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Local recurrence of carcinoma of the tongue after glossectomy: patient prognosis.

We conducted a retrospective review of the prognosis for patients with local recurrence after surgical treatment of carcinoma of the tongue. Glossectomy for squamous cell carcinoma of the tongue was performed in 167 patients. Local recurrence developed in 32 patients including 21 with local recurrence alone, 10 with locoregional recurrence and one with locodistant recurrence. The incidence of local recurrence increased with tumor stage (from 16% of T1 tumors to 46% of T4 carcinomas). Eleven (34%) patients underwent surgical salvage for local recurrence, with only one (9%) patient surviving free of carcinoma at 43 months post-surgical salvage. All of the remaining 21 patients with local recurrence were treated palliatively and all died within one year. Patients who underwent surgical salvage had significantly higher survival rates compared to those treated palliatively. Close follow-up after glossectomy is important for early detection of local recurrence amenable to surgical salvage. However, the overall prognosis for patients with local recurrence was poor, with a three-year actuarial survival rate of only 3%. Therefore, prevention of local recurrence with adequate initial surgical treatment is essential.

Adult↗

Incidence of port site recurrence after laparoscopic cholecystectomy for preoperatively unsuspected gallbladder carcinoma.

BACKGROUND: We sought to determine the incidence of recurrence of carcinoma at the port site and the outcome of patients with such recurrences after exploratory laparoscopy/laparoscopic cholecystectomy for unsuspected gallbladder carcinoma and analyzed aspects of the laparoscopic procedure associated with recurrences at the port site. METHODS: Thirty-seven patients with preoperatively unknown adenocarcinoma of the gallbladder were analyzed. The patients were part of a large prospective study of the Swiss Association of Laparoscopic and Thoracoscopic Surgery including 10,925 patients undergoing laparoscopic cholecystectomy. RESULTS: Preoperatively undiagnosed adenocarcinoma of the gallbladder is rarely encountered in patients undergoing laparoscopic cholecystectomy (0.34%). The incidence of recurrence of carcinoma at the port site in these patients is 14% (5 of 37) and is similar whether the primary tumor is confined to the gallbladder (T1/T2) or locally advanced (T3/T4). The recurrences at the port site were diagnosed within 6 to 16 months (median 10 months) after the operation. Patients with an intraoperative perforation of the gallbladder had a higher incidence of recurrences at the port site (40%) than had patients without perforation (9%; P = .13). All patients with recurrences at the port site had distant metastases and all died of the disease 12 to 35 months (median 19 months) after cholecystectomy; all patients with such recurrences and stage T1/T2 tumors subsequently had peritoneal metastases. CONCLUSIONS: Patients with a preoperatively undiagnosed adenocarcinoma of the gallbladder undergoing laparoscopy or laparoscopic cholecystectomy have a high incidence of recurrences at the port site, and the incidence increases when a gallbladder perforation occurs during the operation. All patients with such recurrences died of the disease. The diagnosis of an isolated recurrence at the port site may therefore be an indicator of disseminated disease in most cases.

Adenocarcinoma↗

Role of cytokine gene polymorphism and hepatic transforming growth factor beta1 expression in recurrent hepatitis C after liver transplantation.

Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is nearly universal. Cytokines play an important role in the immune response to viral infection, and cytokine gene polymorphism affects the overall expression and secretion of cytokines. The objective of this study was to define the relationship between cytokine polymorphism and recurrent hepatitis C after OLT. Blood samples were collected from 36 patients at a mean of 44.6+/-30.4 months after OLT for chronic HCV infection. DNA was extracted from peripheral blood mononuclear cells, and polymerase chain reaction-sequence specific primers (PCR-SSP) analysis was performed on promoter sequences of transforming growth factor beta1 (TGF-beta1), interleukin 6 (IL-6) interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). Liver biopsies performed at diagnosis of recurrent disease were graded with the Knodell score, and hepatic TGF-beta1 expression was determined semiquantitatively by immunohistochemistry. The gene polymorphism of TGF-beta1 was correlated with its expression on hepatocytes and sinusoids. Polymorphism in all studied cytokine genes was correlated with recurrence, and interval to recurrence (>12 or < or =12 months post-OLT), and clinical (ascites, Child-Pugh score and death), biochemical parameters of recurrent HCV (serum alanine aminotransferase (ALT)), INR, albumin, bilirubin), and virological parameters (HCV genotype and load). Biopsies revealed recurrent HCV in 31 patients (86.1%); in 21 (67.7%), the interval to recurrence was 12 months. There was a statistically significant correlation between TGF-beta1 gene polymorphism, i.e., the genetic ability to produce high levels of TGF-beta1, and the intensity of TGF-beta1 staining on hepatocytes (p=0.003) and sinusoids (p=0.003), and the degree of fibrosis (p=0.02). A borderline correlation was found with the presence of ascites (p=0.007), but not with Child-Pugh score, synthetic liver function tests or HCV genotype and load. The genetic ability to produce low levels of IFN-gamma was correlated with recurrent disease (p=0.015). No such correlation was found for TGF-beta1 gene polymorphism. In conclusion, polymorphism in the TGF-beta1 gene correlates with its in situ hepatic expression in patients with recurrent HCV after liver transplantation. INF-gamma, but not TGF-beta1 gene polymorphism, correlates with early recurrent hepatitis C after transplantation. These findings might help to design preemptive prevention therapy in selected patients at risk.

Cohort Studies↗

Allergic fungal sinusitis: can we predict the recurrence?

OBJECTIVE: The goal of the present study was to find out if recurrence can be predicted in cases of allergic fungal sinusitis. We also studied the influence of postoperative corticosteroid therapy on recurrence following surgery. STUDY DESIGN AND SETTING: This study was conducted at the ENT Department of Al Nahdha Hospital, which is a tertiary referral and teaching hospital in Muscat, Sultanate of Oman. The study is a retrospective analysis of 32 cases of allergic fungal sinusitis. Age, sex, extent of disease, and preoperative serum IgE levels were compared in patients who had recurrence with those who did not. We also studied the incidence, onset, and severity of recurrence in patients who received systemic corticosteroid as postoperative therapy and compared these values to those who received nasal corticosteroid spray only. RESULTS: No statistically significant difference was noted in the parameters of age, sex, extent of disease, and preoperative serum IgE levels when these values were compared in the group of patients who had recurrence (8 patients) with the group of patients who did not (32 patients). No statistically significant difference was found in the incidence of recurrence in patients in whom systemic corticosteroids were used postoperatively (17 patients) compared with patients who used nasal corticosteroid spray only (15 patients). However, when the patient had a recurrence, when it occurred it was earlier and more severe in patients who used nasal corticosteroid spray only (4 patients). CONCLUSIONS: At the present time, it is not possible to predict recurrence using parameters of age, sex, extent of disease, and serum IgE levels. Larger number of patients preferably in a prospective multicenter meta study are required to address this issue. Though use of systemic corticosteroid does not decrease the incidence of recurrence, it may delay the onset of recurrence and decrease the severity of recurrence.

Administration, Intranasal↗

[Azathioprine and mesalazine in the prevention of postsurgical recurrence of Crohn's disease: a retrospective study].

OBJECTIVES: Surgical resection is still a mainstay of the treatment of Crohn's disease (CD). However, recurrence is the rule. The aim of the present study was to evaluate CD recurrence in a series of patients who underwent surgical resection with subsequent treatment with azathioprine (AZA) or mesalazine (5-ASA) and to identify the factors associated with recurrence. METHODS: The medical records of patients with CD who underwent bowel resection during a 4-year period were reviewed. Only patients who received AZA or 5-ASA as prophylaxis for recurrence were included. RESULTS: Thirty-three patients treated with AZA and 16 treated with 5-ASA were included. Endoscopic recurrence was found in 8.6% of the AZA group and in 87.5% of the 5-ASA group (p <0.001). Clinical recurrence occurred in 31.2% of patients in the 5-ASA group and in none in the AZA group (p=0.004). The accumulated probability of both clinical and endoscopic recurrence was significantly lower in the AZA group (p=0.0025 and p=0.005, respectively). Factors associated with a greater risk of endoscopic recurrence were termino-terminal anastomosis and 5-ASA treatment. The only factor associated with clinical recurrence was 5-ASA treatment. CONCLUSION: AZA seems to be more effective than 5-ASA in the prevention of postsurgical endoscopic recurrence of CD. Prospective studies with long-term follow-up are required to establish the true utility of AZA in the prophylaxis of CD recurrence.

Adult↗

Reduction of recurrent HSV disease using imiquimod alone or combined with a glycoprotein vaccine.

The aim of this study is to evaluate the effects of an immune modulator, imiquimod, given alone or in combination with an HSV vaccine on HSV immune responses and as immunotherapy of a genital recurrence model. After recovery from primary genital HSV infection, animals were randomized to placebo, 21 days of imiquimod plus a placebo vaccine, or 21 days of imiquimod plus an HSV-2 glycoprotein vaccine. Placebo or HSV vaccine was given in the footpad on days 16 and 37 after HSV-2 genital inoculation. Daily imiquimod or placebo was given subcutaneously in the shoulder on days 16 through 37. Genital recurrences were monitored and HSV specific NK activity, IL-2 response and ELISA antibody were assayed. For the entire 15 week observation period, imiquimod alone reduced recurrences 62.6%, while addition of HSV vaccine to imiquimod reduced recurrences 80.6% compared to placebo/placebo. The duration of significant recurrence reduction was more notable with the addition of vaccine. Imiquimod alone significantly reduced the weekly HSV recurrent disease in the first 10 weeks (53-94% reduction, mean 75.9%), as did imiquimod plus HSV-vaccine (71-98% reduction, mean 89.5%). In weeks 10-15, imiquimod alone reduced recurrences significantly only in week 10 (20-53% reduction, mean 33%), whereas the addition of vaccine extended the significant recurrence reduction to 14 weeks (44-71% reduction, mean 56.8%). The recurrence reduction is correlated to an increased HSV-induced in vitro IL-2 response and NK activity against HSV targets in treated groups. Both imiquimod and the imiquimod/vaccine combination significantly reduced genital HSV recurrences, but the combination extended the duration and extent of protection for recurrences compared to imiquimod alone. Enhanced HSV specific immune responses correlated to the protection.

Adjuvants, Immunologic↗

Endoscopic color Doppler ultrasonographic evaluation of recurrent esophagogastric varices following endoscopic injection sclerotherapy.

BACKGROUND: Endoscopic injection sclerotherapy (EIS) for treatment of esophagogastric varices is well established in Japan. However, varices may still recur unpredictably following EIS. We studied this problem using endoscopic color Doppler ultrasonography (ECDUS) and specifically examined esophagogastric blood flows. METHODS: Prophylactic EIS was performed by intravariceal injection of 5% ethanolamine oleate (EO) in 49 patients with esophageal varices secondary to liver cirrhosis. No patient had documented hepatocellular carcinoma (HCC) before EIS, and patients who developed HCC during follow-up were excluded. We performed ECDUS before EIS, and 2 weeks and 2 years later. The esophagogastric intra- and extramural venous blood flows, including flow in the azygos vein, were compared between these observations. Gastric intramural blood flow and changes in extramural gastric blood flow, including the azygos vein flow, were scored. Dynamic computer tomography (CT), ultrasonography (US), and color Doppler-ultrasonography (CDUS) were also performed before EIS and 1 month following the procedure. Thereafter, patients underwent CT and US examinations every 6 months for 2 years to detect any development of porto-systemic shunts or HCC. RESULTS: The average number of EIS procedure per patient was 3.1+/-0.8 (mean+/-SD), and the total amount of sclerosant injected was approximately 33.5+/-6.5 ml. The overall recurrence rate over the 2-year follow-up was 36.7%. The gastric intra- and extramural blood flows did not differ between those patients with or without major shunts before EIS. In patients with recurrent variceal formation, the gastric intramural blood flow score following EIS (2.1+/-0.5) was significantly higher than that in patients without recurrence (0.8+/-0.6) (P<0.01). In addition, gastric extramural blood flow score following EIS (0.8+/-0.6) was significantly lower in patients with recurrence than that in those without recurrence (1.7+/-0.5) (P<0.01). The same differences held after exclusion of patients with major shunts. The gastric intramural blood flow score in patients with recurrent variceal formation (2.1+/-0.4) was significantly higher than that in patients without recurrence score (P<0.01). Moreover, gastric extramural blood flow score in patients with recurrent variceal formation (1.0+/-0.7) was significantly lower than in patients without recurrence (1.6+/-0.5) (P<0.01). CONCLUSIONS: Two characteristics were observed in patients with recurrent cases of esophageal varices 2 weeks following EIS. The first was the maintenance of gastric intramural blood flow. The second was the absence of dilation of the gastric extramural blood vessels. These observations may enable us to predict the recurrence of esophagogastric varices using ECDUS within 2 weeks following EIS.

Journal Article↗

Prevention of recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir.

BACKGROUND: Although the primary treatment of symptomatic cytomegalovirus (CMV) disease in organ transplant recipients is successful in >90% of individuals, relapsing disease, particularly in those with primary infection, remains an important problem. Previously, we had observed that the rate of symptomatic recurrence was >60% in those with primary disease (seronegative for CMV prior to transplant), and approximately 20% in those who were seropositive prior to transplant. The present study was undertaken to determine whether a maintenance regimen of oral ganciclovir for 2-3 months added to the routine 14-21 days of intravenous ganciclovir would further prevent symptomatic CMV recurrence. METHODS: From May 1995 until June 1998, all kidney and liver transplant recipients with confirmed tissue-invasive CMV disease or CMV syndrome were treated with 14-21 days of intravenous ganciclovir (5 mg/kg b.i.d. with dose adjusted for renal dysfunction) followed by 2-3 months of oral ganciclovir (2 g daily). The incidence of recurrence of CMV disease and/or viremia during and after oral therapy was then determined over a mean follow-up of 530.6 days. RESULTS: Thirty-seven patients, 19 kidney and 18 liver transplant recipients, were studied; 5 had biopsy-proven tissue-invasive disease (13.5) and 32 suffered a CMV syndrome (86.5). Twenty-one of these patients (58.6) were seronegative for CMV prior to transplant and received an allograft from a seropositive donor (D+/R-). Overall, 10 patients (27.0) developed CMV recurrence. Eight of 21 patients who were D+/R- for CMV (38.1) developed recurrence as opposed to 2 of 16 patients with other serologic status (12.5) (P=0.14). Patients with recurrent CMV disease and/or viremia had a peak antigenemia assay titer during their initial CMV event of 319.2 positive cells/2 slides compared with 109.8 positive cells/2 slides for patients without recurrent CMV infection (P=0.14); the trend of having a higher peak antigenemia assay titer among patients who recurred occurred both in patients who were at risk of primary CMV infection (D+/R- for CMV) and in those who were not. Two patients developed recurrent infection with strains of CMV that were resistant to ganciclovir. CONCLUSIONS: This new therapeutic regimen of oral ganciclovir following intravenous ganciclovir slightly reduced the overall rate of recurrent CMV disease and/or viremia, but it still did not adequately prevent CMV recurrence in patients who are at risk of primary infection prior to transplant. Of particular concern, 2 patients with primary infection treated with this regimen developed ganciclovir-resistant recurrent disease.

Acyclovir↗

A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test.

The aim of this study was to assess the efficacy of lipophilic beta-blockers in preventing recurrent neurocardiogenic syncope and the value of head-up tilt test (HUT) in predicting response to therapy. The efficacy of beta-blockers in recurrent syncope is controversial. The value of HUT in predicting efficacy of therapy has not been investigated. Fifty-six patients (44+/-18 years, 36 women) with recurrent syncope (> 1 event in the last 6 months) of suspected neurocardiogenic origin were included in the study. Independent of the response to HUT, patients were randomized to receive metoprolol or propanolol at the maximal tolerated dose (28 patients, group A, 86+/-23 vs 98+/-29 mg/d) or no pharmacological therapy (28 patients, group B). The primary endpoint was the first recurrence of syncope. During the 1-year of follow-up, 20 patients of group A and 8 of group B had no recurrence. In group A, of 20 patients without recurrences 12 had a positive and 8 a negative HUT result while of 8 patients with recurrences 5 had a positive and 3 a negative response to HUT. In the group B, of 20 patients with recurrences 10 had a positive and 10 a negative HUT result while of 8 patients without recurrences 4 had a positive and 4 a negative response to HUT. In a multivariate Cox-regression analysis, medical therapy was the only independent factor for predicting recurrence of syncope (P = 0.004); HUT had no influence in this regard (P = 0.773). In conclusion, lipophilic beta-blockers appear efficacious in preventing recurrent syncope of suspected neurocardiogenic origin. The efficacy of therapy seems to be not predicted by HUT.

Adrenergic beta-Antagonists↗

Preemptive plasmapheresis and recurrence of FSGS in high-risk renal transplant recipients.

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre-transplant PP in decreasing the incidence of recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri-operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow-up (238-1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end-stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients. Definitive conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.

Adult↗

Two kinds of recurrent inhibition of cat spinal alpha-motoneurones as differentiated pharmacologically.

1. The effects of i.v. administration of the glycine-antagonist strychnine nitrate and the GABA-antagonists bicuculline hydrochloride and picrotoxin on the recurrent inhibition of lumbosacral alpha-motoneurones were studied in cats anaesthetized with pentobarbitone sodium. 2. As revealed from both monosynaptic reflex experiments and intracellular recordings, each of the drugs generally reduced, but rarely abolished, the recurrent inhibition. The amount of reduction was more or less identical for bicuculline and picrotoxin. 3. By applying de- and hyperpolarizing currents intracellularly it could be shown that both the strychnine-resistant and bicuculline/picrotoxin-resistant recurrent inhibitory potentials were genuinely post-synaptic in nature. 4. The strychnine-resistant part of the recurrent inhibition had a later maximum and a longer duration than the part which was resistant to bicuculline/picrotoxin. 5. The time course of the strychnine-resistant recurrent inhibition was more or less identical to that of the bicuculline/picrotoxin-sensitive recurrent inhibition. 6. The bicuculline/picrotoxin-resistant recurrent inhibition was blocked by strychnine and, vice versa, the strychnine-resistant recurrent inhibition was blocked by bicuculline/picrotoxin. The combined administration of strychnine and bicuculline/picrotoxin always resulted in a virtual abolition of the recurrent inhibitory effects. 7. The values for central delay suggested that both the strychnine-resistant and bicuculline/picrotoxin-resistant inhibitions were mediated via disynaptic pathways. 8. The results suggest that both glycine and GABA act as transmitter substances of Renshaw cells in mediating recurrent inhibition to alpha-motoneurones. 9. No organizational pattern of the two types of recurrent inhibition based on motor pool category or motor unit type could be detected.

Animals↗

Assessment of physical examination and magnetic resonance imaging findings of hamstring injury as predictors for recurrent injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To examine clinical and magnetic resonance imaging (MRI) features of hamstring muscle injury to determine if any are predictive for recurrent injury. BACKGROUND: Hamstring muscle strain injury and subsequent recurrent injury are common. Little information exists on factors that may increase the risk for recurrent injury. METHODS AND MEASURES: The subjects were athletes from 3 professional Australian Rules football teams (n = 162). Anthropometric measurements, clinical signs, convalescent interval, and MRI assessment and measurement were undertaken and recorded in athletes with hamstring muscle strain injury. Athletes were followed for the presence, or absence, of recurrent injury to the same-side posterior thigh over the same and subsequent playing seasons. RESULTS: Thirty athletes met criteria for hamstring injury. Twelve (40%) of 30 athletes had recurrent injury within the same season, with an additional 7 athletes having recurrent injury in the subsequent season. None of the features examined were associated with increased recurrent injury risk within the same playing season. Statistical analysis demonstrated that when combining the same with the subsequent playing season a larger size of initial hamstring injury, as measured by MRI, was associated with an increased risk for recurrent injury (P<.01). A measured transverse size of injury greater than 55% of the muscle, or calculated volume of injury greater than 21.8 cm3, resulted in an increased risk for hamstring recurrence of 2.2 (95% CI, 0.88-5.32) and 2.3 (95% CI, 0.94-5.81) times, respectively, when compared to athletes with hamstring injuries below these measurements. CONCLUSIONS: A larger size of hamstring injury was indicative of higher risk for recurrent injury but only after the subsequent playing season was considered along with the same playing season. None of the other parameters tested, including a shorter convalescent interval and clinical features, were associated with an increased risk for recurrent injury. However, due to low sample size the certainty of these conclusions may be limited.

Adult↗

Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases. Association Francaise de Chirurgie.

PURPOSE: Resection is the only chance for cure in patients with colorectal liver metastases (LM). Five-year survival rates are close to 25%. Unfortunately, recurrences occur in most patients. Some recurrent LM are technically resectable. The aim of this study was to determine the risks and benefits of repeat resections for recurrent LM. PATIENTS AND METHODS: Data from 130 patients who received 143 repeat liver resections for recurrent LM were collected. In 116 patients, only the liver was involved, while 14 had both liver and extrahepatic recurrences. RESULTS: In the first group, the operative mortality and morbidity rates were 0.9% and 24.7%, respectively. Two- and 3-year survival rates were 57% and 33%, respectively. Recurrences were observed in 66% of patients. Twelve patients underwent a third hepatectomy for recurrence. The mortality rate was nil, and the mean survival time was 12.5 months. In the group with liver and extrahepatic metastases, the operative mortality and morbidity rates were 0% and 25%. The mean survival time was 16 months. Eleven patients died and 13 had recurrences during the follow-up period. CONCLUSION: Some hepatic recurrences after surgical excision of colorectal metastases can be resected with a low operative risk and with a long-term survival rate similar to that obtained after first resections. This emphasizes the need for a careful follow-up after hepatectomy for colorectal metastases to detect resectable recurrences.

Adult↗

Mechanisms of recurrence in subtypes of ischemic stroke: a hospital-based follow-up study.

BACKGROUND: Information on the mechanism of recurrent stroke may help physicians treating patients with ischemic stroke. However, the mechanisms of recurrence in each stroke subtype are not well known, especially in Asians. OBJECTIVE: To compare the mechanisms of the index and recurrent stroke. DESIGN: Analysis of data from a prospective acute stroke registry. SETTING: University hospital. PATIENTS: Using the clinical syndrome, diffusion-weighted imaging, and vascular studies, we divided 901 patients into 5 groups: large-artery atherosclerosis, cardioembolism, small-artery disease, parent-artery disease occluding the deep perforators, and no determined cause. The patients with large-artery atherosclerosis were subdivided into 2 groups: intracranial and extracranial. MAIN OUTCOME MEASURES: The mechanisms of recurrent vascular events (strokes or coronary heart disease) in subtypes of ischemic stroke were compared. RESULTS: Ninety-three recurrent vascular events (86 strokes and 7 instances of coronary heart disease) were evaluated. The pattern of recurrent stroke differed for the intracranial and extracranial groups; unlike the patients with intracranial large-artery atherosclerosis, recurrent strokes in the extracranial group were often unpredictable with respect to the site of recurrence and degree of preexisting stenosis. None of the patients in the extracranial group had recurrences that were caused by intracranial large-artery atherosclerosis or vice versa. In patients with small-artery disease and stroke with no determined cause, intracranial stenosis was often found at the time of recurrence. CONCLUSIONS: From prognostic and therapeutic perspectives, patients with atherosclerosis should be divided into those with intracranial large-artery atherosclerosis and extracranial large-artery atherosclerosis. In addition, intracranial large-artery atherosclerosis may be important in the development of small-artery disease and stroke with no determined cause, especially in the population with a higher frequency of intracranial large-artery atherosclerosis.

Adult↗

Persistent and recurrent neovascularization after laser photocoagulation for subfoveal choroidal neovascularization of age-related macular degeneration. Macular Photocoagulation Study Group.

OBJECTIVE: To determine the incidence and visual impact of and risk factors for persistent and recurrent neovascularization after laser photocoagulation of subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. DESIGN, PATIENTS, AND METHODS: The records of 189 eyes in the Subfoveal New CNV Study and 100 eyes in the Subfoveal Recurrent CNV Study assigned to laser photocoagulation were examined. Persistent CNV (detected within 6 weeks of treatment) and recurrent CNV (detected after 6 weeks) were defined angiographically by fluorescein leakage from the periphery of the treatment scar. Incidence was estimated using survival analysis methods. RESULTS: In both studies, persistent CNV was observed in approximately 13% of the eyes, and recurrent CNV was estimated to have developed by 3 years in an additional 35% of the eyes. In the New CNV Study, by 3 years, 36% of the eyes with persistent CNV had lost 6 or more lines of visual acuity as had 19% of the eyes with recurrent CNV and 27% of the eyes without persistence or recurrence. The presence of neovascular maculopathy in the fellow eye was associated with an increased risk for persistence or recurrence in the study eye. In the New CNV Study, partial coverage of the lesion with heavy laser treatment and/or runoff was associated with increased risk for persistence; less extensive natural scarring of the lesion at study entry was associated with increased risk for recurrence. CONCLUSIONS: Close to half of the eyes treated for subfoveal CNV have persistent or recurrent CNV within 3 years. There is a strong association between neovascular maculopathy in the fellow eye and the inability of laser photocoagulation to permanently obliterate signs of CNV from the study eye. Within these two studies, there was little additional damage to visual function resulting from persistent or recurrent neovascularization. There appears to be no reason to deviate from the protocol goal of covering the entire neovascular complex when treating eyes with subfoveal CNV.

Aged↗

Patterns of recurrence in anal canal carcinoma.

HYPOTHESIS: The initial modality of treatment of anal canal carcinoma (ACC) influences the pattern of recurrence of disease. DESIGN: A retrospective analysis comparing patterns of recurrence in patients with ACC undergoing either surgery or chemoradiotherapy as their initial therapeutic intervention. Anal margin cancers and adenocarcinomas were excluded. SETTING: A university-affiliated urban medical center. PATIENTS: Eighty-one patients were given a diagnosis of ACC between February 1, 1952, and December 31, 1998. Fifty-one (63%) of the patients initially underwent surgery: abdominoperineal resection in 38 patients (75%) and local excision in 13 patients (25%). Chemoradiotherapy was the initial therapeutic intervention in 30 patients (37%). MAIN OUTCOME MEASURES: The patterns of recurrence (local vs distant disease) and survival were compared between the group that underwent palliative surgery (hereafter referred to as the surgical group) and the group that received chemoradiotherapy (hereafter referred to as the chemoradiotherapy group). RESULTS: The mean follow-up was 40 months. Local recurrence occurred in 7 patients (14%) in the surgical group vs 7 patients (23%) in the chemoradiotherapy group (P =.46). Using Kaplan-Meier actuarial analysis, local recurrence rates for the surgical and chemoradiotherapy groups at 1 year were 0% and 6%, respectively (P =.32), and at 5 years were 17% and 36%, respectively (P =.02). The average (+/-SD) time to local recurrence in the surgical group was 23 +/- 0.7 months and for the chemoradiotherapy group 16 +/- 2.9 months (P =.27). Five (71%) of the 7 patients with local recurrences in the chemoradiotherapy group underwent salvage abdominoperineal resection with 100% disease-free survival at a mean follow-up of 35 months. When patients presenting with metastatic disease were excluded, distant recurrences developed in 7 patients (16%) in the surgical group and 2 (7%) in the chemoradiotherapy group (P =.31). Actuarial 5-year distant recurrence rates for the surgical and chemoradiotherapy groups were 26% and 19%, respectively (P =.65). Five-year survival was 42% in the surgical group and 74% in the chemoradiotherapy group (P =.01). CONCLUSION: There was a higher rate of local recurrence in patients with ACC treated with chemoradiotherapy vs surgical resection as the initial therapeutic intervention. However, when this occurred, abdominoperineal resection was effective salvage therapy and was associated with a 100% disease-free survival at 3 years. Therefore, chemoradiotherapy is justified as the initial treatment for ACC and has an overall 5-year survival that is significantly higher than that attained with initial surgical treatment.

Adult↗

D-dimer levels and risk of recurrent venous thromboembolism.

CONTEXT: Widespread screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors has become common clinical practice. Because of the increasing number of risk factors, assessing the risk of recurrence in an individual patient is intricate; therefore, a laboratory method that measures multifactorial thrombophilia is required. OBJECTIVE: To prospectively study the relationship between the risk of recurrent VTE and D-dimer, a global marker of coagulation activation and fibrinolysis. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 610 patients older than 18 years who were treated with oral anticoagulants for at least 3 months with a first spontaneous VTE, in whom D-dimer levels were measured shortly after discontinuation of oral anticoagulation. The study was conducted at the Department of Internal Medicine I, University Hospital, Vienna, Austria. Patients entered the study at time of discontinuation of oral anticoagulants and were observed at 3-month intervals during the first year and every 6 months thereafter from July 1992 to October 2002. MAIN OUTCOME MEASURE: Objectively documented symptomatic recurrent VTE. RESULTS: A total of 79 (13%) of 610 patients had recurrent VTE with a mean observation time of 38 months. Patients with recurrence had significantly higher D-dimer levels compared with those without recurrence (553 ng/mL vs 427 ng/mL, P =.01). Compared with patients with D-dimer levels of 750 ng/mL or higher, the relative risk (RR) of recurrence was 0.6 (95% confidence interval [CI], 0.3-1.4), 0.6 (95% CI, 0.3-1.2), and 0.3 (95% CI, 0.1-0.6) in patients with D-dimer levels of 500 to 749 ng/mL, 250 to 499 ng/mL, and less than 250 ng/mL, respectively. The cumulative probability of recurrent VTE at 2 years was 3.7% (95% CI, 0.9%-6.5%) among patients with D-dimer levels of less than 250 ng/mL compared with 11.5% (95% CI, 8.0%-15.0%) among patients with higher levels (P =.001). Patients with D-dimer levels of less than 250 ng/mL had a 60% lower RR of recurrence compared with patients with higher levels (RR, 0.4; 95% CI, 0.2-0.8). CONCLUSION: Patients with a first spontaneous VTE and a D-dimer level of less than 250 ng/mL after withdrawal of oral anticoagulation have a low risk of VTE recurrence.

Adult↗

Postoperative recurrence of solitary small hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma after hepatic resection remains poor. The major cause is postoperative recurrence, most frequently intrahepatic. During the past 7 years, we conducted a detailed study of recurrence after hepatectomy in 34 patients with solitary small hepatocellular carcinoma measuring no larger than 4 cm in diameter, in which 13 cases had postoperative recurrent tumors, and two cases were considered multicentric. Eighty-five percent of recurrences were diagnosed at 6-18 months after the operation. The cumulative recurrence rates were 61% at 5 years after operation. When analyzing the factors affecting recurrence, a significant difference was observed regarding tumor diameter. After recurrence, most patients underwent percutaneous ethanol injection treatment and/or transcatheter arterial chemoembolization and lipiodolization. Four patients died of progressive disease within 1 year after recurrence; the treatment thus seemed to have no effect. The other patients with recurrence remain alive with the disease. The overall cumulative survival rates in this series were 76% at 3 years and 60% at 5 years after operation. To obtain better results after hepatectomy, even for small hepatocellular carcinoma, careful, long-term follow-up evaluation is therefore necessary for the multidisciplinary treatment of the postoperative recurrence, as well as the early diagnosis of tumors in high-risk patients.

Adult↗