Stapled intestinal anastomoses are more cost effective than hand-sewn anastomoses in a diagnosis related group system.

PURPOSE: Creation of an optimal bowel anastomosis with low postoperative leakage rate is an immanent part of colorectal surgery contributing to recovery, length of hospital stay and overall hospital costs. We aimed to investigate costs of small and large bowel resection, length of hospital stay, anastomotic leakage rate and its risk factors depending on the anastomotic technique. METHODS: Retrospective analysis of 198 patients (67 stapled and 131 hand-sewn anastomoses) undergoing elective bowel resection with a single anastomosis without protective ileostomy either stapled or in double-rowed running suture technique between 1st October 2012 and 30th September 2018 at Charité University Hospital Berlin, Campus Benjamin Franklin. We analyzed costs of treatment, total length of hospital stay, rate of anastomotic leakage and possible risk factors for anastomotic leak. RESULTS: No significant difference between both anastomotic techniques could be detected for hospital stay (p = 0.754), 30-day-readmission rate (p = 0.827), or anastomotic leakage (p = 606). Neither comorbidities (p = 0.449), underlying disease (p = 0.132), experience of the surgical team (p = 0.828) nor scheduling of the operation (p = 0.531) were associated with anastomotic leakage. Stapled anastomoses took 22 min less operation time than sutured anastomoses (130 vs. 152 min. Median) (p = 0.001). Operations with stapled anastomoses saved 183 € in operation costs and 496 € in overall hospital costs. CONCLUSION: Stapled and hand-sewn bowel anastomoses can be performed equally safe without differences in postoperative outcome. No patient, procedure or surgeon related risk factors for anastomotic leakage could be detected. Bowel resections with stapled anastomoses take less time and save operation and overall hospital costs.

First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A-results of a retrospective analysis.

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.

The effectiveness of two silicone dressings for sacral and heel pressure ulcer prevention compared with no dressings in high-risk intensive care unit patients: a randomized controlled parallel-group trial.

BACKGROUND: There is a high incidence of pressure ulcers in high-risk settings such as intensive care. There is emerging evidence that the application of dressings to pressure ulcer predilection areas (sacrum and heels) improves prevention strategies. OBJECTIVES: To determine whether preventive dressings, applied to the sacrum and heels of high-risk patients in intensive care units, in addition to standard prevention, reduces the incidence of pressure ulcers. METHODS: Between June 2015 and July 2018, a randomized, controlled, two-arm, superiority pragmatic study was performed with a concealed 1 : 1 allocation to the intervention and control group. Patients assigned to the intervention group had dressings applied to the sacrum and heels. RESULTS: In total, 7575 patients were screened for eligibility and 475 patients were included and allocated to both groups. Finally, 212 patients in the intervention group and 210 in the control group were analysed. The mean age was 63·5 years and the majority of patients were male (65·4%). The cumulative pressure ulcer incidence category II and above was 2·8% in the intervention, and 10·5% in the control group (P = 0·001). Compared with the control group, the relative risk in the intervention group was 0·26 [95% confidence interval (CI) 0·11-0·62] and the absolute risk reduction was 0·08 (95% CI 0·03-0·13). CONCLUSIONS: The results indicate that the application of dressings, in addition to standard prevention, in high-risk intensive care unit patients is effective in preventing pressure ulcers at the heels and sacrum. What's already known about this topic? Pressure ulcers are severe soft tissue injuries and wounds, which occur worldwide in all healthcare settings. Despite preventive interventions, pressure ulcers still develop. There is emerging evidence that dressings help to prevent pressure ulcers. What does this study add? The incidence of pressure ulcers in intensive care units among high-risk patients remains high. The application of dressings to the sacrum and heels, in addition to standard preventive measures, reduces the relative and absolute risks for the development of pressure ulcers. The application of preventive dressings at the heels and sacrum seems to be feasible in intensive care settings.

Noninvasive monitoring of plant-based formulations on skin barrier properties in infants with dry skin and risk for atopic dermatitis.

BACKGROUND: Dry skin and the associated impaired epidermal barrier function are postulated to constitute a major element in the development of atopic dermatitis. OBJECTIVE: The aim of this study was to evaluate the effect of two plant-based formulations on the epidermal barrier function in a defined cohort of infants with a predisposition for atopic dermatitis. METHODS: Over a period of 16 weeks, 25 infants who were ages 3 to 12 months and had an atopic predisposition and dry skin received two emollients that contained pressed juice of the ice plant. The infants received both cream and lotion on the forearm, only cream on the face, and only lotion on the leg. Stratum corneum hydration (SCH), transepidermal water loss (TEWL), skin surface pH, and sebum were assessed on the infants' forehead, leg, and forearm. The Scoring Atopic Dermatitis (SCORAD) index was used for the clinical assessment. RESULTS: SCH significantly increased in all body regions that were assessed. The forearm and leg revealed stable levels of pH and TEWL, but a decline in pH (week 16) and TEWL (week 4) was noted on the forehead. At week 16, sebum levels were lower on the forehead compared with those at baseline. SCORAD scores improved significantly during the study. CONCLUSION: A daily application of both emollients was associated with increased SCH levels and a stable course of TEWL, pH, and sebum on the forehead except for the forehead when compared with the forearm and leg. Clinically, improved SCORAD scores were noted.

Influence of pelvic volume on surgical outcome after low anterior resection for rectal cancer.

BACKGROUND: Low anterior resection (LAR) for rectal cancer is a potentially challenging operation due to limited space in the pelvis. CT pelvimetry allows to quantify pelvic space, so that its relationship with outcome after LAR may be assessed. Studies investigating this, however, yielded conflicting results. We hypothesized that a small pelvis is associated with a higher rate of incomplete mesorectal excision, anastomotic leakages, and increased rate of urinary dysfunction in patients operated for rectal cancer. METHODS: In a single-center retrospective analysis, we studied 74 patients that underwent LAR for rectal cancer with primary anastomosis. Thin-layered multi-slice CT datasets were used for slice by slice depiction of the inner pelvic surface, and the inner pelvic volume was automatically compounded. The primary outcome was quality of total mesorectal excision (TME; Mercury grading); secondary outcomes were anastomotic leakage and urinary dysfunction with regard to pelvic dimensions. Univariate analyses and multiple logistic regression analyses were performed for the primary and the secondary outcomes. RESULTS: Shorter obstetric conjugate diameters were associated with a higher probability of a worse TME quality (110.8 ± 10.2 vs. 105.0 ± 8.6 mm; OR 0.85; 95% CI 0.73-0.99; p = 0.038). Short interspinous distance showed a trend towards an increased risk for deteriorated TME quality (OR 0.88; 95% CI 0.76-1.0; p = 0.06). Anastomotic leakage was associated with anemia (OR 2.77; 95% CI 1.0-7.7; p = 0.047). Association between pelvic diameters or pelvic volume and anastomotic leakage or urinary dysfunction was not observed. Perioperative blood transfusions were administered more often in patients with postoperative urinary dysfunction (OR 17.67; 95% CI 2.44-127.7; p = 0.004). CONCLUSION: Shorter obstetric conjugate diameter might be a risk factor for incompleteness of total mesorectal excision. Anastomotic leakage seems to be influenced more by clinical factors such as anemia rather than pelvic dimensions. Further studies have to prove the influence of pelvic diameter on local recurrence of rectal cancer after LAR.

Risk factors for reoperation after ileostomy reversal - Results from a prospective cohort study.

BACKGROUND: Ileostomy reversal is frequently performed in abdominal surgery. Postoperative complications after ileostomy reversal are encountered in around 20% of patients. Data regarding risk factors for reoperation after ileostomy closure are scarce. The purpose of this prospective trial was to determine risk factors for operative revision after ileostomy closure. MATERIALS AND METHODS: This is an additional post hoc analysis of a two center prospective trial. After enrollment, patient characteristics and intraoperative details were analyzed. Patients were followed up at one postoperative visit before discharge and at a three months postoperative visit by standardized questionnaire. All reoperations occurring in the three months period after surgery were analyzed, and immediate reoperations which were directly related to the ileostomy reversal were analyzed separately. RESULTS: 118 patients with elective ileostomy reversal were included in the trial. 12 out of 106 patients (11.3%) underwent any reoperation within three months after surgery (Clavien-Dindo grade IIIb). On multivariate analysis, anemia was associated with any reoperation p = 0.004; OR 6.93 (95% CI 1.37-30.07). Six out of 114 patients (5.3%) required an immediate reoperation (small bowel perforation, anastomotic leakage, postoperative ileus, deep wound infection) due to surgical complications directly related to the ileostomy reversal. Higher body mass index and anemia were associated with immediate reoperations (BMI: p = 0.038; OR 0.73 (95% CI 0.55-0.98); anemia: p = 0.001; OR 25.50 (95% CI 3.87-168.21). CONCLUSION: Surgical complications after ileostomy reversal occurred to a substantial extent. Rate of reoperations was associated with anemia and high body mass index. Optimizing patients in terms of preoperative hemoglobin and BMI may reduce surgical complications after ileostomy closure.

Necessity of subcutaneous suction drains in ileostomy reversal (DRASTAR)-a randomized, controlled bi-centered trial.

PURPOSE: Data regarding length of hospital stay of patients undergoing ileostomy reversal are very heterogeneous. There are many factors that may have an influence on the length of postoperative hospital stay, such as postoperative wound infections. One potential strategy to reduce their incidence and to decrease hospital stay is to insert subcutaneous suction drains. The purpose of this study was to examine the influence of the insertion of subcutaneous suction drains on hospital stay and postoperative wound infections in ileostomy reversal. Risk factors for postoperative wound infection were determined. METHODS: This is a randomized controlled two-center non-inferiority trial with two parallel groups. The total length of hospital stay as primary endpoint and the occurrence of a surgical site infection, the colonization of the abdominal wall with bacteria, and the occurrence of hematomas/seromas as secondary endpoints were monitored. RESULTS: One hundred eighteen patients with elective ileostomy reversal were included. Fifty-nine patients were randomly assigned to insertion of a subcutaneous suction drain, and 59 patients were randomly assigned to receive no drain. After 3 months of follow-up, 50 patients in the group with drain and 53 patients in the group without drain could be analyzed. Median total length of hospital stay was 8 days in the SD group and 9 days in the group without SD (p = 0.17). Fourteen percent of patients with SD and 17 % without SD developed SSI, p = 0.68. Multivariate analysis revealed anemia (p < 0.01), intraoperative bowel perforation (p = 0.02) and resident (p = 0.04) or fellow (p = 0.048) performing the operation as risk factors for SSI. CONCLUSIONS: This trial shows that the omission of subcutaneous suction drains is not inferior to the use of subcutaneous suction drains after ileostomy reversal in terms of length of hospital stay, surgical site infections, and hematomas/seromas.

Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

BACKGROUND: Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. OBJECTIVES: To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. METHODS: An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. RESULTS: In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. CONCLUSIONS: 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis.

Pancreatic progenitor-derived hepatocytes are viable and functional in a 3D high density bioreactor culture system.

The rat pancreatic progenitor cell line B-13 is of interest for research on drug metabolism and toxicity since the cells trans-differentiate into functional hepatocyte-like cells (B-13/H) when treated with glucocorticoids. In this study we investigated the trans-differentiation and liver-specific functions of B-13/H cells in a three-dimensional (3D) multi-compartment bioreactor, which has already been successfully used for primary liver cell culture. Undifferentiated B-13 cells were inoculated into the bioreactor system and exposed to dexamethasone to promote hepatic trans-differentiation (B-13/HT). In a second approach, pre-differentiated B-13 cells were cultured in bioreactors for 15 days to evaluate the maintenance of liver-typical functions (B-13/HP). During trans-differentiation of B-13 cells into hepatocyte-like cells in the 3D bioreactor system (approach B-13/HT), an increase in glucose metabolism and in liver-specific functions (urea and albumin synthesis; cytochrome P450 [CYP] enzyme activity) was observed, whereas amylase - characteristic for exocrine pancreas and undifferentiated B-13 cells - decreased over time. In bioreactors with pre-differentiated cells (approach B-13/HP), the above liver-specific functions were maintained over the whole culture period. Results were confirmed by gene expression and protein analysis showing increased expression of carbamoyl-phosphate synthase 1 (CPS-1), albumin, CYP2E1, CYP2C11 and CYP3A1 with simultaneous loss of amylase. Immunohistochemical studies showed the formation of 3D structures with expression of liver-specific markers, including albumin, cytokeratin (CK) 18, CCAAT/enhancer-binding protein beta (CEBP-ß), CYP2E1 and multidrug resistance protein 2 (MRP2). In conclusion, successful culture and trans-differentiation of B-13 cells in the 3D bioreactor was demonstrated. The requirement for only one hormone and simple culture conditions to generate liver-like cells makes this cell type useful for in vitro research using 3D high-density culture systems.

Impact of prior treatment on outcome of transformed follicular lymphoma and relapsed de novo diffuse large B cell lymphoma: a retrospective multicentre analysis.

Transformation of follicular lymphoma (FL) into aggressive disease and relapse of de novo diffuse large B cell lymphoma (DLBCL) are considered highly unfavourable events. However, most published data were acquired when rituximab was not routinely used. We retrospectively analysed 50 patients with transformed FL (tFL) in a multicenter study and compared them to 50 individuals with relapsed DLBCL (rDLBCL) who all obtained rituximab for the treatment of their disease. Our goal was to identify factors that predict a more favourable prognosis. After a median follow-up of 5.4 years from diagnosis, there was no significant difference in median overall survival (OS) from the date of transformation (tFL) or date of the first relapse (rDLBCL) (1.9 versus 3.9 years, P = .542). Of note, 5-year OS of patients with tFL was 46 %. Follicular lymphoma patients, treatment naïve prior to transformation, fared significantly better than pretreated patients (median not reached versus 1.4 years, P = .014). Regarding rDLBCL, female gender (13.9 versus 1.8 years, P = .019) and absence of rituximab prior to the first relapse (14.0 versus 1.8 years, P = .035) were favourable prognostic factors in a uni- and multivariate analysis. Only a proportion of patients received high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT), i.e. 38 and 52 % of patients with tFL and rDLBCL, respectively. Our data indicate that a favourable prognosis is conferred by treatment naivety in tFL and by rituximab naivety in rDLBCL. In contrast, we did not find a prognostic impact of HDT-ASCT in our series.

Postnatal maturation of skin barrier function in premature infants.

BACKGROUND: In preterm infants, skin barrier maturation entails regional variability. OBJECTIVES: To characterize postnatal skin barrier development in covered, uncovered and diapered regions in healthy premature infants over a longitudinal observation period. METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH and sebum were measured at postnatal ages of 1-7 days and 2-7 weeks on the forehead, abdomen, thigh and buttock of preterm infants (gestational age 30-37 weeks; n = 48) under monitored ambient conditions. A standard minimal skin care regimen was practised. RESULTS: TEWL increased significantly on the buttock (p = 0.007), while remaining stable on the forehead, abdomen and thigh. SCH and sebum remained stable in all studied body regions with increasing age. On the buttock, pH increased (p = 0.049), while other body regions exhibited a significant decrease (p ≤ 0.019). TEWL (p < 0.001) and SCH (p ≤ 0.002) revealed significantly higher values on the buttock, compared to other body regions. CONCLUSIONS: Stable TEWL, SCH and sebum values may indicate a lack of skin barrier maturation. Postnatal decrease in skin pH suggests an adaptation process with acid mantle formation. Differences in skin barrier development were observed between anatomical regions. SCH, TEWL and pH values demonstrated a distinct course in the diaper area, indicating an impaired skin barrier function in this region.

Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study.

BACKGROUND: In women with breast cancer, chemotherapy-induced alopecia is a highly feared but common side-effect of antineoplastic treatment. The onset, pattern and amount of hair loss differ depending on the therapy regimen and have not yet been quantified using standardized techniques. OBJECTIVES: To evaluate objectively and compare the effect of antineoplastic therapy with chemotherapy or tamoxifen on hair loss, quantifying trichological parameters. METHODS: Female patients with breast cancer were included (n = 34), who were receiving chemotherapy (group C, n = 17) or tamoxifen (group T, n = 17) after surgery. Trichological parameters were evaluated once before [week 0 (w0)], twice during (w3, w6) and twice after (w18, w28) the normal 16-week course of chemotherapy, or at corresponding time points during continuous tamoxifen intake. At each visit, anagen and telogen hairs and hair density were quantified by automated phototrichogram in two defined areas: frontal and occipital. RESULTS: Group T generally showed no changes in anagen and telogen hairs or hair density. In group C, anagen hairs and hair density generally followed the same course, decreasing until w6, remaining at a low level during w6-18 and increasing after cessation of chemotherapy, reaching values comparable with or higher than baseline at w28. Telogen hairs increased until w3 then decreased until w6, remaining stable afterwards. CONCLUSIONS: Diffuse hair loss begins shortly after initiation of chemotherapy, mainly as anagen effluvium, with a proportion of anagen to telogen conversion. Hair loss is most prominent after 6 weeks of chemotherapy. Within 3 months after cessation of chemotherapy, hair growth rate returns to baseline values. Tamoxifen did not affect hair growth parameters.

Transformation and additional malignancies are leading risk factors for an adverse course of disease in marginal zone lymphoma.

BACKGROUND: Marginal zone lymphoma (MZL) is a non-Hodgkin lymphoma that occurs as extra nodal, nodal, or splenic. While MZL is generally considered an indolent disease, a substantial percentage of patients follow an unfavorable course. The objective of this retrospective analysis was to identify predictors for a reduced overall survival (OS), or conversely an increased OS. PATIENTS AND METHODS: One hundred and ninety-seven MZL patients were analyzed. Apart from assessing previously published risk factors, concomitant morbidity at diagnosis, transformation into aggressive lymphoma, and occurrence of additional malignancies were evaluated. RESULTS: Next to the known risk factors, i.e. above 60 years of age and elevated serum lactate dehydrogenase (LDH), we demonstrate that transformation into aggressive lymphoma, as well as additional malignancies, are important independent risk factors for a shortened OS in a multivariate analysis, irrespective of the MZL localization. Impressively, in the group of patients lacking LDH elevation, transformation, and/or additional malignancies, only 1 of 63 patients died during follow-up compared with 37 of 87 patients in the high-risk group (HR = 22.8; 95% confidence interval 3.1-167.0; P = 0.002). CONCLUSIONS: Our analysis proposes novel risk factors and warrants for a continuous follow-up to detect the occurrence of transformation and additional malignancies early on.

Hair shaft abnormalities after chemotherapy and tamoxifen therapy in patients with breast cancer evaluated by optical coherence tomography.

BACKGROUND: Antineoplastic treatment for breast cancer is frequently associated with alopecia. Increasingly, changes in the texture and shape of regrowing hair after chemotherapy have been reported, without evaluation on a scientific basis. Optical coherence tomography (OCT) provides highly reproducible measurements of hair shaft parameters. OBJECTIVES: This study aims to evaluate hair shaft alterations using OCT in chemotherapy-induced alopecia and in patients taking tamoxifen. METHODS: The measurements of this prospective case series were performed on women aged 29-68 years, receiving either tamoxifen (n = 17) or chemotherapy (n = 17) prior to (T1) and after (T2) treatment. Each time, 20 hairs from two different sites of the scalp (frontal, occipital) were examined by OCT. The hair parameters were characterized by cross section (CS) and form factor (FF). The ratio of maximal to minimal hair diameters determined the FF. RESULTS: After chemotherapy, the CS of hairs was significantly lower compared with hairs taken at T1. The FF did not vary between T1 and T2 for the frontal area, but it did for the occipital area. In patients treated with tamoxifen, changes were observed neither in CS nor in FF. However, comparing both therapeutic groups, there were significant differences in CS and FF for T2, but not for T1. CONCLUSIONS: Reported changes in hair structure after chemotherapy may be due to reduction of hair shaft calibre and increase of FF in regrowing hair. The OCT technique is a promising method to gain more insight into chemotherapy-induced changes of hair morphology.

Reduction of wound infections in laparoscopic-assisted colorectal resections by plastic wound ring drapes (REDWIL)?--A randomized controlled trial.

INTRODUCTION: Surgical site infections (SSIs) are frequent complications in colorectal surgery and may lead to burst abdomen, incisional hernia, and increased perioperative costs. Plastic wound ring drapes (RD) were introduced some decades ago to protect the abdominal wound from bacteria and reduce SSIs. There have been no controlled trials examining the benefit of RD in laparoscopic colorectal surgery. The Reduction of wound infections in laparoscopic assisted colorectal resections by plastic wound ring drapes (REDWIL) trial was thus designed to assess their effectiveness in preventing SSIs after elective laparoscopic colorectal resections. MATERIALS/METHODS: REDWIL is a randomized controlled monocenter trial with two parallel groups (experimental group with RD and control group without RD). Patients undergoing elective laparoscopic colorectal resection were included. The primary endpoint was SSIs. Secondary outcomes were colonization of the abdominal wall with bacteria, reoperations/readmissions, early/late postoperative complications, and cost of hospital stay. The duration of follow-up was 6 months. RESULTS: Between January 2008 and October 2010, 109 patients were randomly assigned to the experimental or control group (with or without RD). Forty-six patients in the RD group and 47 patients in the control group completed follow-up. SSIs developed in ten patients with RD (21.7 %) and six patients without RD (12.8 %) (p = 0.28). An intraoperative swab taken from the abdominal wall was positive in 66.7 % of patients with RD and 57.5 % without RD (p = 0.46). The number of species cultured within one swab was significantly higher in those without RD (p = 0.03). The median total inpatient costs including emergency readmissions were 3,402 ± 4,038 in the RD group and 3,563 ± 1,735 in the control group (p = 0.869). CONCLUSIONS: RD do not reduce the rate of SSIs in laparoscopic colorectal surgery. The inpatient costs are similar with and without RD.

Prognostic relevance of circulating tumor cells in metastatic uveal melanoma.

OBJECTIVE: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance. METHODS: Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics. RESULTS: CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis. CONCLUSION: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.

BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia.

Over expression of BAALC (brain and acute leukemia, cytoplasmic) predicts an inferior outcome in acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients. To identify BAALC-associated genes that give insights into its functional role in chemotherapy resistance, gene expression signatures differentiating high from low BAALC expressers were generated from normal CD34(+) progenitors, T-acute lymphoblastic leukemia (T-ALL) and AML samples. The insulin-like growth factor binding protein 7 (IGFBP7) was one of the four genes (CD34, CD133, natriuretic peptide receptor C (NPR3), IGFBP7) coexpressed with BAALC and common to the three entities. In T-ALL, high IGFBP7-expression was associated with an immature phenotype of early T-ALL (P<0.001), expression of CD34 (P<0.001) and CD33 (P<0.001). Moreover, high IGFBP7-expression predicted primary therapy resistance (P=0.03) and inferior survival in T-ALL (P=0.03). In vitro studies revealed that IGFBP7 protein significantly inhibited the proliferation of leukemia cell lines (Jurkat cells: 42% reduction, P=0.002; KG1a cells: 65% reduction, P<0.001). In conclusion, IGFBP7 was identified as a BAALC coexpressed gene. Furthermore, high IGFBP7 was associated with stem cell features and treatment failure in T-ALL. In contrast to BAALC, which likely represents only a surrogate marker of treatment failure in acute leukemia, IGFBP7 regulates the proliferation of leukemic cells and might be involved in chemotherapy resistance.

Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion.

We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4(+) and CD8(+) T cell reconstitution, whereas ATG only delayed CD4(+) T cell reconstitution. Considering the reconstitution kinetics of CD4(+) and CD8(+) T cells, CMV-specific CD8(+) T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (< or =161 versus >161/microl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8(+) T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4(+)/CD8(+) T cell reconstitution kinetics in patients after allo-SCT.

Short-term outcomes from a prospective randomized trial comparing laparoscopic and open surgery for colorectal cancer.

BACKGROUND: Randomized trials in low-risk populations have failed to show any benefit for laparoscopic compared with open colorectal resection in terms of morbidity. Furthermore, it is not known whether laparoscopic colorectal resection would yield advantages if randomization were revealed during surgery after a diagnostic laparoscopy. METHODS: Patients with cancer of the colon or upper rectum were randomly assigned to laparoscopic or open resection. All patients underwent diagnostic laparoscopy to assess whether laparoscopic resection was feasible and the result of randomization was then revealed to the surgeon. Main endpoints were overall, general and surgical morbidity, and mortality. RESULTS: Some 679 patients underwent diagnostic laparoscopy which led to the exclusion of 207; 250 patients were allocated to laparoscopic and 222 to open resection. Conversion to laparotomy occurred in 28 patients (11.2 per cent). There were no differences in morbidity (overall 25.2 versus 23.9 per cent) or mortality (1.2 versus 0.9 per cent) between laparoscopic and open groups. Postoperative hospital stay was shorter after laparoscopic resection (median (range) 10 (1-123) versus 12 (4-109) days; P = 0.032). CONCLUSION: Laparoscopic resection of colorectal cancer is associated with increased operating time but does not decrease morbidity even in a moderate-risk population.