Perioperative factors that influence the outcome of microsurgical reconstructions in craniomaxillofacial surgery.

Microsurgical tissue transfer is a well-established way of reconstructing the head and neck, but there are still many postoperative complications that require revision. The aim of this study was to clarify perioperative factors and characteristics of patients that influence the success of the flap and the need for revision. We retrospectively studied 368 patients who were treated with microsurgical free tissue transfer in the head and neck area at the Department of Oral and Maxillofacial Surgery at the University Medical Centre, Erlangen, between 2004 and 2009. Investigations concentrated on patients' characteristics and operative factors. Free scapular or parascapular flaps (n=161, 44%) and radial forearm flaps (n=119, 32%) were predominantly used for the reconstruction of major defects in the mandible and the floor of the mouth. In 39 patients (11%) revision was required, which resulted in a success rate of 96%. There was a significant association between preoperative American Society of Anesthesiologists (ASA) grade and postoperative survival of the flap (p=0.04). Patients previously treated by irradiation required significantly more revisions than those not so treated (p=0.04). The use of vein grafts was also significantly associated with the need for revision (p=0.02). The ASA grade influenced the success rate but was not associated with the number of revisions. These factors must be taken into consideration when intervention is planned to reduce the number of postoperative complications and interventions further.

Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

OBJECTIVES: Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. MATERIAL AND METHODS: An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. RESULTS: Labelling indices were significantly lower for Msx-1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP-2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx-1, 22-fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP-2 in ONJ bone. CONCLUSIONS: Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future.

Echocardiographic measures of ventricular function and pulmonary artery size: prognostic markers of congenital diaphragmatic hernia?

OBJECTIVE: To compare echocardiographic measures of biventricular function and pulmonary artery size in infants with congenital diaphragmatic hernia (CDH) and normal controls, and examine their correlation, if any, with outcomes in CDH. STUDY DESIGN: We included consecutive neonates (<1 month old) with CDH and term controls without structural heart defects. Clinical and outcomes data were recorded and echocardiograms evaluated for right ventricular (RV) and left ventricular (LV) myocardial performance index (MPI), cardiac output index (CI) and McGoon index, among others. Statistical analyses (SPSS version 17, SPSS, Chicago, IL, USA) included between-group comparisons, using analysis of variance and χ(2)-test and binary regression, with significance set at P<0.05. RESULT: Infants with CDH (n=34) were comparable with controls (n=35) in their age, weight, gestational age and gender. CDH was left sided in 24 (70%) neonates. Extracorporeal membrane oxygenation (ECMO) was required in 15 (45%) neonates; 18 (53%) infants survived. MPIs, CI and eccentricity index in systole were significantly worse in the CDH group, compared with controls and among CDH infants who died, compared with survivors. Infants with CDH who died or needed ECMO had significantly impaired MPIs and CI than survivors. On regression analyses, LV CI and MPIs were independently associated with mortality. CONCLUSION: Infants with CDH had significantly impaired ventricular function and pulmonary hypertension, compared with controls. In the CDH group, LV dysfunction was associated with death and adverse outcomes. Further studies incorporating echocardiographic indices as prognostic markers of CDH are warranted.

[Hereditary head and neck tumors]. / Hereditäre Tumoren des Kopf-Hals-Bereichs.

Hereditary paraganglioma, Gorlin-Goltz syndrome and Fanconi anemia are among the rare hereditary tumor syndromes of the head and neck. Patients with hereditary paraganglioma often develop multiple tumors of the glomus caroticum and glomus jugulotympanicum. The corresponding genetic defects of the mitochondrial succinate dehydrogenase complex induce autonomous tumor cell growth. In patients with Gorlin-Goltz syndrome basal cell carcinomas and keratocystic odontogenic tumors usually occur much earlier than in patients with sporadic tumors. The associated germline mutations are located in the patched gene which is a modulator of the cell cycle. Fanconi anemia represents a chromosomal instability syndrome which is characterized by early onset of pancytopenia, i.e. bone marrow failure and subsequent development of acute myeloid leukemia and/or squamous cell carcinomas, especially of the head and neck. A total of 13 different gene clusters have been identified in 2 DNA associated complexes which play an important role in DNA repair mechanisms.

Static and dynamic periosteal elevation: a pilot study in a pig model.

The osteoinductive potential of periosteum and bone can be stimulated by elevating the periosteum in a distraction-like modus, but also by an ad-hoc elevation. This was tested and proved in an experiment in 9 Goettingen mini-pigs with elevation heights of 5, 10 and 15mm. Specially designed and perforated titanium meshes were implanted subperiosteally to compare the dynamic elevation procedure with static shielding. The cumulative results for bone formation underneath the mesh were 66% in dynamic and 67% in non-dynamic elevation. The cumulative results for mineralization of the bone regenerates in comparison with the underlying basal bone of the skull showed independently from the technique applied no difference bigger than 5%. No major difference in bone formation could be observed in this pilot study. The main advantages of dynamic periosteal elevation and static shielding are minimal invasion and morbidity. Periosteal elevation could be applied in cranio-maxillofacial surgery, in preimplantological augmentation and in reconstructive surgery of the skull; applications in other specialties may be possible.

Air gun pellet remaining in the maxillary sinus for 50 years: a relevant risk factor for the patient?

The authors report the case of a 62-year-old man referred to the department of oral and maxillofacial surgery because of a clinical suspicion of palate carcinoma. Incidentally, diagnostic radiology showed a metallic foreign body in the left maxillary sinus. Anamnestic data revealed that a shot from an air gun accidentally hit the patient's left cheek in 1957. The lead-containing air gun pellet was removed by endoscopic antrostomy and the diagnosis of squamous cell carcinoma was confirmed by histopathological examination. 50 years after the pellet's impact, toxicological blood analysis showed no increased blood lead level. It remains unclear whether the air gun pellet has a potential toxicological effect or is related to the development of the patient's oral carcinoma. In this context the article reviews the literature and discusses the necessity of removing metal-containing foreign bodies, the role of lead in chronic toxicity and its possible carcinogenic effect in humans.

[Prognostic value of immunohistochemistry in salivary gland cancer]. / Immunhistochemie als Prognoseindikator bei Speicheldrüsenkarzinomen.

BACKGROUND: The diversity of salivary gland malignancies as to morphology and clinical course makes it difficult to establish prognostic factors. The aim of this study was to evaluate the prognostic significance of, a. o., immunohistochemical criteria in a retrospective study of salivary gland cancer. PATIENTS AND METHODS: Clinical and histologic data were recorded for 101 patients with carcinomas of the salivary glands. Immunohistochemistry was performed for Ki-67, P53, C-KIT, HER2, EGFR, and maspin. Correlations to disease-specific long-term survival (mean follow-up 4.7 years) were followed by univariate and multivariate analysis. RESULTS: Findings included the following: an association between loss of maspin and the presence of nodal metastasis, residual tumour, and poor overall survival for adenoid cystic carcinoma; common C-KIT expression in adenoid cystic carcinoma (92%); correlation of loss of C-KIT with high malignancy grade, nodal metastases, high proliferative activity (Ki-67>30%), and unfavourable survival in all tumours; common HER2 expression (83%) in salivary duct carcinoma but no relation to the total collective's survival. Overexpression of EGFR was associated with poor survival rates. In multivariate analysis, a high proliferation index was the strongest predictive factor, followed by the presence of residual tumour, overexpression of EGFR, and advanced clinical stage. CONCLUSIONS: The clinical stage is of higher prognostic value than histology and grade of malignancy. High proliferative activity (Ki-67>30%) is the strongest negative predictor in salivary gland cancer. Besides well-known clinicopathological factors, current immunohistochemical markers such as maspin, EGFR, and C-KIT can contribute to establish prognosis in salivary gland cancer.

Evaluation of contrast media for bronchography.

BACKGROUND: Bronchography is occasionally needed for the evaluation and management of some congenital pulmonary anomalies as well as some acquired diseases, usually of the tracheo- bronchial tree. There is currently no effective, approved contrast agent for this imaging techniq ue. OBJECTIVE: We evaluated five agents (barium sulfate, iohexol, propyliodone oily, propyliodone aqueous, and perflubron) in terms of image quality, histologic changes, and effects on hemodynamics, blood gases, and standard laboratory tests in New Zealand White rabbits. MATERIALS AND METHODS: Animals were anesthetized and intubated. Each contrast agent (0.25 ml/kg) was administered intratracheally. Three animals in each group had intravenous lines placed for blood sampling and blood pressure monitoring and were sacrificed at 1 h. An additional three animals for each agent were sacrificed at 24 h and 1 week after imaging. Blood samples were taken immediately before contrast instillation and at 1 h postbronchography. Fluoroscopic images were recorded on standard VHS video tape and evaluated in blind fashion. Segments of lung tissue and bronchi were obtained for histologic examination. RESULTS: Necrosis and/or inflammatory infiltrates were noted in 78 % of the bronchograms performed with propyliodone aqueous, 67 % with propyliodone oily, 55 % with perflubron, and 33 % with iohexol 120, 240 and 350. No histologic damage was observed with barium. The propyliodones gave the best-quality imaging results and the most histologic changes. Iohexol, in any concentration, gave the least acceptable images and a moderate number of histologic changes. Barium sulfate demonstrated acceptable images with virtually no histologic changes. CONCLUSION: From the histologic and imaging results, barium is the best available contrast material for bronchography.

Intestinal perforation due to an ingested foreign body: laparoscopic management.

The authors report the case of a previously healthy 10-year-old boy who accidentally ingested a toothpick. He presented to the hospital 7 days after the incident with left lower quadrant abdominal pain and fever; there was evidence of localized peritoneal irritation by exam. He had mild leukocytosis. An abdominal CT scan showed the toothpick in the sigmoid colon with extension through the bowel wall. Laparoscopic exploration was undertaken and an 8-cm toothpick was identified and removed from the perforation site in the sigmoid colon. Via a small suprapubic incision the sigmoid was delivered and repaired. The patient had an uneventful recovery and was discharged home 2 days after the procedure.Laparoscopic exploration can be diagnostic and therapeutic in the management of ingested foreign bodies with suspected intestinal perforation.

Mesenteric cysts in children.

BACKGROUND: Mesenteric cysts are uncommon benign abdominal masses. Approximately one third of patients with these lesions are children. METHODS: We reviewed our clinical records for the past 14 years (corresponding to the period of time in which ultrasonography and computed tomography became reliable methods for imaging pediatric patients) and found 10 patients with mesenteric cysts. RESULTS: We were surprised to discover that abdominal pain was a presenting complaint in all but one patient. Five of the patients had the findings of an acute surgical abdomen and were thought to have appendicitis. Two patients operated on for appendicitis were transferred to our hospital with the diagnosis of an abdominal mass. In each case the mass was a mesenteric cyst. Cyst distribution included the small-bowel mesentery in seven patients, the transverse mesocolon in two patients, and the right mesocolon in one patient. Six cases required concomitant bowel resection for the cyst removal, and all were cystic lymphangiomas. The resected specimens were described as cystic lymphangiomas in eight of the 10 cases. CONCLUSIONS: Mesenteric cysts should be considered as an origin for abdominal pain in children, particularly after exclusion of more common diagnoses. We have found ultrasonographic imaging to be a reliable method for the diagnosis of appendicitis in children and advocate its use as an initial imaging study in patients with an acute surgical abdomen and presumed appendicitis. If appendicitis is indicated unlikely by ultrasonogram, the examination can be extended to the remainder of the abdomen, which can reveal mesenteric cysts or other pathologic conditions.

Diagnosis and management of biliary complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has become the operation of choice for symptomatic cholelithiasis. However, this operation may result in serious biliary complications. Our aims were to review our experience with biliary complications of laparoscopic cholecystectomy and to document the mechanisms of the injuries and the techniques of managing these complications. We treated 20 patients with biliary complications of laparoscopic cholecystectomy. Symptomatic collections of bile (bilomas) were present in five patients. One of these patients underwent operative ligation of an accessory bile duct in the gallbladder bed, whereas the others had percutaneous or endoscopic therapy. In the remaining 15 patients (of whom 13 were referred from other hospitals), injuries to the major bile ducts were managed by combined radiologic, endoscopic, and operative therapies. In 10 of these patients (67%), the mechanism of injury was the misidentification of the common bile duct as the cystic duct. In 3 of 15 patients, a noncircumferential injury to the lateral aspect of the common bile duct occurred. The Bismuth levels of the remaining bile duct injuries were type I in 3, type II in 4, type III in 3, and type IV in 2. Early outcome of therapy for these bile duct injuries has been favorable. One patient was lost to follow-up, and 2 died of nonbiliary causes, whereas 12 patients are alive and well with normal serum liver enzyme levels at 4 to 19 months postoperatively (mean: 14 months). The most common cause of major bile duct injury during laparoscopic cholecystectomy is mistaking the common bile duct for the cystic duct. Most bilomas can be managed successfully with noninvasive methods. Coordinated efforts by radiologists, endoscopists, and surgeons are necessary to optimize the management of patients with major bile duct injury, suggesting that patients with biliary complications of laparoscopic cholecystectomy should be referred to specialty centers for optimal care.

Laparoscopic cholecystectomy. The new 'gold standard'?

Laparoscopic cholecystectomy has rapidly been adopted by surgeons, but concerns remain about its safety, the management of common bile duct stones, and the means of appropriate training. Of 647 patients referred for cholecystectomy, preoperative endoscopic retrograde cholangiography was performed in 49 (7.6%), with 27 patients (4%) undergoing sphincterotomy and stone extraction. Traditional cholecystectomy was performed in 29 patients (4.5%). Laparoscopic cholecystectomy was attempted in 618 patients and completed successfully in 600 (97.1%). Surgical trainees functioned as the primary surgeon in 70% of cases. Technical complications occurred in three patients (0.5%), including one patient with a common bile duct laceration (0.2%). Major complications occurred in 10 patients (1.6%), with no perioperative mortality. Mean postoperative hospital stay was 1 day, with return to work or full activity a mean of 8 days after surgery. Two cases of retained common bile duct stones (0.3%) were identified. We now regard laparoscopic cholecystectomy as the "gold standard" therapy for management of symptomatic cholelithiasis.

Maximizing the natriuretic effect of endogenous atriopeptin in a rat model of heart failure.

The effect of pharmacological manipulation of atriopeptin (AP) activity on sodium excretion and blood pressure was examined in the rat aortovenocaval (A-V) fistula model of cardiac failure. Introduction of an A-V shunt led to a marked and sustained elevation of plasma AP immunoreactivity and urinary cGMP levels. Further elevation of plasma AP levels by infusion of exogenous peptide induced modest increases in urinary sodium and cGMP excretion and a decrease in blood pressure but these responses were significantly attenuated compared to sham-operated animals. In contrast, low-dose infusion of M + B 22948 (a cGMP phosphodiesterase inhibitor) or thiorphan [a neutral endopeptidase (membrane metallo-endopeptidase, EC 3.4.24.11) inhibitor] induced a natriuresis in A-V fistula rats, which exceeded that seen in control animals given these compounds and matched the peak natriuresis produced in sham-operated animals by high doses of AP. In the doses used, these compounds had little effect on blood pressure. The greater renal efficacy of M + B 22948 in A-V fistula rats is consistent with postreceptor facilitation of AP activity. The effect of thiorphan on sodium excretion was accompanied by a pronounced increase in urinary cGMP and AP immunoreactivity excretion (and was attenuated by anti-AP monoclonal antibody) but could not be explained solely in terms of an increase in circulating AP levels. It is proposed that thiorphan allows filtered AP to reach renal tubule sites that are normally inaccessible to the peptide and are thus protected from down-regulation by high circulating AP levels. The implication of these observations for patients in cardiac failure is the potential for using pharmacological agents to maximize the response to endogenous AP without compromising cardiac function.

Reversible induction of right ventricular atriopeptin synthesis in hypertrophy due to hypoxia.

Right ventricular hypertrophy produced in rats exposed to 10% oxygen for 3 weeks resulted in a ninefold increase in atriopeptin immunoreactivity (APir) and a 160-fold increase in atriopeptin messenger RNA (AP mRNA) in the right ventricular myocardium. A small but significant increase in left ventricular APir and AP mRNA was also present, probably representing the interventricular septum. Right atrial APir was decreased by 50%, but left atrial APir was not different from normoxic controls. Purification of ventricular tissue extracts by high-performance liquid chromatography revealed primarily the high molecular weight prohormone. The development of right ventricular hypertrophy and right ventricular APir content followed a similar time course, each evident at 7 days of hypoxia and reaching a plateau at 14 days. Hypoxia followed by normoxia caused right ventricular APir to fall to control levels within 3 days, despite persistent right ventricular hypertrophy. This data demonstrates that hypoxia can reversibly induce extra-atrial expression of atriopeptin synthesis in the cardiac ventricle.

Development, validation and application of an enzyme immunoassay (EIA) of atriopeptin.

A rapid, convenient, and sensitive enzyme immunoassay (EIA) for atriopeptin (AP) has been developed. The tracer-ligand for the assay is the 24-amino acid peptide, AP24, which has been covalently coupled to the tetrameric form of acetylcholinesterase (AChE) (EC 3.1.1.7). Tracer, unknown, and primary antibody are incubated in a 96-well microtiter plate precoated with secondary antibody. After washing, a colorimetric reaction is used to measure acetylcholinesterase activity. A direct linear correlation was obtained when comparing the conventional radioimmunoassay and the EIA by using the same primary antibody to assay: plasma samples (rat or human), HPLC column fractions, or atrial extracts. Besides being technically much less demanding and not requiring the use of the radioisotopes, the EIA is more sensitive than the radioimmunoassay and thereby lends itself to a "flash" same-day assay of samples.

The effect of various ions on uptake2 of catecholamines.

The effects of a decrease of the K+ gradient on the extraneuronal inward transport and outward movement of catecholamines were studied in rat heart, rabbit aortic rings and guinea-pig trachealis smooth muscle. Elevation of the extracellular K+ concentration caused a) inhibition of the corticosteroid-sensitive extraneuronal uptake (uptake2) of 3H-isoprenaline in rat heart and of 3H-noradrenaline in rabbit aorta, and b) acceleration of efflux of 3H-isoprenaline from rat heart, 3H-noradrenaline from rabbit aorta and adrenaline (measured by microphotometry) from guinea-pig trachealis muscle. In rat heart and rabbit aorta, the acute omission of one or the other of the ions Na+, Cl-, K+ or Ca2+ from the perfusion of incubation medium had no effect on initial rates of uptake2 of catecholamines, except that the absence of K+ had a small inhibitory effect in the rat heart. The prolonged absence of Na+, Ca2+ or K+ from the perfusion or incubation medium caused a marked inhibition of uptake2 of catecholamines. These inhibitory effects developed more quickly in rat heart than in rabbit aorta. These results are compatible with the possibility that either the K+ gradient across the cell membrane or the resting membrane potential is the force driving uptake2.

High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers.

In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics.