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This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage 1 cancers, the stage-specific sensitivities trended to improve with higher stages. Early results from this preliminary clinical, prospective evaluation of the DEEPGENTM liquid biopsy platform suggests the platform offers a clinically relevant ability to differentiate individuals with and without known cancer, even at early stages of cancer.

Introduction: Laparoscopic abdominoperineal resection (APR) for low rectal cancers is technically demanding. Robotic assistance may be of help and can be hybrid (HAPR) or totally robotic (RAPR). The present study describes outcomes of robotic APR and compares both approaches., Material and Methods: A multicentric retrospective analysis of rectal cancer patients undergoing either HAPR or RAPR was conducted. Patients' demographics, surgeons' experience, oncologic results, and intraoperative and postoperative outcomes were collected., Results: One hundred twenty-five patients were included, 48 in HAPR group and 77 in RAPR group. Demographics and comorbidities were comparable. Operative time was reduced in RAPR group (266.9 ± 107.8 min vs 318.9 ± 75.1 min, P = .001). RAPR patients were discharged home more frequently (91.18% vs 66.67%, P = .001), and experienced fewer parastomal hernias (3.71% vs 9.86%, P = .001)., Conclusion: RAPR is safe and feasible with appropriate oncologic outcomes. Totally robotic approach reduces operative time and may improve functional outcomes., (© 2019 John Wiley & Sons, Ltd.)

Aims: To compare (1) complication and (2) conversion rates to open surgery (OS) from laparoscopic surgery (LS) and robotic-assisted surgery (RA) for rectal cancer patients who underwent rectal resection. (3) To identify patient, physician, and hospital predictors of conversion., Materials and Methods: A US-based database study was conducted utilizing the 2012-2014 Premier Healthcare Data, including rectal cancer patients ≥18 with rectal resection. ICD-9-CM diagnosis and procedural codes were utilized to identify surgical approaches, conversions to OS, and surgical complications. Propensity score matching on patient, surgeon, and hospital level characteristics was used to create comparable groups of RA\LS patients (n = 533 per group). Predictors of conversion from LS and RA to OS were identified with stepwise logistic regression in the unmatched sample., Results: Post-match results suggested comparable perioperative complication rates (RA 29% vs LS 29%; p = .7784); whereas conversion rates to OS were 12% for RA vs 29% for LS (p < .0001). Colorectal surgeons (RA 9% vs LS 23%), general surgeons (RA 13% vs LS 35%), and smaller bed-size hospitals (RA 14% vs LS 33%) have reduced conversion rates for RA vs LS (p < .0001). Statistically significant predictors of conversion included LS, non-colorectal surgeon, and smaller bed-size hospitals., Limitations: Retrospective observational study limitations apply. Analysis of the hospital administrative database was subject to the data captured in the database and the accuracy of coding. Propensity score matching limitations apply. RA and LS groups were balanced with respect to measured patient, surgeon, and hospital characteristics., Conclusions: Compared to LS, RA offers a higher probability of completing a successful minimally invasive surgery for rectal cancer patients undergoing rectal resection without exacerbating complications. Male, obese, or moderately-to-severely ill patients had higher conversion rates. While colorectal surgeons had lower conversion rates from RA than LS, the reduction was magnified for general surgeons and smaller bed-size hospitals.

Background: The purpose of this paper is to introduce a robotic assisted approach to extralevator abdominoperineal excision in the modified Lloyd-Davis position with reconstruction of the perineum using pedicled gracilis flaps, and to discuss outcomes in a cohort of six patients., Methods: Data was collected by chart review on six patients who underwent extralevator excision with gracilis flap reconstruction from 10/2013 to 06/2015. Technical details, operative data, oncologic outcomes, and wound healing complications were evaluated., Results: There were no instances of intraoperative perforation or positive circumferential resection margin, and one case of locoregional recurrence. Two patients experienced flap venous congestion and one patient developed a perineal abscess. All patients went on to complete healing., Conclusions: The combination of a minimally invasive robotic assisted extralevator abdominoperineal excision performed in the modified Lloyd-Davis position with reconstruction of the perineum with pedicled gracilis flaps has excellent oncologic outcomes and acceptable wound healing complications. Copyright © 2016 John Wiley & Sons, Ltd. StartCopTextCopyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Conventional laparoscopy has been applied to colorectal resections for more than 2 decades. However, laparoscopic rectal resection is technically demanding, especially when performing a tumor-specific mesorectal excision in a difficult pelvis. Robotic surgery is uniquely designed to overcome most of these technical limitations. The aim of this study was to confirm the feasibility of robotic rectal cancer surgery in a large multicenter study., Methods: Retrospective data of 425 patients who underwent robotic tumor-specific mesorectal excision for rectal lesions at seven institutions were collected. Outcome data were analyzed for the overall cohort and were stratified according to obese versus non-obese and low versus ultra-low resection patients., Results: Mean age was 60.9 years, and 57.9 % of patients were male. Overall, 51.3 % of patients underwent neoadjuvant therapy, while operative time was 240 min, mean blood loss 119 ml, and intraoperative complication rate 4.5 %. Mean number of lymph nodes was 17.4, with a positive circumferential margin rate of 0.9 %. Conversion rate to open was 5.9 %, anastomotic leak rate was 8.7 %, with a mean length of stay of 5.7 days. Operative times were significantly longer and re-admission rate higher for the obese population, with all other parameters comparable. Ultra-low resections also had longer operative times., Conclusion: Robotic-assisted minimally invasive surgery for the treatment of rectal cancer is safe and can be performed according to current oncologic principles. BMI seems to play a minor role in influencing outcomes. Thus, robotics might be an excellent treatment option for the challenging patient undergoing resection for rectal cancer.

Background: The use of radiofrequency ablation (RFA) for cancer is increasing; however, post-discharge outcomes have not been well described. The aim of the present study was to determine rates of hospital-based, acute care utilization within 30 days of discharge after RFA., Methods: Using state-level data from California, patients were identified who were at least 40 years of age who underwent RFA of hepatic tumours without a concurrent liver resection from 2007-2011. Our primary outcome was hospital readmissions or emergency department visits within 30 days of discharge. A multivariable regression model was constructed to identify patient factors associated with these events., Results: The final sample included 1764 patients treated at 100 centres. Hospital readmissions (11.3/100 discharges), emergency department visits (6.0/100 discharges) and overall acute care utilization (17.3/100 discharges) were common. Most encounters occurred within 10 days of discharge for diagnoses related to the procedure. Patients with renal failure [adjusted odds ratio (AOR) = 1.98 (1.11-3.53)], obesity [AOR = 1.69 (1.03-2.77)], drug abuse [AOR = 2.95 (1.40-6.21)] or those experiencing a complication [AOR = 1.52 (1.07-2.15)] were more likely to have a hospital-based acute care encounter within 30 days of discharge., Conclusions: Hospital-based acute care after RFA is common. Patients should be counselled regarding the potential for acute care utilization and interventions targeted to high-risk populations., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Hypoperfusion is an important risk factor for anastomotic leakage in colorectal surgery. This study was designed to evaluate the impact of fluorescence imaging on visualization of perfusion and subsequent change of transection line during left-sided robotic colorectal resections., Methods: Patients scheduled for robotic left-sided colon or rectal resections were enrolled in this prospective, multicenter study. Resections were performed as per each surgeon's preference. After complete colorectal mobilization, ligation of blood vessels, and distal transection of the bowel, the mesocolon was completely divided to the planned proximal or distal transection line, which was marked in white light. Indocyanine green was injected intravenously and the transection location(s) and/or distal rectal stump, if applicable, were re-assessed in fluorescent imaging mode. Imaging information, perioperative, and early postoperative outcomes were recorded. An independent video review of the surgeries was performed., Results: Data for 40 patients (20 female/20 male) with a mean age of 63.9 years and a mean body mass index of 27.6 kg/m(2) were analyzed. Fluorescence imaging resulted in a change of the proximal transection location in 40 % (16/40) of patients. There was one change in the distal transection location in a patient with benign disease. The use of fluorescence imaging took an average of 5.1 min of the mean overall operative room time of 232 min. Two patients (5 %) with a change in transection line developed an anastomotic leak at postoperative days 15 and 40., Conclusion: Fluorescence imaging provides additional information during determination of transection location in left-sided colorectal procedures. This results in a significant change of transection location, particularly at the proximal transection site. Further research needs to be conducted with larger patient cohorts and in comparative design to determine actual effect on anastomotic leak rate.

Background: Radiofrequency ablation (RFA) for the treatment of hepatic tumors has been increasingly used across the United States. Whether treatment-related morbidity has remained low with broader adoption is unclear. We conducted this study to describe in-hospital morbidity associated with RFA for hepatic tumors and to identify predictors of adverse events in a nationally representative database., Methods: Using the 2006-2009 Nationwide Inpatient Sample, we evaluated all patients aged ≥40 years who underwent an elective RFA for primary or metastatic liver tumors (N = 1298). Outcomes included in-hospital procedure-specific and postoperative complications. Multivariable logistic regression analyses were performed to identify patient and facility predictors of complications., Results: Most patients underwent a percutaneous (39.9 %) or laparoscopic (22.0 %) procedure for metastatic liver tumors (57.5 %). Procedure-specific complications were frequent (18.2 %), with transfusion requirements (10.7 %), intraoperative bleeding (4.3 %), and hepatic failure (2.8 %) being the most common. Arrhythmias [adjusted odds ratio (AOR) = 1.93 (1.23-3.04)], coagulopathy [AOR = 4.65 (2.95-7.34)], and an open surgical approach [AOR = 2.77 (1.75-4.36)] were associated with an increased likelihood of procedure-specific complications, whereas hospital RFA volume ≥16/year was associated with a reduced likelihood [AOR = 0.59 (0.38-0.91)]. Postoperative complications were also common (12.0 %), with arrhythmias, heart failure, coagulopathy, and open surgical approach acting as significant predictors., Conclusions: In-hospital morbidity is common after RFA for hepatic tumors. While several patient factors are associated with more frequent procedure-specific complications, treatment at hospitals with an annual volume ≥16 cases/year was associated with a 41 % reduction in the odds of procedure-specific complications.

Background: Laparoscopic liver resection for malignant disease has shown short-term benefit. This study aimed to compare in-house, 30-day, and 1-year morbidity between laparoscopic and open liver resections., Methods: The charts for all patients who underwent liver resection for malignant disease between April 2006 and October 2009 were reviewed. Patient, operative, and outcomes data at 30 days and 1 year were collected., Results: For 76 patients, 49 open and 27 laparoscopic resections were performed. The two groups were similar in terms of age, gender, body mass index (BMI), extent of liver resection, use of ablation therapy, and tumor pathology (P > 0.05). The laparoscopic group had less blood loss (P = 0.004) and shorter hospital stays (P = 0.002). During their hospital stay, patients treated laparoscopically had fewer complications, but the difference was not significant. Home disposition was similar in the laparoscopic (96%) and open (90%) groups. More patients were readmitted at 30 days (2 vs. 9; P = 0.31) and 1 year (4 vs. 19; P = 0.04) in the open group. The all-cause 1-year mortality rates were similar between the laparoscopic and open groups (14.8% vs. 10.2%)., Conclusion: The benefits of laparoscopic liver resection may extend beyond the initial postoperative period, with fewer readmissions despite shorter hospital stays. This also may suggest lower long-term hospital costs.

Background: Previous work has demonstrated YPEL3 to be a growth-suppressive protein that acts through a pathway of cellular senescence. We set out to determine whether human colon tumors demonstrated downregulation of YPEL3., Methods: We collected colon tumor samples with matched normal control samples and analyzed them for YPEL3 gene expression by reverse transcriptase-polymerase chain reaction and CpG hypermethylation of the YPEL3 promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116(-/-) p53) were used to assess YPEL3 gene expression after treatment with 5-azadeoxycytidine or trichostatin A., Results: Reverse transcriptase-polymerase chain reaction analysis demonstrated a decrease in YPEL3 expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the YPEL3 promoter CpG island does not play a role in YPEL3 regulation in human colon tumors or colon cancer cells lines, consistent with the inability of 5-azadeoxycytidine treatment to induce YPEL3 expression in colon cancer cell lines. In contrast, colon cell line results suggest that histone acetylation may play a role in YPEL3 regulation in colon cancer., Conclusions: YPEL3 is preferentially downregulated in human colon adenocarcinomas. DNA hypermethylation does not appear to be the mechanism of YPEL3 downregulation in this subset of collected patient samples or in colon cell lines. Histone acetylation may be a relevant epigenetic modulator of YPEL3 in colon adenocarcinomas. Future investigation of YPEL3 and its role in colon cancer signaling and development may lead to increased understanding and alternative treatment options for this disease.

Background: During laparoscopic right hemicolectomy, the anastomosis can be created intra- or extracorporeally. This study aimed to determine whether a difference exists in short-term outcomes between these techniques., Methods: Prospectively collected data of 80 consecutive patients who underwent laparoscopic right hemicolectomies since 2004 were reviewed retrospectively. An intracorporeal anastomosis was performed in 23 patients, an extracorporeal anastomosis in 57., Results: There were no significant differences in median length of stay (4 days), number of removed lymph nodes, estimated blood loss, operative time (190 minutes intracorporeal vs. 180 minutes) and postoperative ileus (22% intracorporeal vs. 16%). The incision length was significantly shorter in the intracorporeal group (4cm vs. 5cm; P=0.004). Complications related to the anastomosis including twisting of the mesentery (n=2), anastomotic volvulus (n=1), or leak (n=1) occurred in 4 patients in the extracorporeal group compared with one minor anastomotic leak in the intracorporeal group. Major complication rates were similar between the 2 groups (4.3% intracorporeal vs. 5.3% extracorporeal)., Conclusion: The type of anastomosis does not influence short-term outcomes after laparoscopic right hemicolectomy. An intracorporeal anastomosis results in shorter incision length and may decrease wound-related complications.

Some limitations of conventional laparoscopy have been overcome by the enhanced dexterity of the robotic da Vinci system, and its use in gastrointestinal procedures is evolving. However, difficulties accessing multiple quadrants of the abdomen with the first robotic system led to a rather slow introduction of the da Vinci into the field of abdominal surgery compared with its success with urologic and cardiac procedures. The new da Vinci S HD system offers improved range of motion that allows for easier access to a wider surgical field. The authors developed a new "one-step" setup to perform a low anterior resection with total mesorectal excision and splenic flexure mobilization for rectal cancer using a completely robotic approach. This technical report describes all the major aspects for successful performance of this complex minimally invasive procedure.

Objectives: The role of lymph node (LN) dissection for pancreatic cancer remains uncertain, and guidelines for a minimum LN number have not been established. We hypothesized that LN number in node-negative (N0) pancreatic cancer influences survival., Methods: The Surveillance, Epidemiology, and End Results database was queried for patients undergoing resection for N0 pancreatic adenocarcinoma between 1988 and 2003. Lymph node number was categorized as 1-10, 11-20, and >20., Results: In a cohort of 1915 patients, the median LN number was 7 (range 1-57); 1365 (71%) patients had <11 LN. Survival was significantly better in the 11 to 20 compared with the 1-10 group (median, 20 vs 15 months, respectively, P < 0.0001); no difference was observed between the 11-20 and >20 groups (median, 20 vs 23 months, respectively, P = 0.14). Multivariate analysis demonstrated the prognostic significance of LN number for determining overall survival (hazard ratio 0.98, 95% confidence interval: 0.97-0.99; P<0.0001)., Conclusions: Pancreatic cancer lymphadenectomy with examination of >10 LN is associated with improved survival in N0 disease and should be considered a benchmark for adequacy of surgery and/or pathology. Currently, only a minority of patients are assessed by this measure. The variation in LN number may be indicative of diverse surgical technique and/or pathologic analysis and warrants further investigation.

Hepatic arterial infusion chemotherapy can be of value to patients with metastatic liver disease from colorectal cancer. Arterial infusion therapy requires surgical placement of a catheter into the gastroduodenal artery connected to a subcutaneous infusion pump or port, a procedure involving major abdominal surgery. Placement of chemotherapy infusion catheters by conventional laparoscopic techniques has been described, but is a technically challenging procedure. The purpose of this report is to introduce a new, minimally invasive approach for hepatic artery catheter placement using the DaVinci robotic system with the potential to minimize surgical trauma, pain, and hospital stay, and to render this minimal access procedure more feasible and widely applicable.

Background: Although chemoradiation often is administered as an adjuvant to pancreatic cancer surgery, recent reports have disputed the benefit of radiation therapy. The objective of this study was to determine the effect of adjuvant radiation therapy in patients with locally confined, lymph node-negative (N0) pancreatic cancer., Methods: The Surveillance, Epidemiology, and End Results registry was used to identify patients who had undergone cancer-directed surgery for N0 pancreatic adenocarcinoma between 1988 and 2003. Kaplan-Meier survival curves were constructed to compare overall survival between patients who did and did not receive adjuvant external-beam radiation therapy (EBRT). Multivariate Cox regression analysis was used to determine the prognostic significance of EBRT when additional clinicopathologic factors were assessed. The analysis also examined the potential treatment selection bias of patients with survival <3 months., Results: A cohort of 1930 surgical patients with N0 disease was identified. The median survival was 17 months. Irradiated patients had significantly better survival compared with nonirradiated patients (20 months vs 15 months, respectively; P < .001). On multivariate analysis, adjuvant EBRT (hazard ratio [HR], 0.72; 95% confidence interval [95% CI], 0.63-0.82; P < .001), age, grade, tumor classification, and tumor location were independent predictors of survival. When patients with survival <3 months were excluded from the analysis, no difference in survival between the EBRT group and the nonradiation group was noted on univariate comparison (P value not significant). However, on multivariate analysis, EBRT remained an independent predictor of improved overall survival (HR, 0.87; 95% CI, 0.75-1.00; P = .044)., Conclusions: Adjuvant EBRT was associated with improved survival in patients with operable, N0 pancreatic cancer. Its use should be considered in patients who have early-stage N0 disease., (2007 American Cancer Society)

Background: Laparoscopic total mesorectal excision for rectal cancer remains a difficult procedure with high conversion rates. We have sought to improve on some of the pitfalls of laparoscopy by using the DaVinci robotic system. Here we report our two-year experience with robotic-assisted laparoscopic surgery for primary rectal cancer., Methods: A prospectively maintained database of all rectal cancer cases starting in November 2004 was created. A series of 39 consecutive unselected patients with primary rectal cancer was analyzed. Clinical and pathologic outcomes were reviewed retrospectively., Results: 22 patients had low anterior, 11 intersphincteric and six abdominoperineal resections. Postoperative mortality and morbidity were % and 12.8%, respectively. The median operative time was 285 minutes (range 180-540 mins). The conversion rate was 2.6%. A total mesorectal excision with negative circumferential and distal margins was accomplished in all patients, and a median of 13 (range 7-28) lymph nodes was removed. The anastomotic leak rate was 12.1%. The median hospital stay was 4 days. There have been no local recurrences at a median follow-up of 13 months., Conclusions: Robotic-assisted surgery for rectal cancer can be carried out safely and according to oncological principles. This approach shows promising short-term outcomes and may facilitate the adoption of minimally invasive rectal surgery.

Background: Robotic surgery is evolving as a therapeutic tool for thoracic and urologic applications; however, its use in gastric cancer surgery has not been extensively reported. The objective of this pilot series was to assess the feasibility of using robotic surgery in performing an extended lymphadenectomy for gastric cancer., Methods: Between June 2005 and July 2006, seven patients (3 female, 4 male) underwent combined laparoscopic subtotal gastrectomy with omentectomy and robot-assisted extended lymphadenectomy using the da Vinci Surgical System for early distal gastric tumors. The mean age of the patients was 64 years. Tumor staging ranged from 0 to II. Six patients had adenocarcinoma and one patient had a high-grade dysplastic adenoma., Results: All procedures were completed successfully without conversion. The median operating time was 420 min. There was one intraoperative complication requiring a colon resection for a devascularized segment. The median number of nodes harvested was 24 (range = 17-30). Resection margins were negative in all specimens. Patients were hospitalized a median of 4 days (range = 3-9). Thirty-day mortality was 0%. Patients resumed a solid diet a median of 4 days postoperatively. Median followup was 9 (range = 0-10) months. There have been no tumor recurrences to date., Conclusion: Extended lymphadenectomy for gastric cancer using robotic surgery is safe and allows for an adequate lymph node retrieval. Our preliminary results suggest that this novel technique offers short hospital stays and low morbidity for patients undergoing surgical resection of distal gastric malignancies. Future studies will be necessary to better define the role of robotic surgery in gastric cancer treatment.

Objective: : There have been few reports of the use of robotic surgery to resect lung malignancies. Feasibility and safety of robotic lung resection for malignant lung lesions will be assessed by performing a retrospective analysis., Methods: : Between September 2004 and November 2006, 21 patients (11 male and 10 female patients) underwent robotic lung resection. Twenty resections were performed for primary nonsmall cell lung cancer and two for metastatic lesions. One patient had bilateral resections for two primary tumors. Fourteen lobectomies, five segementectomies, one wedge resection, and two bilobectomies were performed. Seventy-two percent of operative procedures included mediastinoscopy and/or bronchoscopy at the time of resection., Results: : Thirty-day mortality and conversion rate was 0%. The median operating room time and estimated blood loss was 3.6 hours and 100 mL, respectively. The median intensive care unit and total length of hospital stays were 2 and 4 days, respectively. Chest tubes were removed after a median of 2.0 days. The complication rate was 27%, which included atrial fibrillation, need for postoperative bronchoscopy, and pneumonia. The median tumor size and number of lymph nodes harvested was 2.3 cm and 16, respectively. All resection margins were negative. Median follow-up time was 9.8 months, with no local recurrences at this time., Conclusion: : Robotic lung resection appears safe and feasible and allows for significant lymph node retrieval, offers short hospital stays and low morbidity for patients undergoing surgical resection of lung malignancies. Future studies are needed to define the role of robotic surgery in lung cancer treatment.

Laparoscopic colectomy is a difficult procedure with a long learning curve. We describe in this study our technique for right- and left-sided laparoscopic medial-to-lateral colectomy. The medial approach involves division of the vascular pedicle first, followed by mobilization of the mesentery toward the abdominal wall, and finally freeing of the colon along the white line of Toldt. This approach allows immediate identification of the plane between the mesocolon and the retroperitoneum and renders the dissection fast and safe. Our series of 50 consecutive laparoscopic colectomies supports this concept. We believe that surgeons familiar with this technique will have an important tool in their armamentarium to circumvent some of the challenges of laparoscopic colectomy.

Purpose: Monocytes derived from patients with early breast cancer (EBC) have shown functional deficiencies. These functional deficiencies are characterized by changes in phenotype and morphology. We have expanded these investigations to dendritic cells generated from monocytes from patients with early breast cancer. -, Patients and Methods: Peripheral blood from 36 patients with EBC and from 26 healthy age-matched women was drawn and prepared for ex vivo generation of dendritic cells (DC) by incubation with granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL4). The phenotype of DC was examined by flow-cytometry. T cell - proliferation was induced with tetanus toxoid pulsed autologous dendritic cell. -, Results: Dendritic cells generated from monocytes from EBC-patients showed a significantly lower expression of the phenotype-associated antigens CD1a, CD83, CD80, CD86 and CD54 than the dendritic cells from healthy controls. T cell - proliferation in response to TT-pulsed autologous dendritic cells was significantly decreased when induced with dendritic cells from patients with early breast cancer, when compared to healthy controls. Morphologically, only dendritic cells from healthy women possessed prominent dendrites indicating maturity. -, Conclusions: These findings indicate that dendritic cells generated from monocytes from patients with early breast cancer express an immature phenotype, exhibit immature morphology and show functional deficits when compared to the cells derived from healthy age-matched controls. Whether these findings offer a potential target for therapeutic interventions remains to be elucidated.

Background: Gastrointestinal stromal tumors (GISTs), the specific kit-positive mesenchymal tumors of the gastrointestinal tract, are rarely found in the anorectum and account for only 0.1% of all colorectal tumors. The main stem of therapy remains surgical excision. The standard surgical approach for anorectal GISTs includes transanal resection or enucleation for smaller and anterior or abdominoperineal resection for larger tumors., Methods: We present an alternative, transvaginal approach for a local excision of a large rectal GIST. In our case, a 5 x 5 x 8 cm large GIST located 3 cm above the dentate line in the anterior rectal wall was removed through the vagina., Results: In our experience, this approach enables a safe alternative even for larger tumors in the anterior rectal wall with a very low morbidity, sparing the patient from an unnecessary abdominoperineal resection.

Van Buchem disease is an autosomal recessive disease characterized by overgrowth of the skeleton. In a group of Dutch patients the disease is thought to be due to a 52-kb deletion that results in decreased expression of the SOST gene. To further characterize the disease, the morphology of the metacarpals of six adult subjects and two juveniles with Van Buchem disease were measured on hand x-rays along with nine normal adults and nine adult carriers of the disease. Serum bone formation markers, alkaline phosphatase, type I procollagen peptide, and osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide, were determined. Van Buchem patients had increased metacarpal outer diameter, inner diameter, cortical thickness, and bone mineral density. Calculated bone volume and derived polar moment of inertia were markedly elevated (elevations of 158 +/- 33% and 497 +/- 95%, respectively) consistent with increased bone strength. Serum procollagen peptide and osteocalcin were significantly higher in Van Buchem patients. Urinary cross-linked N-telopeptide was significantly elevated in Van Buchem patients. None of these changes was found in Van Buchem carriers. These observations indicate that decreased expression of the SOST gene can lead to increased bone formation and to stronger bones.

Previous experiments from our laboratory have shown that immune mechanisms aiming at the destruction of tumour cells including the recognition of target cells and their elimination via the expression of intercellular adhesion molecule-1 (ICAM-1; CD54), the production of tumour necrosis factor-alpha (TNF-alpha) by monocytes and appropriate function of lymphocyte subpopulations were defective in breast cancer. Previous observations were extended to assess expression levels and regulatory mechanisms of costimulatory molecules CD54, CD80 and CD86 on monocytes derived from patients with early breast cancer (EBC). In addition, antigen presentation by antigen-presenting cells (APC) was analyzed within this context. We report that monocytes derived from patients with EBC exhibited significantly decreased expression levels of CD54 (p = 0.0002), CD80 (p = 0.009) and CD 86 (p = 0.002) compared with monocytes derived from healthy females. Simultaneously, lipopolysaccharide (LPS)-induced TNF-alpha production of monocytes was found to be defective in patients with EBC. Finally, T-cell proliferation in response to tetanus toxoid (TT) was significantly decreased in patients with EBC compared with healthy control females (p < 0.0001). Furthermore, T-cell proliferation in response to TT-pulsed APC derived from healthy controls was significantly inhibited in the presence of anti-CD54 and/or anti-CD80 antibodies in a dose-dependent manner, thus corroborating the necessity of the presence of CD54 and CD80 as costimulatory molecules in the present setting. We conclude that monocytes derived from patients with EBC showed a simultaneous defect of expression of CD54 and its regulation via TNF-alpha, CD80 and CD86 as well as T-cell proliferation following exposure to TT-pulsed APC. Based upon these findings, it is speculated that defects in costimulatory molecule expression might contribute to tolerance of the immune system towards the presence of malignant cells in patients with EBC., (Copyright 2000 Wiley-Liss, Inc.)

Mechanisms of growth inhibition by the novel marine compound dehydrothyrsiferol (DHT) were investigated in a sensitive and an MDR+ human epidermoid cancer cell line. DHT was found to circumvent multidrug resistance mediated by P-glycoprotein. Cell cycle analysis revealed an accumulation in S-phase. The anchorage independent clonogenic growth in soft agar was not significantly reduced at IC50 concentrations. Reduced cell growth caused by induction of apoptotic or necrotic cell death could not be verified. Therefore, cell proliferation during an incubation period of five days was measured and found to be significantly reduced. We conclude that growth inhibition by dehydrothyrsiferol in KB cancer cells is not mediated by apoptosis but by growth retardation; the reasons for this are worth being investigated in detail.

The antiphospholipid antibody (APLA) syndrome is defined by the presence of a lupus anticoagulant or markedly elevated plasma levels of anticardiolipin antibodies (ACAs), associated with venous or arterial thromboembolic events, fetal loss or thrombocytopenia. Familial clustering of raised APLA levels has been described, but the reports are heterogeneous with regard to the characterization of the APLA syndrome, coexisting autoimmune diseases and clinical complications. We describe two siblings with a lupus anticoagulant, elevated ACA-immunoglobulin G levels and systemic lupus erythematosus or related autoimmune disorders. Both patients experienced venous thrombotic complications at an early age. We provide a review of the literature, giving special consideration to the familial occurrence of lupus anticoagulants complicated by venous thrombosis, and emphasize the importance of family screening.