Analysis of TNF-α and interleukin-6 in seroma of patients undergoing mastectomy with or without flap fixation: is there a predictive value for seroma formation and its sequelae?

BACKGROUND: Seroma formation is a common complication after mastectomy. Flap fixation has the potential to prevent seroma formation, but identifying patients that are at risk of developing seroma, remains challenging. The aim of this study was to assess the association between pro-inflammatory cytokines in seroma fluid one day after surgery and seroma formation and it sequelae. METHODS: Patients undergoing mastectomy were randomized into one of three groups: no flap fixation, flap fixation using sutures or flap fixation using tissue glue. Seroma samples from 40 consecutive patients undergoing mastectomy were collected on the first postoperative day for analysis of interleukin-6 and tumor necrosis factor-α. Seroma formation and its sequelae were assessed in the outpatient clinic ten days, six weeks and three months after surgery. RESULTS: TNF-α concentrations were not detectable in the seroma samples of any of the 40 patients. BMI (p = 0.001) and weight of the resected surgical specimen (p = 0.003) were associated with higher IL-6 levels in seroma on the first postoperative day after mastectomy. A higher seroma concentration of IL-6 was associated with significantly fewer patients with clinical seroma formation three months after surgery (p = 0.027). CONCLUSION: IL-6 is associated with clinical seroma formation three months after surgery. There is however no evident association between IL-6 and complications related to seroma formation. Higher IL-6 levels are predictive of less long-term seroma formation. Application of flap fixation does not seem to influence the level of IL-6.

A double-blind sham-controlled study of the effect of radiofrequency energy on symptoms and distensibility of the gastro-esophageal junction in GERD.

OBJECTIVES: Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients treated with radiofrequency delivery (Stretta procedure) at the gastro-esophageal junction (GEJ), but the mechanism underlying this improvement is unclear. The objective of this study was to test the hypothesis that Stretta alters GEJ resistance. METHODS: We conducted a double-blind randomized cross-over study of Stretta and sham treatment. Consecutive GERD patients were included in the study. The study was conducted in a tertiary care center. Patients underwent two upper gastrointestinal endoscopies with 3 months interval, during which active or sham Stretta treatment was performed in a randomized double-blind manner. Symptom assessment, endoscopy, manometry, 24-h esophageal pH monitoring, and a distensibility test of the GEJ were done before the start of the study and after 3 months. RESULTS: Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measure. In all, 22 GERD patients (17 females, mean age 47±12 years) participated in the study; 11 in each group. Initial sham treatment did not affect any of the parameters studied. Three months after initial Stretta procedure, no changes were observed in esophageal acid exposure and lower esophageal sphincter (LES) pressure. In contrast, symptom score was significantly improved and GEJ compliance was significantly decreased. Administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-Stretta level, arguing against GEJ fibrosis as the underlying mechanism. CONCLUSIONS: The limitation of this study was reflux evaluation did not include impedance monitoring. In this sham-controlled study, Stretta improved GERD symptoms and decreased GEJ compliance. Decreased GEJ compliance, which reflects altered LES neuromuscular function, may contribute to symptomatic benefit by decreasing refluxate volume.

Bilateral lobar lung transplantation--the first two cases in Belgium.

In the last twenty years lung transplantation has become an established treatment for end-stage lung failure refractory to medical management. Over this time, better short and long-term results have been achieved due to improvements in organ procurement, perfusion and preservation strategies, newer immunosuppressant regimes and better post-transplant care. The limiting factor for the number of lung transplantation procedures performed is the shortage of available donor organs. This results in longer waiting times for listed patients, with a substantially increased risk of dying prior to transplantation, especially in the paediatric population. Several surgical strategies have evolved to overcome the donor shortage, with lobar transplantation becoming a viable alternative. We describe our initial experience with two young patients with end-stage cystic fibrosis (CF) who required lung transplantation. Given their small size it was not possible to transplant an entire lung from an adult donor in each hemithorax. We describe lobar transplantation as a technique used to overcome this, in the first such operation in Belgium.

Influence of radiofrequency energy delivery at the gastroesophageal junction (the Stretta procedure) on symptoms, acid exposure, and esophageal sensitivity to acid perfusion in gastroesophagal reflux disease.

Several studies have demonstrated that radiofrequency energy delivery at the gastroesophageal junction (the Stretta procedure) induces symptom relief in gastroesophageal reflux disease (GERD), although improvement of acid exposure on pH monitoring was usually limited. A role for decreased esophageal sensitivity has been suggested. Our aim was to evaluate the influence of Stretta on symptoms, acid exposure, and sensitivity to esophageal acid perfusion in GERD. Thirteen patients with established proton pump inhibitor (PPI)-dependent GERD (three males; mean age, 51+/-10 years) participated in the study. Before and 6 months after the procedure symptom score, pH monitoring and Bernstein acid perfusion test were performed. The latter was done by infusing HCl (pH 0.1) at a rate of 6 ml/min 15 cm proximal to the gastroesophageal junction for a maximum of 30 min or until the patients experienced heartburn. Results were compared by Student's t-test. Stretta procedure time was 51+/-4 min and no complications occurred. After 6 months, the symptom score was significantly improved (12.5+/-2.0 to 7.5+/-2.1; P<0.05), seven patients no longer needed daily PPI, and acid exposure was significantly decreased (11.6%+/-1.6% to 8.5%+/-1.8% of time pH<4; P<0.05). The time needed to induce heartburn during acid perfusion decreased from 9.5+/-2.3 to 18.1+/-3.4 min (P=0.01), and five patients became insensitive to 30-min acid perfusion, versus none at baseline (P=0.04). In conclusion, the Stretta procedure induces subjective improvement of GERD symptoms and decreases esophageal acid exposure. In addition, esophageal acid sensitivity is decreased 6 months after the Stretta procedure. The mechanism underlying this finding and its relevance to symptom control require further studies.

Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer.

AIMS: This prospective study was designed to determine the utility of 18F-labelled deoxyglucose (FDG) in positron emission tomography (PET) (FDG-PET) for assessing the response to neoadjuvant chemoradiation therapy (CRT) in locally advanced oesophageal tumours. PATIENTS AND METHODS: Thirty-six patients with locally advanced oesophageal cancer (clinical T4 stage) without organ metastases, underwent FDG-PET before and 1 month after CRT. Patients were classified as major responders by serial FDG-PET when the post-CRT PET demonstrated a strong reduction of FDG uptake at the primary tumour site (>80% reduction of tumour-to-liver uptake ratio) without any abnormal FDG uptake elsewhere in the body. PET response was compared with histology obtained during post-induction transthoracic oesophagectomy. RESULTS: A strong correlation was found between the extent of lymph node (LN) involvement as shown by the pre-CRT PET and the major response rate (P = 0.001): such response occurred in nine of 11 N0M0 patients (82%), in three of nine N(1-2)M0 patients (33%) and in two of 16 patients (13%) with distant lymphatic spread. Such a correlation was not found for computed tomography or endoscopic ultrasonography. The sensitivity of serial FDG-PET for a major CRT response was 10 of 14 (71%), its specificity 18 of 22 (82%). The concordance between the response assessment by PET and histopathology was 78%. The median survival time after CRT of PET major responders compared with PET non-major responders was 16.3 months and 6.4 months, respectively. The metabolic response as measured by serial FDG-PET is a stronger prognostic factor for overall survival (P = 0.002) than the extent of LN involvement seen on the pretreatment FDG-PET (P = 0.087). CONCLUSIONS: These data indicate that CRT response as assessed by serial FDG-PET is strongly correlated with pathological response and survival.

Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings.

BACKGROUND & AIMS: Gastroesophageal reflux can be acid, nonacid, pure liquid, or a mixture of gas and liquid. We investigated the prevalence of acid and nonacid reflux and the air-liquid composition of the refluxate in ambulant healthy subjects and patients with reflux disease (GERD). METHODS: Twenty-four-hour ambulatory recordings were performed in 30 patients with symptomatic GERD and erosive esophagitis and in 28 controls. Esophageal pH and impedance were used to identify acid reflux (pH drop below 4.0), minor acid reflux (pH drop above 4.0), nonacid reflux (pH drop less than 1 unit + liquid reflux in impedance), and gas reflux. RESULTS: The total rate of gastroesophageal reflux episodes was similar in patients and controls. Patients with GERD had a higher proportion (45% vs. 33%) and rate of acid reflux than controls (21.5 [9-35]/24 h vs. 13 [6.5-21]/24 h; P < 0.05). One third of reflux events was nonacid in both groups. Mixed reflux of gas and liquid was the most frequent pattern with gas preceding liquid in 50%-80% of cases. Pure liquid reflux was more often acid in patients with GERD than controls (45% vs. 32%; P < 0.05). CONCLUSIONS: Reflux of gastric contents was similarly frequent in patients with GERD and controls. Although there was no difference in the overall number of reflux episodes, more acidic reflux occurred in symptomatic patients with GERD, suggesting differences in gastric acid secretion or distribution.

Composition of the postprandial refluxate in patients with gastroesophageal reflux disease.

OBJECTIVE: It is not known whether the characteristics of the postprandial refluxate in patients with gastroesophageal reflux disease (GERD) differ from those observed in normal subjects. The aim of this study was to characterize the postprandial refluxate in adult patients with GERD using combined intraluminal electrical impedance and pH measurements. METHODS: Postprandial gastroesophageal reflux was assessed in 16 patients with GERD and 15 controls. pH and intraluminal electrical impedance were used to identify acid and nonacid reflux of liquid, mixed (liquid + gas) or gas. RESULTS: Transient lower esophageal sphincter relaxations (TLESRs) and reflux of gastric contents were equally frequent in both groups. However, patients with GERD had more acid reflux [8 (4.7-10.5)/h vs 3.5 (2.6-6)/h, p < 0.05], and normal subjects had more nonacid reflux [5 (4.3-6.7)/h is 3 (1-3.5)/h, p < 0.05]. Gas reflux was less frequent in GERD than in controls (51% vs 68%; p < 0.05). Pure liquid reflux, however, was more frequent (40% vs 26%, p < 0.05) and twice as likely to be acid in GERD. During TLESRs, liquid acid reflux was more frequent in GERD than in controls. CONCLUSIONS: TLESRs and reflux of gastric contents are similarly frequent in patients with GERD and controls. However, patients with GERD have more acid reflux and less nonacid reflux. Differences in the air-liquid composition of the refluxate may contribute to the higher rate of acid reflux observed in these patients.

The utility of positron emission tomography for the diagnosis and staging of recurrent esophageal cancer.

OBJECTIVE: To study the utility of whole-body positron emission tomography with (18)F-fluoro-deoxy-D -glucose (FDG-PET) for the evaluation of recurrence after curative resection of cancer of the esophagus or gastroesophageal junction. METHODS: Forty-one patients with a clinical or radiologic suspicion of recurrent disease underwent conventional diagnostic work-up, including a spiral computed tomographic scan, an endoscopic ultrasound, and a dedicated whole-body FDG-PET. PET lesions were classified as equivocal or suspicious recurrence. The conventional diagnostic work-up and PET findings were correlated with pathology or with radiologic and clinical follow-up. Equivocal lesions were classified as positive. RESULTS: Forty recurrences were found in 33 patients. The lesions were perianastomotic (n = 9), regional (n = 12), and at distant sites (n = 19). For the diagnosis of a perianastomotic recurrence, the sensitivity, specificity, and accuracy of FDG-PET were 100%, 57%, and 74%, versus 100%, 93%, and 96% for conventional diagnostic work-up, respectively (P = not significant). False-positive PET lesions were found in patients with a progressive anastomotic stenosis requiring repetitive endoscopic dilatation. For the diagnosis of regional and distant recurrences, the sensitivity, specificity, and accuracy of PET were 94%, 82%, and 87%, versus 81% (P = not significant), 82% (P = not significant), and 81% (P =.0771) for conventional diagnostic work-up. All false-positive PET lesions (n = 4) had been reported as equivocal. On a patient base, PET provided additional information in 11 of 41 (27%) patients. A major impact on diagnosis was found in 5 patients with equivocal or negative findings on complete diagnostic work-up in whom PET provided a true-positive diagnosis. In 5 other patients the diagnosis was staged upward from localized to extended recurrent disease, and in 1 patient with an equivocal complete diagnostic work-up, PET correctly excluded malignancy. CONCLUSION: FDG-PET allows a highly sensitive diagnosis and accurate whole-body staging of symptomatic recurrent esophageal cancer. Further studies in asymptomatic patients are needed to assess the potential benefit on survival.

Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma.

PURPOSE: A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS: Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS: FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P: =.004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P: =.027), but the specificity may have been higher (89% v 67%, respectively; P: = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P: =. 025) and a similar sensitivity (46% v 43%, respectively; P: = NS). CONCLUSION: PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.

Femoral venoarterial extracorporeal membrane oxygenation for severe reimplantation response after lung transplantation.

Severe pulmonary reimplantation response after lung transplantation is not very common, although the mortality can be high. We present a patient who developed an extremely severe reperfusion injury after bilateral lung transplantation. Because of severe hypoxia and hemodynamic instability, despite aggressive ventilator settings, venoarterial extracorporeal membrane oxygenation (ECMO) was instituted using the femoral approach at the bedside. During ECMO, the patient developed a thoracic wall hematoma that was treated with transfusion alone. After 50 h of ECMO, his chest radiograph had dramatically improved, his oxygen need had been reduced to 50%, and he was successfully weaned from ECMO. Two years later, he is doing extremely well. Therefore, institution of ECMO using the femoral approach can be performed safely at the bedside in the ICU, and can be lifesaving in the context of a very severe reimplantation response after lung transplantation.

Incentive spirometry does not enhance recovery after thoracic surgery.

OBJECTIVE: To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. DESIGN: Randomized controlled trial. SETTING: University hospital, intensive care unit, and surgical department. PATIENTS: Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. INTERVENTIONS: Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. MEASUREMENTS AND MAIN RESULTS: Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay. CONCLUSIONS: Pulmonary complications after lung and esophagus surgery were relatively low. The addition of IS to PT did not further reduce pulmonary complications or hospital stay. Although we cannot rule out beneficial effects in a subgroup of high-risk patients, routine use of IS after thoracic surgery seems to be ineffective.

Relationship between potential doubling time (Tpot), labeling index and duration of DNA synthesis in 60 esophageal and 35 breast tumors: Is it worthwhile to measure Tpot?

BACKGROUND: In recent years Tpot (potential doubling time) has been measured before treatment in human tumors in an attempt to estimate the proliferation taking place during a course of irradiation. Tpot is defined as Ts/LI, where Ts is the duration of DNA synthesis and LI is the labeling index (proportion of cells synthesizing DNA). Ts is more difficult to measure than LI, so the question arises whether variation introduced during the determination of Ts is compensated by the theoretically better relevance of the quotient Tpot than of LI alone. It is not clear from comparisons with clinical outcome whether Tpot is a useful indicator of proliferation or whether LI is more prognostic, as suggested by a currently ongoing multicenter analysis elsewhere. Therefore, we investigated intercomparisons between Tpot and its components LI and Ts in two in their proliferation rates contrasting types of tumor where multiple biopsies were taken from each tumor. MATERIALS AND METHODS: Sixty patients with esophageal carcinoma and 57 patients with breast cancer were included in this study. All patients were injected with IUdR 6-8 h before surgery. From each tumor three to five biopsies were taken at surgery. Using flow cytometry, LI and Ts were measured on all biopsies in order to calculate Tpot. Logarithmic transformations of the distributions were used to examine correlations. Kappa-tests were used to assess how reliable an LI value could be in predicting the corresponding Tpot. RESULTS: Ts and LI were not completely independent, based on the within-tumor coefficients of variation (CVw). The ratio of between-tumor coefficient of variation (CVb) to the CVw suggested that the discriminative power of Tpot was higher than LI for esophagus, but the reverse in breast tumors, which had a larger range. Pearson correlation coefficients were high for log Tpot versus log LI in both types of tumor, but the predictive power was low, as shown by kappa-values of only 0.3-0.41 starting with LI and trying to predict the corresponding value of Tpot. Increasing widths of a central 'gray zone' were investigated for improved discrimination between fast and slow proliferation. Multiples of the within-tumor standard deviation, equally on each side of the median, were used to vary the width of the gray zone. Without a gray zone no more than 70% successful matching was obtained in esophagus tumors, compared with 80% in breast tumors. However, by excluding about half of the esophageal tumors an 80% success rate was achieved. In breast tumors over 90% matching was obtained more easily, keeping 80% of the tumors classifiable. For both tumor types correlations between Ts and Tpot were weak, with a trend towards short Ts associated with short Tpot and also with low LI. The latter correlation was significant for esophageal tumors and resulted in Tpot values having a smaller range than the LIs. CONCLUSION: Although there were good correlation coefficients between Tpot and LI, the predictive power of either from the other was not reliable, except by excluding a significant number of tumors close to the medians. The predictive value of LI for Tpot was higher for breast tumors because the spread in cell kinetic measurements was wide. Until more clinical data become available on outcome in comparison with LI or Tpot, it is still worthwhile to measure Tpot and to assess the prognostic value of both LI and Tpot in relation to outcome.

Relation between endoscopic ultrasound findings and outcome of patients with tumors of the esophagus or esophagogastric junction.

BACKGROUND: Endoscopic ultrasound (EUS) is considered to be the best staging technique for cancer of the esophagus or the esophagogastric junction. This study evaluates the relation between preoperative EUS staging results of these tumors and survival. It also examines how EUS staging predicts resectability. METHODS: Survival data of 86 patients who underwent EUS for staging of tumors of the esophagus or esophagogastric junction were analyzed. Most patients (78 of 86) were treated surgically (73 resections, 5 bypasses). Eight patients did not undergo surgery. RESULTS: Survival of patients was significantly related to EUS T staging (log rank test: p = 0.05), EUS N staging (p = 0.02), detection of celiac lymph node metastasis (p = 0.0027), and the presence of stenosis (p = 0.02). Also, the endosonographic AJCC classification was significantly related to survival (p = 0.0012). Total accuracy for T staging amounted to 59%. Accuracy for recognition of transmural growth was 82%. There was a good association between endosonographic findings (EUS stage II, absence of lymph nodes) and the possibility of complete resection. Incomplete resection was less well predicted. CONCLUSION: Survival of patients with tumors of the esophagus or esophagogastric junction is strongly related to EUS TNM staging results. Tumor resectability is related to endosonographic findings. However, more advanced EUS findings do not necessarily predict unresectability.

Amnioinfusion with Hartmann's solution: a safe distention medium for endoscopic fetal surgery in the ovine model.

In this study, we have investigated the maternal effects of distending the uterine cavity with Hartmann's solution in 2nd trimester equivalent pregnant sheep. In 7 pregnant ewes, double endoscopic cannulation of the amniotic cavity was performed under general anesthesia, and 1 liter of Hartmann's solution at 38 degrees C, radiolabeled with 99mTc-red blood cells, was infused. Maternal central venous pressure, hematocrit, serum and amniotic fluid osmolarity, and amniotic fluid volume were measured at nine time points within a 2-hour period. Over this time interval, no significant fluid shift to the maternal compartment was observed. We detected no adsorption of radioactivity to the fetus or membranes, and no diffusion of radioactivity to maternal or fetal tissues was noticed. We conclude from these experiments that following double cannulation and intra-amniotic infusion of Hartmann's solution into the 2nd-trimester pregnant ovine uterus, no significant shift of fluid to the maternal compartment was observed over a 2-hour time period.

Arterial infection following renal transplantation: successful management using transperineal femorofemoral crossover graft.

Infection of a vascular prosthesis or an arterial receptor site is one of the most challenging situations for the vascular surgeon. In some instances the standard extraanatomic routes to bypass infected areas cannot be used. Two cases of arterial infection following renal transplantation are presented. An infrascrotal perineal approach for a femorofemoral bypass was used to achieve revascularization of a threatened limb.