[Results of the Limberg flap procedure in acute and chronic pilonidal abscesses]. / Ergebnisse des Limberg-Plastik-Verfahrens bei akuten und chronischen Pilonidalabszessen.

BACKGROUND: A number of different treatment algorithms are recommended for the treatment of an acute pilonidal abscess and a chronic pilonidal sinus. While a 1-stage surgical procedure using excision or plastic reconstruction according to Limberg or Karydakis is suggested for chronic pilonidal sinus, a 2­stage procedure is recommended for an acute pilonidal abscess. The aim of this study was to compare the results of the 1­stage surgery with plastic reconstruction according to Limberg for acute pilonidal abscess and chronic pilonidal sinus in terms of recurrence, disorders of wound healing, inpatient length of stay and patient satisfaction. METHODS: From 2009 to 2014 a total of 39 patients were included in this prospective observational study: 21 patients with acute pilonidal abscess and 18 patients with chronic pilonidal sinus. All patients were surgically treated with a 1­stage procedure using the Limberg flap method. The groups were compared in terms of postoperative complication rates and frequency of recurrence. RESULTS: Both groups were basically comparable with respect to demographic characteristics and risk factor profiles. Analysis of the postoperative results showed a comparable rate of postoperative wound healing disorders (10% vs. 17%, p = 0.647). In the group with acute pilonidal abscesses there was no recurrence during the observational period, while in the chronic pilonidal sinus group there were 2 (11%) recurrences (p = 0.206). CONCLUSION: The results of the Limberg flap procedure regarding acute pilonidal abscesses were comparable to those of chronic pilonidal sinus. The results of this study show a trend to a lower risk of recurrence. The use of the Limberg flaps therefore also seems to be an adequate treatment option in an acute infection situation.

Perioperative platin-based chemotherapy for locally advanced esophagogastric adenocarcinoma: Postoperative chemotherapy has a substantial impact on outcome.

BACKGROUND: A combination of platin-based perioperative chemotherapy (PBPC) plus surgical resection has become the standard of care in Europe for locally advanced esophagogastric adenocarcinoma (EGAC). In contrast to preoperative chemotherapy, the postoperative administration of chemotherapy is omitted in a high percentage of patients. We conducted this database study to analyse the impact of postoperative completion of perioperative chemotherapy on patient outcome. METHODS: Patients with EGAC (cT3-4 and/or cN+) were treated with preoperative PBPC plus curative surgical resection. Patient demographics, postoperative tumour stages, histopathological regression (HPR) and administration of postoperative chemotherapy were correlated with overall survival. RESULTS: Of one-hundred-thirty-four patients, 76 received preoperative docetaxel, folinic acid, fluorouracil, oxaliplatin (FLOT), 53 patients epirubicin, cisplatin, folinic acid (ECF) and 5 epirubicin, oxaliplatin, capecitabine (EOX) chemotherapy. The 5-year-survival for the whole collective was 58%. Designated postoperative chemotherapy was omitted in 36% of the patients. 5-year-survival was 75.8% in patients who received pre- and post-operative chemotherapy and 40.3% in patients with only preoperative chemotherapy (p < 0.001). Histopathological regression, postoperative nodal status and administration of postoperative chemotherapy were identified as independent prognostic factors. Analysis of subgroups revealed a pronounced survival benefit after administration of postoperative chemotherapy in patients with ypN+ stages (5-year-survival 64.5% vs 9.7%, p = 0.002) and poor HPR (5-year-survival 55.5% vs 19.3%, p = 0.015). CONCLUSION: Our study provides further evidence that administration of postoperative chemotherapy may contribute to the achieved survival benefit of PBPC in patients with EGAC and implies a beneficial effect especially in presence of lymphonodular tumour involvement and limited HPR.

[Surgical treatment of esophageal cancer : Evolution of management and prognosis over the last 3 decades]. / Chirurgische Therapie des Ösophaguskarzinoms : Entwicklung von Management und Prognose über die letzten drei Jahrzehnte.

BACKGROUND: An increasing incidence of adenocarcinoma, a modified surgical strategy and the increasing use of multimodal therapeutic protocols have had a major impact on the surgical treatment of esophageal cancer during the last 3 decades. OBJECTIVES: This study analyzed the development of these factors and their impact on the short and long-term prognosis of esophageal cancer over the last 25 years. PATIENTS AND METHODS: The study included 366 patients with esophageal cancer treated by esophagectomy at the University Hospital in Freiburg from 1988 to 2012. The study period was split into four time periods for further comparisons, i.e. 1988-1994, 1995-2001, 2001-2006 and 2007-2012. RESULTS: Within the time periods analyzed a marked increase in adenocarcinoma was found (time periods1988-1994, 1995-2001, 2001-2006 and 2007-2012: 21%, 37%, 61% and 64%, respectively, p<0.001). The initially commonly used transhiatal approach and reconstruction with cervical anastomosis was gradually replaced by the thoracoabdominal procedure with intrathoracic reconstruction (i.e. Ivor Lewis esophagectomy, 2007-2012: 98 %). During the study period increasingly more patients received multimodal therapy (13%, 85%, 72% and 84%, p<0.001), the overall rate of perioperative complications (70%, 88%, 73% and 56%, p<0.001) and perioperative mortality (16%, 18%, 8% and 2.5%, p<0.001) were significantly reduced, while the overall 5-year survival (12%, 34%, 41% and 62%, p<0.001) improved. An early tumor stage (p=0.002), N0 status (p<0.001) and histological type of adenocarcinoma (p=0.011) were identified as independent predictors of improved survival. CONCLUSION: During the period from 1988 to 2012 a significant improvement of long-term survival as well as a marked reduction of perioperative mortality after esophagectomy were observed. The improved outcome was associated with an increased use of multimodal therapeutic protocols, the preferred use of thoracoabdominal esophagectomy and epidemiological changes in histology over the study period.

[Hybrid laparoscopic thoracotomic esophagectomy with intrathoracic esophagogastric anastomosis]. / Laparoskopisch-thorakotomische Ösophagusresektion mit intrathorakaler Ösophagogastrostomie als Hybridverfahren.

INTRODUCTION: In the past decades various techniques of esophagectomy for the curative treatment of esophageal cancer have been described. Especially minimally invasive techniques of esophagectomy have been used increasingly in the last decade. Technical issues and results of hybrid laparoscopic-thoracotomic en bloc esophagectomy with intrathoracic esophagogastric anastomosis (HMIE) are presented and discussed in the article. PATIENTS AND METHODS: Between May 2013 and April 2014 a total of 23 patients underwent esophagectomy for esophageal cancer at the University of Freiburg Medical Center. Of these patients 10 were treated by HMIE and the other 13 patients had open esophagectomy (OE). RESULTS: A detailed description of the operative technique of HMIE is given in a step-by-step fashion. Margin negative resection was achieved in all patients after HMIE and OE and the median lymph node yield of lymphadenectomy in HMIE and OE (29 vs. 27) was nearly the same. The medium duration of the operation (347 min vs. 412 min) and median length of stay on the intensive care unit (6 days vs. 9 days) and hospital (13 days vs. 17 days) were decreased in HMIE patients compared to OE, respectively. Overall postoperative morbidity (40 % vs. 69 %) and especially pulmonary morbidity (10 % vs. 46 %) were also favorable in HMIE. No anastomotic leakage and postoperative in-hospital mortality occurred after HMIE. CONCLUSION: The HMIE procedure combines the advantages of minimally invasive operative approaches on especially postoperative pulmonary morbidity after esophagectomy with the high safety of anastomosis and reconstruction achieved in OE. Further advantages are shorter duration of operation and shorter length of hospital stay in HMIE.

[The surgical technique of laparoscopic right hemihepatectomy. Technical aspects and results]. / Chirurgische Technik der laparoskopischen Hemihepatektomie rechts. Machbarkeit und Ergebnisse.

INTRODUCTION: This study compared the technical aspects and results for two different techniques of total laparoscopic anatomical right hemihepatectomy. PATIENTS AND METHODS: From September 2010 to February 2013 a total of 16 patients underwent total laparoscopic right hemihepatectomy at the University Hospital of Freiburg. Of the patients 8 received an intraglissonian approach (IGA) and the other 8 patients an extraglissonian approach (EGA). In the patients of the IGA group, vascular inflow control of the right liver was accomplished by dissection and dividing the right hepatic artery, the right portal vein and the right bile duct separately before parenchymal dissection. In contrast, vascular control for patients in the EGA group was performed by enclosure and transsection of the whole right pedicle using a vascular linear stapler. RESULTS: Indications for right hemihepatectomy were benign tumors in 2 and malignancies in 14 cases. The average maximum tumor diameter was 5.5 cm (range 1.5-10.0 cm). Adequate tumor-free surgical margins (R0) were confirmed in all patients with malignancies. The perioperative mortality rate was 0 %, surgical complications according to Clavien's classification were grade I (n = 1 trocar site superficial wound infection), grade II (n = 2 cholangitis) and grade IIIb (n = 1 wound dehiscence after conversion to open procedure). The median operating time was 366 min (range 265-422 min) and 313 min (range 247-417 min) in the IGA and EGA groups, respectively. Conversion from laparoscopic to open minimal access procedure was necessary in three patients in the IGA group and two patients in the EGA group. Mean intraoperative blood loss was 644 ml (200-1000 ml) and 518 ml (200-1500 ml) in the IGA and EGA groups, respectively. Transfusion of two units of packed red blood cells was necessary for one patient in group EGA. No patient in either group needed a Pringle maneuver. Mean postoperative hospital stay was 11 days (range 7-23 days) and 13 days (range 7-31 days) in the IGA and EGA groups, respectively. CONCLUSIONS: Total laparoscopic anatomical right hemihepatectomy is a feasible procedure. The extraglissonian technique can provide shorter operating times by correctly facilitating vascular control of the right liver.

Saturated phosphatidylcholine secretion and the effect of natural surfactant on premature and term lambs ventilated for 2 days.

Lambs prematurely delivered by cesarean section and term lambs were supported on ventilators and studied over a period of 2 days. Sequential measurements of ventilatory requirements, lung compliance, and arterial pH, pO2, and pCO2 values documented the course of the lung disease. In five premature lambs the pCO2 increased to 77 +/- 5 mm Hg (mean +/- SE) by 40.5 +/- 3.1 hr of age, at which time treatment with 50 mg natural sheep surfactant lipid/kg body weight by tracheal instillation resulted in improvements in pH, pO2, and pCO2 measurements. Radiolabeled palmitic acid was injected systemically after birth to detect the appearance of endogenously synthesized and secreted saturated phosphatidylcholine in sequential airway samples. Radiolabeled saturated phosphatidylcholine specific activity increased in a relatively linear fashion for about 30 hr in lambs treated with natural surfactant, in untreated premature lambs, and in term lambs. The study demonstrates that surfactant therapy can improve the ventilatory status of premature lambs despite many hours of ventilation for pulmonary immaturity. The overall kinetics of secretion of saturated phosphatidylcholine is similar in lambs with and without pulmonary immaturity.

Metabolism of exogenously administered natural surfactant in the newborn lamb.

[3H]-Palmitate labeled natural lamb surfactant and free [14C]-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to 96 h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent t 1/2 of phosphatidylcholine in the whole lung of 6.0 days. This half-life can be interpreted only as a rough estimate. Appearance of considerable [3H] labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered [14C]-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered [3H] and [14C] were found in pulmonary alveolar macrophages.

Premature lambs rescued from respiratory failure with natural surfactant: clinical and biophysical correlates.

Thirty-four Western mixed breed lambs were delivered prematurely at 120 days gestational age (term = 150 days). Four lambs were sacrificed at birth, and four lambs were sacrificed with the onset of respiratory failure (PCO2 greater than 80 torr) at about 30 min of age. The remaining lambs were treated by tracheal instillation with 50 mg of natural sheep surfactant lipid/kg body weight. These lambs were sacrificed 10 min, 40 min, 1.5 h and 3 h after surfactant treatment. Frequent blood gas and compliance measurements documented the clinical responses of the lambs. Lungs from treated lambs showed large increase relative to untreated lungs in air volumes as assessed by pressure-volume curves and by histology. However, the pressure-volume and histologic measurements did not distinguish between the posttreatment groups of lambs. Minimum surface tensions of alveolar washes fell from greater than 30 dynes/cm to 6.3 dynes/cm 10 min after treatment and again rose to 21.6 dynes/cm within 3 h. Minimum surface tensions correlated well with the PO2 values but not with the PCO2 values measured before sacrifice. The combination of dilated distal airways and atelectasis resulted from increasing surface tensions with time and mechanical ventilation and may explain the clinical deterioration without much change in the volume of gas within the airways.

Plasma oxytocin concentrations in men, nonpregnant women, and pregnant women before and during spontaneous labor.

Baseline plasma oxytocin (OT) concentrations were measured in 25 healthy men, 102 nonpregnant women, and 59 pregnant women from 15-42 weeks gestation. In addition, plasma OT levels were measured at the onset, peak, and immediately after a single uterine contraction in 6 women in the latent phase and 14 women in the active phases of labor, as well as in 19 women at initial presentation of the fetal head on the perineum (+3 station) and 11 women at the time of delivery of the head during a normal vaginal delivery. Baseline plasma OT concentrations did not vary significantly among men (1.5 +/- 0.2 microunits/ml), nonpregnant women (1.4 +/- 0.2 microunits/ml), or pregnant women before labor (1.3 +/- 0.1 microunits/ml) and did not differ in an additional subgroup of 20 women receiving oral contraceptive medication (1.8 +/- 0.7 microunits/ml). In studies conducted during labor, plasma OT concentrations did not correlate with uterine pressure measurements and did not increase significantly over baseline pregnancy concentrations during the latent (1.3 +/- 0.2 microunits/ml) or active (1.6 +/- 0.2 microunits/ml) phases of labor. There was a significant increase in plasma OT levels from the time of initial visualization of the fetal head to the time of delivery of the head (1.1 +/- 0.1 to 4.2 +/- 1.1 microunits/ml, respectively; P less than 0.05). These data support the view that maternal plasma OT levels remain low during pregnancy until late in the second stage of labor.

Surface activity following natural surfactant treatment in premature lambs.

Premature lambs with respiratory failure [CO2 partial pressure (PCO2) greater than 70 Torr] were treated with 50 mg/kg 3H-labeled natural surfactant by tracheal instillation. Minimum surface tensions of sequential samples suctioned from the airways fell from 25 +/- 3 dyn/cm before treatment to 8 +/- 5 dyn/cm after treatment and again rose to 32 +/- 2 dyn/cm at death. Minimum surface tensions of alveolar wash samples taken at death were 27 +/- 4 dyn/cm, whereas surfactant fractions reisolated from the alveolar washes lowered surface tension to under 10 dyn/cm. The alveolar washes, surfactant reisolated from the alveolar washes, and natural surfactant had similar phospholipid compositions; however, the alveolar washes contained about 40 times more protein per micromole phosphatidylcholine. The natural surfactant used for treatment apparently was inactivated by an inhibitor of surfactant function. After intravenous injections of [14C]palmitic acid, labeled saturated phosphatidylcholine appeared on the airways, indicating endogenous synthesis and secretion. However, the specific activity of the 3H-labeled saturated phosphatidylcholine in the natural surfactant used for treatment decreased by only 30 +/- 4% in the alveolar wash; thus the treatment dose was not diluted to a large extent by endogenous pools.

Plasma norepinephrine, epinephrine, and dopamine concentrations in maternal and fetal sheep during spontaneous parturition and in premature sheep during cortisol-induced parturition.

The plasma catecholamine response to parturition was studied in two groups of chronically catheterized fetal sheep. Group I consisted of full term pregnancies with a mean gestation of 147 days at delivery. Group II was comprised of fetal sheep infused with cortisol to induce premature delivery at a mean gestational age of 135 days. Plasma catecholamine concentrations were measured in group I mothers and fetuses and group II fetuses by radioenzymatic assay using 50 microliter samples. Uterine contractions began 4--14 h before delivery in both groups. Significant increases in fetal plasma norepinephrine (NE) concentrations occurred within 3 h of delivery in both groups. Group I plasma epinephrine (E) and group I and II plasma dopamine levels were significantly increased within 1 h of delivery. Only plasma E levels differed in group I and II fetuses; there was no significant rise in plasma E concentrations in cortisol-infused (group II) fetuses. Maternal plasma NE and E concentrations were increased 2--3 h before delivery in group I animals. Maternal plasma dopamine concentrations were only elevated 30 min before delivery when plasma NE and E levels were highest.

Ovine maternal and fetal plasma oxytocin concentrations before and during parturition.

To study the relationships between fetal and maternal oxytocin (OT) levels and the initiation of labor in sheep, paired maternal and fetal plasma OT concentrations (microunits per ml) were measured by RIA. Samples were obtained daily from pregnant ewes and their fetuses for 5 days before spontaneous delivery and frequently during the first and second stages of labor and during the 3 h after delivery. The mean maternal plasma OT concentration during the first stage of labor was not different from that preceding labor. In contrast, the mean maternal plasma OT level during stage 2 of labor was significantly higher than the earlier baseline maternal values or the mean paired fetal concentration. There was no significant increase in the mean fetal plasma OT concentration before delivery. The newborn plasma OT concentration was elevated 15 min after delivery. From these data, we conclude that in the sheep, 1) the onset of labor is not associated with increased maternal plasma OT levels, 2) cervical or vaginal distension may be the stimulus for maternal OT release during stage 2 of labor, 3) an increase in the fetal plasma OT concentration does not occur before the initiation of labor or during the course of labor, and 4) stress in the final moments of labor or in early neonatal life may be responsible for elevated cord and early neonatal plasma OT levels.

A combined radioimmunoassay for the measurement of unconjugated and sulfoconjugated pregnenolone, 17 hydroxypregnenolone, dehydroepiandrosterone, and estrone applied to fetal and maternal ovine plasma.

This report describes a radioimmunoassay (RIA) method for the combined measurement of four steroid sulfoconjugates and their four unconjugated counterparts in maternal and fetal ovine plasma: pregnenolone (delta 5P), 17-hydroxypregnenolone (17 delta 5P), dehydroepiandrosterone (DHEA), and estrone (E1). In the procedure a preliminary ether extraction is utilized to isolate the unconjugated steroids followed by salting out, ethyl acetate extraction, and mineral acid solvolysis of the remaining sulfated steroids. The hydrolyzed sulfoconjugates are then separated chromatographically and measured in a manner identical to their unconjugated counterparts. The combined measurement of these eight steroids in single samples of fetal and maternal ovine plasma has not been reported previously and plasma concentrations of these steroids were heretofore unknown. Since no previous data was available for comparison, rigorous specificity evaluation of this RIA system was required prior to its use for physiologic studies and the reporting of concentrations in this species.

Duration and characteristics of treatment of premature lambs with natural surfactant.

Premature lambs were treated with 50 mg/kg of natural surfactant lipid by tracheal instillation either at birth or shortly thereafter when respiratory failure was documented. All lambs were delivered by cesarean section and supported on infant ventilators with 100% oxygen under conditions to mimic the care of human infants with the respiratory distress syndrome. The natural surfactant used for therapy was recovered by lavage from sheep lung. Six 120-d gestational age lambs treated at birth had an initial mean oxygen pressure (pO2) value of 270 +/- 35 mm Hg; this fell within 3 h to less than 100 mm Hg. By 8.3 +/- 0.3 h after birth the lambs were in severe respiratory failure with a mean pH less than 7.1 and a mean pCO2 greater than 70 mm Hg. Six untreated lambs had pH values below 7.0 within 40 min of life despite more intensive respiratory support than was given the treated animals. Treatment with natural surfactant of 17 lambs of 120 and 130 d gestational age after early respiratory failure resulted in a prompt increase in pO2 values from about 35 mm Hg to values over 200 mm Hg and a fall in pCO2 values to normal levels in the majority of animals. This response lasted only approximately 3 h, and a second treatment was less predictably effective.

Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition.

Using a cortisol RIA carefully validated for specificity in fetal ovine plasma, we studied plasma cortisol time-trend changes in eight chronically catheterized sheep fetuses in the last 22 days of gestation before the spontaneous onset of labor. Best fit exponential type curves were drawn for each individual fetus to define the time before the onset of labor at which fetal plasma cortisol was rising at different rates. Fetal plasma cortisol increased at a rate of 0.5 ng ml-1 day-1 as early as 17.1 days before labor in one fetus, whereas the mean value for all eight fetuses occurred 11.8 +/- 1.0 (SEM) days before labor. The rate of increase doubled to 1.0 ng cortisol ml-1 day-1 as early as 14.4 days before labor in one fetus, whereas the mean value for all eight fetuses occurred 9.3 +/- 0.9 days before labor. These findings suggest that the regulatory mechanisms responsible for the prelabor increase in fetal cortisol production are activated earlier in gestation than we previously thought.

Metabolic clearance rate and transplacental passage of oxytocin in the pregnant ewe and fetus.

The MCR and placental permeability to oxytocin were determined in chronically catheterized pregnant sheep. Simultaneous maternal and fetal plasma oxytocin (OT) concentrations were measured by RIA before and during continuous infusion of synthetic OT to steady state conditions. Baseline fetal plasma OT concentrations were significantly higher than simultaneously collected maternal concentrations (1.6 +/- 0.13 vs. 1.1 +/- 0.13 muU/ml, respectively; P less than 0.01). Mean fetal OT MCRs were 12.0 +/- 1.35 and 12.1 +/- 1.09 ml/kg . min at OT infusion rates of 64 and 640 muU/kg . min. Mean maternal MCRs were 12.1 +/- 2.64 and 12.4 +/- 1.38 ml/kg . min at OT infusion rates of 80 and 800 muU/kg . min. Uterine contractions were induced by maternal OT infusion of 800 muU/kg . min but not by lower infusion rates; no uterine contractions were induced by fetal OT infusion. OT did not appear to cross the placenta in either direction under the present study conditions.

The effect of acute maternal hemorrhage on the release of catecholamines in the pregnant ewe and the fetus.

Five chronically instrumented pregnant ewes and their fetuses were studied to assess the effect of acute maternal hemorrhage. The hemorrhage was produced in two stages; during the first stage 15% of the total maternal blood volume was removed, and then in a second stage an additional 15% was removed. Biophysical and biochemical variables were monitored. Plasma dopamine, norepinephrine, and epinephrine were determined by a sensitive radioenzymatic assay. A significant rise in maternal and fetal catecholamines was observed following an estimated maternal blood volume depletion of 30%. During a 15-minute recovery period, the maternal catecholamine concentrations returned to normal, while the fetal concentrations remained elevated. These changes were accompanied by significant changes in maternal and fetal homeostasis. The significance of these findings is discussed.

Thyrotropin-releasing hormone stimulates release of arginine vasopressin and oxytocin in vivo.

The effects of TRH upon neurohypophyseal hormone release were studied in conscious rabbits. Intravenous infusion of 250 nm/kg TRH had no significant effect on either arginine vasopressin (AVP) or oxytocin (OT) release, but a 5-fold greater dose led to significant increases in plasma levels of both AVP and OT and behavioral arousal. Intraventricular injection of 3 nm TRH produced significant elevations of both plasma AVP and OT, with even greater effects on behavior than after iv infusion. The maximal hormone response to intraventricular injection was observed considerably earlier than that for iv injection and the response occurred after an almost 1000-fold lower dose of TRH. Neither artificial cerebrospinal fluid vehicle nor the inactive analogue D-tyrosine2 TRH (p-Glu-d-Tyr-Proamide) had any effect on neurohypophyseal hormone release or on behavior. MK-771 [L-N-(2-oxopiperidin-6-YL-carbonyl)-L-histidyl-L-thiazolidine-4-carboxamide], a TRH analog with enhanced central nervous system effects, had effects on AVP and OT release comparable to equimolar doses of TRH. TRH stimulates release of both AVP and OT after both intraventricular and iv injection, and these effects may be independent of behavioral activation.