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Thrombophilia, clinical factors, and recurrent venous thrombotic events.

CONTEXT: Data on the recurrence rate of venous thrombotic events and the effect of several risk factors, including thrombophilia, remain controversial. The potential benefit of screening for thrombophilia with respect to prophylactic strategies and duration of anticoagulant treatment is not yet known. OBJECTIVES: To estimate the recurrence rate of thrombotic events in patients after a first thrombotic event and its determinants, including thrombophilic abnormalities. DESIGN, SETTING, AND PATIENTS: Prospective follow-up study of 474 consecutive patients aged 18 to 70 years without a known malignancy treated for a first objectively confirmed thrombotic event at anticoagulation clinics in the Netherlands. The Leiden Thrombophilia Study (LETS) was conducted from 1988 through 1992 and patients were followed up through 2000. MAIN OUTCOME MEASURES: Recurrent thrombotic event based on thrombophilic risk factors, sex, type of initial thrombotic event (idiopathic or provoked), oral contraceptive use, elevated levels of factors VIII, IX, XI, fibrinogen, homocysteine, and anticoagulant deficiencies. RESULTS: A total of 474 patients were followed up for mean (SD) of 7.3 (2.7) years and complete follow-up was achieved in 447 (94%). Recurrence of thrombotic events occurred in 90 patients during a total of 3477 patient-years. The rate of thrombotic event recurrence was 25.9 per 1000 patient-years (95% confidence interval [CI], 20.8-31.8 per 1000 patient-years). The incidence rate of recurrence was highest during the first 2 years (31.9 per 1000 patient-years; 95% CI, 20.3-43.5 per 1000 patient-years). The risk of thrombotic event recurrence was 2.7 times (95% CI, 1.8-4.2 times) higher in men than in women. Patients whose initial thrombotic event was idiopathic had a higher risk of a thrombotic event recurrence than patients whose initial event was provoked (hazard ratio [HR], 1.9; 95% CI, 1.2-2.9). Women who used oral contraceptives during follow-up had a higher thrombotic event recurrence rate (28.0 per 1000 patient-years; 95% CI, 15.9-49.4 per 1000 patient-years) than those who did not (12.9 per 1000 patient-years; 95% CI, 7.9-21.2 per 1000 patient-years). Recurrence risks of a thrombotic event by laboratory abnormality ranged from an HR of 0.6 (95% CI, 0.3-1.1) in patients with elevated levels of factor XI to an HR of 1.8 (95% CI, 0.9-3.7) for patients with anticoagulant deficiencies. CONCLUSIONS: Prothrombotic abnormalities do not appear to play an important role in the risk of a recurrent thrombotic event. Testing for prothrombotic defects has little consequence with respect to prophylactic strategies. Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.

Adult↗

Clinical importance of late recurrence in soft-tissue sarcomas.

BACKGROUND AND OBJECTIVES: Soft-tissue sarcomas (STS) represent a diverse histologic group of malignancies at risk for local and distant failure. We studied the impact of late (5 or more years) vs. early recurrence (less than 5 years) on subsequent outcome. METHODS: Four hundred sixty-eight patients with STS treated between 1962 and 1992 were evaluated for late (n = 39; 8%) or early (n = 253; 54%) recurrence. Clinical and pathologic factors were reviewed. Survival data were analyzed by the Kaplan-Meier method and the log-rank test. RESULTS: Of the 39 patients with a late recurrence (median follow-up 156 months), 18 patients had local recurrence, 7 patients developed distant recurrence, and 14 patients had local and distant recurrence. Thirty patients with late local and/or distant recurrence underwent complete or wide excision (n = 16), amputation (n = 4), or local resection (n = 10). The overall 5-year survival rate following late recurrence was 61%. The 5-year overall survival rate was statistically better for patients with a late local recurrence alone than for patients with distant failure, 94% vs. 36%, respectively (P = 0.003). Neither the site of the primary STS, age, primary margin status, nor histology had any effect on subsequent local or distant failure and subsequent survival. CONCLUSIONS: These data suggest that an aggressive approach is appropriate in patients who present with late recurrence (more than 5 years) following treatment of the primary STS. Impressive survival rates can be achieved in the treatment of local recurrences.

Adult↗

Tumor markers at the time of recurrence in patients with germ cell tumors.

BACKGROUND: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence. METHODS: The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977-1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14-78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%). RESULTS: Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence. CONCLUSIONS: Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation.

Adolescent↗

Prognostic indicators in patients with isolated local-regional recurrence of breast cancer.

A retrospective review was undertaken of 129 patients with isolated local-regional recurrence of breast cancer following radical or modified radical mastectomy. The overall survival and disease-free survival for these patients five years from the time of local-regional recurrence was 36 and 13%, respectively. The clinical stage at initial diagnosis, the number of histologically positive nodes at mastectomy, menopausal status, and the location of the recurrence (chest wall vs. nodal) were all found to have no significant effect on survival or disease-free survival. On the other hand, the number of recurrences, the size of the largest recurrence, and the time interval between mastectomy and recurrence (disease-free interval) had definite prognostic significance. A single recurrence, the size of the largest recurrence being less than or equal to 1 cm, and a disease-free interval of longer than 24 months predicted a good prognosis; on the other hand, multiple recurrences, the size of the largest recurrence being greater than 1 cm, and a disease-free interval of less than 24 months predicted a bad prognosis. Eighty-one percent of the patients ultimately developed distant metastases; the incidence of distant metastases was the same for patients with factors predicting a good prognosis as it was for those with factors predicting a bad prognosis. The time to appearance of distant metastases, however, was significantly longer in the former group of patients than in the latter. The information from this analysis should be useful in designing future clinical trials involving patients with isolated local-regional recurrence of breast cancer.

Breast Neoplasms↗

The influence of surgical margins and prognostic factors predicting the risk of local recurrence in 3445 patients with primary cutaneous melanoma.

Risk factors associated with local recurrences were analyzed from a series of 3445 clinical Stage I melanoma patients. In single-factor analysis, tumor thickness, ulceration, and increasing age were highly significantly predictive of recurrence (p less than 0.00001). After 5 years of follow-up, local recurrence rates were 0.2% for tumors less than 0.76 mm thick, 2.1% for tumors 0.76 to 1.49 mm thick, 6.4% for tumors 1.5 to 3.99 mm thick, and 13.2% for tumors 4.0 mm or greater in thickness. Ulcerated melanomas recurred more often than nonulcerated lesions (11.5% versus 1.9%). When analyzed as a continuous variable, increasing age increased the risk of local failure. In multifactorial analysis, all of these three factors remained independently predictive of local recurrence. Recurrences were more common with nodular melanomas (5.6%) compared to superficial spreading (2.5%) or lentigo maligna melanoma (2.5%), but this difference did not reach statistical significance (P = 0.115). Lower extremity (4.7%) and head and neck lesions (4.4%) recurred more frequently than upper extremity (1.6%) or trunk (1.2%) melanomas (P = 0.0217). The highest recurrence rates were observed in patients with melanomas located on the foot (11.6%) and hand (11.1%). The safety of conservative margins for the excision of low-risk melanomas was demonstrated in a review of 1151 consecutive patients with melanomas less than 1 mm thick where only one local recurrence was observed. Sixty-two percent of these patients had resection margins of 2 cm or less. In 95 patients local recurrence developed as the first site of relapse and were treated with surgical excision. The median survival for this group was 3 years, whereas 20% of this group survived 10 years. These data demonstrate that: (1) the risk of local recurrence rises with increasing tumor thickness, presence of ulceration, and age; (2) melanomas less than 1 mm thick have a very low local recurrence rate, even when excised with margins of 2 cm or less; and (3) local recurrence is a poor prognostic sign because regional and systemic metastases subsequently develop in many patients.

Humans↗

Recurrent ulceration after highly selective vagotomy for duodenal ulcer.

Recurrent peptic ulceration was diagnosed in 9 per cent of 433 patients who were treated by elective highly selective vagotomy (HSV) for duodenal ulcer (DU) between 1969 and 1980. In 233 patients followed up for 5-12 years (12 per cent being lost to follow-up), the incidence of recurrence was 10.7 per cent. The site of recurrence was duodenal in 23 patients, pyloric in 4, gastric in 6 and combined duodenal and gastric in 2 (total of 35 patients). One patient presented with a perforation, l4 with haemorrhage and 30 with epigastric pain. Asymptomatic patients were not endoscoped and so asymptomatic recurrence would have been missed. Nine patients were treated by reoperation (5 Polya partial gastrectomy, 4 vagotomy + antrectomy), the remainder with cimetidine. There was no mortality. When the 35 patients with recurrence were compared with the patients without recurrence, no preoperative factors could be identified that might be used to predict recurrence. Thus, for the two groups, the sex distribution, age, length of ulcer history, previous ulcer complications and preoperative acid outputs (basal and maximal) were very similar. This was true also when the data for patients with true recurrence in the duodenum were examined separately. Hence, contrary to some previous reports, no evidence was found that patients who are hypersecretors of acid, either basal or maximal, before operation should be treated by vagotomy combined with antrectomy. After HSV, however, patients with recurrent DU secreted more acid (basal, insulin and pentagastrin-stimulated) than patients without recurrence, the difference between the two groups being statistically significant for basal acid output (BAO) and the response to insulin. The only factor which was found to influence the incidence of recurrent ulceration after HSV strongly was the surgeon who performed the operation.

Adolescent↗

Value of positron emission tomography in the diagnosis of recurrent oesophageal carcinoma.

BACKGROUND: Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) might be useful for staging oesophageal squamous cell carcinoma (SCC). FDG-PET may be more accurate than computed tomography (CT) in diagnosing lymph node metastasis. This retrospective study compared the ability of FDG-PET and CT to diagnose recurrent oesophageal carcinoma. METHODS: Fifty-five patients with thoracic oesophageal SCC who had undergone radical oesophagectomy were studied. The accuracy of FDG-PET and CT in detecting recurrence during follow-up was calculated using data from the first images generated by either modality that suggested the presence of recurrent disease. Lesions deemed to be equivocal on these scans were considered as positive for recurrence. RESULTS: Twenty-seven of the 55 patients had recurrent disease in a total of 37 organs. Locoregional recurrence was observed in 19 patients (35 per cent). Distant recurrent disease occurred in 15 patients (27 per cent) in 18 organs. Six patients had recurrence in the liver, four in the lung, six in bone and two in distant lymph nodes. FDG-PET showed 96 per cent sensitivity, 68 per cent specificity and 82 per cent accuracy in demonstrating recurrent disease. The corresponding values for CT were 89, 79 and 84 per cent. The sensitivity of FDG-PET was higher than that of CT in detecting locoregional recurrence, but its specificity was lower because of FDG uptake in the gastric tube and thoracic lymph nodes. In distant organs the sensitivity of PET in detecting lung metastasis was lower than that of CT, but its sensitivity for bone metastasis was higher. CONCLUSION: FDG-PET has a larger field than CT. Combined PET-CT would appear to be an appropriate modality for the detection of recurrent oesophageal cancer.

Adult↗

Pattern of disease recurrence and prognostic factors in patients with osteosarcoma treated with contemporary chemotherapy.

BACKGROUND: The goal of the current study was to define the clinical features and outcome of recurrent osteosarcoma (OS) in children and young adults initially treated with contemporary chemotherapy. METHODS: The authors reviewed the clinical features, therapy, and outcome for 59 patients from the Mayo Clinic (Rochester, MN) and Children's Hospital and Regional Medical Center (Seattle, WA). They were diagnosed initially with OS between January 1990 and December 2000, received multiagent chemotherapy (most frequently cisplatin, doxorubicin, high-dose methotrexate, and ifosfamide), and developed disease recurrence after achieving an initial complete response (CR). RESULTS: The most common site of initial disease recurrence was the lung only (n = 36 patients), followed by distant bone (n =8 patients), combined lung and other sites (n =7 patients), and other sites (n =8 patients). The median time to first disease recurrence was 15 months (range, 2-92 months) from the initial diagnosis. Thirty patients with isolated pulmonary recurrence achieved a second CR, either with surgery alone (n =15 patients) or surgery and salvage chemotherapy (n =15 patients). For this group, the 4-year disease-free survival (DFS) and overall survival rates were 7% (95% confidence interval [95% CI], 0-16%) and 28% (95% CI, 11-45%), respectively. For all 59 patients with recurrent OS, the 4-year DFS and overall survival rates were 6% (95% CI, 0-12%) and 23% (95% CI, 10-36%), respectively. The only factors associated with improved DFS and overall survival rates were unilateral pulmonary recurrence, solitary pulmonary nodule at recurrence, more than 24 months between the initial diagnosis and first disease recurrence, and achievement of a second CR. CONCLUSIONS: The DFS and overall survival rates for recurrent OS after contemporary therapy remained poor even for patients with isolated pulmonary recurrence. Therefore, new treatment strategies are needed.

Adolescent↗

Outcome after local recurrence of osteosarcoma: the St. Jude Children's Research Hospital experience (1970-2000).

BACKGROUND: Despite improvements in therapy for osteosarcoma, approximately 4-10% of patients experience a local recurrence and have a poor prognosis. METHODS: The authors analyzed prognostic factors for survival in 26 patients with a local recurrence of osteosarcoma who were treated between 1970 and 2000. RESULTS: The initial surgical procedure was amputation in 20 patients (76.9%) and limb salvage in 6 patients (23.1%). The median time from the diagnosis of osteosarcoma to local recurrence was 1.2 years (range, 1.2 months-6.1 years). Eleven patients (42.3%) developed an isolated local recurrence and 15 patients (57.7%) developed local and distant recurrence. The 5-year estimate of postrecurrence survival (PRS) (+/- 1 standard error) for the 26 patients was 19.2% +/- 7.7%. Recurrence > or = 2 years from the time of diagnosis was found to predict a better outcome (5-year PRS of 50.0% +/- 20.4%) compared with earlier recurrence (10.0% +/- 5.5%) (P = 0.037). Patients with negative margins after initial surgery were found to have improved survival (5-year PRS of 33.3% +/- 13.6%) compared with patients with positive margins (7.1% +/- 4.9%) (P = 0.015). Patients who underwent complete surgical resection at the time of recurrence were found to have a better PRS (5-year PRS of 41.7% +/- 14.2%) compared with patients who did not undergo surgery (0% +/- 0%) (P < 0.001). CONCLUSIONS: The prognosis for patients after local recurrence of osteosarcoma is poor. Complete surgical resection at the time of recurrence is essential for survival. Positive margins at the time of initial surgical resection and early recurrence appear to be poor prognostic factors.

Adolescent↗

The role of craniospinal irradiation in adults with a central nervous system recurrence of leukemia.

BACKGROUND: Although central nervous system (CNS) prophylaxis in patients with leukemia has reduced the incidence of CNS disease recurrence, it still is reported to occur in approximately 5-10% of cases, resulting in a median survival of 6 months. Craniospinal irradiation (CSI) has been shown to improve survival in children who develop a CNS recurrence of acute lymphocytic leukemia (ALL). However, to the authors' knowledge, the role of CSI in adults with a CNS recurrence of leukemia is unknown. METHODS: A retrospective review of adult patients treated with CSI for a CNS recurrence of leukemia identified 16 patients treated between 1986 and 2001. The median age of the patients was 34 years (range, 16-58 years). The diagnoses included seven patients with acute myelogenous leukemia (AML), eight patients with ALL, and one patient with chronic myelogenous leukemia in blast crisis. All patients had achieved a complete disease remission prior to the CNS recurrence. Eleven patients had an isolated CNS recurrence and 5 patients had concurrent disease identified in the blood/bone marrow. The median dose of radiation was 24 grays (Gy) (range, 18-34.5 Gy) to the cranium and 18 Gy (range, 15-30 Gy) to the spine. The median fraction size was 1.8 Gy (range, 1.5-2.0 Gy) to the cranium and 1.5 Gy (range, 1.5-2.0 Gy) to the spine. Fifteen patients were also treated with intrathecal chemotherapy. RESULTS: One patient failed to complete radiation treatment because of disease progression. Thirteen patients achieved a complete response in the cerebrospinal fluid (CSF). The median time to disease progression was 3 months from the first day of CSI and 7 months from CNS recurrence. The median survival was 4 months and 9 months, respectively. No CNS recurrences occurred, but there were 11 bone marrow failures, 2 patients without recurrence at > 5 years, and 3 deaths without a documented site of failure. Thirteen patients had no evidence of disease in the CSF until their death or the time of last follow-up. CONCLUSIONS: CSI with or without intrathecal chemotherapy appears to be effective at eliminating leukemia in the craniospinal axis. However, the eradication of disease in the CNS was not found to be effective at preventing disease recurrence in the bone marrow, and despite improved control of disease in the CNS, adult patients with a CNS recurrence still had a poor prognosis. Furthermore, the rapidly fatal course of disease prevented an assessment of the durability of CNS response to irradiation.

Adolescent↗

Relationship of intraoperative rupture of pleomorphic adenomas to recurrence: an 11-25 year follow-up study.

BACKGROUND: Intraoperative rupture of the capsule of a pleomorphic adenoma is reported to be associated with an increased recurrence rate. For many years, we have noted few recurrences among patients who experienced rupture of the capsule during surgery. Therefore, we asked "How often has surgical rupture of the capsule of a mixed parotid tumor resulted in recurrence among our patients?" This study is a summary of our clinical observations and not a methodologic one. METHODS: The medical records of 346 patients operated on between 1965 and 1981 were reviewed. The surgical notes and histopathologic descriptions were examined with special reference to the relationship between surgical margins and tumor capsule. Satisfactory follow-up was obtained from 238 patients primarily operated on in our department. The average observation time was 18 years. None of our patients received postoperative irradiation. RESULTS: Six (2.5%) patients had a recurrence 7 to 18 years postoperatively (mean 11.8 years). This recurrence rate is of the same order of magnitude as other reports. Rupture of the capsule with macroscopic spillage of tumor cells occurred in 26 patients and two (8%) of them developed recurrent tumors. Surgical dissection close to the capsule was performed in 87 cases, with one recurrence. In the remaining 121 patients the surgical dissections were done without visualizing the tumor capsule. Three (2.5%) of these cases developed recurrent tumor. The 8% recurrence rate after capsule rupture is not statistically different from the 2% for the other patients. There was also no difference in recurrence rate between patients with microscopic positive or negative surgical resection margins. CONCLUSIONS: We question whether spillage of tumor cells from a pleomorphic adenoma plays such an important role in the development of recurrent tumors as has been previously postulated. We also question the justification and benefit of postoperative radiotherapy for patients with this benign disease.

Adenoma, Pleomorphic↗

Prognosis of recurrent laryngeal carcinoma after laryngectomy.

BACKGROUND: Recurrence is common after total laryngectomy for advanced laryngeal carcinoma. The aim of the present study was to review the prognosis of recurrent laryngeal carcinoma after total laryngectomy. METHODS: The records of 165 patients who developed recurrences after total laryngectomy for laryngeal squamous cell carcinoma between January 1971 and December 1990 were reviewed. RESULTS: Of the 165 patients who developed recurrences, 34 (21%) patients had surgical salvage. The sites of recurrence of these 34 operable patients included 11 pharyngeal, 3 tracheostomal, 15 nodal, 2 pharyngeal with nodal, and 3 pulmonary metastasis. Pharyngeal recurrence had the highest salvage rate, followed by nodal and pulmonary recurrence. All patients with tracheostomal had recurrence after salvage surgery. After the surgical salvage, the tumor recurrence rate was 44% and the 5-year actuarial survival rate was 42%. Of the other 131 patients who had palliative treatment without surgical salvage, the 5-year actuarial survival rate was 2%. CONCLUSIONS: The present study showed that patients who had surgical salvage for recurrent tumor after total laryngectomy had satisfactory prognosis. Close follow-up of patients after initial operation is essential to detect recurrence early, while surgical salvage is still feasible.

Actuarial Analysis↗

Identification of loci associated with putative recurrence genes in transitional cell carcinoma of the urinary bladder.

Following an earlier study linking monosomy 9 with recurrence of transitional cell carcinomas (TCCs) of the urinary bladder, 109 primary and recurrent TCCs (from 47 patients) were examined to explore genetic alterations at chromosome 9 associated with recurrence. Patient DNA was microdissected and extracted from archival tissue sections and analysed for loss of heterozygosity (LOH) at three regions on chromosome 9 where tumour suppressor genes (TSGs) are known to reside (INK 4A, DBC1, and TSC1). Patients were categorized into two groups, non-recurrent TCC (NR, n=18) and recurrent TCC (REC, n=29). It was noted that 12% of NR tumours, compared with 54% of REC primary tumours (p=0.01), had LOH at all informative markers spanning the TSC1 region. The risk of recurrence was significantly higher in patients with deleted TSC1 than in those who retained the TSC1 region (p=0.035). Levels of LOH at DBC1 or INK 4A were not significantly different in NR tumours than in REC primary tumours and recurrence-free survival was not affected by loss of either of these genes. Loss of all informative markers spanning chromosome 9 was observed in 0% of NR tumours compared with 25% of REC primary tumours (p=0.04). The probability of recurrence was also significantly increased in patients who had LOH at all informative markers spanning chromosome 9 (p=0.016), confirming earlier fluorescence in situ hybridization results. This study provides further evidence that recurrence in bladder cancer is a distinct event, with underlying molecular causes. It also identifies the TSC1 locus as a candidate for a TSG, which drives recurrence in a proportion of TCC patients. Loss of all informative markers, including those residing in the TSC1 region, spanning chromosome 9 was also linked to recurrence.

Carcinoma, Transitional Cell↗

Surveillance for recurrent endometrial carcinoma: development of a follow-up scheme.

We examined the method of diagnosis for a group of women who developed recurrent endometrial carcinoma after being rendered clinically disease-free by primary therapy. We then used this information to develop a follow-up protocol that maximizes the chances for detecting recurrence while minimizing surveillance costs. In brief, we evaluated all women with clinical stage I endometrial carcinoma who were treated with curative intent during a 7-year period. Medical records were examined to identify patients who had tumor recurrence diagnosed during follow-up in our clinic. Clinical presentation, time to diagnosis, method of diagnosis, and subsequent outcome were analyzed. This information was used to design a surveillance protocol for further clinical testing. Ninety-six percent of 412 women treated between 1985 and 1992 were clinically disease-free after primary surgery with or without adjuvant treatment. Median follow-up is 64 months. Overall, 44 patients (11%) developed recurrent cancer after a median interval of 14.8 months. Complete follow-up data were available for the 39 patients who had their recurrence diagnosed in our clinic. The cumulative percentages of diagnosed recurrences were 51, 82, and 95% at 12, 24, and 36 months, respectively. Sixteen women (41%) had symptoms that led to the identification of recurrent disease. Recurrences in the 23 asymptomatic women (59%) were diagnosed by physical examination in 13, chest radiograph in 1, serum CA-125 level in 6, vaginal cytology in 1, and computed tomography in 2. Only 1 patient with a grade 1 adenocarcinoma had treatment failure. At the time of analysis, 30 patients with recurrent cancer had died of disease, 6 were alive with disease, and 3 were free of disease. A surveillance scheme consisting of an examination, vaginal cytology, and serum CA-125, combined with immediate evaluation of symptomatic women, could be expected to identify 95% of recurrences. Such an approach, performed at 6- to 12-month intervals for 3 years, could be limited to patients with grade 2-3 adenocarcinomas or variant cell types. However, given the high failure rate of salvage therapy, the prompt detection of recurrence may not convey a survival advantage.

Endometrial Neoplasms↗

Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy.

OBJECTIVES: The aim of this study is to examine the patterns of failure after extended surgical staging and postoperative vaginal vault brachytherapy as the only adjuvant treatment in high-risk surgical Stage I patients with endometrial carcinoma. METHODS: The records of all patients with endometrial carcinoma (adenocarcinoma or adenosquamous) receiving vaginal vault brachytherapy as the only adjuvant treatment from January 1989 to December 1997 were examined. A total of 489 patients were found. Of these, 133 had extended surgical staging. The study group consists of 77 surgical Stage I patients with Substages IBG3 and any grade IC. Recurrences were recorded as in the vagina, pelvis, or distant. RESULTS: The mean follow-up interval was 45 months (range 14 to 96 months). Eleven patients had recurrence (14%). Median time to recurrence was 15 months (range 6 to 56 months). Recurrences occurred in the vagina in 7, pelvis in 1, and distantly in 3 patients. Five of 7 vaginal recurrences occurred within 2 years. All patients with distant recurrence died from disease. One patient with pelvic recurrence is alive with disease. Only 1 patient with vaginal recurrence died from disease. Six patients with isolated recurrences in the vagina were successfully treated with radiotherapy with or without local excision. All 6 have no evidence of disease at follow-up (median survival 29 months, range 20 to 71 months). CONCLUSIONS: The vagina remains the most common site of recurrence for high-risk surgical Stage I patients treated with postoperative vaginal vault brachytherapy. Close follow-up in the first 2 years is essential to detect isolated vaginal recurrences. These are amenable to salvage treatment with good disease-free survival.

Adenocarcinoma↗

Ventral incisional hernia recurrence.

During the period October 1993 to December 1996, 31 patients were operated on by the author for primary or recurrent ventral incisional hernia (VIH). Three patients were excluded from analysis because their records were unavailable for review. The median age of the 28 remaining patients at their initial procedure was 57.5 years (range, 37-78 years). The repair was performed with interrupted O-Ethibond sutures in all but 3 cases where Prolene suture was used secondary to noniatrogenic contamination or recurrent hernia. There were no unplanned enterotomies in the entire series and prophylactic intravenous antibiotics were used in all cases. The only significant complications were skin hyperemia after five repairs in 3 patients who were treated empirically with intravenous antibiotics, and 1 patient who had an antibiotic-associated rash. There were no 30-day mortalities. Prolene mesh was used exclusively in all repairs performed with mesh. Seven of these repairs (25%) were for recurrent VIH. Three of these seven patients had previous mesh repairs. Six of these seven patients who presented with recurrent VIH had a mesh repair and four developed a recurrence. Five of seven were active smokers, with one having severe obstructive lung disease. Four of seven related significant occupational lifting. Of the 21 patients having initial repair of VIH, mesh was used in 8 (38%). After a median follow-up of 13 months, there were 2 recurrent hernias (25%). The remaining 13 patients had primary closure of their hernias. After median follow-up of 25 months, there were 5 recurrences (38%). A total of 34 VIH repairs were performed on these 28 patients, of which 13 were for recurrent hernias. Five of thirteen (38%) of the mesh repairs for recurrent VIH failed. The median body mass index (BMI) for the 13 patients having primary repair was 26.4, and that for all 21 cases having mesh repair was 28.8. Patients with recurrent VIH frequently recur despite use of mesh, avoidance of contamination, and consistent technique. No difference in BMI was apparent in those who recurred. Continued smoking and occupational lifting may be important risk factors for recurrent VIH.

Adult↗

Reasons for early recurrence following laparoscopic hernioplasty.

The incidence and reasons for early recurrences following laparoscopic hernioplasty have not been studied. Because the incidence is small and the follow up is short, a multi-institutional study was performed among the pioneers in the field. The incidence figures were obtained by survey of surgeons who had significant experience (over 100 cases) and kept concurrent records. Fifty-four recurrences (1.7%) occurred after 3229 laparoscopic hernia repairs. There were 1944 transabdominal preperitoneal (TAPP) repairs with 19 recurrences (1%) and 578 preperitoneal repairs with no recurrences. There were 345 onlay mesh (IPOM) repairs with seven recurrences (2%), and 286 plug and patch repairs with 26 recurrences (9%). Simple closures were performed 76 times with two recurrences (2.6%). Fifty-seven patients (three cases were referred to the author without incidence data but complete records for analysis) had 60 recurrent hernias. Recurrences were noted, on average, 5.1 months postoperatively (range 0-30 months). The most common reason for recurrence was that the mesh was too small - 36 (60%). The mesh was never stapled in 19 instances (32%), and the hernia was never repaired in three cases (20%). The clips pulled through the tissue in six cases (8%), and in 10 cases (15%) the repair has not yet been undertaken because the etiology was unclear. There was more than one reason in 19 patients. Technical factors were responsible for nearly all recurrences.

Hernia↗

Cell kinetic analysis in recurrent neuro-epithelial tumours.

The biological behaviour of brain tumours is variable. In the majority of cases, recurrence of the tumour is the decisive factor determining the prognosis and individual survival of patients suffering from a neuro-epithelial neoplasm. The time course of recurrences varies significantly according to differences in tumour cell proliferation. In this study, predictive factors concerning the expected prognosis following the resection of neuro-epithelial tumours were investigated with the aim of improving the histological diagnosis. A retrospective analysis of 22 recurrent neuro-epithelial tumours (recurrent tumour group) and 12 neuro-epithelial tumours with a minimum survival rate of 5 years following radical excision (cured tumour group) was performed by means of flow cytometry and immunohistochemistry using the MIB 1 antibody. Histological samples of the subgroups of the recurrent tumour group, i. e., the primary tumours and their recurrences were compared with each other, and the subgroups were compared with the cured tumour group. A multivariate analysis of the data was performed with the BMPD Hotteling T square test. A statistically significant difference was found between the recurrent tumour group (primary tumours + recurrences) and the cured group from every investigated aspect. On the other hand, no difference could be found between the sub-groups primary tumours and their recurrences. All tumours in the recurrent group had an accelerated, active cell cycle, which was expressed in a high proliferation activity. The following conclusion was drawn: an increased risk of recurrence is to be expected in neuro-epithelial tumours characterized by: an S-phase fraction higher than 6-9%, an MIB 1-labelled cell number higher than 2-3/high-power fields, and a number of mitoses higher than 1/10 high-power fields.

Adolescent↗