Crystalloid volume versus catecholamines for management of hemorrhagic shock during esophagectomy - assessment of microcirculatory tissue oxygenation of the gastric conduit in a porcine model using hyperspectral imaging - an experimental study.

INTRODUCTION: Oncologic esophagectomy is a two-cavity procedure with considerable morbidity and mortality. Complex anatomy and the proximity to major vessels constitute a risk for massive intraoperative hemorrhage. Currently, there is no conclusive consensus on the ideal anesthesiologic countermeasure in case of such immense blood loss. The objective of this work was to identify the most promising anesthesiologic management in case of intraoperative hemorrhage with regards to tissue perfusion of the gastric conduit during esophagectomy using hyperspectral imaging (HSI). MATERIAL AND METHODS: An established live porcine model (n=32) for esophagectomy was used with gastric conduit formation and simulation of a linear stapled side-to-side esophagogastrostomy. After a standardized procedure of controlled blood loss of about 1 L per pig, the four experimental groups (n=8 each) differed in anesthesiologic intervention i.e. (I) permissive hypotension, (II) catecholamine therapy using noradrenaline, (III) crystalloid volume supplementation and (IV) combined crystalloid volume supplementation with noradrenaline therapy. HSI tissue oxygenation (StO2) of the gastric conduit was evaluated and correlated with systemic perfusion parameters. Measurements were conducted before (T0) and after (T1) laparotomy, after hemorrhage (T2) and 60 minutes (T3) and 120 minutes (T4) after anesthesiologic intervention. RESULTS: StO2 values of the gastric conduit showed significantly different results between the four experimental groups with 63.3% (±7.6%) after permissive hypotension (I), 45.9% (±6.4%) after catecholamine therapy (II), 70.5% (±6.1%) after crystalloid volume supplementation (III) and 69.0% (±3.7%) after combined therapy (IV). StO2 values correlated strongly with systemic lactate values (r=-0.67; CI -0.77 to -0.54), which is an established prognostic factor. CONCLUSION: Crystalloid volume supplementation (III) yields the highest StO2 values and lowest systemic lactate values and therefore appears to be the superior primary treatment strategy after hemorrhage during esophagectomy with regards to microcirculatory tissue oxygenation of the gastric conduit.

Spectral characterization of intraoperative renal perfusion using hyperspectral imaging and artificial intelligence.

Accurate intraoperative assessment of organ perfusion is a pivotal determinant in preserving organ function e.g. during kidney surgery including partial nephrectomy or kidney transplantation. Hyperspectral imaging (HSI) has great potential to objectively describe and quantify this perfusion as opposed to conventional surrogate techniques such as ultrasound flowmeter, indocyanine green or the subjective eye of the surgeon. An established live porcine model under general anesthesia received median laparotomy and renal mobilization. Different scenarios that were measured using HSI were (1) complete, (2) gradual and (3) partial malperfusion. The differences in spectral reflectance as well as HSI oxygenation (StO2) between different perfusion states were compelling and as high as 56.9% with 70.3% (± 11.0%) for "physiological" vs. 13.4% (± 3.1%) for "venous congestion". A machine learning (ML) algorithm was able to distinguish between these perfusion states with a balanced prediction accuracy of 97.8%. Data from this porcine study including 1300 recordings across 57 individuals was compared to a human dataset of 104 recordings across 17 individuals suggesting clinical transferability. Therefore, HSI is a highly promising tool for intraoperative microvascular evaluation of perfusion states with great advantages over existing surrogate techniques. Clinical trials are required to prove patient benefit.

Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging and machine learning in an experimental model for minimally invasive esophagectomy.

INTRODUCTION: Esophagectomy is the mainstay of esophageal cancer treatment, but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome. Therefore, the objective of this work was to optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis. MATERIAL AND METHODS: A live porcine model (n = 58) for MIE was used with gastric conduit formation and simulation of linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and simulation of anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic simulation site was evaluated using HSI and was validated with histopathology. RESULTS: The tissue oxygenation (ΔStO2) after the anastomotic simulation remained constant only for the short stapler in caudal position (-0.4 ± 4.4%, n.s.) while it was impaired markedly in the other groups (short-cranial: -15.6 ± 11.5%, p = 0.0002; long-cranial: -20.4 ± 7.6%, p = 0.0126; long-caudal: -16.1 ± 9.4%, p < 0.0001). Tissue samples from avascular stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7 ± 9.7% of the surface area. CONCLUSION: Tissue oxygenation at the site of anastomotic simulation of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the simulated anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. The experimental model with HSI and ML allow for systematic optimization of gastric conduit perfusion and anastomotic technique while clinical translation will have to be proven.

Robotic colorectal resection in combination with a multimodal enhanced recovery program - results of the first 100 cases.

PURPOSE: In Germany, colorectal robot-assisted surgery (RAS) has found its way and is currently used as primary technique in colorectal resections at our clinic. We investigated whether RAS can be extensively combined with enhanced recovery after surgery (ERAS®) in a large prospective patient group. METHODS: Using the DaVinci Xi surgical robot, all colorectal RAS from 09/2020 to 01/2022 were incorporated into our ERAS® program. Perioperative data were prospectively recorded using a data documentation system. The extent of resection, duration of the operation, intraoperative blood loss, conversion rate, and postoperative short-term results were analyzed. We documented the postoperative duration of Intermediate Care Unit (IMC) stay and major and minor complications according to the Clavien-Dindo classification, anastomotic leak rate, reoperation rate, hospital-stay length, and ERAS® guideline adherence. RESULTS: One hundred patients (65 colon and 35 rectal resections) were included (median age: 69 years). The median durations of surgery were 167 min (colon resection) and 246 min (rectal resection). Postoperatively, four patients were IMC-treated (median stay: 1 day). In 92.5% of the colon and 88.6% of the rectum resections, no or minor complications occurred postoperatively. The anastomotic leak rate was 3.1% in colon and 5.7% in rectal resection. The reoperation rate was 7.7% (colon resection) and 11.4% (rectal resection). The hospital stay length was 5 days (colon resection) and 6.5 days (rectal resection). The ERAS® guideline adherence rate was 88% (colon resection) and 82.6% (rectal resection). CONCLUSION: Patient perioperative therapy per the multimodal ERAS® concept is possible without any problems in colorectal RAS, leading to low morbidity and short hospital stays.

[Thrombotic occlusion of the extracorporeal circulation during hepatic chemosaturation despite targeted anticoagulation : A case report]. / Thrombotischer Verschluss der extrakorporalen Zirkulation während hepatischer Chemosaturation trotz zielgerechter Antikoagulation : Ein Fallbericht.

Percutaneous hepatic chemosaturation is a treatment option for unresectable primary or secondary liver tumors. In this procedure the part of the inferior vena cava (VCI) that collects blood from the hepatic veins is isolated using a double balloon catheter. Like this, systemic distribution of the chemotherapeutic agent melphalan which is administered via the hepatic artery can be prevented. After passage through the liver and drainage from the retrohepatic VCI, the chemosaturated blood passes through two extracorporeal filters. Subsequently, the filtered blood is returned via the jugular vein. The procedure is often accompanied by severe hemodynamic instability, the cause of which is still not completely understood. In addition, coagulation management of extracorporeal circulation is often challenging. The authors report a case in which a thrombus formed in the returning leg of the extracorporeal circulation despite sufficient activated clotting time (ACT). Targeted problem search and resolution were necessary simultaneously to hemodynamic stabilization and interdisciplinary collaboration to successfully perform the intervention and provide the patient with safe treatment.

When to operate after SARS-CoV-2 infection? A review on the recent consensus recommendation of the DGC/BDC and the DGAI/BDA.

Since the eruption of the worldwide SARS-CoV-2 pandemic in late 2019/early 2020, multiple elective surgical interventions were postponed. Through pandemic measures, elective operation capacities were reduced in favour of intensive care treatment for critically ill SARS-CoV-2 patients. Although intermittent low-incidence infection rates allowed an increase in elective surgery, surgeons have to include long-term pulmonary and extrapulmonary complications of SARS-CoV-2 infections (especially "Long Covid") in their perioperative management considerations and risk assessment procedures. This review summarizes recent consensus statements and recommendations regarding the timepoint for surgical intervention after SARS-CoV-2 infection released by respective German societies and professional representatives including DGC/BDC (Germany Society of Surgery/Professional Association of German Surgeons e.V.) and DGAI/BDA (Germany Society of Anesthesiology and Intensive Care Medicine/Professional Association of German Anesthesiologists e.V.) within the scope of the recent literature. The current literature reveals that patients with pre- and perioperative SARS-CoV-2 infection have a dramatically deteriorated postoperative outcome. Thereby, perioperative mortality is mainly caused by pulmonary and thromboembolic complications. Notably, perioperative mortality decreases to normal values over time depending on the duration of SARS-CoV-2 infection.

[First 18 months as certified ERAS® center for colorectal cancer : Lessons learned and results of the first 261 patients]. / Achtzehn Monate als zertifiziertes ERAS®-Zentrum für kolorektale Resektionen : "Lessons learned" und Ergebnisse der ersten 261 Patienten.

BACKGROUND: Enhanced recovery after surgery (ERAS®) describes a multimodal, interdisciplinary and interprofessional treatment concept that optimizes the postoperative convalescence of the patient through the use of evidence-based measures. GOAL OF THE WORK: The aim of this article is to present the experiences of our center certified by the ERAS® Society for colorectal resections 18 months after successful implementation. MATERIAL AND METHODS: Since the beginning of the certification 261 patients have been treated in our clinic according to the specifications of the ERAS® concept. As a comparison group the last 50 patients prior to implementation were evaluated in terms of compliance with ERAS® requirements, length of hospital stay and readmission rate, the need for care in an intensive or intermediate care ward, the number of necessary reoperations and the complication rate. RESULTS: Compliance increased from 39.3% preERAS® to 81.1% after ERAS® implementation (p < 0.001). At the same time the length of stay of ERAS® patients was reduced from 7 days to 5 days (p = 0.001). While the rate of surgical complications was the same between the two groups (p = 0.236), nonsurgical complications occurred significantly less frequently in the ERAS® cohort (p = 0.018). DISCUSSION: There are well-known stumbling blocks in implementing and maintaining an ERAS® concept; however, it is worthwhile for the patient to circumnavigate this and establish ERAS® as the standard treatment path.

[Perioperative fluid management in major abdominal surgery]. / Perioperatives Flüssigkeitsmanagement bei großen viszeralchirurgischen Eingriffen.

Intravascular fluid administration belongs to the cornerstones of perioperative treatment with a substantial impact on surgical outcome especially with respect to major abdominal surgery. By avoidance of hypovolemia and hypervolemia, adequate perioperative fluid management significantly contributes to the reduction of insufficient tissue perfusion as a determinant of postoperative morbidity and mortality. The effective use of intravascular fluids requires detailed knowledge of the substances as well as measures to guide fluid therapy. Fluid management already starts preoperatively and should be continued in the postoperative setting (recovery room, peripheral ward) considering a patient-adjusted and surgery-adjusted hemodynamic monitoring. Communication between all team members participating in perioperative care is essential to optimize fluid management.

[Reconstructive surgery in penile cancer]. / Rekonstruktive Operationen beim Peniskarzinom.

BACKGROUND: Due to the rising incidence of penile cancer and increasing life expectancy in western nations, the current international guidelines recommend a less aggressive surgical approach with reduced safety margins and preferably with organ preservation. OBJECTIVES: The goal of this review is to review the current data on stage-dependent reconstructive surgical techniques and their oncological and functional results. MATERIALS AND METHODS: Five recently published reviews and several single studies and publications on the topic of organ-sparing surgical techniques and penile reconstruction were evaluated to draw conclusions for surgery in penile cancer. RESULTS: Due to the rare incidence of penile cancer and the absence of comparative, prospective studies in the literature, evidence levels of the actual statements and conclusions are low. CONCLUSIONS: Organ-sparing techniques in penile cancer lead to slightly elevated local recurrence rates compared with traditional partial or total penile amputation. Thus, sufficient patient compliance is mandatory and an intensified follow-up for more than the usual 5 years postoperatively is required. On the other hand, these techniques enable the surgeon to offer improved functional and esthetic outcomes to the patient, maintaining erectile capacity and sensitivity. After extended partial or total penile amputation, penile reconstruction using free radial forearm flaps with later prosthetic implantation may be offered to younger and sexually active patients in cooperation with experienced plastic surgeons, even if the previously published case numbers do not permit standardization of these procedures.

Intraoperative imaging of the distal radioulnar joint using a modified skyline view.

PURPOSE: Nonanatomic reduction of the sigmoid notch in distal radius fractures may lead to limited motion, instability, or pain with pronation and supination. Standard radiological projections only poorly capture the sigmoid notch contours in the axial plane. The purpose of this study was to find an intraoperatively feasible radiological projection that will facilitate an axial view of the distal radioulnar joint. METHODS: We modified a previously described radiographic projection termed the skyline view for evaluating the distal radius axially. We created intra-articular steps at the sigmoid notch in solid foam forearm models to identify the best of 12 projections using an image intensifier. Four observers scored each projection based on the clarity of the sigmoid notch contour and indicated the presence and location of an intra-articular stepoff. RESULTS: The sigmoid notch was best visualized in the modified skyline view with the wrist in extension and 10° to 15° of dorsal forearm angulation relative to the x-ray path. All observers correctly recognized the presence and location of intra-articular steps at the sigmoid notch with this view. The same forearm angulation with the wrist in flexion did not reach equally good visibility of the sigmoid notch. Arm position (wrist flexion, forearm rotation, or forearm angulation) and intra-articular stepoff (none, palmar, or dorsal) were dependent determinates. Elimination of the variable forearm rotation had minimal effect, indicating that forearm rotation is not important for visualization of the sigmoid notch. CONCLUSIONS: The modified skyline view for visualization of the distal radioulnar joint in an axial plane allows good visibility of the sigmoid notch and reliable identification of stepoffs. Further cadaver and in vivo studies are required to verify the validity of this method.

Primary anastomosis vs Hartmann's procedure in patients undergoing emergency left colectomy for perforated diverticulitis.

OBJECTIVE: Comparison of primary anastomosis (PA) and Hartmann's procedure (HP) in perforated diverticulitis is biased as the patient groups are different in age, comorbidity and severity of disease. Still, PA has been advocated as the procedure of choice. The aim of this study was to compare the two surgical procedures after eliminating this selection bias using a propensity score model. METHOD: Sixty-five HP and 46 PA patients who underwent emergency laparotomy for perforated diverticulitis were analysed. Multivariate logistic regression using the Mannheim peritonitis index, Colorectal Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity, Charlson comorbidity index and Hinchey score was performed to determine the propensity score. RESULTS: Patients with HP had significantly higher scores, median age and were more often on immunosuppressive medication. Unadjusted logistic regression for outcome showed a significant risk of HP vs PA for nonsurgical morbidity (odds ratio 3.25, 95% CI: 1.26-8.43; P = 0.015), but not for mortality and surgical morbidity. After adjusting for the propensity score, outcome was not significantly different. Patients with PA had a clinical leak rate of 28% and none of the patients with leakage had a protective ileostomy. Patients with PA and leak had higher Charlson scores whereas all other scores were similar to nonleak patients. CONCLUSION: The theory that PA is generally superior to HP cannot be supported. HP remains a safe technique for emergency colectomy in perforated diverticulitis, especially in elderly patients with multiple comorbidities. If PA is performed, a protective ileostomy must be considered.

[Complex fracture of the proximal humerus in the elderly. Locking plate osteosynthesis vs hemiarthroplasty]. / Komplexe proximale Humerusfraktur beim alten Menschen. Winkelstabile Plattenosteosynthese vs. Hemiarthroplastik.

BACKGROUND: The purpose of the present study was a direct comparison of fixed-angle plate fixation (FAPF) and shoulder hemiarthroplasty (SHA) for complex fractures of the proximal humerus in the elderly. PATIENTS AND METHODS: A single-institution case series of 52 consecutive geriatric patients (age > or =70 years) treated with FAPF for three- and four-part fractures of the proximal humerus between 2003 and 2005 was analysed 1 year after surgery. The analysis included Constant Score (CS), Oxford Shoulder Score (OSS), and radiological evaluation. Outcome was compared with a similar historic group of patients (n=59) who received SHA in an earlier period (1995--1997). RESULTS: The patient groups showed no differences in age, gender, or fracture type. Median CS was significantly better for FAPF (71 vs 41). Evaluation of pain demonstrated no differences between the two treatment modalities in the OSS. Revision surgery was performed more often in the FAPF group (25% vs 2%). CONCLUSION: Compared to SHA, functional outcome was superior with FAPF. However, this was associated with a higher rate of revision surgery. Most patients were still able to live independently in their original environment, regardless of the type of surgery.

Decalcification of the mitral annulus: surgical experience in 81 patients.

OBJECTIVE: Mitral valve surgery in the presence of extensive calcification of the mitral annulus is a technical challenge and increases perioperative risk. This study reviews our experience with decalcification of the mitral annulus in patients undergoing mitral valve reconstruction or replacement. METHODS: From 1995 to 2003, 81 patients (mean age 64 +/- 13 years, 30 male, 51 female) with extensive calcification of the mitral annulus underwent mitral valve repair (n = 42) or replacement (biological n = 20, mechanical n = 19). The mean follow-up was 24 months. Patients presented with a mean EuroSCORE of 7. Concomitant surgical procedures were performed in 62 %. Patient outcomes were retrospectively assessed. RESULTS: Perioperative survival was 97.5 % (n = 79) and hospital survival was 91.3 % (n = 74). Two-year survival was 88.9 %. Eight patients needed reexploration due to bleeding and five patients required prolonged mechanical ventilation. No perioperative stroke was observed. Freedom from reoperation was 90.2 % (n = 73). Early reoperation for recurrent incompetence was necessary in 3 patients and late reoperation in 5 patients. CONCLUSIONS: Despite the elevated perioperative risk and the high risk of reoperation with this procedure, decalcification of the annulus and repair/replacement of the mitral valve could be performed with good clinical results.

Continent catheterizable channels and the timing of their complications.

PURPOSE: We reviewed our experience with continent catheterizable channels with interest in the timing of conduit related complications. MATERIALS AND METHODS: A retrospective review was performed of the outcome of continent catheterizable channels in all patients between 1998 and 2003 who had undergone construction of an antegrade continence enema and/or a Mitrofanoff procedure using appendix, small bowel or continent cutaneous vesicostomy. We performed a total of 117 such stomas in 37 male and 41 female patients 2.5 to 20 years old (mean age 8.9). For the antegrade continence enema we used appendix in 92% of cases, an ileal Yang-Monti tube in 6% and a cecal tube in 2%. For the continent catheterizable channel we used appendix in 43% of cases, a Yang-Monti tube in 38% and continent cutaneous vesicostomy in 19%. RESULTS: Continence was achieved in 98% of patients. Followup was 6 to 71 months (mean 28.4). There were 27 channel related complications (23%). Stomal stenosis occurred in 7 antegrade continence enema procedures (14%) within 1 to 10 months (mean 6.2) and in 9 continent bladder channels (13%), including 5 continent cutaneous vesicostomies, within 1 to 24 months (mean 9.4) after surgery. False passages occurred in 5 antegrade continence enema procedures (10%) within 1 to 13 months (mean 3.6) and in 4 continent catheterizable channels (6%) within 1 to 13 months (mean 6.5) after surgery. Of patients with stomal stenosis 50% were treated with surgical revision, while the remainder was successfully treated with dilation. Most false passages were managed by catheter drainage alone. Reasons for revision were contained perforation, colovesical fistula and inability to catheterize. Patient noncompliance appeared to have a role in stomal stenosis. CONCLUSIONS: Continent catheterizable stomas help patients achieve bowel and bladder continence. Stomal incontinence after reconstruction is rare. In our experience most stoma related complications occurred in the first year after reconstruction. Experience with more patients and longer followup will help determine whether such problems continue to accumulate with time or whether continent stomas function well with time, particularly after the initial period of healing.

Behavior of gaseous microemboli in extracorporeal circuits: air versus CO2.

BACKGROUND: Open heart surgery is associated with serious risk of cerebral and peripheral organ dysfunction, attributed in part to air microbubbles generated in or not eliminated from the extracorporeal circuit (ECC). Venous air leakage leads to increased arterial bubble load. CO2 replacing air in cardiac chambers show faster resorption times, reducing possible cerebral or peripheral organ damage after heart valve interventions. In two models of ECC the effect of air entering closed circuits was demonstrated and compared to the effect of CO2 entry. METHODS: Fragmentation and dissolution of gas (0.5 mL) was evaluated in an in vitro model of ECC, using ultrasonic bubble detection. Air leakage (10 mL) in the venous line of the ECC was simulated and compared to the effect of the same quantity of CO2 entering the circuit. Both models used whole blood priming and physiological conditions, verified with blood gas analyses. RESULTS: Fragmentation and dissolution of gas bubbles injected into a closed ECC could be demonstrated, complete resorption of CO2 bubbles was observed earlier than complete resorption of room air (5.0+/-0.6 vs. 14.4+/-5.9 min, p=0.0009). CO2 entering the venous line lead to 40% less arterial bubble load as compared to the same amount of room air entering the circuit (2099+/-991 vs. 3555+/-632, p=0.005). CONCLUSIONS: Current ECC systems fail to eliminate gas entering the circuit, leading rather to microbubble dispersion. CO2 is much faster resorbed within the circuit than room air. In open heart surgery as valvular operations, CO2 insufflation into the operative field is protective, as we have demonstrated in our models.

Vaccination with leukemia cells expressing cell-surface-associated GM-CSF blocks leukemia induction in immunocompetent mice.

The fundamental basis for immunotherapy of leukemia is that leukemic cells express specific antigens that are not expressed by normal hematopoietic cells. However, the host immune system appears to be tolerant to leukemia cells. To overcome this tolerance, we vaccinated immunocompetent mice with murine leukemia cells (WEHI-3B and BCR-ABL+ 32D cells) transduced with a specifically constructed transmembrane form of granulocyte-macrophage colony-stimulating factor (tmGM-CSF). The transduced cells expressed tmGM-CSF on the cell-surface. To determine whether tmGM-CSF-expressing WEHI-3B leukemia cells would prevent leukemia formation as a vaccine, immunocompetent mice (BALB/c and C3H/HEJ) were immunized with lethally irradiated murine leukemia cells expressing cell-surface tmGM-CSF before challenging mice with murine leukemia cells. Two immunocompetent mouse models were investigated, either WEHI-3B cells in BALB/c mice or BCR-ABL+ 32D cells in C3H/HEJ mouse. The results showed that 100% of WEHI-3B/tmGM-CSF-vaccinated BALB/c mice and about 65% of 32D+ BCR-ABL/tmGM-CSF-vaccinated C3H/HEJ mice were protected from leukemia after leukemia cell challenge, whereas all non-vaccinated mice succumbed to leukemia. Spleen and marrow cell suspensions from vaccinated mice challenged with WEHI-3B cells lacked detectable GFP+ WEHI-3B cells at 82 days post-challenge. A significant delay of death was observed in C3H/HEJ mice challenged with the very aggressive DA-1 cell line expressing BCR-ABL. Vaccination of mice with WEHI-3B/CD40L cells protected 80% of the mice from the WEHI-3B challenge. Notably, 60% of the WEHI-3B/BALB/c mice were also protected from leukemia when WEHI-3B/tmGM-CSF vaccination was carried out after the leukemia challenge. In order to determine whether cellular immunity is involved in this vaccine-mediated protection, either CD4+ or CD8+ T cells were depleted from mice after the WEHI-3B/tmGM-CSF vaccination. The results indicate that CD8+ T-cells mediated the protective immune response provided by the irradiated tmGM-CSF-expressing WEHI-3B cells. In addition, vaccination of nude mice did not provide protection from WEHI-3B leukemia induction. Importantly, 80% of non-vaccinated mice were also protected from a WEHI-3B cell challenge after receiving spleen cells from vaccinated mice 1 day before challenge with leukemia cells. These results indicate that overexpression of tmGM-CSF on the leukemia cell-surface can enhance the recognition of leukemic cells by CD8+ T cells, and can either prevent or significantly delay leukemia induction. These findings suggest that injection of irradiated leukemia cells expressing cell-surface-bound GM-CSF has the potential as an immunological approach to treat leukemia.

Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein.

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15-1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16-0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13-0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35-5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann-Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152-1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94-445) for patients with fever of unknown origin, 177 pg/ml (IR, 142-208) for patients with non-microbial fever and 942 pg/ml (IR, 181-2,807) for patients with bacteremia. Using the Mann-Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.

Phase I dose-finding study of biweekly irinotecan in combination with fixed doses of 5-fluorouracil/leucovorin, gemcitabine and cisplatin (G-FLIP) in patients with advanced pancreatic cancer or other solid tumors.

This phase I trial was initiated based on encouraging clinical data with 5-fluorouracil (5-FU)/leucovorin (LV), gemcitabine and cisplatin (G-FLIP) in the therapy of solid tumors. In this trial, G-FLIP has been modified to facilitate outpatient administration and to optimize sequence-dependent synergistic activity. Treatment consisted of biweekly (once every 14 days) cycles of sequential gemcitabine 500 mg/m, irinotecan per dose escalation schedule, bolus 5-FU 400 mg/m and LV 300 mg on day 1 followed by a 24-h 5-FU infusion 1500 mg/m, followed by cisplatin 35 mg/m on day 2. The irinotecan starting dose was 80 mg/m and escalated by 20 mg/m in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Twenty-three patients were enrolled (13 men/10 women) with the following cancers: 11 pancreatic, five gallbladder, three squamous cell carcinoma of the head and neck, one hepatocellular carcinoma, one melanoma, one gastric, and one breast cancer. Median patient age was 63 years (range 44-78) and median Karnofsky performance status (KPS) was 80. Patients received a median of 8 cycles (range 1-16) over five irinotecan dose levels (80, 100, 120, 140 and 160 mg/m). Dose-limiting toxicity consisting of grade 3 nausea/vomiting despite aggressive anti-emetic therapy occurred in one patient at dose level 1 and three patients at dose level 3. Grade 3-4 hematological toxicities per patient consisted of thrombocytopenia (3%), anemia (6%), thrombosis (23%), neutropenia (16%) and neutropenic fever (10%). Of 18 patients evaluable for response, one complete response (pancreatic) and eight partial responses (three gallbladder, two pancreatic, two head and neck, and one breast) were attained. Seven patients had disease stabilization (five pancreatic, one hepatocellular and one gastric) for a median of 16 weeks (range 10-22). Median time to disease progression among all 23 patients enrolled to the phase I portion of the trial was 20.5 weeks (range 4-37). We conclude that G-FLIP is a novel outpatient chemotherapy regimen with acceptable toxicity at the maximum tolerated irinotecan dose of 120 mg/m. The phase II trial of G-FLIP using an irinotecan dose of 120 mg/m for patients with metastatic pancreatic cancer is ongoing.

Elimination of microbubbles from the extracorporeal circuit: dynamic bubble trap versus arterial filter.

BACKGROUND: Open heart surgery is associated with important risk of cerebral and peripheral organ dysfunction, attributed in part to microbubbles generated in or not eliminated from the ECC. For elimination of microbubbles, a dynamic bubble trap (DBT) was developed for the arterial line of ECCs. METHODS: Bubble eliminating properties of an arterial filter were evaluated in four CABG patients and compared to the performance of the DBT in four patients. One patient received both devices. RESULTS: Elimination of bubbles between 40-120 microm was significantly higher with the DBT (88% vs. 57% with arterial filter, p=0.034). Reduction of bubbles below 40 microm was equivalent in both groups. The combination of both devices was most effective (94% for bubbles >40 microm). CONCLUSION: Arterial filter and DBT are equally effective in elimination of smaller gas bubbles. However, bigger bubbles possibly causing cerebral and peripheral organ damage are eliminated to a greater degree by the DBT.