Smartphone Application to Reinforce Education Increases High-Quality Preparation for Colorectal Cancer Screening Colonoscopies in a Randomized Trial.

BACKGROUND & AIMS: Sufficient bowel preparation is crucial for successful screening and surveillance colonoscopy. However, rates of inadequate preparation are still high. We investigated the effects of reinforced patient education using a smartphone application software (APP) for colonoscopy preparation in participants in a CRC screening program. METHODS: We performed a prospective, endoscopist-blinded study of 500 patients undergoing split-dose bowel preparation for CRC screening or surveillance colonoscopies at multiple centers in Germany, from November 2017 through January 2019. Participants (n = 500) were given oral and written instructions during their initial appointment and then randomly assigned (1:1) to groups that received reinforced education starting 3 days before the colonoscopy (APP group) or no further education (controls). The primary outcome was quality of bowel preparation according to the Boston bowel preparation scale. Secondary outcomes included polyp and adenoma detection rates, compliance with low-fiber diet, split-dose laxative intake, perceived discomfort from the preparation procedure. RESULTS: The mean Boston bowel preparation scale score was significantly higher in the APP-group (7.6 ± 0.1) than in the control group (6.7 ± 0.1) (P < .0001). The percentage of patients with insufficient bowel preparation was significantly lower in the APP group (8%) than in the control group (17%) (P = .0023). The adenoma detection rate was significantly higher in the APP group (35% vs 27% in controls) (P = .0324). Use of the APP was accompanied by a lower level of non-compliance with correct laxative intake (P =.0080) and diet instructions (P = .0089). The APP group reported a lower level of discomfort during preparation (P < .0001). CONCLUSIONS: In a randomized trial, reinforcing patient education with a smartphone application optimized bowel preparation in the 3 days before colonoscopy, increasing bowel cleanliness, adenoma detection, and compliance in patients undergoing CRC screening or surveillance. ClinicalTrials.gov no: NCT03290157.

Improving the quality and acceptance of colonoscopy preparation by reinforced patient education with short message service: results from a randomized, multicenter study (PERICLES-II).

BACKGROUND AND AIMS: Sufficient bowel preparation is crucial for successful screening and surveillance colonoscopy. However, the rates of inadequate preparation are still high. We investigated the effects of reinforcing patient education and guidance by using the short message service (SMS). METHODS: In this prospective, endoscopist-blinded, multicenter study, standard instructions pertaining to split-dose preparation were provided in a verbal and written format to all patients during the initial appointment. Patients were randomly assigned (1:1) to a group that received reinforced education starting 4 days before the colonoscopy (SMS group) or to the control group which did not receive further education. The primary outcome was the percentage of insufficient preparation results (Boston Bowel Preparation Scale [BBPS] score <6). The secondary outcomes included quality of bowel preparation according to the BBPS, polyp and adenoma detection rates, and patients' perceived discomfort in the preparation procedure. RESULTS: The percentage of patients with insufficient bowel preparation was significantly lower in the SMS group (9%) than in the control group (19%) (P = .0013). The mean BBPS score was significantly higher in the SMS group (7.4 ± 0.1) than in the control group (6.5 ± 0.1) (P < .0001). Each colon segment had significantly higher BBPS scores in the SMS group. The adenoma detection rate and number of detected adenomas in the right segment of the colon were higher in the SMS group. SMS messages were accompanied by a lower level of discomfort during preparation (numeric rating scale) (5.2 SMS vs 5.8 controls) (P = .0042). CONCLUSIONS: Reinforced patient education by using SMS messages during the 4 days before colonoscopy increased bowel cleanliness, adenoma detection in the right segment of the colon, and reduced discomfort. (Clinical trial registration number: NCT02272036.).

Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma.

BACKGROUND: Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects. METHODS: This phase I study evaluated dose limiting toxicity (DLT) of imatinib combinated with chemotherapy according to a 3-patient cohort dose-escalating design. Thirty-five patients received cisplatin (60 mg/m(2) d1 q 3w)/ capecitabine (1250 mg/m(2) bid d1-14 q 21) or cisplatin (50 mg/m(2) d1 q 2w)/ 5-fluoruracil (2 g/m(2) d1, q 1w). Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps. RESULTS: At imatinib dose level 1 (300mg) one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients. CONCLUSIONS: Combination of imatinib and chemotherapy is well tolerated. Response rates were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib. TRIAL REGISTRATION: European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510.

Truncated IRAG variants modulate cGMP-mediated inhibition of human colonic smooth muscle cell contraction.

Nitric oxide (NO) induces relaxation of colonic smooth muscle cells predominantly by cGMP/cGMP-dependent protein kinase I (cGKI)-induced phosphorylation of the inositol 1,4,5-trisphosphate receptor (IP(3)R)-associated cGMP kinase substrate (IRAG), to block store-dependent calcium signaling. In the present study we analyzed the structure and function of the human IRAG/MRVI1 gene. We describe four unique first exon variants transcribed from individual promoters in diverse human tissues. Tissue-specific alternative splicing with exon skipping and alternative splice donor and acceptor site usage further increases diversity of IRAG mRNA variants that encode for NH(2)- and COOH-terminally truncated proteins. At the functional level, COOH-terminally truncated IRAG variants lacking both the cGKI phosphorylation and the IP(3)RI interaction site counteract cGMP-mediated inhibition of calcium transients and relaxation of human colonic smooth muscle cells. Since COOH-terminally truncated IRAG mRNA isoforms are widely expressed in human tissues, our results point to an important role of IRAG variants as negative modulators of nitric oxide/cGKI-dependent signaling. The complexity of alternative splicing of the IRAG gene impressively demonstrates how posttranscriptional processing generates functionally distinct proteins from a single gene.

Pancreatic cancer and depression: myth and truth.

BACKGROUND: Various studies reported remarkable high incidence rates of depression in cancer patients compared with the general population. Pancreatic cancer is still one of the malignancies with the worst prognosis and therefore it seems quite logical that it is one of the malignancies with the highest incidence rates of major depression.However, what about the scientific background of this relationship? Is depression in patients suffering from pancreatic cancer just due to the confrontation with a life threatening disease and its somatic symptoms or is depression in this particular group of patients a feature of pancreatic cancer per se? DISCUSSION: Several studies provide evidence of depression to precede the diagnosis of pancreatic cancer and some studies even blame it for its detrimental influence on survival. The immense impact of emotional distress on quality of life of cancer patients enhances the need for its early diagnosis and adequate treatment. Knowledge about underlying pathophysiological mechanisms is required to provide the optimal therapy. SUMMARY: A review of the literature on this issue should reveal which are the facts and what is myth.

Interleukin 1 beta gene promoter SNPs are associated with risk of pancreatic cancer.

Epidemiological and experimental data demonstrate, that inflammation contributes significantly to pancreatic carcinogenesis. IL1beta, a pleiotropic cytokine produced by inflammatory cells and tumor cells, promotes cancer progression. Single nucleotide polymorphisms (SNPs) of the IL1beta promoter were found to be associated with an increased risk for certain cancers. In this case-control study we determined IL1beta promoter SNPs in 73 patients with pancreatic cancer and 235 controls. We found that the IL1beta -511CT/-31TC genotype was significantly associated with an increased risk for pancreatic cancer (OR 1.42, p=0.0456). Among pancreatic cancer cases, patients with the -511CT/-31TC genotype had less frequently resectable disease than patients with other IL1beta -511/-31 genotypes (p=0.0323). Furthermore, the IL1beta -511CT/-31TC genotype was more frequent observed in UICC stage IV (p=0.039) and undifferentiated tumors (G3) (p=0.019). In addition, we found that the proinflammatory IL1beta -511CT/-31TC alleles define an IL1beta secretory phenotype in pancreatic cancer cell lines in vitro. These findings provide a first evidence for an association of the IL1beta gene promoter SNPs with risk for pancreatic cancer.

Weight-dependent differential contribution of insulin secretion and clearance to hyperinsulinemia of obesity.

Obesity is associated with insulin resistance and the resulting hyperinsulinemia has been attributed to an increase of insulin secretion and a reduction of insulin clearance. The present study was intended to further characterize the relative contribution of secretion and clearance especially in the postprandial state. In relation to WHO body weight classes 291 subjects were divided in 5 subgroups Basal insulin concentrations rose stepwise and significantly with increasing BMI. This was paralleled by C-peptide concentrations and insulin secretion, while the reduction of insulin clearance was less stringent in relation to BMI. Basal glucose was unchanged in the BMI25 group and 8% higher in the obese groups (BMI 30, 35, 40) compared to normal weight (NW). Although postprandial insulin concentrations were significantly higher in the overweight and obese groups compared to NW the correlation was not as tight as in the basal state. Furthermore, the present data demonstrate for the first time that insulin secretion only increased in the overweight group without further augmentation in the obese groups. Further hyperinsulinemia of the latter was due to weight-dependent reduction of insulin clearance. The postprandial glucose response was 38-82% higher with increasing weight compared to NW. In summary basal hyperinsulinemia is mainly due to weight related increase of insulin secretion with moderate contribution of reduced insulin clearance. Postprandially, hyperinsulinemia of overweight is predominantly due to secretion while further postprandial hyperinsulinemia of obese subjects is mainly due to reduced clearance. Thus, postprandial insulin secretion cannot respond adequately to the challenge of weight-dependent insulin resistance already in non-diabetic obese subjects.

Assessment of the patency of microvascular anastomoses using microscope-integrated near-infrared angiography: a preliminary study.

BACKGROUND: : Technical problems at the site of the anastomosis compromise an underappreciated proportion of microsurgical free tissue transfers. Intraoperative identification of technical errors may be able to prevent reexploration surgery and early flap failure. We report the first human study on a new microscope-integrated fluorescence angiography technique, which allows for intraoperative imaging of the anastomotic site. METHODS: : Fifty consecutive patients undergoing reconstructive microsurgical procedures were enrolled in the study. Intraoperative near infrared indocyanine green videoangiography (ICGA) was performed on all microsurgical anastomoses, after they had been assessed by the operating surgeon by conventional clinical patency tests. Anastomoses deemed to be occluded by the ICG-angiography were intraoperatively revised, and the result of revision was compared with angiographic findings. RESULTS: : In 11/50 (22%) of patients, where the surgeon had classified the anastomoses as patent, microangiography identified a total luminal occlusion (six) and/or significant alterations in blood flow (five), potentially predisposing toward postoperative flap failure. Intraoperative revision confirmed angiographic findings in 100% of cases, and was always associated with flap survival. The decision not to revise despite anastomotic occlusion by the intraoperative angiogram was always followed by flap loss or early reexploration. A delayed return of venous blood from the flap predisposed toward postoperative flap failure. CONCLUSIONS: : Hand-sewn anastomoses are subject to technical errors, and conventional patency tests have a low sensitivity for revealing anastomotic failure. Microscope integrated microangiography is an excellent method for identifying significant anastomotic problems, which would have otherwise gone unnoticed. The potential impact on early flap failure and reexploration surgery is considerable. (c) 2009 Wiley-Liss, Inc. Microsurgery 2009.

Comparison of Two Measurement Devices for Pulse Wave Velocity in Children: Which Tool Is Useful to Detect Vascular Alterations Caused by Overweight?

Vascular alterations may lead to manifest cardiovascular disease in future life. There is a tremendous time delay between the onset and obvious clinical appearance of vascular alterations. Pulse wave velocity (PWV) is one subclinical parameter to detect vascular alterations at a very early stage. Different techniques exist to measure PWV non-invasively as a vascular parameter-all with their own technique-inherent advantages, challenges, and pitfalls. The aim of this study was to compare two techniques to measure PWV, to assess their agreement, and interchangeability. In 780 (♀ = 49.4%) healthy children and adolescents (mean age: 11.61 ± 2.11 years), PWV was obtained with two different techniques. Ultrasound-measured local PWV (PWVß) at the carotid artery was graphically compared by a Bland-Altman plot with aortic PWV (aPWV), measured oscillometrically on the brachial artery. Reproducibility was assessed with the concordance correlation coefficient by Lin (ρc). Furthermore, participants were categorized by BMI as normal weight (N) or overweight/obese (O) to identify differences in PWVß and aPWV caused by an increased BMI. Mean PWVß was lower (4.01 ± 0.44 m/s) than mean aPWV (4.67 ± 0.34 m/s). The two methods differ by mean Δ0.66 ± 0.47 m/s (95% CI: 0.62 to 0.69 m/s; p < 0.001). Bland-Altman analysis indicated the 95% limits of agreement (-0.26 to 1.57) without any evidence of systemic difference. Lin's ρc represented a weak concordance between PWVß and aPWV (ρc = 0.122; 95% CI: 0.093-0.150). There was no difference in PWVß between N and O, whereas aPWV was higher in O: 4.81 ± 0.42 m/s than in N: 4.65 ± 0.32 m/s (p < 0.001). The difference, Δ0.16 m/s, 95% CI [-0.25; -0.08], was significant, t (121) = -3.76, p < 0.001, with a medium-sized effect. PWVß (ultrasound) and aPWV (oscillometry) show a level of disagreement that includes clinically important discrepancies. A discrimination between normal and altered vascular function was possible with aPWV but not with PWVß.

Assessment of splanchnic perfusion by gastric tonometry in patients with acute hypovolemic burn shock.

OBJECTIVE: To compare the changes in pHi and intramucosal-arterial CO(2)-gap with invasive haemodynamic and global perfusion measurements during hypovolemic burn shock and to evaluate the sensitivity of these parameters as an early predictor of mortality in patients with extensive burns. DESIGN: Prospective, controlled, clinical study. SETTING: An eight-bed intensive burn care unit in a university-affiliated hospital. PATIENTS: Fifty severely burned patients with TBSA burned >25% BSA. METHODS: During the first 48h after burn, gastric intramucosal CO(2) was measured every 8h using automated air tonometry. pHi and intramucosal-arterial CO(2)-gap were calculated. Simultaneously invasive haemodynamic data were registered by the transpulmonary thermodilution technique, using the mean of triplicate injections. The intramucosal-arterial CO(2)-gradient and pHi were compared with haemodynamic and global perfusion data by regression analysis. Mean pHi and CO(2)-gap values at 8 and 24h after injury were compared between survivors and non-survivors to evaluate the prognostic significance of this parameter. RESULTS: Regression analyses revealed no or a negligible correlation between intramucosal and haemodynamic or perfusion data, even during the critical low flow-high resistance phase of resuscitation. Mean pHi and PCO(2)-gap at 8 and 24h did not differ significantly between survivors and non-survivors. CONCLUSION: Gastric tonometry is a poor indicator of splanchnic perfusion in patients with burn shock, even when all precautions are taken to prevent methodological errors. The intramucosal-arterial PCO(2)-gap and pHi do not distinguish survivors from non-survivors. Therefore, gastric tonometry does not seem to improve the ability to anticipate and avert regional anaerobic metabolism during burn shock and its routine use in these patients cannot be recommended.

Phase II trial of weekly 24-hour infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma.

BACKGROUND: Patients with advanced gallbladder and biliary tract carcinoma face a dismal prognosis, as no effective palliative chemotherapy exists. The antitumor effect of gemcitabine is schedule-dependent rather than dose-dependent. We evaluated the activity of a prolonged infusion of gemcitabine in advanced gallbladder and biliary tract carcinomas. METHODS: Nineteen consecutive eligible patients were enrolled. All patients were required to have histologically confirmed diagnosis and measurable disease. Gemcitabine was infused over 24 hours at a dose of 100 mg/m2 on days 1, 8, and 15. Treatment was repeated every 28 days until progression of disease or limiting toxicity. Tumor response was evaluated every second course by computed tomography (CT) scans. RESULTS: Eighteen patients were evaluable for response. A total of 89 cycles of therapy were administered. One partial response was observed (6%; 95% confidence interval (CI): 0-27%) and ten additional patients had stable disease for at least two months (disease control rate 61%; 95% CI: 36-83%). The therapy was well tolerated, with moderate myelosuppression as the main toxicity. The median time to tumor progression and median overall survival was 3.6 months (95% CI 2.6-4.6 months) and 7.5 months (95% CI 6.5-8.5 months), respectively. CONCLUSION: Weekly 24-hour gemcitabine at a dose of 100 mg/m2 is well tolerated. There was a relatively high rate of disease control for a median duration of 5.3 months (range 2.8-18.8 months). However, the objective response rate of this regimen in gallbladder and biliary tract carcinomas was limited.

Reproducibility of transpulmonary thermodilution measurements in patients with burn shock and hypothermia.

Thermal noise, including hypothermia and short-term variations in body temperature, has been reported to influence the accuracy and reproducibility of thermodilution measurements. This variation might theoretically limit the usefulness of this technique in patients with acute burns. We therefore sought to determine the reproducibility of hemodynamic parameters derived from arterial thermal dilution in patients with acute burns and hypothermia. This was a prospective, clinical study of 50 mechanically ventilated patients with burns involving more than 25% of the body surface area that were treated at an eight-bed intensive care burn unit in a university-affiliated hospital. A total of 750 arterial thermodilution measurements were analyzed using the COLD system. Triplicate measurements of the intrathoracic blood volume, cardiac output, total blood volume, and extravascular lung water were performed at regular intervals during the first 48 hours after the thermal injury. Reproducibility was assessed by the coefficient of variation of the triplicate measurements. The correlation of variation was less than 10% at all measurement times for cardiac output, intrathoracic blood volume, and total blood volume. For the extravascular lung water, the coefficient of variation ranged from 9.5% to 12.9%. A maximum of 12.9% was found at 48 hours after burn. No correlation was found between body core temperature and the reproducibility of intrathoracic blood volume index (r = 0.145), cardiac index (r = 0.217), or extravascular lung water index (r = 0.167). The parameters derived from arterial thermodilution show a clinically sufficient reproducibility in patients with acute burns associated with thermal instability.

Effect of crystalloid resuscitation and inhalation injury on extravascular lung water: clinical implications.

STUDY OBJECTIVE: Arterial thermal dilution with an integrated fiberoptic monitoring system (COLD Z-021; Pulsion Medical Systems; Munich, Germany) allows measurement of extravascular lung water (EVLW) and pulmonary permeability index (PPI). The aim of this study was to evaluate the widespread clinical assumption that early respiratory failure following burn and inhalation injury is due to interstitial fluid accumulation in the lung. DESIGN: Clinical, prospective study. SETTING: ICU of a university referral center of burn care. PATIENTS: Thirty-five severely burned adults (> 20% of body surface area). INTERVENTIONS: Resuscitation therapy was guided by the results of hemodynamic monitoring using the intrathoracic blood volume (ITBV) as a cardiac preload indicator. The resuscitation goals included a normalization of preload (ITBV > 850 mL/m(2)) and cardiac index (> 3.5 L/min/m(2)) within 24 h after ICU admission. Fluid loading was implemented to reach these goals. MEASUREMENTS AND RESULTS: One hundred forty lung water measurements were performed at 0 h, 12 h, 24 h, and 48 h after admission to the ICU. Significant elevation of EVLW and PPI was found in three measurements (2%) at 48 h after ICU admission, and was in one patient associated with inhalation injury. EVLW and PPI were not significantly different between patients with and without inhalation injury. No correlation was found between resuscitation volume and EVLW (r(2) = 0.02) or between the alveolar-arterial oxygen pressure difference and EVLW (r(2) = 0.017). Chest radiograph abnormalities were found in 2 of 22 patients with inhalation injury; these were not associated with increased values of EVLW. CONCLUSION: Early fluid accumulation in the lung in burned patients is very uncommon, even in the presence of inhalation injury. There is no evidence that thermal injury causes an increase in pulmonary capillary membrane permeability.

Prevention of oxaliplatin-induced peripheral sensory neuropathy by carbamazepine in patients with advanced colorectal cancer.

Oxaliplatin plays a key role in the treatment of advanced colorectal cancer. The dose-limiting side effect of this platinum analogue is neurotoxicity. Significant efforts have been undertaken in an attempt to prevent and/or circumvent the development of neurotoxicity. Sodium channel inactivation kinetics on rat sensory sural nerve preparations are altered after exposure to oxaliplatin. Carbamazepine antagonizes this effect in vitro. Results from preliminary clinical studies indicate that the sodium channel blockers carbamazepine and gabapentin may be effective in preventing neurotoxicity. The role of amifostine is not yet clear. Randomized clinical studies are necessary to confirm the potential benefit of carbamazepine and other sodium channel blockers in preventing and/or overcoming the development of oxaliplatin-induced neurotoxicity.

Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2 diabetes mellitus.

OBJECTIVE: Weight gain and obesity are of substantial importance for the development of insulin-resistance and type-2 diabetes mellitus. Fetuin-A, a liver-derived glycoprotein, may also play a role in these alterations. Several studies have demonstrated an association between fetuin-A and body weight which, however, was within a fairly small range at the border of overweight to obesity. The present study examines the relationship between fetuin-A and a wide range of BMI, together with basal insulin, and HOMA-IR. In addition, matched groups of non-diabetic patients and those with type-2 diabetes mellitus were compared. METHODS: We examined the relationship between fetuin-A and BMI, insulin, HOMA-IR, glucose and HbA1c in a cohort of 445 non-diabetic obese subjects and 150 obese patients with type-2-diabetes mellitus (DM2). RESULTS: In relation to quintiles of fetuin-A a significant increase of BMI, basal insulin and HOMA-IR was observed between the 1st and 2nd quintile with no further change thereafter. Correspondingly, fetuin-A levels increased significantly only between the 1st and 2nd quintile of BMI, insulin or HOMA-IR, respectively. When patients with type 2 diabetes were compared with non-diabetic subjects matched for BMI, insulin, and age median fetuin-A levels were not significantly different. CONCLUSION: At the early stage of weight gain fetuin-A could be of relevance for the development of insulin resistance. For the further progressive resistance with increasing weight in the obesity range the present data do not support a role of fetuin-A. Similarly its contribution to the resistance of type-2 diabetes seems to be of minor importance.

Interindividual variability of the SIEA Angiosome: effects on operative strategies in breast reconstruction.

BACKGROUND: The vascular territory of the superficial inferior epigastric artery (SIEA) remains to be clarified. The SIEA flap has traditionally been classified as a hemiabdominal flap, but recent evidence points to the fact that a sizable superficial artery is capable of supplying the entire abdominal ellipse. METHODS: Twenty-five patients who met the anatomical criteria for undergoing SIEA flap surgery were studied. The abdominal flap was raised on a superficial inferior epigastric pedicle; the dominant musculocutaneous perforators were preserved and clamped above the abdominal fascia on either side. The vascular territory of the superficial epigastric artery and the contribution of the deep epigastric system were visualized using laser-induced fluorescence of indocyanine green. The surgical technique was modified (SIEA, deep inferior epigastric perforator, or bipedicle) based on perfusion measurements and the indication for surgery. RESULTS: The SIEA vascular territory did not cross the midline in 16 patients (64 percent), and ranged from 0 percent (two patients) to the entire abdominal ellipse (five cases). Fourteen patients (56 percent) were operated on with a unipedicle SIEA flap, five patients (20 percent) were operated on with a bipedicle flap, and in six (24 percent), a conventional deep inferior epigastric perforator flap was used. As a SIEA flap was originally intended in all patients, intraoperative perfusion measurements changed the surgical plan in 11 patients (44 percent). CONCLUSIONS: The SIEA angiosome is variable and ranges from 0 to 100 percent of the lower abdominal flap. Intraoperative perfusion measurements are indispensable for evaluating the sufficiency of this pedicle for tissue transfer, especially if the contralateral flap zones are needed for reconstruction.

The versatility of the SIEA flap: a clinical assessment of the vascular territory of the superficial epigastric inferior artery.

UNLABELLED: Following the TRAM and the DIEP the SIEA flap is the next logical step to reduce the donor site morbidity in autologous breast reconstruction. The vascular axis of the SIEA flap, however, is completely different from the deep epigastric pedicle, on which previous lower abdominal flaps were based. Therefore, a mapping of the vascular territory, which can be reliably harvested on this pedicle, seems mandatory before this new technique can become established. AIM: To chart the angiosome of the superficial inferior epigastric artery with regard to breast reconstruction and to evaluate the random extension of the vascular territory, which can be reliably raised on this pedicle. STUDY DESIGN: Clinical, prospective study in a university-affiliated department of plastic surgery. PATIENTS: Ten patients undergoing autologous breast reconstruction with the superficial inferior epigastric perforator flap and five patients undergoing aesthetic abdominoplasty with isolation of the abdominal flap on the superficial epigastric vessels. MATERIAL AND METHODS: After isolation of the abdominal panniculus on a single superficial inferior epigastric artery pedicle, the flap was divided in the four conventional zones according to Hartrampf. Perfusion in each of the four zones was measured on the table using the technique of dynamic laser-fluorescence videoangiography. RESULTS: Perfusion of Hartrampf Zone III occurred first (25s post-injection) and the perfusion index amounted median 89% of reference. Perfusion of Zone I occurred median 5s later and the relative perfusion was 80%. Perfusion of the contralateral zones II and IV was dramatically reduced to 8% and zero, respectively, and this reduction was statistically significant (p<0.0001). CONCLUSION: The true angiosome of the superficial epigastric artery is located laterally on the ipsilateral hemiabdomen. Its random extension is unreliable and ranges most frequently only to the midline. Based on the results of this study, survival of the skin and subcutaneous fat taken laterally to the border of the contralateral rectus sheath seems questionable. Therefore, the versatility of the SIEA flap for autologous breast reconstruction seems limited when compared with the conventional methods based on the deep inferior epigastric system.

Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study.

BACKGROUND: Oxaliplatin-induced neurotoxicity is a growing, relevant clinical problem. In this study we evaluated the efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer. METHODS: Chemotherapeutic treatment consisted of oxaliplatin 85 mg/m(2) given biweekly and weekly folinic acid 500 mg/m(2) followed by a 24-h infusion of 5-FU 2000 mg/m(2) (FUFOX). One cycle consisted of six consecutive weeks of treatment followed by two weeks of rest (=Treatment B). For Treatment A carbamazepine was added in a dosage for targeted plasma levels of 4-6 mg/L. Neurotoxicity was regularly assessed using a specific scale. Moreover, an evaluation of chronic sensory symptoms and a neurologic examination including tests for vibrational sense, strength and deep tendon reflexes were added creating a peripheral neuropathy (PNP) score. RESULTS: The prospectively defined adequate number of patients needed to provide power for the primary outcome could not be achieved. 19 patients were assigned to Treatment A and 17 to Treatment B. At baseline, the distribution of all clinicopathologic variables was comparable between the two groups. Overall response rates were 16% and 24% and overall survival 15.1 months and 17.4 months for Treatment A and Treatment B, respectively. Between Treatment A and Treatment B there were no major differences when considering worst neurotoxicity during the study period (p=0.46). Grade 3/4 neurotoxicity occured in 4 patients with Treatment A vs. 6 patients with Treatment B. There were no major differences between both groups in each category of the PNP score. CONCLUSIONS: Based on the small number of patients and low statistical power of our study definite conclusions regarding efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer cannot be drawn.