.001) and the radicality of the operation (p<0.001) in multivariate analysis. Recurrence was not associated with localization or histologic type of the tumor. CONCLUSIONS: Recurrence after transhiatal resection is an early event. Almost 40% of patients developed locoregional recurrent disease. For this patient group a more extended procedure may be of benefit, especially in the patients (23.4%) with locoregional recurrence in whom this is the only site of recurrent disease. But the potential benefit of a more extended procedure has to be balanced against a possible increase in perioperative morbidity and mortality.

Adenocarcinoma↗

PubMed2004

Patterns of initial recurrence in completely resected gastric adenocarcinoma.

OBJECTIVE: To review recurrence patterns in completely resected gastric adenocarcinoma. SUMMARY BACKGROUND DATA: Despite improvements in the surgical treatment of gastric adenocarcinoma, recurrence rates remain high in patients with advanced stage disease. Understanding the timing and patterns of recurrence is essential to develop effective adjuvant treatment strategies. METHODS: A retrospective review of a prospectively maintained gastric cancer database was carried out. The timing and pattern of recurrence were reviewed. Univariate and multivariate analyses were performed to identify factors predictive of recurrence patterns. RESULTS: From July 1985 through June 2000, 1172 patients underwent an R0 resection. Of these, 496 (42%) had recurrence and complete data on recurrence could be obtained in 367 patients (74%). Among the documented recurrences, 79% were detected within 2 years of operation. Locoregional sites were involved as any part of the recurrence pattern in 199 patients (54%). Distant sites were involved as any part of the recurrence in 188 patients (51%) and peritoneal recurrence was detected as any part of the recurrence in 108 patients (29%). On multivariate analysis, peritoneal recurrence was associated with female gender, advanced T-stage, and distal and diffuse type tumors; locoregional recurrence was associated with male gender and proximal location; distant recurrence was associated with proximal location, early T stage, and intestinal type tumors. The median time to death from the time of recurrence was 6 months. CONCLUSIONS: Recurrence after complete resection of gastric adenocarcinoma usually occurs within 2 years and is rapidly fatal. Patterns of recurrence are variable and may be associated with specific clinicopathologic factors.

Adenocarcinoma↗

PubMed1998

Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences.

OBJECTIVES: Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure <6 months, relative low temperature at the initial seizure, multiple type initial seizure, and frequent febrile illnesses. Prevention of seizure recurrences serves two useful purposes: meeting parental fear of recurrent febrile seizures in general and reducing the (small) risk of a long-lasting and eventually injurious recurrent seizure. In daily practice, children with febrile seizures often are treated with antipyretics during fever to prevent febrile seizure recurrences. Thus far, no randomized placebo-controlled trial has been performed to assess the efficacy of intermittent antipyretic treatment in the prevention of seizure recurrence. METHODS: We performed a randomized, double-blind, placebo-controlled trial. Children 1 to 4 years of age who had had at least one risk factor for febrile seizure recurrence were enrolled. They were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5 mg) per kilogram of body weight per dose, or matching placebo, to be administered every 6 hours during fever (temperature, >/=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be administered every 6 hours until the child was afebrile for 24 hours. The parents were instructed not to administer any other antipyretic drug to the child. For measuring rectal temperature, a Philips HP5316 digital thermometer (Philips, Eindhoven, The Netherlands) was distributed. During subsequent treatment of the fever episode, parents had to call the investigator at least once each day to notify the investigator in case of febrile seizure recurrence. The investigator could be contacted by parents 24 hours per day. The primary outcome was the first recurrence of a febrile seizure. Kaplan-Meier curves and Cox regression were used for the statistical analysis. The treatment effect on the course of the temperature was assessed using analysis of covariance, with temperature at fever onset as covariate. Two analyses were performed. In an intention-to-treat analysis, all first recurrences were considered regardless of study medication compliance. A per-protocol analysis was limited to those recurrences that occurred in the context of study medication compliance. RESULTS: Between October 1, 1994, and April 1, 1996, 230 children were randomly assigned to ibuprofen syrup (111 children) or placebo (119 children). Median follow-up time was 1.04 years (25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98 years (0.7-1.6 years) in the placebo group. Of all children, 67 had a first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in the placebo group. The 2-year recurrence probabilities were 32% and 39%, respectively. The recurrence risk in the ibuprofen group was 0.9 (95% confidence interval: 0.6-1.5) times the recurrence risk in the placebo group (intention to treat). Adjustment for baseline characteristics did not affect the risk-reduction estimate. Of the 67 recurrences, 30 occurred in the context of study medication compliance (13 ibuprofen, 17 placebo). The per-protocol analysis, which was limited to these events, showed similar results. A significant reduction in temperature (0.7 degrees C) after fever onset in the ibuprofen group compared with the placebo group was demonstrated if all 555 fever episodes were considered. In the fever episodes with a seizure recurrence, a similar temperature increase was shown in both groups, with no significant difference between the intention-to-treat and the per-protocol analysis. DISCUSSION: (ABSTRACT TRUNCATED)

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

Recurrence after radiotherapy for glottic carcinoma.

A series of 478 patients with T1-3N0 glottic carcinoma treated by irradiation is presented. Of these patients, 320 were previously untreated, whereas 158 patients were referred for treatment of a recurrence after receiving radiotherapy elsewhere. The primary recurrence rate in the previously untreated patients was 10%. The rate was higher in T2 and T3 tumors, poorly differentiated tumors, and in patients who were in poor general condition. Over 80% of the recurrent tumors were Stage pT3 or pT4, whereas 12% of total laryngectomy specimens showed necrosis only with no evidence of tumor. The necrosis rate in previously untreated patients was 1% for T1 tumors, 4% for T2 tumors, and 3% for T3 tumors. Of all tumors, 60% were transglottic when they recurred, whereas only 29% were confined to the glottis at recurrence. Histologic diagnosis had a high sensitivity but a low specificity, indicating that a negative histologic report is unreliable. Of patients with a recurrent primary tumor, 13% were untreatable. The 5-year survival after a primary recurrence was 39%, and the main prognostic factors were sex, T stage at recurrence, and time to recurrence. Of patients available for follow-up at 5 years 49% were alive with a larynx, 5% were alive without a larynx, 13% were dead of the original cancer, and 33% had died of other causes. In those suffering a primary recurrence, the commonest cause of death was a subsequent lymph node metastasis, followed in order of frequency by stomal recurrence and recurrence in the pharyngeal remnant. The hospital mortality rate after laryngectomy was 3%, and 30% of patients undergoing laryngectomy developed a pharyngocutaneous fistula. The recurrence rate in lymph nodes was 14% at 5 years, general condition and T stage being the only significant predictors of recurrence. Only 17% of patients had small (N1) nodes by the time the diagnosis of cervical lymph node recurrence was made, and 27% of all patients were unsuitable for treatment. Host, tumor factors, and time to recurrence were not significant predictors of survival after node recurrence. The survival rate 5 years after node recurrence was 16%, and the main cause of death in those who died was uncontrolled disease in the neck. The hospital mortality after salvage neck dissection was 4.7%.

Adolescent↗

PubMed2000

Patterns of recurrence in patients with squamous cell carcinoma of the vulva. A multicenter CTF Study.

BACKGROUND: Invasive vulvar carcinoma is a rare disease with an incidence rate of 3-5% of all female genital neoplasms. The current study discusses the limited number of articles in the literature regarding the patterns of recurrence as well as the clinical outcome of patients with recurrent disease based on a consistent and consecutive series of cases. METHODS: A common clinical chart focusing on the study of patterns of recurrence was used in five Italian gynecologic institutions with uniform criteria of surgical nomenclature, pathologic variables, and sites of recurrence. Between 1980-1994, 502 cases of primary invasive squamous carcinoma of the vulva were registered consecutively, treated, and considered for this multicentered study. RESULTS: Of 502 patients, 187 (37.3%) developed a recurrence. Distribution of the recurrences by site was as follows: perineal, 53.4%; inguinal, 18.7%; pelvic, 5.7%; distant, 7.9%; and multiple, 14.2%. In a multivariate analysis, 3 characteristics appeared to be statistically correlated with the risk of recurrence: International Federation of Gynecology and Obstetrics Stage > II (P = 0.029), positive lymph nodes (P = 0.009), and vascular space invasion (P = 0.004). The 5-year survival rate was 60% for perineal recurrences, 27% for inguinal and pelvic recurrences, 15% for distant recurrences, and 14% for multiple recurrences. CONCLUSIONS: In the current study the prognostic factors found to have statistical significance as prognostic factors for risk of recurrence were tumor dimension, lymph node involvement, and stromal and vascular space invasion. The presence of inguinal lymph node metastases was predictive of multiple and distant recurrences with a low rate of incidence of isolated perineal recurrence (27%) compared with negative lymph node cases (57.5%). Survival analysis of recurrent disease showed that the surgical resection of local recurrences may provide acceptable results (51% at 5 years). This observation may justify a follow-up program aimed at identifying those patients with early local recurrence suitable for radical resection.

Adult↗

PubMed2002

Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors.

BACKGROUND: Although multiple sequential recurrences are one of the most important characteristics of superficial transitional cell carcinoma (TCC) of the bladder, few studies have examined multiple sequential recurrence patterns and the clinicopathologic and biochemical factors associated with these patterns. METHODS: Two hundred seventy superficial TCC bladder carcinoma patients were followed. Clinical, pathologic, and tumor marker (p53, MIB-1, bcl-2, c-erb B-2, and epidermal growth factor receptor) data were collected at baseline and during followup. The Kaplan-Meier (KM) method was used to describe multiple recurrences. The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to assess the effects of clinicopathologic and immunohistochemic factors on multiple recurrences. RESULTS: Among the 270 patients, 126 (46.7%) had one or more recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or more recurrences during the followup. The median times for the first, the second, and the third recurrences were 23 months, 15 months, and 13 months, respectively. In KM analysis, Stage T1, higher grades, and Ki-67 stain positivity were associated with the first recurrence, and p53 stain positivity was marginally significant. Other markers were not significant. For the second recurrence, only p53 stain positivity was significant. In multivariate analysis (WLW method), stage was significantly associated with the first recurrence (risk ratio [RR] = 2.03), and Ki-67 was marginally significant (RR = 1.49). For the second recurrence, only p53 positivity was statistically significant (RR = 2.73). CONCLUSIONS: Among superficial TCC bladder carcinoma patients, multiple recurrences are common phenomena. The time for recurrence becomes shorter as the number of recurrences increases. In addition to tumor stage and grade, Ki-67 can be used to identify patients at high risk for a first recurrence; and p53 can be used to identify patients at high risk for a second recurrence.

Biomarkers, Tumor↗

PubMed2003

Relation between the method of detection of initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma.

BACKGROUND: Mammography and physical examination are routine methods for the detection of ipsilateral local recurrence and contralateral breast carcinoma in patients initially undergoing breast conservation treatment. The current study reports the relation between the method of detection of the initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma. METHODS: A retrospective review was performed of the records of female patients with initial American Joint Committee on Cancer (AJCC) Stage I and II invasive breast carcinoma who developed ipsilateral local recurrence or contralateral breast carcinoma after breast conservation treatment. The method of detection of local recurrence in the ipsilateral breast and the method of detection of contralateral breast carcinoma were compared with the method of detection of the primary tumor. RESULTS: There were 125 ipsilateral breast local recurrences and 71 contralateral breast carcinoma cases detected. Of the 125 recurrences in the ipsilateral breast, 38% (48 recurrences) were detected by mammography only, 37% (46 recurrences) were detected by physical examination only, and 25% (31 recurrences) were detected by both methods. Of the 71 contralateral breast carcinoma cases, 53% (38 cases) were detected by mammography only, 23% (16 cases) were detected by physical examination only, and 24% (17 cases) were detected by both methods. When the primary tumors were detected by mammography only, 21% of the local recurrences (3 of 14 local recurrences) and 19% of the contralateral breast carcinoma cases (4 of 21 cases) were detected by physical examination only. When the primary tumors were detected by physical examination only, 24% of the local recurrences (14 of 58 local recurrences) and 42% of the contralateral breast carcinoma cases (8 of 19 cases) were detected by mammography only. When stratified by the interval between diagnosis of the primary tumor and ipsilateral local recurrence or contralateral breast carcinoma (< or = 5 years vs. > 5 years) or age of the patient at the time of ipsilateral breast recurrence or contralateral breast carcinoma (age < or = 49 years vs. age > or = 50 years), both breast examination and mammography were found to be important in the detection of locally recurrent tumor and contralateral breast carcinoma in each subgroup of the patients, regardless of the method of presentation of the primary tumor. CONCLUSIONS: Both mammography and physical examination were found to be significant in the detection of locally recurrent tumor in the ipsilateral breast and in the detection of contralateral breast carcinoma, regardless of the method of detection of the primary tumor.

Adult↗

PubMed2001

Recurrence and follow-up after urinary tract infection under the age of 1 year.

In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978-1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P < 0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P = 0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3-5 VUR than in those with grade 0-2 VUR (log rank test P = 0.0005). Children without VUR and children with grade 1-2 VUR did not differ in the recurrence rate, and thus grade 1-2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3-5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3-5 VUR.

Bacterial Infections↗

PubMed2004

Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy.

BACKGROUND: Extended radical esophagectomy with three-field lymphadenectomy for patients with thoracic esophageal cancer has been shown to be effective. But even if this operation is performed, some patients still experience relapse of the disease. The purpose of this study was to clarify the pattern and timing of recurrence after extended radical esophagectomy. STUDY DESIGN: Recurrence of esophageal squamous cell carcinoma was examined in 171 of 174 patients who underwent extended radical esophagectomy with three-field lymphadenectomy. Recurrence patterns were classified as locoregional (at the site of the primary tumor, the anastomotic site, or the lymph nodes), hematogenous, and other (pleura or site of gastrostomy). Factors associated with recurrence were identified using univariate and multivariate statistical methods for survival analysis. RESULTS: The overall 5-year survival rate was 55.6%. Recurrence was recognized in 74 patients (43.3%). The median disease-free interval until recurrence was 11 months. Thirty patients (17.5%) developed a locoregional recurrence, and 24 (14.0%) developed a hematogenous recurrence. Five patients (2.9%) developed both recurrences simultaneously and were classified as hematogenous recurrences. Of 30 patients with cervical lymph node metastasis, recurrent disease was recognized in 19 patients (63.3%). In multivariate analysis of 160 patients, the depth of invasion and pM-lym (cervical or celiac lymph node metastasis) were significant factors for locoregional recurrence; the depth of invasion and number of lymph node metastases at operation were significant factors for hematogenous recurrence. Survival time for patients with hematogenous recurrence (median 16 months) was significantly shorter than that of patients with locoregional recurrence (median 25.5 months). CONCLUSIONS: Locoregional recurrence is associated mainly with the extent of the local tumor and lymph node metastasis; hematogenous recurrence is not only associated with tumor stage but also with the tumor's oncologic behavior.

Aged↗

PubMed2005

Recurrent primary intracerebral hemorrhage in Izumo City, Japan.

BACKGROUND: Recurrent intracerebral hemorrhage (ICH) is a devastating illness among stroke survivors. We investigated the rate and characteristics of ICH recurrence in Izumo City, Japan. METHODS: The recurrence rate of ICH was calculated for 279 patients who suffered their first-ever ICH between 1991 and 1998 and were followed up during a mean period of 3.0 years (range, 1 month to 11 years). The characteristics of recurrent ICH were evaluated for 42 patients who were treated for it between 1991 and 1998. RESULTS: Of the 279 patients with ICH, 19 (7%) had rebleeding; the recurrence rate was 2.3% per year. Analysis of the 42 patients with recurrent ICH showed that the most common pattern of recurrence was ganglionic-ganglionic (n = 25). The crude and the age- and sex-adjusted annual incidence rates for recurrent ICH were both 6 per 100,000 population. Of the 42 patients with recurrent ICH, 16 (38%) had a favorable outcome at discharge and 10 (24%) died. The overall 1-year survival rate for recurrent ICH was 72%. Intraventricular hemorrhage on computed tomography scans was the only significant predictor of not only ICH recurrence but also the 1-year case-fatality rate in patients with recurrent ICH. CONCLUSIONS: Recurrence after an initial ICH is not rare, and the most common pattern of recurrence is ganglionic-ganglionic. Whereas the functional outcome of recurrent ICH is unsatisfactory, the 1-year survival rate is not necessarily low. Intraventricular hemorrhage on computed tomography scans is an important predictor of both ICH recurrence and the 1-year case-fatality rate in patients with recurrent ICH.

Adult↗

PubMed2001

Risk factors for multiple intravesical recurrences of superficial bladder cancer.

OBJECTIVES: To elucidate the risk factors for a second or third intravesical recurrence in patients with superficial bladder cancer. METHODS: Of 84 consecutive patients newly diagnosed as having superficial bladder cancer in Sapporo Medical University Hospital, 30 patients who had at least one recurrent superficial bladder cancer and were followed up for more than 3 years were included in this study. Multivariate analysis by Cox's proportional hazards model was used to determine which clinical and pathologic variables significantly affected the second and third recurrences. Stepwise regression analysis was used to determine which clinical and pathologic variables significantly affected multiple recurrences of bladder cancer. RESULTS: The 1, 2, and 5-year recurrence-free rates as determined by the Kaplan-Meier method were 66.1%, 43.8%, and 29.8% for a second recurrence and 67.4%, 61.8%, and 39.2% for a third recurrence, respectively. Multivariate analysis revealed that only the interval between the initial transurethral resection of the bladder cancer and the first recurrence was a significant and independent factor affecting the second recurrence. In the study of the third recurrence, the interval between the first and second recurrences was the only definite risk factor for the third one. When multiple recurrences were considered, stepwise regression analysis revealed that a time of 6 months or less from the initial transurethral resection until the first recurrence was a significant factor that affected the total frequency of bladder cancer recurrence (R(2) = 0.220, P = 0.0078). CONCLUSIONS: The results of our study indicate that patients will have the potential for frequent recurrences if they have the disease with recurrence after a short interval. This result may contribute to the selection of patients with superficial bladder cancer to receive aggressive adjuvant treatments to prevent frequent recurrences.

Adult↗

PubMed2003

Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans.

BACKGROUND AND OBJECTIVES: Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. METHODS: Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. RESULTS: Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = -1.0, P =.0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = -0.68, P =.034), but 5-HT1D receptor potency was not correlated with recurrence (r = -0.20, P =.54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P =.53) and for therapeutic gain, -0.11 (P =.71). CONCLUSION: The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence.

Animals↗

PubMed2000

Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma.

OBJECTIVE: To evaluate the current knowledge on the risk factors for recurrence, efficacy of adjuvant therapy in preventing recurrence, and the optimal management of recurrence after resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The long-term prognosis after resection of HCC remains unsatisfactory as a result of a high incidence of recurrence. Prevention and effective management of recurrence are the most important strategies to improve the long-term survival results. METHODS: A review of relevant English articles was undertaken based on a Medline search from January 1980 to July 1999. RESULTS: Pathologic factors indicative of tumor invasiveness such as venous invasion, presence of satellite nodules, large tumor size, and advanced pTNM stage, are the best-established risk factors for recurrence. Active hepatitis activity in the nontumorous liver and perioperative transfusion also appear to enhance recurrence. Recent molecular research has identified tumor biologic factors such as the proliferative and angiogenic activities of the tumor as new risk factors for recurrence. There is a lack of convincing evidence for the efficacy of neoadjuvant or adjuvant therapy in preventing recurrence. Retrospective studies suggested that postoperative hepatic arterial chemotherapy might improve disease-free survival, but results were conflicting. For the management of postoperative recurrence, studies have consistently indicated that surgical resection should be the treatment of choice for localized recurrence, be it in the liver remnant or extrahepatic organs. Transarterial chemoembolization and percutaneous ethanol injection are widely used to prolong survival in patients with unresectable intrahepatic recurrence, and combined therapy with these two modalities may offer additional benefit. CONCLUSIONS: Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to prevention. Minimal surgical manipulation of tumors to prevent tumor cell dissemination, avoidance of perioperative blood transfusion, and suppression of chronic hepatitis activity in the liver remnant are strategies that may be useful in preventing recurrence. The efficacy of postoperative adjuvant regional chemotherapy deserves further evaluation. New concepts on the influence of tumor biologic factors such as angiogenic activity on recurrence of HCC suggest a potential role of novel approaches such as antiangiogenesis for adjuvant therapy in the future. Currently, the most realistic approach in prolonging survival after resection of HCC is early detection and aggressive management of recurrence. Randomized trials are needed to define the roles of various treatment modalities for recurrence and the benefit of multimodality therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 31 patients and prognostic factors.

OBJECTIVES/HYPOTHESIS: Nasopharyngectomy is a well-established treatment option for recurrent nasopharyngeal carcinoma. Over a period of 4 years and 3 months, in a total of 43 patients, 45 nasopharyngectomies were performed. Thirty-one patients with follow-up ranging from 12 to 58 months were studied. Twenty-two patients (58%) survived; of these, 18 patients (82%) remained disease free. All patients who developed repeat recurrence or died (n = 12) had a high recurrent T-stage tumor, skull base involvement, multiple recurrences, positive surgical margins, or concurrent neck node metastasis. These factors are poor prognostic parameters and might mitigate the indications for aggressive salvage surgery. However, low recurrent T-stage tumor without neck metastasis carries a good prognosis. Modern minimally invasive surgery carries minimal morbidity. STUDY DESIGN A retrospective study was made to determine prognostic indicators in patients treated with salvage surgery for recurrent nasopharyngeal carcinoma. METHODS: Medical records were analyzed for all patients who had received nasopharyngectomy for recurrent nasopharyngeal carcinoma from March 1997 to June 2001. They were followed up from March 1997 to January 2002. Recurrent T stage, nodal metastasis, surgical approach, surgical margins, and pathological nodal status, together with surgical mortality, morbidity, and the delivery of postoperative irradiation, were compared with survival. RESULTS: In all, 43 patients underwent 45 nasopharyngectomies over a period of 4 years and 3 months. Patients with less than 1 year of follow-up were excluded. Four patients with residual disease, who represent a more favorable group, and five patients with planned debulking, nasopharyngectomy, and postoperative stereotactic irradiation were also excluded. The study group comprised 25 men and 6 women (ratio of 4:1) with age ranging from 26 to 69 years (mean age, 49.5 y). In 28 patients (90.3%), the recurrence of nasopharyngeal carcinoma was their first recurrence; in 3 patients (9.7%), the recurrences were second recurrences. Twenty-two patients (71%) survived, achieving a mean survival of 28.5 months. Nine patients died with a mean interval of 7.8 months (range, 1-14 mo). Of the nine patients who died, six (67%) had T3 or T4 tumor, four (44.4%) had concurrent recurrent neck disease, and five (55.5%) had positive surgical margins. Two patients died of perioperative meningitis. Fifteen (83.3%) of the 18 disease-free survivors had a low recurrent T-stage tumor. Mean intervals for development of repeat recurrence or distant metastasis were 16 and 7.9 months, respectively. CONCLUSIONS: High recurrent T stage, skull base involvement, repeated recurrence before surgery, nodal metastasis, and positive surgical margins carry a poor prognosis. This is particularly evident with high T stage and concurrent nodal metastasis. However, patients with low T stage have a survival advantage and benefit most from surgical treatment.

Adult↗

PubMed2001

Local recurrence of soft tissue sarcoma. A Scandinavian Sarcoma Group Project.

The aim of this project was to investigate the diagnosis, treatment and consequences of local recurrence of soft tissue sarcoma (STS). It is based on patients reported to the Karolinska Hospital Sarcoma Register and the Scandinavian Sarcoma Group Register. Demographic and treatment data, based on 1613 adult patients reported to the Scandinavian Sarcoma Group Register by sarcoma centers in Norway, Sweden and Finland are presented. They all had STS of the extremities or trunk wall, and were diagnosed between 1986 and 1995. One third of the tumors were subcutaneous and two thirds deep-seated. The median size was 7 (1-35) cm and 75% were high grade. Metastases at presentation were diagnosed in 8% of the patients. Two thirds of the patients were referred to a sarcoma center before surgery. The preoperative morphologic diagnosis was made by fine-needle aspiration cytology in 72%. Among patients with final treatment for primary tumor at a sarcoma center (n = 1331), the surgical margins were wide or better in 76% of subcutaneous lesions, and in 58% of deep-seated lesions. Adjuvant radiotherapy has not generally been considered indicated after wide or compartmental excisions in Scandinavia. Overall, 23% of patients managed by surgery had adjuvant radiotherapy. Among patients with an intralesional or marginal excision, 44% had postoperative radiotherapy. Patients treated outside of sarcoma centers were seldom referred for radiotherapy. The crude local recurrence rate was 225/1331 (17%) among the patients with final treatment for primary tumor at a sarcoma center. The local recurrence rate after local surgery for high-malignant deep-seated STS was 103/391 (26%). The rate was 25/64 (39%) after an intralesional/marginal margin without postoperative radiotherapy versus 28/119 (24%) when radiotherapy was given. Fine-needle aspiration cytology (FNAC) was used to diagnose suspected local recurrences. 95 FNAC were performed in 86 patients from Karolinska Hospital. There were 47 local recurrences, of which 44 were diagnosed correctly by FNAC; one biopsy was inconclusive, and two lesions were incorrectly assessed as benign. 39 patients proved to have benign lesions in the scar examined cytologically on 50 occasions. None of the specimens was regarded as malignant, but in 4 cases FNAC was inconclusive. The inconclusive or false cytological diagnoses had no serious clinical consequences. Among 205 patients with local recurrence identified in the SSG Register 1987-1995, 169 patients were surgically treated. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence was treated using surgery with a marginal margin alone, compared to 0.28 if treated using either surgery with a marginal margin and radiotherapy, or a wide margin (p = 0.0008). In extremity STS, the amputation rate for local recurrences was 0.22, compared to 0.09 for primary tumors. The overall 5-year MFS was 0.72 (95% CI 0.68-0.76). High histopathological malignancy grade (Relative Risk 3.0; 95% CI 1.5-6.3) and an inadequate surgical margin (2.9; 95% CI 1.8-4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumor size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (4.4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (1.1; 95% CI 0.8-1.7). In conclusion, it is unlikely that local recurrence of STS is a major source of metastases. It nevertheless represents a costly, complicated and emotionally difficult problem. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved for center-operated patients without increasing the amputation rate. Instead, local control will improve by giving radiotherapy to all patients after marginal surgery, and to selected patients with wide margins. Radiotherapy is indicated especially after a previous open biopsy or when a local recurrence might lead to an amputation. Furthermore, radiotherapy seems indicated after local recurrence, regardless of margin or grade. The most effective way of reducing costs and detriment associated with local recurrence is to increase referral to sarcoma centers before biopsy or surgery as primary surgical margins would then improve.

Adolescent↗

PubMed2006

[Case analysis on treatment and recurrence of giant cell tumor of bone].

OBJECTIVE: To analyze the clinical features, treatment methods, and recurrence factors of giant cell tumor of the bone and to investigate the surgical therapy choice for the tumor around the knees. METHODS: Thirty-eight patients (13 males and 25 females; average age 31.1 years, range 14-59 years) with giant cell tumor of the bone were treated and followed up from January 1993 to January 2005. The patients' diagnoses were established by biopsies of the specimens from the preoperative punctures or operations. The clinical features and the radiological and laboratory data from the 38 patients were reviewed. By the Campanacci's radiological grading system, 5 patients were in Grade I, 22 in Grade II, and 11 in Grade III . By the Enneking classification, 9 patients were in Grade I, 21 in Grade II, and 8 in Grade III . By the Jaffe's classification, 7 patients were in Grade I, 24 in Grade II, and 7 in Grade III. The intralesional excision (curettage) with the bone grafting was performed on 4 patients; the curettage with some adjuvant treatments (high-speed burring, phenol, alcohol, cement, hydrogen peroxide, 50% ZnCl2, 3% iodine tincture, or bone cement) was used in 26 patients; and resection of the whole tumor was performed on 8 patients. RESULTS: The follow-up of the 38 patients for 12-144 months (average, 67 months) revealed that giant cell tumor of the bone was found around the knees in 29 of the 38 patients (13 at the distal femur, 16 at the proximal tibia), at the proximal femur in 2, at the proximal ulna in 2, at the distal radius in 2, at the sacroiliac area in 2, and at lumbar spine in 1. Of the 38 patients, 4 had a recurrence after simple curettage, 8 had no recurrence after resection of the whole tumor, and 8 of the remaining 26 patients had a recurrence after curettage with some adjuvant treatments. Five patients in Grade I (Campanacci's radiological grading) had no recurrence, 6 of the 11 patients in Grade II had a recurrence, and 6 of the 11 patients in Grade III had a recurrence. Two of the 9 patients in Grade I (Enneking grading) had a recurrence, 6 of the 21 patients in Grade II had a recurrence, and 4 of the patients in Grade III had a recurrence; all the recurrent lesions were around the knee, with a duration of the recurrence ranging from 2 months to 36 months (average, 14.3 months). Of the patients with the recurrence, 12 underwent reoperations (8 by the total resection of the recurrent tumor, 4 by the curettage with adjuvant treatments), and there was no recurrence after the reoperation. CONCLUSION: Giant cell tumor of the bone usually recurs around the knee joint, especially at the proximal tibia, usually graded as Grade II or III by the Campanacci's radiological grading system. Simple curettage has a higher recurrence rate; therefore, extensive curettage and resection of the lesions combined with some adjuvant treatments after the correct diagnosis can be used to reduce the high recurrence rate of giant cell tumor of the bone.

Adolescent↗

PubMed2000

Benign anastomotic stricture following transthoracic subtotal oesophagectomy and stapled oesophago-gastrostomy: risk factors and management

AIMS: Benign anastomotic stricture (BAS) is a common cause of dysphagia following oesophagectomy. The aim of this study was to assess the incidence of BAS, identify risk factors for its development and evaluate the results of postoperative endoscopic dilatation. METHODS: A consecutive series of 234 patients undergoing oesophagectomy with a stapled intrathoracic oesophagogastric anastomosis (Autosuture CEEA gun) between April 1990 and April 1999 were studied. BAS was defined as dysphagia with anastomotic narrowing (XQ200 endoscope) and no suspicion of recurrence. Statistical analysis was by the chi2 and Mann-Whitney U tests. RESULTS: The postoperative mortality rate was 5 per cent (12 of 234) and the anastomotic leak rate 3 per cent (six of 234). One-third of patients (70 of 222) who survived surgery re-presented with dysphagia; 5 per cent (11 of 222) were found to have proven local recurrence and 27 per cent (59 of 222) BAS. The median time to development of BAS was 92 (range 24-210) days. BAS formation was significantly related to the size of the staple gun employed: 21 mm, 80 per cent (eight of ten); 25 mm, 32 per cent (25 of 78); 28 mm, 23 per cent (19 of 81); 31 mm, 19 per cent (seven of 37) and 34 mm, 0 per cent (none of five) (chi2 = 18.3, 4 d.f., P < 0.01). All patients underwent radiographically controlled endoscopic dilatation with no complications. Recurrent BAS occurred in over half of these patients (32 of 59), who had a median of 2 (range 2-17) recurrences all resolving within 532 (mean interval 68) days. Recurrent BAS formation was also significantly related to the size of the staple gun employed (chi2 = 11.6, 4 d.f., P < 0.05). Following the introduction of the Autosuture 'tilt-top' device in July 1995 the median size of gun used rose from 25 to 28 mm with an overall decrease in the incidence of BAS from 33 to 21 per cent (chi2 = 4.0, 1 d.f., P < 0.05). All patients with anastomotic leaks survived and none subsequently developed BAS. Similarly, no association was found between the development of BAS and the anastomotic site (measured from incisors), tumour subtype, resection margin length, sex, age or preoperative cardiorespiratory status. CONCLUSIONS: Staple gun size is an important risk factor for BAS formation and 'tilt-top' devices enable the use of a larger head with a subsequently lower incidence of BAS. Endoscopic dilatation is an effective treatment for BAS which rarely recurs and always resolves within 18 months.

Journal Article↗