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Early detection of recurrent hepatocellular carcinoma.

BACKGROUND/AIMS: Early detection and treatment of recurrent hepatocellular carcinoma (HCC) are keys to patient survival after hepatic resection. In attempts at early detection, we make use of the alpha-fetoprotein (AFP) test every month and abdominal ultrasound (US) and computed tomography (CT) are carried out every three months after hepatectomy. The objective of the present study was to evaluate the most appropriate interval for follow-up re-examinations after resection for HCC. PATIENTS AND METHODS: Eighty-five patients with recurrent HCC were divided into two groups according to the state of the tumor when recurrence was detected: Group I (n = 70); tumor size < or = 2.0 cm, and group II (n = 15); tumor size > or = 2.1 cm. Clinicopathological comparisons were made between the two groups. RESULTS: AFP positivity in group I was significantly lower than group II at the time of recurrence. Rates of extrahepatic intra-abdominal recurrences, i.e. recurrence at the surgical stump and in the abdominal cavity and lymph nodes around the liver, were more frequent in group II than in group I (47% vs 4%; p < 0.001). The average tumor size was larger in 10 patients with extrahepatic intra-abdominal recurrence than in 75 patients with intrahepatic recurrence (3.4 +/- 2.0 vs 1.6 +/- 0.6 cm; p < 0.0001). There was a statistically significant difference regarding the histological grade of initial HCC between the two patterns of recurrence. CONCLUSIONS: Measurements of AFP were seen to have limited value for detecting recurrence, at an early stage. Close postoperative follow-up, including bedside US in the outpatient clinic, should be carried out when the initial HCC is histologically less differentiated HCC.

Abdomen↗

[Value of tianeptine in treating major recurrent unipolar depression. Study versus placebo for 16 1/2 months of treatment].

OBJECTIVES: The aim of this study was to assess the efficacy of tianeptine vs placebo in the long-term treatment of unipolar major recurrent depression. METHOD: 286 patients who met DSM-III-R criteria for major depression with a Hamilton Depression Rating Scale (HDRS-21 items) score > or = 17, and with a history of at least one previous episode within the last 5 years, were treated in an open trial with tianeptine for 6 weeks. 185 patients who responded to treatment at day 42 (intent-to-treat) were randomly assigned to tianeptine 37.5 mg/day (n = 111), or placebo (n = 74). Among these patients 173 were strict responders to tianeptine (per-protocol-population), as defined in the present study by a 50% reduction in the HDRS score, a global score lower than 15 and confirmation by clinical evaluation. Both groups were comparable except for the severity of the depressive episode (significantly more severe in the tianeptine group (33%) than in the placebo group (18%)) (p = 0.018). Relapses and recurrences were defined by a HDRS score > or = 15, and/or a CGI score > or = 4, the recurrences being confirmed by the clinician. Patients were subsequently evaluated at day 63, and the 3rd, 6th, 9th, 12th, 15th and 18th month. RESULTS: Special attention was given to the number of relapses and recurrences, and to the delay of onset (Kaplan Meier Method). Between day 42 and 18th month (intent-to-treat group), the rate of relapses and recurrences was significantly higher in the placebo group (36%), than in the tianeptine group (16%) (p = 0.002). Long term comparison of the rate of patients without recurrence or relapse, also showed a significant difference in favour of tianeptine (p < 0.001). The difference between teh 2 groups increased within time. Secondary analysis of relapses and recurrence in the intent-to-treat group showed a significantly higher rate of relapses for the placebo group (p = 0.002); the rate of patients without recurrences in the long term appeared to be at the limit in the intent-to-treat group (p = 0.067) but significant in the per-protocol-group, in favour of tianeptine (p = 0.36). Furthermore, no difference was observed between the 2 groups, in terms of tolerance. Secondary effects attributed to treatment by investigators were rare and benign in each group. CONCLUSIONS: These data support the use of tianeptine in the long term treatment of unipolar major recurrent depression. Relapses and recurrences were 2 to 3 times less frequent with tianeptine as compared to placebo. Furthermore, prolonged treatment with tianeptine appeared to be very well tolerated.

Adolescent↗

Ultra-late recurrence (15 years or longer) of cutaneous melanoma.

BACKGROUND: Melanoma can remain clinically quiescent for decades before regional or distant recurrence appears. This protracted disease free interval challenges the concept of a "cure" for melanoma. METHODS: To understand this prolonged dormancy better, the authors retrospectively studied patients who developed recurrent melanoma 15 years or longer after their initial diagnosis ("ultra-late" recurrence). These cases were identified from 2766 melanoma diagnoses available in the Cancer Registry at the Massachusetts General Hospital (MGH). Histologic features of the primary lesion were also included when possible. RESULTS: Twenty cases were retrieved from the MGH database. There were equal numbers of women and men, although women were younger at the time of initial diagnosis (mean age of women: 29.8 years vs. 43.0 years for men). No patients had more than one primary cutaneous melanoma. The trunk was the most common primary site (35%), although there was no predominant anatomic localization. The average disease free interval was 17.3 years for women, 20.0 years for men, 18.1 years for patients with regional recurrence, and 19.0 years for patients with distant metastases. Distant recurrence was the most common type of recurrence (50% of women and 60% of men). The estimated probability of survival (5 years after recurrence) was 0.8 for regional disease and 0.2 for distant disease. With the available histologic records, it appears that almost all tumors were Clark Level III or IV with thicknesses ranging from 0.8-2.3 mm. In contrast to the published cases, this study did not find that women with lower extremity melanomas were at higher risk for developing ultra-late recurrence. CONCLUSIONS: Ultra-late recurrence of melanoma, although uncommon, can occur in any patient without identifiable risk factors. Because many prognostically favorable melanomas (thin melanomas on extremities) can recur after prolonged disease free intervals, the possibility of delayed recurrence remains and must be kept in mind.

Adolescent↗

Recurrence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis.

Thus, controversy remains as to whether PBC or PSC does recur in the allograft. Both diseases are of unknown origin. If PBC does recur in the allograft then, on current evidence, it is likely to recur only in a minority of patients at least in the short to medium term. Furthermore, recurrent does not appear to impact on patient or graft survival. As with chronic hepatitis B, the degree of immunosuppression may also affect the pattern and rate of disease recurrence. Sclerosing cholangitis does affect the graft, but the clinically severe form appears to be related to factors other than recurrent disease. The histological features of PSC are nondiagnostic but one study at least does suggest that, as with PBC, the pattern of disease recurrence is patchy and early in the medium term. Autoimmune hepatitis may recur but the patterns of recurrent disease are uncertain. If some of the reports do show recurrent disease, then it seems that recurrent disease is more aggressive in the allograft than in the native liver. Disease recurrence is of more academic and practical importance. Clinicians need to be aware of possible recurrence and, where appropriate, modify immunosuppression and interpret liver tests and histology appropriately. Finally, the patterns of recurrence may give useful clues to the pathogenesis of these enigmatic diseases.

Cholangitis, Sclerosing↗

Presentation, methods of diagnosis and therapy for pelvic recurrence following radical cystectomy for transitional cell carcinoma of the bladder.

PURPOSE: We evaluated the presentation, methods of diagnosis and treatment of pelvic recurrence following radical cystectomy for transitional cell carcinoma of the bladder. MATERIALS AND METHODS: We reviewed the records of 33 patients who underwent radical cystectomy for transitional cell carcinoma between May 1960 and August 1995 at our cancer center and who later had pelvic recurrence. RESULTS: The majority of patients underwent cystectomy for clinically advanced transitional cell carcinoma. Median time from cystectomy to recurrence was 10 months. Of the patients 25 were symptomatic (76%) at the time recurrence was diagnosed. Recurrence was discovered by digital rectal examination in 4 asymptomatic patients (12%) and by routine pelvic imaging in 2. Treatment included chemotherapy, surgery or radiation (alone or in combination). Of the 33 patients 29 died of progressive disease with a median survival of 7 months from the time of recurrence, and 4 remained free of disease at 7, 14, 26 and 95 months after local recurrence. Despite the poor survival rate following treatment 11 of 14 patients had complete resolution of symptoms following chemotherapy. CONCLUSIONS: The prognosis of patients with local recurrence is poor regardless of therapy. These recurrences are often symptomatic but careful post-cystectomy tumor surveillance, including digital rectal examination and pelvic imaging, provides an opportunity to diagnose local recurrences when they may be amenable to therapy. Systemic chemotherapy offers excellent palliation for symptomatic patients.

Aged↗

Locally recurrent soft tissue sarcoma of the extremities.

BACKGROUND: The management of locally recurrent extremity soft tissue sarcoma remains challenging. This study was undertaken to evaluate the long-term outcome after therapy for isolated locally recurrent soft tissue sarcoma (STS) of the extremity. METHODS: Between January 1, 1980, and December 31, 1990, 52 patients were treated at The University of Texas M. D. Anderson Cancer Center for locally recurrent extremity STS. The records of the subset of these patients (n = 36) with isolated local recurrence were examined to document clinicopathologic and treatment factors and to evaluate outcome using the end points of local recurrence-free, recurrence-free, and overall survival. RESULTS: Limb-sparing conservative surgery was possible in 24 patients (75%). Twelve (33%) of 36 patients were treated by surgery alone, 23 patients (64%) were treated with combined modality therapy (surgery plus radiation and/or chemotherapy), and 1 patient had radiotherapy only. Sixteen (44%) of 36 patients had no further recurrence of any type at a median follow-up of 58 months (range, 4 to 173 months). The 5-year actuarial local recurrence-free, recurrence-free, and overall survival rates were 72%, 45%, and 77%, respectively. CONCLUSIONS: Limb-sparing conservative surgery is possible in the majority of patients with isolated locally recurrent STS. Durable local control can be established with individualized local treatment strategies. These results support aggressive multimodality limb-sparing treatment approaches for these patients.

Adolescent↗

Magnetic resonance imaging in the diagnosis of local recurrences in breast cancer.

Breast conserving therapy (BCT) has turned out to be the standard procedure for the treatment of breast cancer. While the risk of local recurrences was reported as 1-2% or more per year after treatment, follow-up including clinical examination, mammography and even sonography is of priority. This study was performed to assess the efficacy of contrast-enhanced dynamic magnetic resonance tomography (NMR) for the diagnosis of local recurrences after breast conserving therapy, compared to palpation, mammography and ultrasound. In 33 patients local recurrences within the breast were diagnosed after breast conserving surgery. The sensitivity for the diagnosis of local recurrences after BCT was as follows: palpation (51%), mammography (67%), ultrasound (85%) and NMR (91%). All multicentric local recurrences were diagnosed by NMR. Mammography was not able to diagnose 11 local recurrences in radiodense breasts. Here ultrasound was able to diagnose 8 of 11 recurrences, while NMR was able to diagnose 10 of 11 recurrences. Therefore, ultrasound should be included into routine follow-up protocols after BCT to achieve an acceptable sensitivity for the detection of local recurrences. Under defined conditions and indications MRI is the best method to complement mammography and sonography with the highest sensitivity for the diagnosis of local recurrences in the radiodense breast.

Adult↗

Aggressive management of recurrence following surgical resection of hepatocellular carcinoma.

BACKGROUND: Liver resection of hepatocellular carcinoma (HCC) is associated with a high incidence of recurrence, that has a poor prognosis. AIM: Assess the rationale for and result of an aggressive treatment of recurrence following resection of HCC. METHODOLOGY: Retrospective analysis of 132 patients with recurrent HCC with special reference to the topography and time of onset of recurrence as well as outcome following treatment of these recurrences. Case-control analysis of the efficacy of repeat hepatectomy and its influence on the long term prognosis of patients with recurrent tumor. RESULTS: Sixty seven percent of the recurrences were exclusively intrahepatic and half of these were limited in size and number. The 5-year survival rate following treatment of limited intrahepatic recurrence by repeat hepatectomy, arterial chemoembolization or percutaneous ethanol injection was 30%. Repeat hepatectomies improved the long term outcome of patients with recurrent HCC. CONCLUSION: An aggressive approach to tumor recurrence is currently the best way to improve the long term outcome following resection of HCC.

Carcinoma, Hepatocellular↗

The effects of adherence to antidepressant treatment guidelines on relapse and recurrence of depression.

BACKGROUND: Depression is associated with high rates of relapse and recurrence during a patient's lifetime. Current guidelines regarding treatment recommend 4 to 9 months of continuation antidepressant therapy following remission of acute symptoms to allow more complete resolution of the episode. In this article, we test whether adherence to these recommendations reduces the likelihood of relapse or recurrence in a Medicaid population. METHODS: We used a Medicaid database covering 1989 through 1994. The sample consists of the 4052 adult patients who filled an antidepressant prescription at the time of an initial diagnosis of depression. These patients were followed up for up to 2 years. Timing and counts of antidepressant prescription claims are used to construct a proxy measure for adherence to guidelines. Relapse or recurrence is defined by evidence of a new episode requiring antidepressant treatment, hospital admission for depression, electroconvulsive therapy, emergency department visit for mental health, or attempted suicide. We used survival analysis to predict relapse or recurrence for each patient and to examine the effect of following treatment guidelines on relapse and recurrence. RESULTS: Approximately one fourth of the patients had a relapse or recurrence during their follow-up period. Factors that affect relapse and recurrence include comorbidities, race, and guideline adherence. Those who continued therapy with their initial antidepressant were least likely to experience relapse or recurrence; those who discontinued their antidepressant early were most likely to experience relapse or recurrence. CONCLUSION: Adherence to depression treatment guidelines with an antidepressant that is likely to have continuous use by patients reduces the probability of relapse or recurrence.

Adolescent↗

Testicular lymphoma is associated with a high incidence of extranodal recurrence.

BACKGROUND: Testicular lymphoma is a rare extranodal presentation of non-Hodgkin lymphoma. The authors report long term follow-up information regarding a group of patients with testicular lymphoma evaluated at the Mayo Clinic and describe the outcome with special attention to patterns of recurrence. METHODS: The medical records of patients with testicular lymphoma seen at the Mayo Clinic between January 1970 and March 1993 were reviewed. Patients were included if they had evidence of testicular involvement at the time of diagnosis of lymphoma. Pathology specimens were reviewed for confirmation of diagnosis. RESULTS: Sixty-two patients with a diagnosis of testicular lymphoma were identified. Their median age was 68 years, and 60 patients underwent orchiectomy as the initial therapeutic and diagnostic procedure. Most of patients (79%) had localized or regional disease at the time of presentation. Other treatment modalities after diagnosis included radiotherapy (37%), combination chemotherapy (37%), and combination chemotherapy and radiotherapy (16%). Although 88% of patients had no residual disease after primary treatment, 80% subsequently experienced disease recurrence. There was no significant difference in the rate of recurrence, including Ann Arbor Stage I disease. Treatment did not appear to affect the recurrence rate. At a median follow-up of 2.7 years, 60% of patients had died of disease. Late recurrences were observed, and there appeared to be no plateau in the disease free survival curve. In half (51%) of the patients with disease recurrence, only extranodal locations were involved. Thirteen patients experienced recurrence in the central nervous system, 11 of whom had parenchymal lesions. In 8 of these 13 patients, the central nervous system was an isolated site of disease recurrence. CONCLUSIONS: Testicular lymphoma is a unique and aggressive extranodal non-Hodgkin lymphoma. Better treatment strategies are needed to prevent recurrences. The risk of extranodal recurrence is high, especially in the central nervous system.

Adult↗

The salvage of recurrent endometrial carcinoma in the vagina and pelvis.

A retrospective analysis was performed on 93 patients who developed recurrent endometrial carcinoma in the pelvis, vaginal vault, and lower 1/3 vagina. There were 12 lower 1/3 vaginal recurrences, 24 vault recurrences and 57 pelvic recurrences from the 1005 patients treated between 1960 and 1976. Median time to recurrence was 30 months. Twenty-six patients had distant metastases also present at the time of recurrence in the sites mentioned above. Thirty-three percent of lower 1/3 vaginal recurrences, 12.5% of vault recurrences, and 5.3% of pelvic recurrences were salvaged with further treatment. The 10-year actuarial survival rates of isolated lower 1/3 vaginal, vaginal vault, and pelvic recurrences were 50%, 45%, and 24% respectively.

Adenocarcinoma↗

Pregnancy outcome following recurrent spontaneous abortions.

OBJECTIVE: The purpose of the present study was to examine the association between spontaneous consecutive recurrent abortions and pregnancy complications such as hypertensive disorders, abruptio placenta, intrauterine growth restriction and cesarean section (CS) in the subsequent pregnancy. METHODS: A population-based study comparing all singleton pregnancies in women with and without two or more consecutive recurrent abortions was conducted. Deliveries occurred during the years 1988-2002. Stratified analysis, using a multiple logistic regression model was performed to control for confounders. RESULTS: During the study period 154,294 singleton deliveries occurred, with 4.9% in patients with history of recurrent consecutive abortions. Using a multivariate analysis, with backward elimination, the following complications were significantly associated with recurrent abortions-advanced maternal age, cervical incompetence, previous CS, diabetes mellitus, hypertensive disorders, placenta previa and abruptio placenta, mal-presentations and PROM. A higher rate of CS was found among patients with previous spontaneous consecutive recurrent abortions (15.9% versus 10.9%; OR = 1.6; 95% CI, 1.5-1.7; P < 0.001). Another multivariate analysis was performed, with CS as the outcome variable, controlling for confounders such as placenta previa, abruptio placenta, diabetes mellitus, hypertensive disorders, previous CS, mal-presentations, fertility treatments and PROM. A history of recurrent abortion was found as an independent risk factor for CS (OR = 1.2; 95% CI, 1.1-1.3; P < 0.001). About 58 cases of inherited thrombophilia were found between the years 2000-2002. These cases were significantly more common in the recurrent abortion as compared to the comparison group (1.2% versus 0.1%; OR = 11.1; 95% CI, 6.5-18.9; P < 0.001). CONCLUSION: A significant association exists between consecutive recurrent abortions and pregnancy complications such as placental abruption, hypertensive disorders and CS. This association persists after controlling for variables considered to coexist with recurrent abortions. Careful surveillance is required in pregnancies following recurrent abortions, for early detection of possible complications.

Abortion, Habitual↗

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction &#x2265;0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗

Evolution of valve damage in Sydenham's chorea during recurrence of rheumatic fever.

BACKGROUND: The evolution of valve damage during a recurrence, in a patient who did not have apparent carditis in the initial attack of Sydenham's chorea, has been a subject of debate. METHODS: Thirty-six patients with an initial episode of acute rheumatic fever and Sydenham's chorea (3 patients with subclinical mitral regurgitation) were followed up prospectively for 5 years. Clinical examinations and transthoracic color Doppler echocardiography were done for each patient at initial attacks of Sydenham's chorea and at recurrences of rheumatic fever. RESULTS: Six recurrences of rheumatic fever occurred in 6 of the 36 patients. One recurrence developed in the regular secondary prophylaxis group (27 patients) with a recurrence rate of 0.007 per patient-year. Three of the 18 patients who initially had no heart murmur and no echocardiographic finding of valvular regurgitation had three recurrences of pure chorea with no echocardiographic evidence of significant valvular regurgitation. Interestingly, one of the 3 patients with previous pure chorea and echocardiographic finding of significant mitral regurgitation had a recurrence of pure chorea and new echocardiographic evidence of mitral, aortic and tricuspid regurgitations. Furthermore, two recurrences occurring in 2 of the 15 patients with previous carditis developed echocardiographic evidence of new carditis. CONCLUSIONS: Rheumatic recurrence can develop new valve damage evident by echocardiography for the patient with pure Sydenham's chorea who had previous subclinical valvulitis. Longer duration of secondary prophylaxis is recommended to prevent a recurrence of rheumatic fever in the patient with pure Sydenham's chorea who initially had subclinical valvulitis.

Acute Disease↗

Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer.

PURPOSE: The aim of our study was to assess prognostic factors and overall survival after salvage radiotherapy for patients who had endometrial carcinoma and who experienced an isolated vaginal recurrence. METHODS AND MATERIALS: We reviewed the records of 50 patients treated at our institution between 1967 and 2003 for an isolated vaginal recurrence of endometrial carcinoma. Initial treatment for endometrial carcinoma was definitive surgery in 49 patients and definitive radiotherapy in 1 patient. The median time from initial diagnosis of endometrial carcinoma to recurrence was 25 months (range, 4-179 months). Three patients (6%) received external-beam radiotherapy alone, 8 patients (16%) received brachytherapy only, and 39 patients (78%) received combined external-beam radiation therapy and brachytherapy. Median dose of radiation to the recurrence was 60 Gy (range, 16-85 Gy). Overall survival was calculated by the Kaplan-Meier method. Endpoints were measured from the date of diagnosis of the vaginal recurrence. Median follow-up of survivors after recurrence was 53 months (range, 8-159 months). RESULTS: The 5-year and 10-year disease-free and overall survivals were 68% and 55%, and 53% and 40%, respectively. On multivariate analysis, age (p = 0.0242), Grade 1 or 2 vs. Grade 3 tumor (p = 0.002), and size of recurrence (p < 0.001) were significant predictors of overall survival. All patients who had Grade 3 disease were dead by 3.6 years from the time of recurrence. Five patients experienced a Grade 3 or 4 complication. CONCLUSIONS: Patients treated with radiotherapy for an isolated vaginal recurrence can be cured in over 50% the cases. Radiotherapy is well tolerated, with a low risk of complications. Factors predictive of overall survival include tumor grade, patient age at recurrence, and tumor size.

Adult↗

Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema.

BACKGROUND: Rhinovirus-induced early wheezing has been suggested as a new important risk factor for recurrent wheezing. OBJECTIVE: We sought to investigate the risk factors for recurrent wheezing and to determine post hoc the efficacy of prednisolone in risk groups. METHODS: We followed for 1 year 118 children (median age, 1.1 years) who had had their first episode of wheezing and had participated in a trial comparing prednisolone with placebo in hospitalized children. Demographics and laboratory data were obtained at study entry. The follow-up outcome was recurrent wheezing (3 physician-confirmed episodes). RESULTS: Recurrent wheezing was diagnosed in 44 (37%) children. Independent risk factors were age < 1 year, atopy, and maternal asthma. The probability of recurrent wheezing was higher in rhinovirus than respiratory syncytial virus (RSV)-affected children among placebo recipients (hazard ratio, 5.05; 95% CI, 1.00-25.41). Prednisolone decreased the probability of recurrent wheezing in children with eczema (0.15; 95% CI, 0.04-0.63) but not in those without eczema (1.89; 95% CI, 0.83-4.29; P = .007 for interaction). Prednisolone was associated with less recurrent wheezing in the rhinovirus group (0.19; 95% CI, 0.05-0.71), but not in the RSV (2.12; 95% CI, 0.46-9.76) or in the RSV/rhinovirus-negative groups (2.03; 95% CI, 0.83-5.00; P = .017 for interaction). CONCLUSION: Rhinovirus-induced early wheezing is a major viral risk factor for recurrent wheezing. Prednisolone may prevent recurrent wheezing in rhinovirus-affected first-time wheezers. The presence of eczema may also influence the response to prednisolone. CLINICAL IMPLICATIONS: A prospective trial is needed to test the hypothesis that prednisolone reduces recurrent wheezing in rhinovirus-affected wheezing children.

Child, Preschool↗

Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function.

OBJECTIVE: To compare plasma androgen concentrations in women who have recurrent miscarriages and in fertile women, and to correlate the results with concentrations of the endometrial protein PP14 in uterine flushings and plasma from women who have recurrent miscarriages. DESIGN: Retrospective study. SETTING: Hospital research unit. PATIENT(S): Women attending a recurrent miscarriage clinic and normal fertile volunteers. Ten of the women with recurrent miscarriages had polycystic ovary disease (PCOD) as assessed by ultrasonography or increased follicular LH levels. INTERVENTION(S): Plasma samples were obtained from the women on days LH-7, LH-4, LH+0, and LH+7 or LH+10 of a cycle. An endometrial flushing sample and a biopsy specimen were taken from women with recurrent miscarriages on day LH+7 or LH+10. MAIN OUTCOME MEASURE(S): Androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured in the plasma samples. The endometrial protein PP14 was measured in the uterine flushings and in the LH+7 or LH+10 plasma samples from the women with recurrent miscarriages. RESULT(S): Testosterone concentrations were higher in the women with recurrent miscarriages both with and without PCOD on days LH-7 and LH-4 of the cycle. Concentrations of androstenedione also were higher in the women with recurrent miscarriages, but without PCOD on day LH-7. Testosterone SHBG ratios were higher in the women with recurrent miscarriages, without PCOD compared with the controls on days LH-7, LH+0, and LH+7. Mean follicular testosterone concentrations were correlated negatively with both uterine (r = -0.47) and plasma (r = -0.49) PP14 levels on day LH+10. Mean luteal phase testosterone SHBG ratios were correlated negatively with uterine PP14 concentrations on day LH+7 of the cycle (r = -0.674). CONCLUSION(S): Androgen levels are higher in women who have recurrent miscarriages than in normal fertile controls. These high levels of androgens may have a detrimental effect on endometrial function.

Abortion, Habitual↗

Immunohistochemical study of the relationship between 8-hydroxy-2'-deoxyguanosine levels in noncancerous region and postoperative recurrence of hepatocellular carcinoma in remnant liver.

Hepatocellular carcinoma (HCC) frequently develops in patients with chronic viral hepatitis and cirrhosis. In these chronic liver disorders, an increased production of reactive oxygen species (ROS) causing oxidative DNA damage has been reported. In this study, we immunohistologically (LSAB method) demonstrated the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG) that was generated when oxidative DNA damage was caused by active oxygen species in noncancerous region obtained at hepatectomy for HCC, and investigated the relationship between 8-OHdG and remnant liver recurrence. We found that the 8-OHdG labeling index (LI) for noncancerous region at the time of hepatectomy was significantly higher in recurrent (31.1+/-10.2%) than in nonrecurrent (20.6+/-8.0%) patients (P<0.01). The high 8-OHdG LI (>/=30%) group showed a significantly higher recurrence rate, compared with the low LI (<30%) group (P<0.01). The cancer-free survival curves also showed that the high 8-OHdG LI (>/=30%) group had a significantly poorer prognosis because of remnant liver recurrence than the low 8-OHdG LI (<30%) group (P<0.05). The 8-OHdG LI showed a significant correlation with the histopathologic evaluation of noncancerous region based on the New Inuyama Classification: a higher pathologic Staging and a higher pathologic Grading were associated with a higher 8-OhdG LI. Analysis by Grading and Staging showed that the high 8-OHdG LI group (>/=30%) of Grade A2, Stage F3, or Stage F4 had a significantly higher recurrence rate compared with the low 8-OHdG LI group (<30%) of Grade A2, Stage F3, or Stage F4, respectively. In addition, using multivariate analysis, we compared the influence on recurrence of the histological features that, at the time of hepatectomy, showed significant differences in the rate of remnant liver recurrence, that is, the number of tumors and the presence or absence of portal involvement, and three variables of the Grading, Staging, and 8-OHdG LI of noncancerous regions. The results suggested that 8-OHdG LI (P=0.02) and portal involvement (P=0.04), in this order, were useful as independent prognostic factors for recurrence. From this, we consider that, if patients with high 8-OHdG LI (>/=30%) in noncancerous region at the time of hepatectomy are regarded as being at high risk for remnant liver recurrence (heterochronous multicentric carcinogenesis) and are given careful follow-up treatment with preventive therapy for remnant liver recurrence, the prognosis will be improved.

Journal Article↗