[Psychiatric symptoms and COVID-19: results of a national case register]. / Psychiatrische symptomen en COVID-19: resultaten uit een landelijk register.

BACKGROUND: Psychiatric disorders are associated with a more severe course of COVID-19. COVID-19 can also lead to psychiatric symptoms. AIM: To gain insight into vulnerabilities and protective factors for the course of COVID-19 in a Dutch (neuro)psychiatric population. METHOD: Patients were divided into three groups: patients with pre-existent mental disorders without and with new (neuro)psychiatric symptoms (NPS) during COVID-19 and patients without pre-existent mental disorders who developed de novo NPS during COVID-19. We summarize the characteristics of each group and compare the subgroups with inferential statistics. RESULTS: 186 patients were included in the case register. Patients with NPS showed a more severe course of COVID-19. Mortality in patients with NPS was higher in patients with pre-existent mental disorders compared to patients without pre-existent mental disorders. The most frequently reported de novo psychiatric symptoms during COVID-19 were delirium (46-70%), anxiety (53-54%) and insomnia (18-42%). CONCLUSION: NPS might be an expression of a more severe COVID-19 episode. In patients who developed NPS during COVID-19 we found evidence for a higher mortality risk in patients with pre-existent mental disorders. Extra vigilance for neuropsychiatric symptoms during COVID-19 is warranted.

Posterior malleolar fracture morphology determines outcome in rotational type ankle fractures.

INTRODUCTION: Rotational type ankle fractures with a concomitant fracture of the posterior malleolus are associated with a poorer clinical outcome as compared to ankle fractures without. However, clinical implications of posterior malleolar (PM) fracture morphology and pattern have yet to be established. Many studies on this subject report on fragment size, rather than fracture morphology based on computed tomography (CT). The overall purpose of the current study was to elucidate the correlation of PM fracture morphology and functional outcome, assessed with CT imaging and not with -unreliable- plain radiographs. METHODS: Between January 2010 and May 2014, 194 patients with an operatively (ORIF) treated ankle fracture, were prospectively included in the randomized clinical EF3X-trial at our Level-I trauma center. The current study retrospectively included 73 patients with rotational type ankle fractures and concomitant fractures of the posterior malleolus. According to the CT-based Haraguchi fracture morphology, all patients were divided into three groups: 20 Type I (large posterolateral-oblique), 21 Type II (transverse medial-extension) and 32 Type III (small-shell fragment). At 12 weeks, 1 year and 2 years postoperatively the Foot and Ankle Outcome Scores (FAOS) and SF-36 scores were obtained, with the FAOS domain scores at two years postoperative as primary study outcome. Statistical analysis included a multivariate regression and secondary a mixed model analysis. RESULTS: Haraguchi Type II PM ankle fractures demonstrated significantly poorer outcome scores at two years follow-up compared to Haraguchi Types I and III. Mean FAOS domain scores at two years follow-up showed to be significantly worse in Haraguchi Type II as compared to Type III, respectively: Symptoms 48.2 versus 61.7 (p = 0.03), Pain 58.5 versus 84.4 (p < 0.01), Activities of Daily Living (ADL) 64.1 versus 90.5 (p < 0.01). CONCLUSION: Posterior malleolar ankle fractures with medial extension of the fracture line (i.e. Haraguchi Type II) are associated with significantly poorer functional outcomes. The current dogma to fix PM fractures that involve at least 25-33% of the tibial plafond may be challenged, as posterior malleolar fracture pattern and morphology - rather than fragment size - seem to determine outcome.

[Body integrity identity disorder, relief after amputation]. / Blijvende opluchting na beenamputatie bij body integrity identity disorder.

Body integrity identity disorder (BIID) is a rare condition in which a person, for no apparent physical reason, is tormented by the experience that a body-part, such as a limb, does not really belong to the body. Patients experience an intense desire for the limb to be amputated (a 'desire' formerly referred to as 'apotemnophilia'). We report on a 58-year-old male patient with BIID who froze one of his legs so that he could amputate it himself. A surgeon ultimately intervened and amputated the leg professionally. The patient was extremely relieved and was still experiencing relief at a follow-up three years later.

Comparison of two neoadjuvant chemoradiotherapy regimens in patients with potentially curable esophageal carcinoma.

The implementation of neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients has led to improved survival rates. Worldwide, different CRT regimens are applied. It is unknown how these regimens relate to each other regarding efficacy. Therefore, the aim of this study was to determine the preferred regimen regarding toxicity of, response to CRT, and long-term survival after esophagectomy in EC patients. EC patients in two centers who underwent CRT with different regimens prior to surgery were included in this study. CRT consisted of 50.4Gy combined with two cycles of cisplatin and 5-FU(center A), or 41.4Gy combined with five cycles of carboplatin and paclitaxel (center B). Toxicity, response to therapy and long-term survival were compared between groups. One hundred sisty-five patients were included. Forty-one percent of patients in center A developed ≥1 toxicity ≥ grade 3 versus 25% in center B (P = 0.025). CRT with a cisplatin-based regimen was an independent predictor for development of toxicity ≥ grade 3 (P = 0.043). There were no differences in response between both regimens (P = 0.904). Three-year survival was 61% (A) versus 57% (B) (P = 0.725). The carboplatin/paclitaxel/41.4Gy regimen causes less toxicity compared to the cisplatin/5-FU/50.4Gy regimen with nonsignificant differences in response rates and long-term survival; therefore our results support this regimen to be the preferred regimen for EC patients.

Neoadjuvant chemoradiotherapy followed by esophagectomy does not increase morbidity in patients over 70.

Esophagectomy in elderly esophageal carcinoma patients is correlated with a high morbidity and even mortality. Studies on neoadjuvant chemoradiotherapy (NT) in elderly patients are scarce. The aim of this study was to evaluate the effect of advanced age in combination with NT in esophageal carcinoma patients who underwent an esophagectomy. Patients who underwent NT prior to esophagectomy between 1993 and 2010 were divided into three groups: <70, 70-74, and ≥75 years. Toxicity of NT and postoperative morbidity were compared between groups. Primary endpoints were toxicity, complication rate, and survival. Two hundred thirteen patients underwent NT during the study period, 26 were aged 70-74 years, and 17 were ≥70 years. Toxicity of NT was comparable for younger and elderly patients (46% vs. 54% vs. 47%, P = 0.263). Overall complications occurred in 62% of younger patients versus 73% and 71% among patients aged 70-74 years and ≥75 years, respectively (P = 0.836). Cardiac complications occurred in 14% of younger patients versus 27% and 41% of elderly patients (P = 0.021). Three-year survival rates were 59% versus 44% versus 31% among patients aged <70, 70-74, and ≥75 years, respectively (P = 0.237). Higher age (odds ratio 1.750, P < 0.001) was an independent risk factor for development of cardiac complications. Toxicity of NT and postoperative complications are comparable for patients aged <70, 70-74, and ≥75 years, with the exception of cardiac complications. Therefore, we consider NT followed by esophagectomy in elderly patients a safe treatment modality in our center.

Genome-wide association study of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

Patient preferences in screening for recurrent disease after potentially curative esophagectomy.

BACKGROUND: Routine imaging (RI) as part of follow-up after potentially curative esophagectomy is currently not widely accepted. If detected recurrent disease could be adequately treated, it remains unclear whether patients would want to take part in a screening program. The aim of this study was to determine the extent to which patients who underwent esophagectomy prefer follow-up with or without RI. METHODS: Patients who underwent esophagectomy for carcinoma without evidence of recurrent disease were included. An interview-administered questionnaire was used to assess fear of recurrence and elicit patient preferences for the frequency and duration of follow-up and hypothetical changes of survival chances (1-10%). RESULTS: 45/54 eligible patients (83%) participated in this study. The majority of patients preferred follow-up with RI (67%) even if screening would not provide a survival benefit; this proportion increased up to 93% if the proposed chances of survival improved. Younger patients and patients with a lower histopathological tumor stage were more likely to desire follow-up with RI. CONCLUSION: Most patients who underwent esophagectomy preferred RI as part of follow-up over outpatient clinic visits only, even if such screening would not provide a survival benefit. Further research is needed to determine the most accurate screening modality and most efficient follow-up interval.

A high body mass index in esophageal cancer patients does not influence postoperative outcome or long-term survival.

BACKGROUND: The body mass index (BMI) in the general population has increased over the past decades. A high BMI is a known risk factor for the development of esophageal adenocarcinoma. Several studies on the influence of a high BMI on the postoperative course and survival after esophagectomy have shown contradictory results. The aim of the present study was to determine the influence of a high BMI on postoperative complications and survival among a large cohort of esophageal cancer patients. METHODS: Patients who underwent an esophagectomy between 1993 and 2010 were divided into three groups according to their BMI: normal weight (<25 kg/m(2)), overweight (25-30 kg/m(2)) or obese (≥ 30 kg/m(2)). Severity of complications was scored according to the Dindo classification, which was divided into three categories: no complications, minor to moderate complications, and severe complications. Long-term survival was determined according to the Kaplan-Meier method. RESULTS: A total of 736 esophagectomy patients were divided into three groups: normal weight (n = 352), overweight (n = 308), and obese (n = 72). Complications rates were similar for all groups (65-72%, P = 0.241). The incidence of anastomotic leakage was higher among obese patients compared to the other groups (20% vs. 10-12% respectively, P = 0.019), but there was no significant difference between the three groups regarding the severity of complications according to the Dindo classification (P = 0.660) or in 5-year survival rates (P = 0.517). CONCLUSIONS: A high BMI is not associated with an increased incidence or severity of complications after esophagectomy; however, anastomotic leakage occurred more frequently in obese patients. Five-year survival rates were not influenced by the preoperative BMI. A high BMI is therefore ought not be an exclusion criterion for esophagectomy.

External ultrasonography of the neck does not add diagnostic value to integrated positron emission tomography-computed tomography (PET-CT) scanning in the diagnosis of cervical lymph node metastases in patients with esophageal carcinoma.

One of the objectives of preoperative imaging in esophageal cancer patients is the detection of cervical lymph node metastases. Traditionally, external ultrasonography of the neck has been combined with computed tomography (CT) in order to improve the detection of cervical metastases. In general, integrated positron emission tomography-computed tomography (PET-CT) has been shown to be superior to CT or PET regarding staging and therefore may limit the role of external ultrasonography of the neck. The objective of this study was to determine the additional value of external ultrasonography of the neck to PET-CT. This study included all patients referred our center for treatment of esophageal carcinoma. Diagnostic staging was performed to determine treatment plan. Cervical lymph nodes were evaluated by external ultrasonography of the neck and PET-CT. In case of suspect lymph nodes on external ultrasonography or PET-CT, fine needle aspiration (FNA) was performed. Between 2008 and 2010, 170 out of 195 referred patients underwent both external ultrasonography of the neck and PET-CT. Of all patients, 84% were diagnosed with a tumor at or below the distal esophagus. In 140 of 170 patients, the cervical region was not suspect; no FNA was performed. Seven out of 170 patients had suspect nodes on both PET-CT and external ultrasonography. Five out of seven patients had cytologically confirmed malignant lymph nodes, one of seven had benign nodes, in one patient FNA was not performed; exclusion from esophagectomy was based on intra-abdominal metastases. In one out of 170 patients, PET-CT showed suspect nodes combined with a negative external ultrasonography; cytology of these nodes was benign. Twenty-two out of 170 patients had a negative PET-CT with suspect nodes on external ultrasonography. In 18 of 22 patients, cervical lymph nodes were cytologically confirmed benign; in four patients, FNA was not possible or inconclusive. At a median postoperative follow-up of 15 months, only 1% of patients developed cervical lymph node metastases. This study shows no additional value of external ultrasonography to a negative PET-CT. According to our results, it can be omitted in the primary workup. However, suspect lymph nodes on PET-CT should be confirmed by FNA to exclude false positives if it would change treatment plan.

The value of post-neoadjuvant therapy PET-CT in the detection of interval metastases in esophageal carcinoma.

BACKGROUND: PET-CT scanning is increasingly applied in the primary work-up of esophageal cancer patients. The additional value of a second PET-CT after completion of neoadjuvant therapy (NT) prior to surgery is presently unclear. Therefore, a consecutive series of esophageal cancer patients underwent PET-CT scanning after completion of NT for evaluation of metastatic disease that became manifest under NT. METHODS: A consecutive series of patients planned for curative esophagectomy who underwent a PET-CT prior to and after NT were included in this study. Neoadjuvant therapy consisted of 5FU and cisplatinum combined with 50.4Gy radiotherapy. The first PET-CT was performed as part of the diagnostic work-up, the second PET-CT was performed after completion of NT and prior to surgery. Median interval between NT and second PETCT was 6 weeks. In case of metastatic disease on the post-neoadjuvant therapy PET-CT confirmed by a biopsy, patients were excluded from surgical resection. RESULTS: Between November 2008 and July 2010 a total of 50 patients underwent first and second PET-CT scanning. 80% of patients was diagnosed with adenocarcinoma, 18% with squamous cell carcinoma. Confirmed metastatic disease on the second PET-CT was present in 4/50 patients (8%). These patients were excluded from resection. A false-positive diagnosis concerning a pulmonary lesion was present in 1 patient (2%); this infiltrate had disappeared on follow up imaging. DISCUSSION: This study showed development of metastatic disease during NT detected by PET-CT in 8% of esophageal cancer patients, suggesting an additional value of a second PET-CT in order to prevent unnecessary surgical resections.

Acute Pancreatitis in the Postoperative Course after Esophagectomy: A Major Complication Described in 4 Patients.

BACKGROUND: Postoperative pancreatitis is a rare but devastating complication after esophageal surgery. It has been described in connection with abdominal surgery but the etiology in connection with esophageal surgery has never been evaluated. The present study describes 4 cases of postoperative pancreatitis, and a hypothesis about the etiology is formed. METHODS: We performed a search for patients with postoperative pancreatitis after esophagectomy using our prospective database including all patients that underwent esophageal resection at our institution between 1993 and 2008. Pancreatitis was described as abdominal pain, hyperamylasemia, signs of pancreatitis on CT scan or findings during laparotomy or autopsy. RESULTS: A total of 950 patients underwent esophagectomy at our institution, 4 patients developed postoperative pancreatitis (incidence 0.4%). Two out of four patients died. Discussion: Pancreatitis following esophageal surgery is a serious, potentially lethal complication. Diagnosis can be difficult as clear clinical or laboratory findings might be lacking. Peroperative manipulation of the pancreas, mobilization of the duodenum or compromized vascularization have been suggested as etiological factors; although in the described patients, none of these factors were identified as the cause of pancreatitis. In conclusion, pancreatitis following esophageal surgery is a serious but rare complication that should always be considered in patients who deteriorate postoperatively.

Pharmacological manipulation of neuronal ensemble activity by reverse microdialysis in freely moving rats: a comparative study of the effects of tetrodotoxin, lidocaine, and muscimol.

To be able to address the question how neurotransmitters or pharmacological agents influence activity of neuronal populations in freely moving animals, the combidrive was developed. The combidrive combines an array of 12 tetrodes to perform ensemble recordings with a moveable and replaceable microdialysis probe to locally administer pharmacological agents. In this study, the effects of cumulative concentrations of tetrodotoxin, lidocaine, and muscimol on neuronal firing activity in the prefrontal cortex were examined and compared. These drugs are widely used in behavioral studies to transiently inactivate brain areas, but little is known about their effects on ensemble activity and the possible differences between them. The results show that the combidrive allows ensemble recordings simultaneously with reverse microdialysis in freely moving rats for periods at least up to 2 wk. All drugs reduced neuronal firing in a concentration dependent manner, but they differed in the extent to which firing activity of the population was decreased and the in speed and extent of recovery. At the highest concentration used, both muscimol and tetrodotoxin (TTX) caused an almost complete reduction of firing activity. Lidocaine showed the fastest recovery, but it resulted in a smaller reduction of firing activity of the population. From these results, it can be concluded that whenever during a behavioral experiment a longer lasting, reversible inactivation is required, muscimol is the drug of choice, because it inactivates neurons to a similar degree as TTX, but it does not, in contrast to TTX, affect fibers of passage. For a short-lasting but partial inactivation, lidocaine would be most suitable.

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer.

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European-Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin-paclitaxel regimen over cisplatin-cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Genetic heterogeneity in the apolipoprotein C-III promoter and effects of insulin.

In the present study, we have investigated the in vivo and in vitro role of two newly identified variants (G(-)944A and A(-)1180C) located in the upstream promoter region of the apolipoprotein C-III (apoC-III) gene. These variants were studied in 30 probands diagnosed with FCHL, their relatives, and spouses. The allele frequencies of both variants were not different between the groups. No significant associations between plasma lipid traits and DNA variants were observed. We further analyzed the effect of the presence of these variants in the upstream enhancing region of the apoC-III gene, as five different in vivo occurring haplotypes, on the transcriptional activity of apoC-III in both HepG2 and Caco-2 cells. All five promoter constructs, including the wild type, showed similar enhancing activity of the apoC-III gene. The average transcription efficiency was enhanced 19-fold in HepG2 cells and 11-fold in Caco-2 cells. Previous studies have shown in vitro insulin-dependent down-regulation of the apoC-III gene transcription in HepG2 cells by DNA variation in an insulin response element (IRE) in the apoC-III promoter. We observed a 30% insulin-dependent down-regulation of apoC-III expression that was, however, independent of the presence of the two IRE variants. In contrast, in Caco-2 cells, a more variable insulin-dependent up-regulation was found that was also independent of the presence of the IRE variants.In conclusion, our data suggested that the apoC-III gene transcription in vitro is regulated by insulin but independent of the presence of the two IRE variants at -455 and -482. We were unable to detect associations between these apoC-III variants and plasma lipids and insulin in our FCHL population. This means that in vivo apoC-III transcription not only depends upon insulin but appears to be mediated by other mechanisms.

Stem cell factor and interleukin-4 increase responsiveness of mast cells to substance P.

The response of mast cells (MC) to non-IgE-mediated stimulation is critically dependent on the population of MC examined. The neuropeptide Substance P (SP) has been reported to activate connective tissue-type MC (CTMC), while mucosal MC (MMC) are not activated by SP. We examined the effect of stem cell factor (SCF) plus interleukin-4 (IL-4) on SP-initiated activation of bone marrow-derived MC (BMMC). Mouse MC, derived from a culture of BM cells with IL-3, were subsequently treated with recombinant SCF plus IL-4 for 6 days. Responsiveness to SP was monitored measuring beta-hexosaminidase and lipid mediator release. Histochemical staining, histamine analysis, and granule protease expression were achieved to characterize the cells. In contrast to IL-3 grown cells, SCF/IL-4-exposed cells showed functional responsiveness to release beta-hexosaminidase (42.25% +/- 1.46% at SP concentration of 100 microM) and produce leukotriene C(4) (LTC(4)) (7.4 +/- 1.5 ng/10(6) cells)/prostaglandin D(2) (PGD(2)) (2.0 +/- 0.3 ng/10(6) cells) upon stimulation by SP. The increase in sensitivity of the cells to SP was not due to differentiation into CTMC, as the cells remained heparin negative. Both SCF and IL-4 were needed because SCF or IL-4 alone were insufficient to keep cells viable after 3 to 4 days post coculture. SP-induced secretion from BMMC cultured in medium containing SCF plus IL-4 (25.76% +/- 1.83%) was higher in comparison with cells cultured with SCF plus IL-3 (8.85% +/- 0.68%).These findings indicate that temporal changes in cytokine expression can influence the sensitivity of MC to non-immunologic stimuli. Local cytokine production leading to an increase in MC responsiveness to SP and inducing secretion of granule content and lipid generation may, therefore, propagate and worsen inflammatory conditions.

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases.

Eleven patients with uterine adenosarcoma diagnosed between 1970 and 1995 were evaluated according to DNA ploidy, S-phase fraction, p53 and mdm-2 expression, and traditional clinical and pathological prognostic factors, such as tumor stage, grade and mitotic index. DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. The patients ranged in age from 41 to 90 years (median, 76 years). Only one patient was premenopausal at the time of diagnosis and five (45%) were nulliparous. One patient had received previous pelvic irradiation for anal squamous carcinoma. Six of the tumors (55%) were pure adenosarcoma and five (45%) were adenosarcoma with sarcomatous overgrowth. Nine patients had a stage I tumor and two had a stage II tumor. Among the six adenosarcomas we found three DNA diploid tumors, two DNA aneuploid tumors, and one DNA multiploid tumor. All adenosarcomas had an S-phase fraction less than 10%, except one that was not assessable. None was p53 positive and only one overexpressed mdm-2. All five adenosarcomas with sarcomatous overgrowth were DNA aneuploid, three (60%) had an S-phase fraction > 10%, two (40%) were p53 positive, and one (20%) overexpressed mdm-2. Five of the eleven patients suffered recurrences, and three (60%) of these developed lung metastases. During the observation period four (36%) patients (2 adenosarcomas and 2 adenosarcoma with sarcomatous overgrowth) died of disease, three patients died of intercurrent disease without recurrence, and the remaining four are alive with no evidence of disease. The overall five-year survival rate for all stages was 69%; for patients with AS it was 80%, while for those with adenosarcoma with sarcomatous overgrowth it was 50%. There were no variables which correlated with survival. In conclusion, we found hat the typical adenosarcoma had a tendency to be of low stage, have a lower mitotic rate and an S-phase fraction <10%. On the other hand, adenosarcomas with sarcomatous overgrowth were of high grade, had a high mitotic rate, and were DNA aneuploid with an S-phase fraction >10%. None of the variables studied correlated with survival. Tumors that were p53-positive or overexpressed mdm-2 did not behave worse than their negative counterpart. All patients who recurred with distant metastases died of disease.