International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

Prognosis of small bowel adenocarcinoma in Crohn's disease compares favourably with de novo small bowel adenocarcinoma.

AIM: Limited data exist on Crohn's disease (CD)-associated small bowel adenocarcinoma (SBA). A large-scale retrospective cohort study was conducted comparing the clinical features and outcome of CD-associated SBA and de novo SBA. METHOD: Data for patients with small bowel adenocarcinoma were gathered from the 1992-2010 United States Surveillance, Epidemiology and End Results cancer registry-Medicare linked database. We identified 2123 patients, of whom 179 had CD-associated and 1944 de novo SBA. The main outcome measures were overall survival (OS) and cancer-specific survival (CSS). RESULTS: CD-associated SBA was most commonly located in the ileum (62% vs 31%, P < 0.0001). CD patients were diagnosed at an earlier stage (I/II), compared with de novo SBA (55% vs 32%, P < 0.0001), and were more likely to undergo surgery (81% vs 72%, P = 0.0016). Chemotherapy use was similar (25% vs 21%, P = 0.1886). Patients with CD-associated SBA had better 5-year OS (43% vs 34%, P = 0.0121) but a similar CSS (65% vs 64%, P = 0.77). There was no difference in the OS between the cohorts when stratified by stage. On multivariate analysis, CD was not significantly related to OS [hazard ratio (HR) 0.97, 95% CI: 0.79-1.20, P = 0.7889]. Surgery and the extent of lymphadenectomy improved OS for all SBA patients (HR 0.73, 95% CI: 0.60-0.88, P = 0.001), whereas chemotherapy did not (HR 1.13, 95% CI: 0.99-1.28, P = 0.0665). CONCLUSION: Patients with CD-associated SBA present at an earlier stage than patients with de novo SBA, they receive more surgery but similar rates of chemotherapy, and have similar OS and CSS. The presence of CD does not worsen survival after treatment of SBA.

Significant understaging is seen in clinically staged T2N0 esophageal cancer patients undergoing esophagectomy.

This study aimed to determine the impact of preoperative staging on the treatment of clinical T2N0 (cT2N0) esophageal cancer patients undergoing esophagectomy. We reviewed a retrospective cohort of 27 patients treated at a single institution between 1999 and 2011. Clinical staging was performed with computed tomography, positron emission tomography, and endoscopic ultrasound. Patients were separated into two groups: neoadjuvant therapy followed by surgery (NEOSURG) and surgery alone (SURG). There were 11 patients (41%) in the NEOSURG group and 16 patients (59%) in the SURG group. In the NEOSURG group, three of 11 patients (27%) had a pathological complete response and eight (73%) were partial or nonresponders after neoadjuvant therapy. In the SURG group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged, and 1 (6%) was correctly staged. In the entire cohort, despite being clinically node negative, 14 of 27 patients (52%) had node-positive disease (5/11 [45%] in the NEOSURG group, and 9/16 [56%] in the SURG group). Overall survival rate was not statistically significant between the two groups (P = 0.96). Many cT2N0 patients are clinically understaged and show no preoperative evidence of node-positive disease. Consequently, neoadjuvant therapy may have a beneficial role in treatment.

Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms.

Aggressive cancers often express E-cadherin in cytoplasmic vesicles rather than on the plasma membrane and this may contribute to the invasive phenotype of these tumors. Therapeutic strategies are not currently available that restore the anti-invasive function of E-cadherin in cancers. MDA-MB-231 cells are a frequently used model of invasive triple-negative breast cancer, and these cells express low levels of E-cadherin that is mislocalized to cytoplasmic vesicles. MDA-MB-231 cell lines stably expressing wild-type E-cadherin or E-cadherin fused to glutathione S-transferase or green fluorescent protein were used as experimental systems to probe the mechanisms responsible for cytoplasmic E-cadherin localization in invasive cancers. Although E-cadherin expression partly reduced cell invasion in vitro, E-cadherin was largely localized to the cytoplasm and did not block the invasiveness of the corresponding orthotopic xenograft tumors. Further studies indicated that the glucocorticoid dexamethasone and the highly potent class I histone deacetylase (HDAC) inhibitor largazole cooperated to induce E-cadherin localization to the plasma membrane in triple-negative breast cancers, and to suppress cellular invasion in vitro. Dexamethasone blocked the production of the cleaved form of the CDCP1 (that is, CUB domain-containing protein 1) protein (cCDCP1) previously implicated in the pro-invasive activities of CDCP1 by upregulating the serine protease inhibitor plasminogen activator inhibitor-1. E-cadherin preferentially associated with cCDCP1 compared with the full-length form. In contrast, largazole did not influence CDCP1 cleavage, but increased the association of E-cadherin with γ-catenin. This effect on E-cadherin/γ-catenin complexes was shared with the nonisoform selective HDAC inhibitors trichostatin A (TSA) and vorinostat (suberoylanilide hydroxamic acid, SAHA), although largazole upregulated endogenous E-cadherin levels more strongly than TSA. These results demonstrate that glucocorticoids and HDAC inhibitors, both of which are currently in clinical use, cooperate to suppress the invasiveness of breast cancer cells through novel, complementary mechanisms that converge on E-cadherin.

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.

Comparison of transcolonic NOTES and laparoscopic peritoneoscopy for the detection of peritoneal metastases.

BACKGROUND AND AIMS: Peritoneoscopy by natural orifice transluminal endoscopic surgery (NOTES) could replace laparoscopic staging peritoneoscopy (LAP) if the yield were comparable to that from LAP. In previously performed porcine experiments, transgastric peritoneoscopy seemed inferior to LAP due to limited visualization of the liver. The aim of the present study was to improve liver visualization by using a colonic approach and to compare transcolonic peritoneoscopy (TCP) with the previously set LAP standard. METHODS: Small beads were stapled into porcine peritoneal cavities to simulate metastases. Previously in the same model LAP had detected 95% of beads (95% CI 87% -98%). Using a non inferiority design, a sample size of 33 beads was determined; these were distributed among six animals with randomization for numbers and location. TCP was performed using either standard endoscopic accessories (TCP-s) or a specially designed toolkit (TCP-t) in randomized order by one of two blinded endoscopists. Primary outcome was number of beads found and touched during peritoneoscopy. RESULTS: Locations of beads included abdominal peritoneum (6 beads), diaphragm (8), liver (18), and miscellaneous sites (1). TCP-s found 25 beads (yield 76%, 95% CI 59% -87%). TCP-t found 19 beads (yield 58%, 95% CI 41%-71%). The majority of missed beads were located at the inferior liver surface: TCP-s detected 8/15 (53%) and TCP-t 5/15 (33%) of these simulated metastases. CONCLUSIONS: In this prospective, experimental trial, transcolonic NOTES peritoneoscopy was inferior in comparison with the diagnostic laparoscopy done previously in the same model.

Diagnostic laparoscopy for patients with potentially resectable pancreatic adenocarcinoma: is it cost-effective in the current era?

INTRODUCTION: For patients with potentially resectable pancreatic cancer, diagnostic laparoscopy may identify liver and peritoneal metastases that are difficult to detect with other staging modalities. The aim of this study was to utilize a population-based pancreatic cancer database to assess the cost effectiveness of preoperative laparoscopy. MATERIAL AND METHODS: Data from a state cancer registry were linked with primary medical record data for years 1996-2003. De-identified patient records were reviewed to determine the role and findings of laparoscopic exploration. Average hospital and physician charges for laparotomy, biliary bypass, pancreaticoduodenectomy, and laparoscopy were determined by review of billing data from our institution and Medicare data for fiscal years 2005-2006. Cost-effectiveness was determined by comparing three methods of utilization of laparoscopy: (1) routine (all patients), (2) case-specific, and (3) no utilization. RESULTS AND DISCUSSION: Of 298 potentially resectable patients, 86 underwent laparoscopy. The prevalence of unresectable disease was 14.1% diagnosed at either laparotomy or laparoscopy. The mean charge per patient for routine, case-specific, and no utilization of laparoscopy was $91,805, $90,888, and $93,134, respectively. CONCLUSION: Cost analysis indicates that the case-specific or routine use of laparoscopy in pancreatic cancer does not add significantly to the overall expense of treatment and supports the use of laparoscopy in patients with known or suspected pancreatic adenocarcinoma.

Pericardial lipoma in a geriatric dog with an incidentally discovered thoracic mass.

An intrathoracic mass was discovered as an incidental finding in a 14-year-old, spayed, female Rottweiler cross during evaluation of urinary incontinence. Computed tomography suggested a pericardial or pleural location and high adipose content of the mass. The mass was removed via lateral thoracotomy with partial pericardectomy and was diagnosed as a pericardial lipoma. The dog recovered well, and there was no evidence of recurrence approximately one year later. Adipose tumours of the heart and its associated structures are rare in dogs and have been associated with both successful and fatal outcomes.

Potential predictors of chemotherapy response in ovarian cancer--how do we define chemosensitivity?

OBJECTIVE: The aim of this study was to assess whether microvessel density (measured by CD31), vascular endothelial growth factor (VEGF) or multidrug resistance (MDR1) could determine the response to chemotherapy or act as prognostic factors in ovarian cancer. METHODS: Seventy-nine ovarian specimens were immunostained. Pearson correlation, 1-way ANOVA and chi-square were used for univariate analysis. Kaplan Meier survival curves were used, log-rank was used for univariate analysis and a Cox proportional hazards regression model was used for multivariate evaluation. Response to chemotherapy was assessed after 6 months and again after 1 year. RESULT: Quantifying VEGF proved to be a valuable independent prognostic indicator in progression-free survival (PFS) (p<0.05) and overall survival (OS) (p<0.0001). VEGF correlated with response to chemotherapy at the 6-month interval (r=0.446, p<0.001) but failed to correlate at the 1-year interval. Increased staining with CD31 was associated with decreased PFS (p<0.01) and OS (p<0.01) in univariate but not multivariate analysis. MDR1 failed to act as a prognostic marker or as a predictor of response to chemotherapy. CONCLUSION: VEGF correlates with response to chemotherapy at the 6-month but not the 12-month interval. What should our criteria be for determining sensitivity to chemotherapy? CD31, VEGF and MDR1 do play a role in some ovarian malignancies but other factors are likely to be involved and perhaps molecular profiling will determine which factors will be important for determining the response to chemotherapy.

Genome-wide analysis of deoxyribonucleic acid in endometrial cancer using comparative genomic hybridization microarrays.

The aim of this study was to identify amplified oncogenes in endometrial cancer using array-based comparative genomic hybridization (array CGH). Despite its prevalence, the molecular mechanisms of endometrial carcinogenesis are still poorly understood. The selected array CGH allows the simultaneous examination of 58 oncogenes commonly amplified in human cancers and is capable of achieving increased mapping resolution compared with conventional CGH. A subset of 8 specimens from a bank of 60 malignant and normal specimens was selected for array analysis to identify potential genes of interest. TaqMan polymerase chain reaction was carried out on the 60 specimens to examine if aberrations at the genomic level correlated with gene expression and to compare expression in normal and malignant samples. Oncogenes amplified in the endometrial cancers included AR, PIK3CA, MET, HRAS, NRAS, D17S1670, FGFR1, CTSB, RPS6KB1, LAMC2, MYC, PDGFRA, FGF4/FGF3, PAKI, and FGR. Three genes were examined at the messenger RNA level. AR and PIK3CA were higher in normal specimens, and MET was higher in malignant samples, suggesting a role for MET in endometrial cancer. Newer arrays examining more genes and larger sample numbers are necessary to elucidate the carcinogenic pathway in endometrial cancer.

Ten-year trend in the national volume of bile duct injuries requiring operative repair.

BACKGROUND: The objectives of this study were to determine the national proportions and mortality rate for bile duct injuries resulting from laparoscopic cholecystectomy (LC) that required operative reconstruction for repair over a 10-year period and to investigate the major factors associated with the mortality rate in this group of patients. METHODS: Using the Nationwide Inpatient Sample (NIS) of >7 million patient records per year, we extracted and analyzed data for LC during the years 1990-2000. Procedures that involved biliary reconstructions performed as part of another primary procedure were excluded. Using the Statistical Package for the Social Sciences (SPSS), we used procedure-specific codes that enabled us to calculate national estimates for LC for the time period under review. We then calculated biliary reconstruction procedures that occurred after LC for this cohort of patients. Finally, we analyzed in-hospital mortality, as well as the patient, institutional, and outcome characteristics associated with biliary reconstructions. RESULTS: The percentage of cholecystectomies performed laparoscopically has increased over the years for which data are available (from 52% in 1991 to 75% in 2000). Despite this increase, the mortality rate for this group of patients has remained consistently low over the study period (mean, 0.45%; range 0.33-0.58%). Within this group of patients, the average rate of bile duct injuries requiring operative repair was 0.15% for the years under study. The reconstruction rates ranged from 0.25% in 1992 to 0.09% in 1999. For 2000, the most recent year for which data are available, biliary reconstruction was performed in 0.10% of all patients who underwent LC. The average mortality rate for patients undergoing biliary reconstruction for the years 1991 to 2000 was 4.5%. After multivariate analysis, age, African American ethnicity, type of admission, source of admission, and hospital location, and teaching status were all found to correlate significantly with death after-biliary reconstruction. CONCLUSIONS: These data show an increase in the percentage of cholecystectomies performed laparoscopically over the years under study and an associated low mortality rate. In contrast, although the number of bile duct injuries appears to be decreasing, these procedures continue to be associated with a significant mortality rate.

Randomised, controlled field trial of two new techniques for the castration and tail docking of lambs less than two days of age.

Two methods to reduce the pain associated with the castration and tail docking of lambs with rubber rings were tested by 10 shepherds, each using 60 housed lambs. In 20 of the lambs the innervation to the scrotum, testes and tail was crushed with a 'Big Nipper' bloodless castrator, and in 20 local anaesthetic (2 per cent lignocaine with adrenaline) was injected with a newly developed high-pressure jet injector under the rubber rings after they had been applied; 10 lambs were given a placebo treatment and 10 were treated by the shepherds' routine elastrator ring procedure. Both new methods significantly decreased the incidence of limb and tail movement by 78 per cent and the time spent by the lambs in abnormal postures, when compared with either the shepherds' routine treatment or the placebo treatment. An experienced observer and most of the shepherds also assessed that the lambs suffered signficantly less pain when treated by the two new methods than when they were treated with rubber rings alone. No detrimental long-term effects of the two new methods were observed. On average the new methods took 68 seconds to apply, compared with 29 seconds for the rubber rings; of the two new methods most shepherds preferred using the pressure jet injector.

Transition from open to laparoscopic adrenalectomy: the need for advanced training.

BACKGROUND: We sought to determine the learning curve for laparoscopic adrenalectomy (LA), current use of the procedure, and if indications for adrenalectomy had changed in the past decade. METHODS: A retrospective chart review was performed for all adrenalectomies after 1990. Practicing community surgeons in Oregon were mailed a questionnaire. RESULTS: Seventy-five LAs were performed at the Oregon Health and Sciences University and Portland VA Medical Center. Average operating room (OR) time was 161 min and average estimated blood loss (EBL) was 84 ml. There were four complications and two conversions. Comparing the first 20 to the last 20 patients, OR times were 154 vs 159 min (not significant), and EBL was 102 vs 47 ml ( p < 0.05). There were two vs one complications ( p > 0.05) and one conversion each. Most residents completed less than two procedures during training, and community surgeons performed none during training. Of 17 currently performing LA, 14 had postresidency training. Open technique was used more often for hormonal ablation and malignancy. CONCLUSION: Operative time and complications do not decrease with experience, but EBL does. Few, if any, residents acquire enough experience to perform LA in practice. The procedure is performed laparoscopically more often for benign disease.

Prevention of percutaneous endoscopic gastrostomy stoma metastases in patients with active oropharyngeal malignancy.

The implantation of metastasis of oropharyngeal or esophageal cancer to percutaneous endoscopic gastrostomy (PEG) stomata is considered an uncommon complication, but it is being recognized with increasing frequency. The incidence of this complication is not known. Multiple theories of metastatic spread have been proposed. We describe a case following retrograde endoscopy via a PEG stoma site. A National Library of Medicine literature search was performed, and case reports and bibliographies were reviewed. We estimate the incidence of this complication as 1% minimum. Direct seeding of the site is the only reasonable hypothesis to explain this phenomenon. Health care providers need to be educated about this problem. Although there is no direct evidence that metastases are spread by direct contact, we believe that transgression of the active primary tumor during gastrostomy tube placement should be avoided. Laparoscopic gastrostomy tube placement provides a safe, effective, and minimally invasive method of enteral access, which avoids transgression of the primary tumor site, and may prevent stomal metastases in patients with active aerodigestive tract malignancies who require gastrostomy.

The laparoscopic sponge.

PURPOSE: Hemorrhage and spillage of enteric contents during laparoscopic surgery can be problematic and obscure the operative field. Although the suction device can often clear the field, we have found that use of a sponge is often more efficient and effective. MATERIAL AND METHODS: An unrolled 4 x 4 sponge can be introduced down a 10-mm port without difficulty. The addition of a suture tied to one corner of the sponge allows easy retrieval of the sponge and eliminates the possibility of leaving the sponge in the abdomen. CONCLUSIONS: The laparoscopic sponge is simply constructed and is easily introduced and retrieved through a trocar. It can be used to deal with a troublesome hemorrhage, either to put on direct pressure or to absorb blood. It can also be used as a blunt retractor and dissector. With the addition of the suture tail, it is quickly retrieved and cannot be forgotten within the abdomen.

Haemostatic risk factors in healthy postmenopausal women taking hormone replacement therapy.

OBJECTIVE: To compare changes in haemostatic parameters in healthy postmenopausal women taking either tibolone or 17beta-oestradiol/norethisterone acetate. METHODS: Factor VIIc, antithrombin, fibrinogen, thrombin-antithrombin complex (TAT), FDP (D-Dimer), tissue plasminogen activator (tPA) and plasminogen activator inhibitor I (PAI-1) were measured in 80 healthy postmenopausal women after 3, 6 and 12 months therapy with either 17beta-oestradiol/norethisterone acetate or tibolone. RESULTS: Both treatments significantly reduced fibrinogen, factor VIIc, antithrombin, tPA and PAI-1 antigen. Significantly lower levels of factor VIIc activity were observed on treatment with tibolone compared with 17beta-oestradiol/norethisterone acetate. TAT was unchanged with both treatments as was tPA activity. FDP (D-dimer) was increased on treatment with both preparations. CONCLUSIONS: The enhanced fibrin turnover and reduced antithrombin activity may play a role in the increased risk of venous thromboembolism in some susceptible women taking hormone replacement therapy (HRT) and could explain the lack of benefit of HRT in the secondary prevention of cardiovascular disease. The decreased levels of fibrinogen and factor VIIc found during treatment with 17beta-oestradiol/norethisterone acetate or tibolone may offer some degree of cardioprotection in healthy woman without pre-existing disease.

von Willebrand's disease: an important cause of dysfunctional uterine bleeding.

We assessed the prevalence of von Willebrand's disease (VWD) in patients with objectively confirmed dysfunctional uterine bleeding. A case-control study was designed to include 38 patients with objectively confirmed dysfunctional uterine bleeding and 38 age-matched controls with normal menstrual blood loss (MBL). Menorrhagia was defined as a mean MBL of greater than 80 ml on three consecutive menses as measured by the alkali haematin method. von Willebrand factor antigen, von Willebrand factor activity (VWF:Ac) and factor VIII:C were measured on three serial venous blood samples 1 week apart. VWD was diagnosed in five of 38 (13%) patients with menorrhagia and one of 38 (2.6%) patients with normal menstrual blood loss. The mean VWF:Ac value was significantly reduced in patients with menorrhagia (mean +/- standard deviation, 84.5 +/- 26.7 IU/dl versus 103.9 +/- 34.5 IU/dl; P < 0.01) and this effect persisted after exclusion of patients diagnosed with VWD. Failure to investigate patients for VWD will limit the potential benefits of medical therapies such as tranexamic acid or nasal desmopressin [1-desamino-8-D-arginine vasopressin, (DDAVP)] and, in addition, will lead to an increased risk associated with surgical intervention in patients with undiagnosed VWD.

Serous papillary adenocarcinomas of the ovary display heterogeneity in their response to chemotherapy.

The response of ovarian serous papillary adenocarcinomas to various cytotoxic drugs was examined using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) cytotoxicity assay. Thirty tumors were collected and organized into four groups according to histologic grade and FIGO stage: stage III, grade 2; stage III, grade 3; stage IV, grade 2; and stage IV, grade 3. The MTS chemosensitivity assay was performed on each tumor to examine the response to cisplatin, paclitaxel, hycamtin and the combination of cisplatin and paclitaxel. Ovarian adenocarcinomas of similar stage and grade displayed varying responses to the same drug. A lower concentration of the drug was often as effective as the peak plasma concentration. For some specimens combination therapy was more effective for inhibiting tumor growth, and for others single-agent therapy gave a better response. A chemosensitivity/resistance profile is recommended before deciding on appropriate chemotherapy.

Does neoadjuvant chemoradiation downstage esophageal carcinoma?

BACKGROUND: Neoadjuvant chemoradiotherapy is administered to patients with esophageal carcinoma with the belief that this will both downstage the tumor and improve survival. Endoscopic ultrasound (EUS) is currently the most accurate method of staging esophageal cancer for tumor (T) and lymph node (N) status. Because both EUS and neoadjuvant therapy for esophageal carcinoma are relatively new, there are few data examining the relationship between EUS stage and histological stage (the stage after resection) in patients receiving neoadjuvant therapy. METHODS: To determine the effect of neoadjuvant chemoradiotherapy on T and N stage as determined by EUS, we retrospectively compared two groups of patients with esophageal cancer staged by EUS. One group (33 patients) underwent neoadjuvant therapy (Walsh protocol: 5-fluorouracil, cisplatin, and 4000 rads of external beam radiation) followed by resection. The second group (22 patients), a control group, underwent resection without neoadjuvant therapy. We then compared histological stage to determine if there was a downstaging in the patients receiving neoadjuvant therapy. Survival was evaluated as well. RESULTS: EUS accurately predicted histologic stage. In the control group EUS overestimated T stage in 3 of 22 (13%), underestimated N stage in 2 of 22 (9%), and overestimated N stage in 2 of 22 (9%) of patients. Preoperative radiochemotherapy downstaged (preoperative EUS stage versus pathologic specimen) 12 of 33 (36%) of patients whereas only 1 of 22 (5%) of patients in the control group was downstaged. Complete response (no tumor found in the surgical specimen) was observed in 5 of 33 (15%) of patients receiving radiochemotherapy. Survival was prolonged significantly in patients receiving radiochemotherapy: 20.6 months versus 9.6 months for those (stage II or III) patients not receiving radiochemotherapy (P <0.01). Operative time, operative blood loss, and length of stay were not significantly different between groups. Perioperative mortality was higher in the radiochemotherapy group (13%) compared with the no radiochemotherapy group (5%) but did not achieve statistical significance. CONCLUSIONS: EUS accurately stages esophageal carcinoma. Neoadjuvant radiochemotherapy downstages esophageal carcinoma for T and N status. In our nonrandomized study, neoadjuvant therapy conferred a significant survival advantage. Operative risk appears to be increased in patients receiving neoadjuvant radiochemotherapy prior to esophagectomy.