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Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen.

OBJECTIVES: To determine the ideal cutpoint for defining prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Although various cutpoints have been used, a recent study suggested that 0.4 ng/mL may be the most appropriate. METHODS: A retrospective survey of 358 men undergoing RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 2001 was undertaken. The 3-year and 5-year risk of PSA recurrence was estimated by Kaplan-Meier analyses using various cutpoints of postoperative PSA to define recurrence: greater than 0.1, greater than 0.2, greater than 0.3, greater than 0.4, and greater than 0.5 ng/mL. The 1 and 3-year risk of PSA progression after a detectable PSA level (PSA rising to a higher cutpoint) was evaluated for each definition of PSA recurrence using Kaplan-Meier analyses. Multivariate analysis using a Cox proportional hazards model was used to determine the clinical variables that were significant independent predictors of PSA recurrence at each cutpoint. RESULTS: For patients with a detectable postoperative PSA value from 0.11 to 0.2 ng/mL, the 1 and 3-year risk of PSA progression was 64% (95% confidence interval [CI] 46% to 82%) and 93% (95% CI 74% to 99%), respectively. For patients with a PSA value from 0.21 to 0.3 ng/mL, the 1 and 3-year risk of PSA progression was 86% (95% CI 69% to 97%) and 100% (95% CI 87% to 100%), respectively. The use of higher PSA cutpoints to define recurrence resulted in a lower 5-year risk of PSA recurrence. The 5-year risk of PSA recurrence using a greater than 0.1 ng/mL cutpoint resulted in a 43% (95% CI 36% to 50%) risk of recurrence compared with only 23% (95% CI 18% to 30%) for a greater than 0.5 ng/mL cutpoint. In multivariate analysis, PSA and biopsy Gleason score were significant independent predictors of biochemical recurrence, regardless of the definition of PSA recurrence used (P <or=0.002). CONCLUSIONS: PSA and biopsy Gleason score were significant predictors of biochemical failure, regardless of the definition of failure used. However, the definition of PSA recurrence dramatically affected the perceived success of therapy. Patients with a postoperative PSA value greater than 0.2 ng/mL are at very high risk of developing an additional rise in PSA. On the basis of this finding, a PSA value greater than 0.2 ng/mL is an appropriate cutpoint to define PSA recurrence after RP.

Aged↗

Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection.

BACKGROUND/AIM: Time-dependent intrahepatic recurrence of hepatocellular carcinoma is frequent after different treatment modalities, including percutaneous ethanol injection. We attempted to prospectively analyze the possible risk factors for early intrahepatic recurrence of hepatocellular carcinoma after percutaneous ethanol injection. METHODS: Sixty-five patients with 65 solitary hepatocellular carcinoma nodules < or =6 cm in diameter underwent initial treatment with percutaneous ethanol injection and were examined to ascertain the factors related to recurrence, local and distant, within the liver. A number of clinical and tumor parameters were analyzed. RESULTS: Cumulative overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 15.6% and 45.1%, respectively, irrespective of clinical and tumor parameters. Overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 40% and 67.5%, for tumor > or =3 cm and 7.5% and 37.5%, for tumor <3 cm. Cumulative local recurrence rates at 12 and 24 months were 26.3% and 43.5%, respectively, for tumor > or =3 cm and 11.7% and 18.2%, respectively, for tumor <3 cm. The log-rank test indicated that a tumor size of > or =3 cm and the presence of capsule for a tumor of <3 cm in diameter were significant risk factors for intrahepatic recurrence. A pretreatment serum PIVKA-II level of > or =0.02 AU/ml was the only clinical parameter associated with overall recurrence (p=0.0041) and distant intrahepatic recurrence (p=0.0307). Distant intrahepatic recurrence rates 12 and 24 months after percutaneous ethanol injection were 22.5% and 31.4%, respectively, for PIVKA-II levels of > or =0.02 AU/ml and 8% and 17.8%, for PIVKA-II of <0.02 AU/ml. Cox's proportional hazard model identified that tumor size, tumor capsule and baseline serum PIVKA-II levels were independently related to intrahepatic recurrence. CONCLUSIONS: These data demonstrate that tumor size and peritumoral capsule were associated with overall and local recurrence of hepatocellular carcinoma. Moreover, pretreatment serum levels of PIVKA-II can indicate the risk of early intrahepatic recurrence and may assist in patient selection and appropriate therapy.

Adult↗

Sites of local recurrence after surgery, with or without chemotherapy, for rectal cancer: implications for radiotherapy field design.

PURPOSE: To examine the sites of pelvic recurrence in patients with rectal cancer previously untreated with radiotherapy to determine the relative frequency and location of recurrence within the pelvis. METHODS AND MATERIALS: The records of patients with locally recurrent rectal cancer referred to three radiation oncology departments between 1984 and 1997 were reviewed. The data collected included the date and type of the initial resection and the pathologic findings. The site of recurrence within the pelvis, presence of metastasis, and date of recurrence were documented. RESULTS: A total of 269 patients were included. Tumor had invaded through the muscularis in 74% and involved other organs in 9%. Fifty-two percent of patients were node positive at initial surgery. The median time to local recurrence from surgery was 18 months (range 15-20) and from local recurrence to death was 14 months (range 12-17). Both the initial tumor stage and the resection type influenced the recurrence location within the pelvis (p <0.01). T4 tumors comprised only 9% of initial T stage tumors but accounted for 38% of anterior central pelvic recurrences (p <0.01). All perineal recurrences occurred after abdominoperineal resection. The sites of recurrence within the pelvis were the posterior central pelvis (47%) and anastomotic (21%). CONCLUSION: If those patients with T4 tumors at presentation were excluded, 89% had local recurrence at, or posterior to, the anastomosis. Furthermore, if we exclude both patients who underwent abdominoperineal resection and those with T4 tumors at presentation, the rate increases to 93%. The rate of recurrence anteriorly (7%) does not justify routine radiation of the anterior pelvis beyond that required to adequately cover the anastomotic site.

Anastomosis, Surgical↗

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer.

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0

Adult↗

Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: To analyze the patterns of local-regional recurrence in patients with head and neck cancer treated with parotid-sparing conformal and segmental intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Fifty-eight patients with head and neck cancer were treated with bilateral neck radiation (RT) using conformal or segmental IMRT techniques, while sparing a substantial portion of one parotid gland. The targets for CT-based RT planning included the gross tumor volume (GTV) (primary tumor and lymph node metastases) and the clinical target volume (CTV) (postoperative tumor bed, expansions of the GTVs and lymph node groups at risk of subclinical disease). Lymph node targets at risk of subclinical disease included the bilateral jugulodigastric and lower jugular lymph nodes, bilateral retropharyngeal lymph nodes at risk, and high jugular nodes at the base of skull in the side of the neck at highest risk (containing clinical neck metastases and/or ipsilateral to the primary tumor). The CTVs were expanded by 5 mm to yield planning target volumes (PTVs). Planning goals included coverage of all PTVs (with a minimum of 95% of the prescribed dose) and sparing of a substantial portion of the parotid gland in the side of the neck at less risk. The median RT doses to the gross tumor, the operative bed, and the subclinical disease PTVs were 70.4 Gy, 61.2 Gy, and 50.4 Gy respectively. All recurrences were defined on CT scans obtained at the time of recurrence, transferred to the pretreatment CT dataset used for RT planning, and analyzed using dose-volume histograms. The recurrences were classified as 1) "in-field," in which 95% or more of the recurrence volume (V(recur)) was within the 95% isodose; 2) "marginal," in which 20% to 95% of V(recur) was within the 95% isodose; or 3) "outside," in which less than 20% of V(recur) was within the 95% isodose. RESULTS: With a median follow-up of 27 months (range 6 to 60 months), 10 regional recurrences, 5 local recurrences (including one noninvasive recurrence) and 1 stomal recurrence were seen in 12 patients, for a 2-year actuarial local-regional control rate of 79% (95% confidence interval 68-90%). Ten patients (80%) relapsed in-field (in areas of previous gross tumor in nine patients), and two patients developed marginal recurrences in the side of the neck at highest risk (one in the high retropharyngeal nodes/base of skull and one in the submandibular nodes). Four regional recurrences extended superior to the jugulodigastric node, in the high jugular and retropharyngeal nodes near the base of skull of the side of the neck at highest risk. Three of these were in-field, in areas that had received the dose intended for subclinical disease. No recurrences were seen in the nodes superior to the jugulodigastric nodes in the side of the neck at less risk, where RT was partially spared. CONCLUSIONS: The majority of local-regional recurrences after conformal and segmental IMRT were "in-field," in areas judged to be at high risk at the time of RT planning, including the GTV, the operative bed, and the first echelon nodes. These findings motivate studies of dose escalation to the highest risk regions.

Adult↗

Recurrent unstable angina after directional coronary atherectomy is related to the extent of initial coronary plaque inflammation.

OBJECTIVES: This study was performed to evaluate the relationship between plaque inflammation of the initial culprit lesion and the incidence of recurrent angina for one year after directional coronary atherectomy (DCA). BACKGROUND: A positive correlation between coronary plaque inflammation and angiographic restenosis has been reported. METHODS: A total of 110 patients underwent DCA. Cryostat sections were immunohistochemically stained with monoclonal antibodies CD68 (macrophages), CD-3 (T lymphocytes) and alpha-actin (smooth muscle cells [SMCs]). The SMC and macrophage contents were planimetrically quantified as a percentage of the total tissue area. T lymphocytes were counted as the number of cells/mm2. The patients were followed for one year to document recurrent unstable angina pectoris (UAP) or stable angina pectoris (SAP). RESULTS: Recurrent UAP developed in 16 patients, whereas recurrent SAP developed in 17 patients. The percent macrophage areas were larger in patients with recurrent UAP (27 +/- 12%) than in patients with recurrent SAP (8 +/- 4%; p = 0.0001) and those without recurrent angina (18 +/- 14%; p = 0.03). The number of T lymphocytes was also greater in patients with recurrent UAP (25 +/- 14 cells/mm2) than in patients with recurrent SAP (14 +/- 8 cells/mm2; p = 0.02) and those without recurrent angina (14 +/- 12 cells/mm2; p = 0.002). Multiple stepwise logistic regression analysis identified macrophage areas and T lymphocytes as independent predictors for recurrent UAP. CONCLUSIONS: There is a positive association between the extent of initial coronary plaque inflammation and the recurrence of unstable angina during long-term follow-up after DCA. These results underline the role of ongoing smoldering plaque inflammation in the recurrence of unstable angina after coronary interventions.

Aged↗

The role of surveillance magnetic resonance imaging (MRI) scanning in detecting recurrent brain tumors in asymptomatic children.

BACKGROUND: There is controversy regarding the utility of routine surveillance scanning for asymptomatic children with brain tumors. Although the role of CT or magnetic resonance imaging (MRI) scanning in this setting has been examined in several studies, none have focused on children followed exclusively by MRI. The purpose of this study was to determine how often recurrent brain tumors are detected by routine MRI surveillance in asymptomatic children. METHODS: The medical records of all children with brain tumors treated at Children's Hospital at Strong from 1990-1999 were reviewed. Recurrence was defined as an increase in size of the tumor on MRI scan. Astrocytomas and gangliogliomas were classified as low-grade tumors; high-grade astrocytomas, medulloblastomas, and ependymomas were classified as high-grade tumors. RESULTS: Of the 112 evaluable children with brain tumors during this time period, 46 (41%) suffered an MRI-documented recurrence. Of these 46 patients, 13 (28%) had low-grade tumors and 33 (72%) had high-grade tumors. Twenty-seven of the 46 recurrences (59%) occurred in asymptomatic children. Ten of the 13 children (77%) with recurrent low-grade tumors were asymptomatic compared to 17 of 33 children (52%) with recurrent high-grade tumors (p = 0.18). The median survival from time of recurrence for the symptomatic children was seven months, while the median survival from time of recurrence for the asymptomatic children has not yet been reached (p = 0.025). When the analysis was confined to children with high-grade tumors, there was no difference in median survival from the time of recurrence for symptomatic versus asymptomatic children (5 mo. versus 7 mo.) (p = 0.25). The frequency of detection of recurrences by surveillance scanning in asymptomatic children was 4.2% (one recurrence detected per 24 surveillence MRI scans). CONCLUSION: The majority of recurrent brain tumors are detected by MRI surveillence in asymptomatic children. However, asymptomatic recurrences were detected in only a small proportion of surveillance scans and had no impact on survival in children with high-grade tumors.

Adolescent↗

The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction.

Knowledge of the pattern of recurrence of surgically treated cases of adenocarcinoma of the oesophago-gastric junction is important both for better understanding of their biological nature and for future strategic planning of therapy. The aim of this study is to demonstrate and compare the pattern of dissemination and recurrence in patients with Type I and Type II adenocarcinoma of oesophago-gastric junction. A prospective audit of the clinico-pathological features of patients who had undergone surgery with curative intent for adenocarcinoma of oesophago-gastric junction between 1991 and 1996 was undertaken. Patients were followed up by regular clinical examination. Clinical evaluation was supported by ultrasound, computerised tomography, radio-isotope bone scan, endoscopy and laparotomy each with biopsy and histology where appropriate. One hundred and sixty-nine patients with oesophago-gastric junction tumours (94 Type I and 75 Type II) have been followed up for a median of 75.3 (57-133) months. One hundred and three patients developed proven recurrent disease. The median time to recurrence was 23.3 (14.2-32.4) months for Type I and 20.5 (11.6-29.4) for Type II cancers. The most frequent type of recurrence was haematogenous (56% of Type I recurrences and 54% of Type II) of which 56% were detected within 1 year of surgery. The most frequent sites were to liver (27%), bone (18%) brain (11%) and lung (11%). Local recurrence occurred in 33% of Type I cancer and 29% of Type II recurrences. Nodal recurrence occurred in 18 and 25% of Type I and Type II cancer recurrences, most frequently to coeliac or porta hepatis nodes (64%). Only 7% of Type I and 15% of Type II cancer recurrences were by peritoneal dissemination. Type I and Type II adenocarcinoma of the oesophago-gastric junction have a predominantly early, haematogenous pattern of recurrence. There is a need to better identify the group of patients with small metastases at the time of diagnosis who are destined to develop recurrent disease in order that they may be spared surgery and those with micro metastases in order that they can be offered multi-modality therapy including early post operative or neo-adjuvant chemotherapy.

Adenocarcinoma↗

Competing risks analyses for recurrence from primary breast cancer.

The effects of prognostic factors on local, regional or distant metastasis are standardly assessed separately. Competing risks analyses may be used to assess simultaneously the effects of factors on different types of first recurrence. Data for a cohort of 678 primary invasive breast cancer patients accrued between 1971 and 1990, updated to 1995, included type of first recurrence (local, regional, distant). We investigated the effects of the traditional factors of age, tumour size, nodal status, ER, PgR, adjuvant therapy (hormones, chemotherapy, radiotherapy) on type of recurrence and time to recurrence for all patients and for those aged > or = 65. For all ages of patients, there were five factors with significant associations with type or time to first recurrence. Adjuvant radiation was the only factor which had an effect (P < or = 0.05) on the type of first recurrence: being associated with a reduction in local recurrence. Age, nodal status, tumour size and adjuvant chemotherapy all had significant associations across all types of first recurrence, and in particular with time to recurrence for both local and distant metastasis. This indicates a potential lack of independence in these end-points. For patients > or = 65 years of age, there were no factors which differentially affected type of recurrence, while only nodal status and tumour size had significant associations with time to recurrence. Analyses were used to assess simultaneously the effects of traditional prognostic factors and treatment options on type of first recurrence and time to first recurrence. The extension to evaluations with newer prognostic factors would expedite the determination and mode of biologic activity for such factors.

Age Factors↗

Prognostic implications of seizure recurrence in the first year after anterior temporal lobectomy.

PURPOSE: Seizure recurrence after anterior temporal lobectomy (ATL) incites concerns of whether seizures will eventually be successfully controlled. Our study evaluated the prognostic significance of seizure recurrence in the first year after ATL. METHODS: The postoperative courses of 175 consecutive patients who had undergone ATL and had > or =2 years of follow-up were studied. Recurrence was considered early if the first seizure occurred within 7 days after ATL and late if it occurred >7 days after ATL. Recurrent seizures were considered provoked when precipitating factors were present, such as interruption of antiepileptic drug (AED) intake. Subsequent outcome was determined at terminal follow-up. RESULTS: Percentage of excellent outcome was comparable between patients whose initial recurrent seizures were auras or simple partial seizures and patients without seizure recurrence in the first year (86.7 vs. 93.1%; p > or = 0.05). However, percentage of excellent outcome was less when the initial recurrent seizure was complex partial, either with or without secondary generalization (44.8%; p < or = 0.01). Outcome was not different between early and late seizure recurrence (excellent in 41.7 vs. 55.7%; p > or = 0.05). Nonetheless, patients with either early or late seizure recurrence were less likely to have excellent outcome than were patients with no seizure recurrence in the first year (p < or = 0.001). Percentage of excellent outcome was best when patients were seizure free in the first year (93.1%), intermediate when initial recurrent seizure was provoked (72.0%), and worst when unprovoked (27.8%) (p < or = 0.001). CONCLUSIONS: In the first postoperative year, the type of initial recurrent seizure, whether aura or complex partial and whether provoked or unprovoked, is associated with long-term prognosis in seizure control after ATL. The timing of the initial seizure recurrence is not as important.

Adolescent↗

Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients.

The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic liver transplantation (OLT) is not precisely determined. The aim of this analysis is to study the progression of disease recurrence and its impact on patient and graft survival. Data for 300 patients who underwent OLT for hepatitis C were analyzed regarding the incidence of histological recurrence, risk factors, immunosuppressive regimen, rejection episodes, and survival. For patients with histological recurrence, the timing and risks for disease progression were analyzed. Data for 30 patients who underwent retransplantation were studied. Histological recurrence occurred in 40.3% of patients, 27.2% of whom progressed to bridging fibrosis or cirrhosis. Eighty-seven percent of the patients experienced recurrence of disease within 24 months of OLT. Patients with histological recurrence within 6 months of OLT had an increased risk for progression to cirrhosis compared with patients with recurrence later than 6 months (risk ratio, 2.3). Recurrence within 1 year was associated with decreased patient and graft survival rates at 1 and 5 years (65.1% and 56.4% versus 80.6% and 78.4%; P =.004 and P =.0008, respectively). Patients with histological recurrence had a greater incidence of acute cellular rejection, as well as multiple episodes of rejection, steroid-resistant rejections, and greater cumulative doses of corticosteroids. Histological recurrence after OLT for hepatitis C is common and usually occurs within 2 years of OLT. Early recurrence negatively affects patient and graft survival. Host factors impacting on recurrence need further study. A relation between the hepatitis C virus, allograft rejection, and immunosuppression exists and needs investigation.

Adult↗

[Radiotherapy of recurrences of endometrial carcinoma].

In a retrospective study the data of 79 patients undergoing radiation-therapy for recurrent endometrial cancer during the years 1972-1978 were evaluated. Group I consisted of 43 patients, who primarily underwent irradiation, group II consisted of 36 patients, who primarily underwent surgery (total abdominal hysterectomy) mostly without irradiation. All patients were primarily classified as FIGO-stage I, the median age was 69 and 67 years respectively. In 32 cases (74%) of group I the localisation of the recurrence was the uterus, in 8 (19%) the vagina and in 3 (7%) the small pelvis. In group II a vaginal recurrence was found in 25 patients (69%), in 11 (31%) a pelvic recurrence. In two thirds of all cases the recurrences were diagnosed within three years of the primary treatment. Late recurrences after 5 years occurred in group I in 10%, in group II twice as often. The treatment of all recurrences was irradiation. 54 patients (68%) died within 2 years, 25 survived their recurrence for more than 2 years, (32%). In group I 23% survived for more than 2 years, in group II 42%. At the time of performance of the study the 5-year-survival-rate is 13%. Thus in two thirds of patients we succeeded in extending the survival for at least 2 years. The prognosis of a recurrence following surgery is distinctly better than following primary intracavitary irradiation. 56% of vaginal recurrences following primary surgery survived more than 2 years. The 5-year-survival-rate was similar in these vaginal recurrences however to the uterine recurrences following primary irradiation. The prognosis of patients undergoing primary surgery was the better, the later the recurrence occurred.

Aged↗

Clinicopathologic risk factors for recurrence after a curative hepatic resection for hepatocellular carcinoma.

BACKGROUND: The long-term prognosis after resection for patients with hepatocellular carcinoma is still unsatisfactory because of the high recurrence rate. The survival of patients with multiple intrahepatic or extrahepatic recurrence is especially poor. METHODS: Among the patients who underwent hepatic resection for hepatocellular carcinoma between 1981 and 2000, 216 patients with 3 or less than 3 intrahepatic recurrences (group B); 156 patients with more than 3 intrahepatic recurrences, extrahepatic recurrences, or both (group C); and 51 patients who survived more than 5 years without recurrence (group A) were clinicopathologically studied. RESULTS: The period to recurrence of group C was significantly earlier than that of group B and also showed a significantly poor prognosis after recurrence. Tumor factors, including size, portal venous invasion, intrahepatic metastasis, histologic grade, or the number of tumors at resection in group C was significantly worse than in groups A and B. Although no differences are recognized in the tumor factors between groups A and B, except for the alpha-fetoprotein level, liver function in group B was significantly worse than that in group A. In addition, the frequency of hepatitis B surface antigen in group B and that of hepatitis C virus in group B was significantly less and higher than that in group A, respectively. CONCLUSION: Similar to extrahepatic metastasis, multinodular recurrences are also mainly caused by metastatic recurrence from the main tumor by means of the portal system, and recurrences with up to 3 intrahepatic nodules are mainly caused by metachronous multicentric hepatocarcinogenesis. Because the mechanisms of recurrence differed, determining the patterns of recurrence on the basis of the clinicopathologic findings is important for selecting the optimal postoperative therapy for each individual patient.

Alanine Transaminase↗

Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada.

BACKGROUND: During an epidemic of Clostridium difficile-associated disease (CDAD) caused by a strain that is a hyper-producer of toxins A and B, the frequency of a first recurrence after metronidazole treatment of the initial episode doubled in 2003-2004, compared with 1991-2002. METHODS: To examine whether administration of metronidazole as treatment for a first recurrence of CDAD remained appropriate, we reviewed data for patients with CDAD diagnosed in a hospital in Quebec, Canada, during 1991-2005, who experienced a first recurrence. The frequency of a second recurrence within 60 days after the first one was measured using Kaplan-Meier analysis. Cox regression was used for multivariate analysis. RESULTS: A total of 463 patients had a first recurrence of CDAD, of whom 154 (33.3%) experienced a second recurrence. Independent predictors of a second recurrence were age and duration of hospitalization after the first recurrence; this latter finding suggested that many such episodes were reinfections rather than relapses. Neither choice of treatment drug (metronidazole or vancomycin) nor use of the same drug for treatment of first recurrence, as had been used during the initial episode, was associated with increased risk of a second recurrence. However, 51 patients (11.0%) developed at least 1 complication (i.e., shock, need for colectomy, megacolon, perforation, or death within 30 days) during the first recurrence. Older age, a high leukocyte count, and renal failure at first recurrence were strongly associated with a complicated CDAD. CONCLUSIONS: Metronidazole is not inferior to vancomycin for treatment of patients with a first recurrence of CDAD, but the risk of complications with any treatment of CDAD may be higher than has previously been documented.

Adolescent↗

Recurrent Hodgkin's disease after bone marrow transplantation.

Histologic features of recurrent Hodgkin's disease (HD) after conventional therapy are well known, but few studies describe HD after bone marrow transplantation (BMT). Histologic material from 63 patients who underwent BMT performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994 was examined; 13 of the 63 patients had histologically proved recurrent disease after BMT. Histologic material and clinical findings from the original diagnostic biopsy specimen and pre-BMT and post-BMT specimens were available from our study population of eight patients (five male, three female; age range, 16 to 38 years; median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of recurrence included lymph nodes only (four patients), and lymph nodes and lung, lung and liver, and lung only (one patient each). In one patient, a high-grade non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT. In another, disease progressed from grade 1 in the original biopsy specimen to grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT biopsy specimens of recurrent HD with lung involvement revealed a substantial increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase studies in seven patients demonstrated substantial change in phenotype of Reed-Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a +2 reaction with CD30 (Ki-1). No substantial differences in the reactive component were noted between the original biopsy specimen and pre-BMT and post-BMT specimens of recurrent disease. In summary, histologic findings of post-BMT recurrent NSHD do not differ significantly from those of the original diagnostic biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell lymphoma developed after BMT performed to treat recurrent HD.

Adolescent↗

Characteristics associated with recurrence among women with ductal carcinoma in situ treated by lumpectomy.

BACKGROUND: Clinical and histopathologic characteristics that may predict risks of recurrence in women with ductal carcinoma in situ (DCIS) have not been consistently identified. We identified factors associated with recurrence as DCIS versus invasive breast cancer and determined the 5-year absolute risks of recurrence as a function of these factors. METHODS: We conducted a population-based cohort study among 1036 women in the San Francisco Bay Area who were aged 40 years or older when diagnosed with DCIS and treated by lumpectomy alone from January 1983 through December 1994. Standardized pathology reviews were conducted to determine disease recurrence, defined as DCIS or invasive breast cancer diagnosed in the ipsilateral breast containing the initial DCIS lesion or at a distant site more than 6 months after the initial diagnosis and treatment of DCIS. Conditional logistic regression models were used to determine factors associated with recurrence. All statistical significance tests were two-sided. RESULTS: During a median follow-up of 77.9 months, 209 women (20.2%) experienced a recurrence. Overall, the 5-year risks of recurrence as invasive cancer and as DCIS were 8.2% (95% confidence interval [CI] = 6.6% to 9.8%) and 11.7% (95% CI = 9.9% to 13.3%), respectively. The 5-year risks of recurrence as invasive cancer and as DCIS were 4.8% (95% CI = 3.7% to 6.8%) and 4.8% (95% CI = 3.8% to 5.8%), respectively, for women with low-nuclear-grade DCIS; 11.8% (95% CI = 9.9% to 14.1%) and 17.1% (95% CI = 15.5% to 18.7%), respectively, for women with high-nuclear-grade DCIS; 11.6% (95% CI = 11.3% to 12.0%) and 8.6% (95% CI = 7.1% to 10.2%), respectively, for women whose initial DCIS lesion was detected by palpation; and 6.6% (95% CI = 6.2% to 7.1%) and 14.1% (95% CI = 11.4% to 17.8%), respectively, for women with DCIS detected by mammography alone. High- (versus low-) nuclear-grade DCIS lesions and detection of the initial DCIS lesion by palpation (versus mammography) were associated with recurrence as invasive cancer. High- (versus low-) nuclear-grade lesions; resection margins that were positive, uncertain, or less than 10 mm disease-free (versus > or = 10 mm disease-free); and age 40-49 years at diagnosis (versus > or =50 years) were associated with recurrence as DCIS. CONCLUSIONS: Nuclear grade is strongly associated with recurrence but not with the type of recurrence. Women with high-nuclear-grade DCIS or DCIS detected by palpation who are treated by lumpectomy alone are at relatively high risk of having an invasive breast cancer recurrence, compared with women with low-nuclear-grade or mammographically detected DCIS, and may be appropriate candidates for additional treatment.

Adult↗

Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors.

OBJECTIVE: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment.

Adult↗

Recurrent breast cancer following immediate reconstruction with myocutaneous flaps.

As immediate breast reconstruction with rectus abdominis and latissimus dorsi myocutaneous flaps has become a recognized technique for patients requiring mastectomy, concerns have arisen regarding the detection and treatment of locoregional recurrence of breast cancer. Because most recurrences develop in the residual native skin of the chest wall following a mastectomy, breast reconstruction procedures involving the placement of a subpectoral prosthesis are unlikely to interfere with postoperative cancer surveillance. Myocutaneous flaps, however, transpose blocs of soft tissues into the mastectomy site. This study was done to evaluate the influence of a myocutaneous flap on the subsequent diagnosis and treatment of locoregional recurrence of breast cancer. Data were obtained from 161 patients with breast cancer who had immediate reconstruction with a myocutaneous flap between 1982 and 1990. Of the 161 patients reviewed, 120 had primary mastectomy with immediate reconstruction; 41 patients had salvage mastectomy and immediate reconstruction after failed conservative surgery and radiation therapy. Modified radical mastectomy was performed on all patients. Either a rectus abdominis (n = 65) or latissimus dorsi (n = 97) myocutaneous flap breast reconstruction was performed. Recurrent tumor was observed in 17 of the 161 patients reviewed (10.6 percent). Fourteen of the 17 recurrences occurred in 120 patients having primary mastectomy and immediate reconstruction for a rate of 11.7 percent; 3 of 41 patients (7.3 percent) who had salvage mastectomy and flap reconstruction developed recurrences. Of the 17 recurrences, 6 patients were stage II, 10 were stage III, and 1 was stage IV. All 17 patients who developed a recurrence had invasive breast cancer, with infiltrating and inflammatory tumors predominating. All locoregional recurrences of breast cancer developed within the native skin and subcutaneous tissues adjacent to the mastectomy and flap reconstruction site. Recurrences were seen as rapidly as 2 weeks or as long as 3.8 years (mean 1.4) after the mastectomy and flap reconstruction. Overall mean follow-up for the entire group of 161 patients was 5.4 years. Thirteen of the 17 patients (76.5 percent) developed distant metastases either concomitantly with the locoregional recurrence or within 4.3 years (mean 1.7). From an oncologic viewpoint, the technique of myocutaneous flap breast reconstruction with rectus abdominis or latissimus dorsi flaps appears to be a safe one. An analysis of locoregional recurrence of breast cancer in patients undergoing primary mastectomy or salvage mastectomy with myocutaneous flap breast reconstruction did not show concealment by the flap of any recurrent tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗