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Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report.

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25-50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.

Biomarkers, Tumor↗

The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders.

The duration of anticoagulant treatment after a first episode of venous thromboembolism primarily depends on the risk of recurrence. Variability of recurrence rates in factor (F) V Leiden carriers may be due to concomitant thrombophilic disorders. A retrospective study was performed in 329 FV Leiden carriers with a history of venous thromboembolism (262 probands, 67 relatives). The annual rate of first recurrence was estimated in relatives. The contribution of concomitant thrombophilic disorders to the recurrence rate was evaluated in probands and relatives by a nested case--control analysis in 105 matched pairs of carriers either with or without recurrence. The overall annual recurrence rate was 2.3 per 100 patient-years. The adjusted risk of recurrence for concomitant thrombophilic disorders was: 9.1 (1.3-62.8) for the FII mutation; 1.0 (0.2-4.9) for homozygosity for FV Leiden; 1.5 (0.2-9.5) for inherited deficiencies of protein C or S; 1.8 (0.7-4.9) for FVIII coagulant activity (FVIII:C) levels >122%; 5.4 (1.6-18.6) for fasting homocysteine levels >15.2 micromol/l; and 4.4 (1.0-18.7) for loading homocysteine levels >45.8 micromol/l. Of these disorders, only the FII mutation and hyperhomocysteinaemia significantly increased the risk of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from 0.45 per 100 patient--years after a secondary first event in the absence of concomitant disorders to 4.8 per 100 patient-years when a spontaneous first event was combined with concomitant disorders. Our study provides supportive evidence that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden carriers depends on the concomitance of other thrombophilic disorders, in addition to whether the first thrombotic event occurred spontaneously.

Adolescent↗

Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast.

BACKGROUND: Local recurrence and death from metastases are occasional, but consistent, themes in reports of patients with phyllodes tumours. Factors that might contribute to these outcomes were sought. METHODS: Data from 38 patients with a phyllodes breast tumour were reviewed retrospectively, reclassifying the pathological material using the Pietruszka and Barnes criteria. RESULTS: At a median of 12 months, nine patients had developed a local recurrence and four had died from metastases. Following local excision in 24 patients (for diagnosis in 13, for 'fibroadenoma' in nine and for phyllodes tumour in two patients), 13 had no further surgery and five had local recurrence (three of eight benign tumours, two of two malignant tumours). Wide local excision or mastectomy in 18 patients was followed by four recurrences (one of eight borderline tumours, three of ten malignant tumours). All patients with recurrence had margin involvement on histological examination, but not all patients with margin involvement developed recurrence. Lack of statistical correlation between local recurrence and age, delay, size, grade or type of surgery was confounded by selection bias for more extensive surgery for malignant tumours. Death correlated with size (P = 0.05) and grade (P = 0.03) of tumour. CONCLUSION: Inadequate preoperative diagnosis ('fibroadenoma' or failure of triple assessment) frequently led to local excision with positive margins. Without revision this often resulted in local recurrence. Local recurrence of any grade was usually followed by further recurrence. Death was related to tumour size and histological grade, confirming these as prognostic factors.

Adolescent↗

Pattern of recurrence following radical oesophagectomy with two-field lymphadenectomy.

BACKGROUND: Despite increasingly radical surgery for oesophageal cancer, many patients continue to develop recurrent disease. The aim of this study was to evaluate the pattern of failure following attempted curative oesophagectomy with two-field lymphadenectomy for adenocarcinoma and squamous cell carcinoma of the middle and lower third of the oesophagus. METHODS: A total of 176 consecutive patients discharged from hospital following R0 resection between 1 April 1990 and 31 December 1999 were followed for evidence of recurrence over a mean interval of 26 months. RESULTS: Adenocarcinoma was the predominant histological subtype (n = 113) compared with squamous cell carcinoma (n = 63). Sex and age distribution were similar for both histological subtypes (M:F ratio 2.5:1, median age 64 (range 40-77) years). Overall 2- and 5-year survival rates were 54 and 31 per cent respectively. Some 85 patients (48 per cent) developed proven recurrence, of whom five are alive and 80 dead. The median time to recurrence was 11.7 (range 1. 5-67) months, with a median survival thereafter of only 2.7 (0-25.9) months. The pattern of recurrence was locoregional in 27 per cent (mediastinal 21 per cent and cervical 6 per cent) and distant in 18 per cent (liver 6 per cent, bone 6 per cent, cerebral 2 per cent, peritoneal 2 per cent, lung 1 per cent, skin 1 per cent). There was no difference in the overall pattern of dissemination or timing of recurrence for either histological subtype. Over 50 per cent of all recurrences occurred within 12 months of surgery, with local, regional and distant recurrence occurring at a median of 11.9 (range 1.8-52), 11.0 (range 5-67) and 11.0 (1.5-58) months respectively. CONCLUSION: The low incidence of cervical recurrence suggests that a more extensive 'three-field' lymphadenectomy is unlikely to improve survival rates. Better staging modalities are needed to identify patients who will have recurrence within 12 months of operation, so that they may be either entered into trials of multimodality treatment or offered non-surgical palliation. British Journal of Surgery prize-winning paper, presented to the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, London, UK, September 1999

Adenocarcinoma↗

Recurrence of biliary symptoms after endoscopic sphincterotomy for choledocholithiasis in patients with gall bladder stones.

BACKGROUND: There are a few reports regarding the long-term results of endoscopic sphincterotomy (EST). However, little data is available on the recurrence of biliary symptoms after EST for choledocholithiasis, in patients with gall bladder stones. METHODS: All patients had gall bladder and common bile duct stones (n = 60; age 32-84 years, median age 55 years), and had received an EST. One group of these patients had a laparoscopic or open cholecystectomy (n = 39; group A), while the other group did not (n = 21; group B). The follow-up- period ranged from 5 to 54 months (average 22 months). RESULTS: Complications included the recurrence of common bile duct stones, recurrent acute cholecystitis, postoperative bile leakage and papillary stenosis. Nine patients (15%) had a recurrence of biliary symptoms. Two significant prognostic factors for the recurrence of biliary symptoms were identified by multivariate analysis; namely an intact gall bladder and a dilated common bile duct. The recurrence rate of biliary symptoms in group B was 20.4%, while in group A it was 10.3% (P< 0.01). Patients with a larger than average common bile duct diameter (mean diameter 14 mm) were more prone to the recurrence of symptoms than those with a smaller common bile duct diameter (mean diameter 10 mm, P< 0.016). The hospital stay period was 8.9 +/- 3.1 days in group A and 2.8 +/- 1.9 days in group B (P< 0.01). CONCLUSIONS: Biliary symptom recurrence occurred in a considerable proportion of patients after EST for the treatment of choledocholithiasis, in patients with gall bladder stones. The prognostic factors associated with the recurrence of biliary symptoms were an intact gall bladder and a dilated common bile duct diameter. Regardless of their short stay in hospital, non-cholecystectomy patients had a higher rate of recurrent biliary symptoms than cholecystectomy patients.

Adult↗

Clinical predictors and time course of arrhythmia recurrence in patients with early reinitiation of atrial fibrillation after successful internal cardioversion.

Early reinitiation of atrial fibrillation (ERAF) was commonly observed after successful electrical cardioversion, however, the effect of ERAF on the subsequent time course of arrhythmia recurrence remains unclear. The aim of this study was to evaluate the clinical predictors and time course of AF recurrence with respect to the occurrence of ERAF after successful cardioversion. The clinical predictors and time course of AF recurrence were prospectively evaluated in 124 patients (94 men, 30 women; mean age 65 +/- 9 years) with persistent AF (mean AF duration 36 +/- 40 months), who underwent internal cardioversion. After cardioversion, all patients received treatment with sotalol and were monitored for AF recurrence. Successful restoration of sinus rhythm was achieved in 104 (84%) of 124 patients. ERAF was observed in 28 (27%) of 104 patients in whom 26 of them were successfully treated acutely with intravenous sotalol and repeated cardioversion. After a mean follow-up of 26 months, 29 (28%) of 104 patients remained in sinus rhythm. Kaplan-Meier analysis revealed a significantly poorer outcome with regard to the recurrence of AF in patients with ERAF (hazard ratio 1.7,P = 0.03) and in those with AF for more than 3 years (hazard ratio 1.6,P = 0.03). Despite treatment with sotalol, patients with ERAF had a significantly higher AF recurrence rate within the first day (13/26 [50%] vs 12/76 [16%],P < 0.01), but not during long-term follow-up (21/26 [81%] vs 52/76 [68%],P = 0.3). In contrast, patients with AF for more than 3 years had a similar AF recurrence rate within the first day (7/29 [24%] vs 18/73 [25%],P = 1.0), but a significantly higher recurrence rate during long-term follow-up (27/29 [93%] vs 46/73 [37%],P < 0.01). In conclusion, the occurrence of ERAF and long AF duration were independent predictors for AF recurrence after successful internal cardioversion. The difference in the time course of AF recurrence in patients with ERAF from those with long AF duration suggests distinct arrhythmogenic mechanisms.

Aged↗

Role of neuropathy and plasma nitric oxide in recurrent neuropathic and neuroischemic diabetic foot ulcers.

Various factors are associated with foot ulceration, including delayed reporting of ulcers, poor glycemic control, and severity of neuropathy. Several studies have looked at the role of nitric oxide in wound healing. However, no studies have examined its role in the occurrence and recurrence of diabetic foot ulceration. In a cross-sectional study we examined the role of neuropathy, retinopathy, nephropathy, and plasma nitric oxide (estimated from plasma nitrite and nitrate) levels in diabetic patients with recurrent and non-recurrent neuropathic and neuroischemic foot ulcers. Patients with recurrent foot ulcers had higher vibration perception threshold values compared to patients with non-recurrent foot ulcers (47.4 +/- 5.7 volts versus 39.5 +/- 10.3 volts respectively, P < 0.05). In addition, subjects with recurrent foot ulcers had significantly higher plasma nitric oxide compared to subjects with non-recurrent foot ulcers (46.9 +/- 6.3 microm/L versus 30.2 +/- 2.4 microm/L respectively, P < 0.01). Multivariate logistic regression analysis adjusted for age, sex, hemoglobin A1c, presence of retinopathy and nephropathy, vibration perception threshold, plasma creatinine, and total nitric oxide, indicated that only vibration perception threshold was independently associated with the presence of an ulcer [odds ratio: 1.26 (1.10-1.46); P <0.001)] and the recurrence of foot ulcers [odds ratio: 1.13 (1.01-1.27); P =0.04)]. This study has shown that although plasma nitric oxide is higher in patients with recurrent neuropathic and neuroischemic foot ulcers, severity of neuropathy was the most important factor associated with the development and recurrence of foot ulcers in diabetic patients.

Adult↗

Recurrent IgA nephropathy in renal transplant allografts.

Previous reports of renal transplantation for patients with underlying immunoglobulin A (IgA) nephropathy suggested a recurrence rate greater than 50% for transplant IgA nephropathy. Initially regarded as a benign condition, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We performed a retrospective analysis in a single center of 48 kidney transplant recipients, all of Chinese origin, with biopsy-proven IgA nephropathy as the cause of end-stage renal failure to determine the recurrence rate of IgA nephropathy in the transplant allograft and subsequent clinical course in Chinese patients. Median duration of follow-up was 52 months (range, 18 to 155 months). Fourteen patients (29%) had biopsy-confirmed recurrent transplant IgA nephropathy after a median of 52 months (interquartile range, 23 to 82 months) posttransplantation. Recurrent transplant IgA nephropathy was associated with greater serum IgA levels (P = 0.01). The presence of HLA-A2 in transplant recipients (P = 0.002) appeared to protect them from developing recurrent IgA nephropathy in the transplant allograft. Twenty-nine percent of patients with recurrent transplant IgA nephropathy had progressive deterioration of graft function. The progressive graft dysfunction (GD) rate was greater in patients with a transplant from a living related donor (LRD; 21%) compared with those with a transplant from a cadaveric or living unrelated donor (URD; 3%; P = 0.062). Although the cumulative graft survival rate was 100% at 5 years for transplants from both LRDs and URDs, the 10-year graft survival rate was only 63% for a graft from an LRD versus 93% for a URD (log-rank test, P = 0.19). A review of other reported series of recurrent transplant IgA nephropathy also showed an apparently greater incidence of GD for a graft from an LRD (28%) compared with a URD (15%). Our data suggest that although recurrent transplant IgA nephropathy is highly prevalent among the Chinese population, the risk for disease recurrence is not particularly increased compared with other ethnic groups. The trend toward a greater risk for GD for living related compared with unrelated allografts in patients with IgA nephropathy needs to be confirmed with further prospective study.

Adult↗

Soft tissue sarcomas: ultrasonographic evaluation of local recurrences.

OBJECTIVE: The diagnosis of early local recurrence of soft tissue sarcomas, especially in those treated with surgery and radiotherapy, is a difficult clinical problem. Financial constraints led us to use ultrasonography instead of CT or MR imaging. The aim of this study was to evaluate the role of ultrasonography (US) in detecting local recurrence. METHODS AND RESULTS: Fifty patients with previous treatment for soft tissue sarcomas were evaluated prospectively for recurrence by US and histopathology. Seven of the 50 patients were clinically suspected to have recurrent tumour. Ultrasonography showed recurrence in 26, no recurrence in 18, benign disease in four and was indeterminate in two cases. Ultrasonography was instrumental in guiding fine needle aspiration biopsies of small local recurrences and indeterminate lesions in 17 patients. In the sonographically tumour positive patients, histopathology confirmed recurrence in 24; one case had benign disease and one patient refused surgery. Thirteen of the 18 sonographically tumour negative patients were operated upon; all were negative for tumour on histopathology. Both the indeterminate cases showed recurrence on histopathology. The benign cases were confirmed by histopathology correlation. Ultrasound guided fine needle aspiration cytology (FNAC) was positive in 14 out of 17 patients (88%). The sensitivity and specificity of US was 92.30% and 94.4% respectively. CONCLUSION: Our study concludes that US is an extremely useful and cost effective method in the detection of early local recurrences of soft tissue sarcomas and should therefore be used for initial routine follow-up and guided biopsies.

Adolescent↗

Late locoregional recurrence in rectal carcinoma.

AIMS: Locoregional recurrence in rectal carcinoma usually occurs within the first five years of treatment. In recent years we have increasingly diagnosed patients with late locoregional recurrence more than 5 years after primary treatment. METHODS: The data of 978 patients with invasive stage I-III rectal carcinoma who underwent curative resection (R0) between 1978 and 1990 were analysed retrospectively. The median follow-up time was 10 years. RESULTS: The earliest locoregional recurrence was observed at 2 months, the latest at 148 months (extramural locoregional recurrence) after primary treatment. Within 1, 2 and 5 years 34, 64 and 91 per cent of all locoregional recurrences had been diagnosed. The 2-, 5- and 10-year locoregional recurrence rates of all patients increased from 11.3 to 16.7 to 18.8 per cent. The time lapse to diagnosis of locoregional recurrence was significantly influenced by the pN category (pN0: later), grading (low grade: later) and tumour cell dissemination (present: earlier). Locoregional recurrence was also diagnosed significantly earlier in patients undergoing regular follow-up. The curative reoperation rate was 22 per cent (n=37), being higher in patients with intramural locoregional recurrence (49 per cent), after primary anterior resection (32 per cent) and in the absence of distant metastases (29 per cent). CONCLUSION: Long-term follow-up beyond five years demonstrates increasing numbers of late locoregional recurrences.

Adult↗

Treatment of recurrent and advanced stage squamous cell carcinoma of the head and neck.

Despite advances in our ability to safely treat patients with recurrent cancer of the upper aerodigestive tract, outcomes for retreatment are generally poor and the first chance to cure these patients remains the best chance. Thorough knowledge of the outlook and options for patients with recurrent disease is also of significance in choosing therapy for patients with newly diagnosed disease. This is especially true for newly diagnosed patients making the choice between surgery and nonsurgical ("organ-sparing") options, who need to know the outlook for salvage surgery, should they recur after radiation with or without concomitant chemotherapy. Salvage surgery is generally the best option for previously irradiated patients who are faced with resectable, recurrent disease. Unfortunately, the results of surgical salvage are generally poor for patients with advanced stage recurrence and for those who recur after treatment of advanced disease. The site of initial and recurrent disease is important. Surgical salvage is most effective for patients with recurrent laryngeal cancer, least effective for recurrent cancer of the pharynx, and is intermediate for recurrence in the oral cavity. Patients choosing nonsurgical treatment for newly diagnosed cancer of the pharynx cannot rely on salvage surgery in the event of recurrence. Reirraditation for patients who have failed initial treatment that included radiation therapy has been used at a number of institutions with some success. Experience using reirradiation with or without concomitant chemotherapy continues to evolve. Palliative chemotherapy is an option for most patients, but response rates are generally poor and of short duration, after failure of initial treatment that includes radiation therapy. The best approach for many patients and families who face advanced recurrent disease is honest but compassionate communication and supportive care with the help of a hospice organization.

Carcinoma, Squamous Cell↗

Recurrent autoimmune hepatitis after liver transplantation: diagnostic criteria, risk factors, and outcome.

Approximately 20% to 30% of patients undergoing liver transplantation for autoimmune hepatitis (AIH) develop features of recurrent disease. Diagnostic criteria for recurrent AIH are similar to those used in the nontransplanted liver and include, in varying combinations, biochemical, serological, and histological abnormalities and steroid dependency. However, these criteria are more difficult to apply in the liver allograft because of potential interactions between recurrent AIH and other complications of liver transplantation, particularly rejection, and the uncertain effects of long-term immunosuppression. In the absence of other reliable diagnostic markers, a number of studies have used the histological finding of chronic hepatitis as the main or sole criterion for diagnosing recurrent AIH. However, this also lacks diagnostic specificity because there are many other possible causes of chronic hepatitis in the liver allograft. In addition, approximately 20% to 40% of biopsies performed on patients as part of routine annual review have histological features of chronic hepatitis, for which no definite cause can be identified. Risk factors that have been associated with the development of recurrent AIH include suboptimal immunosuppression, HLA phenotype, disease type and severity in the native liver, and duration of follow up. In many cases in which recurrent AIH seems to be related to underimmunosuppression, biochemical and histological features rapidly resolve once adequate immunosuppression is restored. However, in other cases, recurrent AIH behaves more aggressively, with progression to cirrhosis and graft failure. Areas that require further study include developing uniform criteria for the diagnosis of recurrent AIH, identifying risk factors for severe recurrent disease, and determining optimal levels of immunosuppression that minimize the impact of disease recurrence without exposing patients to the risks of overimmunosuppression.

Hepatitis, Autoimmune↗

The role of laparoscopy in the management of suspected recurrent pediatric hernias.

BACKGROUND: This report examines recurrent pediatric groin hernias and the role of diagnostic laparoscopy in the management of these recurrences. METHODS: A chart review of 19 children presenting with recurrent hernias was performed, analyzing the type of primary hernia, nature of recurrence, preexisting medical conditions, surgical complications at primary repair, and time to recurrence. Diagnostic laparoscopy (DL) was used during the remedial repair of the last nine patients. RESULTS: Seventeen indirect hernias were repaired during the primary repair, and 1 femoral hernia was identified. In one child, no inguinal hernia was identified at the initial operation. Overall, 11 recurrences were found to consist of indirect sacs, and 4 were found to have attenuation of the inguinal floor. Four additional recurrences were found to be femoral hernias. In only 1 patient was a wound factor (infection) thought to play a role in the recurrence. Diagnostic laparoscopy in 9 patients found 4 (44%) to have unsuspected intraoperative findings. Four femoral hernias were identified (3 with unsuspected contralateral femoral hernias). Additionally, 1 unsuspected recurrence of an indirect sac was identified. CONCLUSIONS: Laparoscopy accurately identifies the nature of the defect in children with recurrent groin hernias, detecting unsuspected contralateral indirect, direct, or femoral hernias in 44% of those undergoing laparoscopy.

Child↗

Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance.

BACKGROUND: Survival rates of hepatitis B patients after liver transplantation improved significantly by introduction of passive immunoprophylaxis. Due to viral escape mutations recurrence still occurs, but recently a combination prophylaxis with hepatitis B immunoglobuline plus lamivudine is evaluated in transplant centers in terms of a further reduction of recurrence rates. PATIENTS AND METHODS: Between 1996 and 2000 a postoperative combination prophylaxis with HBIg and lamivudine was initiated in 44 HBsAg positive liver transplant recipients. In total 14 patients were HBV-DNA negative and 30 were HBV-DNA positive at the time of evaluation. In 22 HBV-DNA positive patients a pre-operative lamivudine treatment (150 mg/die) was started. Five of them developed pre-transplant lamivudine resistance with high viral replication (mean HBV-DNA prior to transplantation 728 +/- 219 pg/ml). In all patients passive immunoprophylaxis was started in the anhepatic phase with application of 10.000 units hepatitis B immunoglobuline. It was continued after seroconversion to HBsAg negativity with an aimed titer of more than 100 U/l and only stopped in case of HBV recurrence. Lamivudine was also continued indefinitely after liver transplantation. RESULTS: Overall recurrence rate in the 44 patients, including retransplantations and patients with pretransplant lamivudine resistance, was 11.5 % under combination prophylaxis. Recurrence was seen only in one of 39 patients (2.6 %) without preoperative lamivudine resistance, in contrast 4 out of 5 patients (80 %) with pre-existing lamivudine resistance suffered from early hepatitis B recurrence. The single patient without preoperative lamivudine resistance, who developed recurrence was pre-transplant HBV-DNA negative without lamivudine treatment, but a postoperative seroconversion to negative HBsAg could not be achieved. The overall 3 year patient survival rate was 91 % in the study population. One patient, who was retransplanted with preoperative lamivudine resistance, died 4.5 months after retransplantation due to hepatitis B recurrence and sepsis, three other patients died for reasons not related to hepatitis B recurrence. Combination prophylaxis was well tolerated in all patients and no severe side effects were observed. CONCLUSION: Combination prophylaxis with hepatitis B immunoglobulin and lamivudine is safe and highly effective in prevention of HBV recurrence after liver transplantation, even in case of positive viral replication. In accordance with the results of other centers it should therefore be the standard regimen. However it fails in the majority of patients with preoperative evolution of YMDD mutations, in which the optimal management has to be determined yet. To minimize preoperative resistance formation universal preoperative antiviral treatment of HBV-DNA positive patients should be replaced by individualized indication for preoperative treatment.

Adult↗

[Recurrences of carpal tunnel syndrome in long-term haemodialysis patients].

BACKGROUND: Multiple recurrences of carpal tunnel syndrome and increased malfunction of the hand caused by tendopathies and arthropathies occur in long-term (20 - 30 years) haemodialysis and are mainly influenced by beta2-microglobulin amyloidosis. METHOD AND CLINICAL MATERIAL: 18 patients undergoing haemodialysis for an average of 29 years had been operated on 96 times for bilateral CTS and recurrent CTS during a mean observation period of 12.6 years. In nine patients (12 hands), removal of the thickened flexor digitorum superficialis tendons III and IV had been performed. All but two patients suffered from amyloidosis, 17 of them suffered from additional tendo- and 13 from additional arthropathies. All procedures were performed under local anaesthesia, and in half of them a tourniquet was used. The outcome was evaluated both clinically and with nerve conduction studies. RESULTS: 77 procedures for CTS-recurrences were performed. The first recurrence was observed after an average of 6.1 years (SD 2.8), the second after 4.6 (SD 3.1) and the third after 3.8 (SD 1.9) years. Whereas in case of a first (occasionally second or extremely seldom in a third) recurrence, another re-opening of the carpal tunnel with or without synovectomy, was sufficient to improve symptoms in the majority of patients, this was occasionally the case with a second but rarely with the third recurrence. In these latter patients, only resection of thickened superficial flexor tendon bundles, showing marked amyloid-deposits histologically, resulted in improvement of pain, as well as finger mobility in one third of the patients. The distal motor latency of the median nerve recovered after the primary operation in 86 %, and after the second (first recurrence) only in 53 %. After the third operation (second recurrence), the results after tendon removal were better than in cases after synovectomy alone. CONCLUSION: In long-term (more than 20 - 30 years) haemodialysis patients suffering from arthropathies, tendopathies and recurrent carpal tunnel syndrome, removal of the flexor digitorum superficial tendons should be considered for the second recurrence to improve pain and finger mobility.

Aged↗

Recurrence of gestational diabetes mellitus: identification of risk factors.

The objective of this paper is to evaluate the influence of maternal and neonatal factors on the recurrence of gestational diabetes mellitus (GDM). A study was conducted on 164 predominantly Hispanic patients whose index pregnancy was complicated by GDM and whose subsequent consecutive pregnancy was managed at our institution between January 1988 and December 1992. The diagnosis of GDM was based on the criteria recommended by the National Diabetes Data Group using a 100-g oral glucose tolerance test. One-hundred and eleven (68%) of the 164 women had recurrence of GDM. Fifty-three (32%) did not demonstrate recurrence in their subsequent pregnancy. Patients with recurrence had GDM diagnosed earlier (30.3 vs 32.5 weeks, p = 0.03), frequently required insulin (25 vs. 8%, p <0.05) and had more hospital admissions (32 vs. 10% p <0.05) in their index pregnancy compared to women who did not have recurrence of GDM. Women who had recurrence had elevated mean third-trimester plasma glucose values: fasting 87.6 vs. 83 mg/dL, (p = 0.009) and 2-hr postprandial 109.7 vs. 102.2 mg/dL, (p = 0.008). Neonates of patients with recurrence were heavier (3656 vs. 3373 g, p = 0.004) and had an increased incidence of macrosomia (26 vs. 10%, p <0.05). No significant differences were observed in maternal age, prepregnancy body mass index, HbgA1C values, second-trimester blood glucose levels, method of delivery, incidence of shoulder dystocia and Apgar scores between the two groups of women. Hispanic patients with history of GDM have significant risk of recurrence in their subsequent pregnancy. The risk for recurrence in women is increased if GDM is diagnosed earlier, they require insulin, have elevated third-trimester plasma glucose level, and deliver macrosomic infants in their index pregnancy. It appears that obesity does not increase the risk of recurrence of gestational diabetes in Hispanics.

Adult↗

High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.

BACKGROUND: A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII. METHODS: We studied 360 patients for an average follow-up period of 30 months after a first episode of venous thromboembolism and discontinuation of oral anticoagulants. Patients who had recurrent or secondary venous thromboembolism, a congenital deficiency of an anticoagulant, the lupus anticoagulant, hyperhomocysteinemia, cancer, or a requirement for long-term treatment with antithrombotic drugs or who were pregnant were excluded. The end point was objectively documented, symptomatic recurrent venous thromboembolism. RESULTS: Recurrent venous thromboembolism developed in 38 of the 360 patients (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosis was 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII. Among patients with a factor VIII level above the 90th percentile of the values in the study population, the likelihood of recurrence at two years was 37 percent, as compared with a 5 percent likelihood among patients with lower levels (P<0.001). Among patients with plasma factor VIII levels above the 90th percentile, as compared with those with lower levels, the overall relative risk of recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden or the G20210A prothrombin mutation, and the duration of oral anticoagulation. CONCLUSIONS: Patients with a high plasma level of factor VIII have an increased risk of recurrent venous thromboembolism.

Factor VIII↗

Treatment response and prognosis of patients after recurrence of esophageal cancer.

BACKGROUND: Although radical operation and adjuvant chemoradiotherapy improve survival in patients with advanced esophageal cancer, more than half of these patients have recurrence. The aim of this study was to explore treatment responses and prognostic factors in patients with recurrent esophageal cancer. METHODS: The operative specimens from 258 patients undergoing radical esophagectomy with extended lymphadenectomy for esophageal squamous cell carcinoma between 1990 and 1999 were analyzed. Depth of tumor invasion, and the extent and location of lymph node metastases were determined. Postoperative recurrence was identified from positive findings on successive 3-month examinations of tumor markers, 6-month examinations of ultrasonography, and annual computed tomography. Of 258 patients, 95 had recurrence by the end of 2000 (mean follow-up was 22 months, range, 2-113). Of those 95 patients, 76 received nonsurgical treatment, 7 received operative intervention, and 12 received no treatment. Clinicopathologic features of recurrent tumors were analyzed to determine prognostic values. Serum anti-p53 antibodies (S-p53-Abs), serum C-reactive protein concentration (S-CRP), and albumin concentration were also analyzed. RESULTS: The main recurrent patterns were nodal (n = 45) and organ (n = 35). Of the nonsurgical treatment group, 47 patients received chemoradiotherapy; 17, chemotherapy; and 12, radiotherapy. Overall clinical response was observed in 26 of 76 patients (34%). Treatment response was significantly associated with the type of recurrence, history of perioperative adjuvant therapy, time of recurrence, number of recurrent tumors, albumin concentration, S-CRP, and S-p53-Abs. Multivariate analysis suggested that S-p53-Abs and S-CRP were independent prognostic factors. CONCLUSION: The status of S-p53-Abs and S-CRP may predict response and outcome of patients with recurrence of esophageal cancer after radical operation.

Adult↗