Breast cancer recurrence after immediate reconstruction: patterns and significance

Local recurrence of cancer after mastectomy and immediate breast reconstruction is generally regarded as a poor prognostic indicator. This study was conducted to identify specific patterns of local recurrence following reconstruction and to determine their biological significance. The records of all patients who had undergone immediate breast reconstruction at The University of Texas M. D. Anderson Cancer Center between June 1, 1988, and December 31, 1998, were reviewed. The records of patients who had local tumor recurrence were then carefully analyzed. During this 10-year period, a local recurrence of cancer was found to have developed in 39 of 1694 patients (2.3 percent). Most recurrences were in the skin or subcutaneous tissue (n = 28; 72 percent), and the remainder were in the "chest wall" (n = 11; 28 percent), as defined by skeletal or muscular involvement. Transverse rectus abdominis myocutaneous flaps were used most often in both groups, but latissimus dorsi myocutaneous flaps and implant techniques were also used in some patients. Patients with subcutaneous tissue recurrence had an overall survival rate of 61 percent at follow-up of 80.8 months, compared with patients with chest wall recurrence, whose survival rate was 45 percent at similar follow-up. Metastases were less likely to develop in patients with subcutaneous tissue recurrence than in those with chest wall recurrence (57 percent versus 91 percent; p = 0.044); the former group also had a greater chance of remaining disease-free after treatment of the recurrence (39 percent versus 9 percent), respectively. Metastasis-free survival was higher in patients with subcutaneous tissue recurrence than with chest wall recurrence (2-year and 5-year survival: 52 and 42 percent versus 24 and 24 percent; p = 0.04). In both groups, the time to detection of the recurrence was similar (subcutaneous tissue recurrence, 27.1 months, versus chest wall recurrence, 29.5 months). Distant disease did not develop in one patient only in the chest wall recurrence group; this patient remained disease-free at 70 months. From these results, it was concluded that (1) not all local recurrences are the same: patients with subcutaneous tissue recurrence have better survival rates, a decreased incidence of metastases, and a greater chance of remaining disease-free than do those with chest wall recurrence; (2) immediate breast reconstruction (although potentially, it can conceal chest wall recurrence) does not seem to delay the detection of chest wall recurrence; and (3) even if a chest wall recurrence develops, it is highly associated with metastatic disease, and the survival rate is not likely to have been influenced by earlier detection. These data support the continued use of immediate breast reconstruction without fear of concealing a recurrence or influencing the oncologic outcome.     

Surgical reconstruction of pediatric pressure sores: long-term outcome.

The long-term outcome after the surgical repair of pressure sores in the adult population has been well studied. Recurrence rates from 25 to 80 percent have been reported, despite improvements in surgical repair and mechanical support devices. Such high recurrence rates have led many investigators to question the rationale for the surgical closure of pressure sores. There are no published long-term data that document pressure sore recurrence after surgical treatment in the pediatric population. A retrospective analysis of all patients who underwent surgical reconstruction of grade III and IV pressure sores at the Children's Hospital of Philadelphia from 1987 to 1999 was performed. During this 12-year period, 19 consecutive patients with a mean age of 16.2 years were operated on for 25 pressure sores. Follow-up was obtained for 15 patients (79 percent), who underwent repair for 20 pressure sores. Mean postoperative follow-up was 5.3 years (range, 11 months to 11 years). Mean age at the time of surgery was 16.5 years. The overall pressure sore recurrence rate was 5 percent (1 of 20 sores). Overall patient recurrence (previous patient who developed a new sore) was 20 percent (3 of 15 patients). In contrast to the recurrence rates reported for the surgical repair of pressure sores in the adult population, the recurrence rate of 5 percent in the pediatric population is significantly lower. This demonstrates that the surgical reconstruction of pressure sores in the pediatric patient can be successful and provide long-term skin integrity.     

Long-Term Outcomes of Patients with Acute Cholecystitis after Successful Percutaneous Cholecystostomy Treatment and the Risk Factors for Recurrence: A Decade Experience at a Single Center

Background

Percutaneous cholecystostomy tube (PCT) has been effectively used for the treatment of acute cholecystitis (AC) for patients unsuitable for early cholecystectomy. This retrospective study investigated the recurrence rate after successful PCT treatment and factors associated with recurrence.

Methods

We reviewed patients treated with PCT for AC from October 2004 through December 2013. Patients with successful PCT treatment were those who were free from persistent PCT drainage. We used multivariable logistic regression analysis sequentially to identify factors associated with each outcome.

Results

The study included 184 patients (mean age: 70.1 years). The average duration for parenteral antibiotics was 14.4 days and 20.0 days for PCT drainage. The one-year recurrence rate was 9.2% (17/184) with most recurrences occurring within two months (6.5%, 12/184) of the procedure. Complicated cholecystitis (odds ratio [OR]: 4.67; 95% confidence interval [CI]: 1.44–15.70; P = 0.01) and PCT drainage duration >32 days (OR: 4.92; 95% CI: 1.03–23.53; P = 0.05) positively correlated with one-year recurrence; parenteral antibiotics duration >10 days (OR: 0.21; 95% CI: 0.05–0.68; P = 0.01) was inversely associated with one-year recurrence.

Conclusions

The recurrence rate was low for patients after successful PCT treatment. Predictors for recurrence included the severity of initial AC and subsequently provided treatments.     

Recurrence following treatment of ductal carcinoma in situ with skin-sparing mastectomy and immediate breast reconstruction

Skin-sparing mastectomy with immediate breast reconstruction can provide an excellent cosmetic result. Despite its increasing popularity, few studies have assessed the risk of recurrence when the procedure is used for the treatment of ductal carcinoma in situ. To evaluate the oncologic safety of skin-sparing mastectomy used for the treatment of ductal carcinoma in situ, the recurrence rate was analyzed. Patients with ductal carcinoma in situ or invasive carcinoma or both who underwent skin-sparing mastectomy with immediate breast reconstruction between 1985 and 1994 and had a follow-up period of at least 6 years were included in this retrospective analysis. The recurrence rates were determined for invasive carcinoma (with or without foci of ductal carcinoma in situ) and ductal carcinoma in situ alone. A total of 221 patients were included, 177 patients with invasive carcinoma and 44 patients with ductal carcinoma in situ alone. The immediate breast reconstructions were performed with transverse rectus abdominis muscle (TRAM) flaps in 62 percent of patients, implants in 34 percent of patients, and latissimus dorsi myocutaneous flaps (with or without implants) in 4 percent of patients. The local recurrence rate was zero of 44 for patients with ductal carcinoma in situ and 5.6 percent (10 of 177) for patients with invasive carcinoma during a mean follow-up period of 9.8 years. There was a 6.8 percent (12 of 177) metastatic recurrence rate in the invasive carcinoma group. All recurrences were invasive ductal carcinoma. Of the patients with ductal carcinoma in situ alone, none developed metastatic disease. The combined metastatic and local recurrence rates for the invasive carcinoma group (n = 177) with each type of reconstruction were 13 percent (14 of 110), 12 percent (seven of 60), and 14 percent (one of seven) for TRAM flaps, implants, and latissimus dorsi flaps, respectively. The risk of recurrence following skin-sparing mastectomy and immediate breast reconstruction for ductal carcinoma in situ is low during this follow-up period. Therefore, skin-sparing mastectomy with immediate breast reconstruction seems to be a safe oncologic treatment option for ductal carcinoma in situ; however, a longer follow-up period is important to determine the long-term risk of recurrence.     

Randomised trial of treatment of hypertension in elderly patients in primary care.

A randomised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years. The principal antihypertensive agents were atenolol and bendrofluazide. There was a reduction in the rate of fatal stroke in the treatment group to 30% of that in the control group (95% confidence interval 11-84%, p less than 0.025). The rate of all strokes (fatal and non-fatal) in the treatment group was 58% of that in the control group (95% confidence interval 35-96%, p less than 0.03). The incidence of myocardial infarction and total mortality was unaffected by treatment. Questionnaires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment.     

Part I – Young Girls with Non-Refluxing Ureters

This paper is the study of 144 girls with histories of urinary tract infection followed at the Stanford Medical Center who were found to be free of ureterovesical reflux. The mean age at onset of infection for the entire group was about four years and ranged from the first few months of life to age 10. Ninety-two percent of the 505 infection episodes in these children presented with symptoms referable to the lower tract, and bacterial localization studies confirmed that 85 percent of the infections were limited to the bladder. Escherichia coli was the most common organism isolated and most infections were caused by a pure culture of a single bacteria.In only two of the 144 patients studied was there any evidence of upper tract damage related to infection. The possibility that these patients had reflux at an earlier age could not be discounted.In response to short-term antibacterial therapy in 66 of the patients followed closely for an average of 40 months each, 20 percent of the patients had no further infections and 80 percent went on to recurrence. With each succeeding treatment an additional 20 percent of the patients were “cured,” but the remainder experienced recurrent infections during the follow-up. This reinfection pattern supports the use of long-term antibacterial prophylaxis in all girls who have more than three or four recurrences of infections. Urethral dilation appeared to have no value in reducing the reinfection rate. While it appears that in the absence of ureterovesical reflux few, if any, of these children will go on to develop upper tract damage, long-term prophylactic suppressive medication can clearly be justified on the grounds of reducing patient morbidity.     

CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation

B cell acute lymphocytic leukemia (B-ALL) patients who have relapsed after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, and there is currently no standard approach available. Chimeric antigen receptor (CAR)-T cells induce high rates of initial response and long-term remission among patients with B-cell malignancies, especially B-ALL. Meanwhile, sequential infusion of CAR19/22 T cells has been proven to be effective at preventing tumor immune escape. In the present study, we retrospectively analyzed 23 B-ALL patients who relapsed after allogeneic (allo)-HSCT and underwent sequential infusion of CAR19/22 T cells, including nine donor-derived and 14 recipient-derived, in our center from July 2016 to July 2020, to evaluate the safety and efficacy of the cocktail of two single-specific CAR-T cells in B-ALL patients relapsed after transplantation. Except for one patient refusing evaluation, the remaining 22 patients achieved minimal residual disease (MRD)-negative complete remission within 30 days after CAR-T infusion. Most toxicities were slight and reversible. The estimated 12-month progression-free survival (PFS) rate was 59.2% (95% confidence interval [CI], 35.9% to 76.5%), and the estimated 12-month overall survival (OS) rate was 67.4% (95% CI, 43.2% to 83.1%). Only two patients had CD19-negative recurrence. In addition, early recurrence after transplantation, graft-versus-host disease (GVHD) and severe infection after CAR-T infusion were poor prognostic factors. Our results indicate that sequential infusion of CAR19/22 T cells is safe and effective for relapsed ALL patients after HSCT. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526.     

The Influence of Surgical Extent and Parafibromin Staining on The Outcome of Parathyroid Carcinoma: 20-Year Experience From a Single Institute

Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial.Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated.Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival.Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent.Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization     

A prospective study of the accuracy of the surgeon's diagnosis and significance of positive margins in nonmelanoma skin cancers

Even with a precise preoperative diagnosis, complete excision of nonmelanoma skin cancer is not always achieved. The conundrum remains the decision for appropriate secondary treatment. Many surgeons, regardless of the nature of the lesion, consider re-excision to be the only option. In a prior 4-year prospective study that ascertained the accuracy of our clinical diagnosis of skin lesions removed in an office setting, one-fifth were found to be malignant and 98 percent (n = 415) of the lesions were nonmelanoma skin cancer. Unfortunately, 65 (15.7 percent) of the malignant nonmelanoma skin cancer lesions had positive margins. The outcome of our management for these specific lesions was followed prospectively over the 7.5 years of this study to determine whether aggressive surgical intervention was justified in every case.Of 65 patients with lesions, early and complete re-excision of margin-positive nonmelanoma skin cancer was performed for 34 (52.3 percent), with residual tumor found in 11 (32.4 percent), followed by a later recurrence in one (2.9 percent). The remaining 31 patients agreed to semiannual office visits, with one (3.2 percent) recurrence in this group. Thus, the overall rate of recurrence for margin-positive nonmelanoma skin cancer was 3.1 percent, with a mean follow-up of 3.6 years (range, 0 to 7.5 years).There were no recurrences for basal cell carcinoma in either treatment group, suggesting that, at least for "simple" primary lesions without confounding risk factors, there is some validity to a "wait and see" attitude, in which treatment of a potential recurrence would be straightforward. Despite our observed infrequent local recurrences of squamous cell cancers (13.3 percent), the small risk of metastases still suggests the appropriateness of complete surgical eradication for these tumors whenever feasible.     

Vascular endothelial growth factor (VEGF) and melanoma. N-acetylcysteine downregulates VEGF production in vitro

Vascular endothelial growth factor (VEGF), the most potent angiogenic factor identified to date, is associated with growth and metastasis of solid tumours, including melanoma. It has been shown in vitro that melanoma cells produce raised concentrations of VEGF. We examined the VEGF concentrations in plasma of 20 patients with primary melanoma, local recurrence and metastatic melanoma. We also studied the inhibiting effect of one antioxidant, N-acetylcysteine, on VEGF production in three human melanoma cell lines. We found elevated levels of VEGF (median 205 pg ml; 95 percent confidence interval, 80-414) in metastatic melanoma, with respect to primary and locally recurrent melanoma (75 pg/ml; 95 percent confidence interval, 35-130). The health control patients had levels of 25 pg/ml (95 percent confidence interval, 10-35). Human melanoma cell lines secreted VEGF in basal conditions (550-963 +/- 125 pg/ml) and N-acetylcysteine (0.5-20 mM) significantly decreased the VEGF production in a dose-dependent manner. VEGF concentrations were found to be raised in patients with primary melanoma, local recurrence, and above all, metastatic melanoma (P=0.008). N-acetylcysteine inhibits VEGF production in three human melanoma cell lines. This antioxidant might have therapeutic applications in metastatic melanoma in combination with other cytotoxic drugs.     

Ultrasound-assisted lipoplasty treatment for axillary bromidrosis: clinical experience of 375 cases

Bromidrosis is a condition of abnormal offensive body odor caused mostly by apocrine gland secretion from the axilla. Although no morbid sequelae are known, the odor can be disturbing enough to cause social impairment and psychological distress. Medical care is available but is temporary and yields limited clinical benefit. Surgical treatment may provide a more definite remedy through reduction of the apocrine gland. However, there are risks for complication following surgical treatment such as subdermal excision, subcutaneous shaving, en bloc excision, and liposuction. The search for a less invasive but still effective procedure has led the authors to use ultrasound-assisted liposuction, which has reduced the risk of complication and recurrence. The purpose of this article was to evaluate the long-term outcome of ultrasound-assisted liposuction for the treatment of bromidrosis. From August 1998 to September 2002, 375 consecutive patients underwent ultrasound-assisted liposuction for bromidrosis of the axilla. The average age of the patients was 25.7 years (range, 15 to 55 years) and the average follow-up period was 18.8 months (range, 7 to 56 months). Subjective complaints of recurrences were noted in 22 patients (5.9 percent) and secondary ultrasound-assisted liposuction was performed, resulting in no further complaints. Complications other than recurrences were mild skin sloughing (3.2 percent), hematoma (1.3 percent), subcutaneous band (0.3 percent), and hypesthesia of the hand (0.3 percent), all of which healed spontaneously. Through a questionnaire that was answered by 264 patients, a subjective satisfaction rate was measured. Among the completed questionnaires, 91.7 percent reported satisfactory reduction of odor. Ultrasound-assisted liposuction to treat bromidrosis of the axilla provides advantages such as rapid recovery, less restriction of movement, unnoticeable scars, and a low rate of recurrence. The long-term outcome supports the benefits of this procedure. The authors recommend the use of ultrasound-assisted liposuction as first-line treatment for bromidrosis of the axilla.     

Recurrences after completion of the treatment of acute lymphoblastic leukemia in children]

Within the past 16 years, 2004 children with the acute lymphoblastic leukemia were treated at the Centres of the Polish Pediatric Study Group. The treatment was completed in 887 patients (44.3%) with the first remission. Recurrence was noted in 180 children (20.3%). This group was analysed in view of the type of therapy and its effect on the survival rate, significance of recurrence following therapy, character and localization of recurrent disease, and further fate of patients. It was found, that patients with isolated late nuclear recurrence have greatest chances to achieve subsequent remission. Most frequent and severe is recurrent bone marrow involvement which requires intensive chemotherapy combined with bone marrow transplantation due to unfavourable prognosis. Patients with the first recurrence of the acute lymphoblastic leukemia have a chance to achieve subsequent remission and long-term survival.     

Long-term survival from adenocarcinoma of the esophagus after transthoracic and transhiatal esophagectomy

ABSTRACT: BACKGROUND: The effects of transthoracic or transhiatal esophagectomy on the long-term survival of patients who had adenocarcinoma of the esophagus were compared, as were factors applicable in preoperative stratification of patient treatment. METHODS: A cohort of 147 consecutive patients with adenocarcinoma of the esophagus was evaluated for esophagectomy between 1984 and 2000. The patients were followed prospectively and observed survival rates of patients with a transthoracic or transhiatal approach to esophagectomy were compared by standardized mortality ratio (SMR) and relative mortality ratio (RMR) using the expected survival of a matched Norwegian population. RESULTS: A R0 resection was performed by transthoracic (n = 33) or a transhiatal (n = 55) esophagectomy in 88 (60%) patients with a median age of 61 (range: 35-77) and 70 (42-88) years, respectively (P <0.001). Tumor stages and other possible risk factors were similar in the two groups. Transthoracic or transhiatal esophagectomy resulted in a median survival time of 20.5 (95% confidence interval (CI): 10.4-57.6) and 16.4 (10.6-28.7) months, respectively. The respective survival rates were 31.2% and 27.8% by 5 years, and 21.3% and 16.6% by 10 years with an overall RMR of 1.14 (P = 0.63). Median survival time in the absence or presence of lymph node metastases was 74.0 (95% CI: 17.5-166.4) and 10.7 (7.9- 14.9) months. The corresponding survival rates by 10 years with non-involved or involved nodes were 48.9% and 3.8% respectively (RMR 2.22, P = 0.007). Patients with a pT1-tumor were few and the survival rate was not very different from that of the general population (SMR = 1.7, 95% CI: 0.7-4.1). The median survival time of patients with a pT2-tumor was 30.4 (95% CI: 9.0-142) months and with a pT3-tumor 14 (9.2-16.4) months. The survival rates by 10 years among patients with a pT1 tumor were 57.0% (95% CI: 14.9-78.9), pT2 33.3% (11.8-52.2), and pT3 7.1% (1.9-15.5). The relative mortality for T3 stages compared to T1 stages was statistically significant (RMR = 3.22, P = 0.024). CONCLUSION: Transthoracic and transhiatal esophagectomy are both effective approaches for treatment of adenocarcinoma of the esophagus and survival of more than 10 years can be expected without adjuvant chemotherapy. However, increasing depth of tumor invasion and lymph node metastases reduce life expectancy.     

Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications.     

Outcome of patients with toxic epidermal necrolysis syndrome revisited

Toxic epidermal necrolysis syndrome is an uncommon, acute, life-threatening, medication-induced disorder with a reported mortality rate of 20 to 60 percent. Different variables have been identified as risk factors. The extent to which these variables, when combined, affect the mortality and outcome in toxic epidermal necrolysis syndrome patients has not yet been reliably defined. Because of the high mortality rate, the logistic analysis of studied variables was performed to see whether a prognostic algorithm could be developed to aid the management of these patients. Thus, a retrospective review of 56 consecutive toxic epidermal necrolysis syndrome patients treated over a period of 13 years was undertaken in the authors' burn center. The demographics included age, sex, race, and total body surface area involved. The other variables studied were comorbidities, sepsis, steroid administration, and the interval between onset of rash and burn center admission. Data were subjected to Fisher's exact test and logistic analysis. Thirty-six patients (64.3 percent) were alive and 20 (35.7 percent) died. Univariate analysis indicated that the male/female ratio was 12:24 for survivors and 9:11 for nonsurvivors (p = 0.4). The white/nonwhite ratio was 80 percent for survivors and 54 percent for nonsurvivors (p = 0.58). The median age was 48.4 +/- 22.8 years (survivors, 41.7 +/- 22.0; nonsurvivors, 60.5 +/- 19.5; p = 0.002). Total body surface area involvement for survivors was 56.9 +/- 32 and 77.7 +/- 21 for nonsurvivors (p = 0.005). The presence of one or more comorbidities between the two groups differed (53 percent survivors and 90 percent nonsurvivors, p = 0.007), indicating eight times higher odds of dying in their presence. The average time between the onset of symptoms and admission to the burn unit was 5.25 +/- 3.4 days for survivors and 7.15 +/- 4.5 days for nonsurvivors (p = 0.08). The presence of sepsis (19.4 percent survivors, 95 percent nonsurvivors, p < 0.001) decreased odds for survival by a factor of 79. Steroids given as a single dose or multiple doses before the patient's transfer to the burn unit were not significantly associated with death (44 percent survivors, 65 percent nonsurvivors, p = 0.14). A multivariate logistic regression model yielded odds ratios of 1.11 (95 percent confidence interval, 1.03 to 1.19) for age in years, 304 (95 percent confidence interval, 8.83 to 10,400) for the presence of sepsis, and 1.03 (95 percent confidence interval, 0.99 to 1.08) for body surface area in percent. All those entering the burn unit with sepsis died. Equivalently, no survivors had sepsis before admission to the burn unit, whereas 55 percent of nonsurvivors had sepsis before admission and 40 percent developed sepsis after admission. When investigating the effect of age and sepsis, no patients over age 60 ever having sepsis survived, whereas all those who were under 60 and without sepsis survived. Likewise, all patients whose age was over 60 and whose total body surface area involved was over 60 percent died. The main factors contributing to the mortality from toxic epidermal necrolysis syndrome, when considering covariates separately, are the presence of sepsis at any time (odds ratio, 79), the presence of comorbidities (odds ratio, 8.05), age, and total body surface area, whereas multivariate models suggested age (odds ratio per year of additional age, 1.11), total body surface area (odds ratio per additional percent of body surface area, 1.03), and the presence of sepsis (odds ratio, 304). By using the actual coefficients in the logistic model, the log odds that the patient will die as the result of his or her condition can be summarized in the following formula: -11.5 + (10 percent of the patient's age + 3 percent of total body surface area + 5.75 if sepsis is present). The awareness of the importance of these covariates, and their early recognition as risk factors, should offer a focused approach to the patients' management and improve their outcome.     

Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34–0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97–2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13–4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications.     

Healing by primary closure versus open healing after surgery for pilonidal sinus: systematic review and meta-analysis

Objective To determine the relative effects of open healing compared with primary closure for pilonidal sinus and optimal closure method (midline v off-midline).Design Systematic review and meta-analyses of randomised controlled trials.Data sources Cochrane register of controlled trials, Cochrane Wounds Group specialised trials register, Medline (1950-2007), Embase, and CINAHL bibliographic databases, without language restrictions.Data extraction Primary outcomes were time (days) to healing, surgical site infection, and recurrence rate. Secondary outcomes were time to return to work, other complications and morbidity, cost, length of hospital stay, and wound healing rate.Study selection Randomised controlled trials evaluating surgical treatment of pilonidal sinus in patients aged 14 years or more. Data were extracted independently by two reviewers and assessed for quality. Meta-analyses used fixed and random effects models, dichotomous data were reported as relative risks or Peto odds ratios and continuous data are given as mean differences; all with 95% confidence intervals.Results 18 trials (n=1573) were included. 12 trials compared open healing with primary closure. Time to healing was quicker after primary closure although data were unsuitable for aggregation. Rates of surgical site infection did not differ; recurrence was less likely to occur after open healing (relative risk 0.42, 0.26 to 0.66). 14 patients would require their wound to heal by open healing to prevent one recurrence. Six trials compared surgical closure methods (midline v off-midline). Wounds took longer to heal after midline closure than after off-midline closure (mean difference 5.4 days, 95% confidence interval 2.3 to 8.5), rate of infection was higher (relative risk 4.70, 95% confidence interval 1.93 to 11.45), and risk of recurrence higher (Peto odds ratio 4.95, 95% confidence interval 2.18 to 11.24). Nine patients would need to be treated by an off-midline procedure to prevent one surgical site infection and 11 would need to be treated to prevent one recurrence.Conclusions Wounds heal more quickly after primary closure than after open healing but at the expense of increased risk of recurrence. Benefits were clearly shown with off-midline closure compared with midline closure. Off-midline closure should become standard management for pilonidal sinus when closure is the desired surgical option.     

Soft-tissue sarcomas of the upper extremity: surgical treatment and outcome

The objective of this retrospective follow-up study was to evaluate the outcome of patients with soft-tissue sarcoma treated by the authors' protocol, which consists of a selective combination of conservative surgery and radiotherapy. Patients who relapsed were especially evaluated to improve treatment results. The authors examined 80 patients with local soft-tissue sarcoma in the upper extremity referred to their multidisciplinary group. Fifteen patients were referred for first or subsequent local recurrence, and 65 patients were treated for primary tumor. The goal of treatment was local control and preservation of a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, postoperative radiotherapy was administered. Eighty-five percent of the patients were treated by limb salvage. Thirty patients needed reconstructive procedures such as pedicled (20 patients) or free flaps (10 patients). No free flaps were lost. The 5-year disease-specific overall survival rate was 75 percent, the local recurrence-free survival rate was 79 percent, and the metastasis-free survival rate was 68 percent. In univariate analysis, prognostic factors for local recurrence were extracompartmental site; for development of metastases, large size and extracompartmental site; and for decreased disease-specific overall survival, large size and extracompartmental site. Intramuscular, cutaneous, and subcutaneous tumors had a 5-year local control rate of 100 percent, and extracompartmental tumors had a local control rate of 69 percent. Extracompartmental tumors clearly have the worst prognosis and should be the main target for improving treatment strategies. After exclusion of patients with inadequate treatment according to the authors' protocol, the local control rate at 5 years was 90 percent. Strict adherence to treatment protocol should be practiced.     

Breast-conservation treatment for early invasive breast cancer: prognostic factors for survival after salvage treatment of local recurrence

The aim of the study was to investigate prognosis of patients who develop an isolated local recurrence (ILR) after conservative surgery (CS) for early-stage invasive breast cancer. Between 1983 and 1987, 415 patients with stage I-II breast cancer were treated with CS. Of these patients, 68 developed an ILR. The mean follow-up time after ILR was 167 months. Cox models taking potential prognostic factors into account were used to estimate the risk of death. On univariate analysis, age (< or =40 vs. >40 years) at first treatment, time to ILR (< or =24 vs. >24 months), type of recurrence (true vs. new primary tumor, NP), and extent of recurrence (operable vs. inoperable) were, but initial tumor stage (pT1 vs. pT2), initial lymph node stage (pN-negative vs. -positive), adjuvant radiotherapy (yes vs. no), type of salvage surgery (wide excision vs. mastectomy), and recurrent tumor grade (1-2 vs. 3) were not significant predictors of post-recurrence survival. On multivariate analysis only time to ILR proved independent predictor of survival (relative risk: 3.2; 95% confidence interval: 1.4-7.3; p = 0.0051), and the age of the patients showed borderline significance (p = 0.0659). The 15-year actuarial rate of cause-specific survival after ILR was 58% for all patients, 60% and 0% for patients with operable or inoperable recurrence, 30% and 71% for patients with age < or =40 or >40 years, 25% and 72% for patients with time to ILR < or =24 or >24 months, 54% and 88% for patients with true recurrence or NP, and 92% for patients with age >40 years with NP, respectively. The rate of second local recurrence after salvage mastectomy or repeated wide excision was 16% and 28%, respectively (p = 0.2265). As a conclusion, many patients with ILR have good prognosis, particularly those with operable recurrence with prolonged time to ILR, or with NP. Salvage mastectomy is not mandatory for all CS patients.