Failed surgery in primary hyperparathyroidism - what has changed with time.

Advanced preoperative imaging of parathyroid adenomas and intraoperative parathyroid hormone determination optimized the results in the surgical treatment of primary hyperparathyroidism patients. We asked, whether reasons for failure have changed during the last 25 years.We retrospectively analyzed operations for persistent primary hyperparathyroidism in our department between 2001 and 2011 (n=67), and compared these results to our experience between 1986 and 2001 (n=80).From 2001 to 2011, 765 primary hyperparathyroidism patients were operated on at our department. All but 4 patients were cured (761/765, 99.5%). 67 operations were performed for persistent primary hyperparathyroidism. Main reasons for failure were a misdiagnosed sporadic multiple gland disease in our own patients (18/29, 62.1%), and an undetected solitary adenoma in patients referred to us after -initial operation in another hospital (22/38, 57.9%) (statistically significant). From 1986 to 2001 (1 105 primary hyperparathyroidism patients), main indications for re-operation due to persistent disease were an undiagnosed sporadic multiple gland disease in our own patients (15/24, 62.5%), and a missed solitary adenoma in patients being operated on primarily somewhere else (38/56, 67.9%) (statistically significant).Comparing our experience in 147 patients with persistent primary hyperparathyroidism being operated on between 2001-2011 and 1986-2001, not much has changed with the modern armamentarium of improved preoperative imaging or intraoperative biochemical control. Whereas sporadic multiple gland disease was the most common reason for unsuccessful surgery in experienced hands, other units mainly failed due to an undetected solitary adenoma. Re-operations for persistent primary hyperparathyroidism performed by us were successful in 93.8% (2001-2011) and 96.0% (1986-2001), respectively.

[Pancreatic hyperinsulinism--changes of the clinical picture and importance of differences in sporadic disease course (experience with 144 patients operated in the period 1986-2009)]. / Pankreatischer Hyperinsulinismus--Wandel des Krankheitsbildes mit spezifischen Unterschieden auch bei sporadischen Erkrankungsformen (Eigene Erfahrung an 144 operierten Patienten von 1986-2009).

The diagnoses of pancreatogenic hyperinsulinism and insulinoma (benign or malignant) were almost synonomously used during the last decades. Only familial forms of hyperinsulinism, i. e., in patients with multiple endocrine neoplasia type 1 were separately discussed. The surgical literature concentrated on technical questions, comparing open and minimal invasive techniques. The clinical diagnosis of patients with pancreatogenic hypo-glycaemia syndrome (NIPHS) and the pathological diagnosis of insulinomatosis has now opened up new questions in the diagnosis and therapy of pancreatogenic hyperinsulinism. On the basis of our experience from 144 patients operated on for pancreatogenic hyperinsulinism during the last 22 years with 16 NIPHS patients and with the help of the relevant literature, we explain the prerequisites that surgical therapy has to fulfil in the treatment of patients with pancreatogenic hyperinsulinism today.

Poor late prognosis of bleeding peptic ulcer.

BACKGROUND AND AIMS: Long-term course of peptic ulcer bleeding is unclear. Because of a more aged and more diseased ulcer population, the long-term prognosis may be expected as poor. MATERIALS AND METHODS: In a prospective study, all patients with peptic ulcer bleeding treated at the Department of Surgery of the Heinrich-Heine-University in Düsseldorf were included between 1986 and 1995. Follow-up covered hospital mortality, 1-month mortality, 1-year mortality, and 5-years mortality. Significant prognostic parameters for death were investigated in univariate and multivariate analysis. RESULTS: One hundred and seventy-one out of 192 patients with peptic ulcer bleeding could be followed up. One-month mortality was similar to hospital mortality with 12.3%, 1-year mortality was 28.7%, and the 5-years mortality was 46.8%! In univariate analysis, statistically significant prognostic factors for death were ages beyond 70 years, concomitant diseases, risk-related drugs, postinterventional complications, and recurrent bleeding. In multivariate analysis, age, postinterventional complications, and type of admission were statistically significant parameters for death. CONCLUSION: Long-term prognosis of peptic ulcer bleeding is poor! The majority of deaths after hospital stay is probably not because of ulcer bleeding, but because of more aged patients with severe concomitant diseases.

Mutation and methylation analysis of TP53 in adrenal carcinogenesis.

AIM: To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. METHODS: Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain amplification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. RESULTS: Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. CONCLUSION: Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.

[Mild head injury]. / Leichtes Schädel-Hirn-Trauma. Wann zu Hause, wann in der Klinik uberwachen?

Mild injuries to the head are a common everyday occurrence. Only one out of 30,000 patients suffering mild traumatization of the brain subsequently goes on to develop a complication that requires treatment. Such patients can be identified on the basis of the Glasgow Coma Scale and the determination of risk factors, and these data also serve as an aid for deciding whether surveillance at home or hospitalization is indicated.

[Economic restraints shorten the length of hospital stay: thyroid operation as a model case]. / Okonomische Zwänge führen zur Reduktion der stationären VerweildauerBeispiel: Schilddrüsenoperation.

INTRODUCTION: Decreasing the length of stay is a possible means of cost control in the medical system. Therefore we performed a study to test the feasibility of reducing hospital stay to 2 days after thyroid operation. METHODS: In a controlled prospective trial, 238 patients were randomly assigned to group A (2 days of stay) or group B (more than 2 days). Studied were medical standard, practicability, patient acceptance, and quality of life. RESULTS: Of those in group A, 56.6% did not leave the hospital at the scheduled 2nd day post operation. Reasons were preoperative hyperthyroidism ( P<0.011), postoperative hypocalcemia ( P<0.03), or unspecific disturbances. In group B, 28% of the patients left before the established borderline of 3-4 days, and only 35% left on the 2nd postoperative day. CONCLUSION: Reduced length of stay has no negative influence on medical standards. The quality of life of patients leaving the hospital on the 2nd postoperative day was significantly higher. Reducing hospital stay after thyroid operation to 2 postoperative days is desirable and possible without a loss in quality of care, except in case of postoperative complications or unspecific complaints.

[Adenocarcinoma of the esophagogastric junction: prognostic factors and results of primary surgery]. / Ergebnisse der primär chirurgischen Therapie beim Adenokarzinom des ösophagogastralen Ubergangs.

INTRODUCTION: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide, and classification systems and resection procedures are being controversially discussed. METHODS AND PATIENTS: We report on 225 AEG patients undergoing primary resection in our unit (1986-2000) with a special focus on perioperative morbidity, mortality, and long-term prognosis under consideration of the AEG type (Siewert classification) and operative procedure performed (subtotal esophagectomy with proximal gastric resection in AEG I, total gastrectomy with distal esophageal resection in AEG II and AEG III). RESULTS: Types I, II, and III carcinomas were found in 32%, 42%, and 26% of the patients, respectively, with R(0) resections in 65%, 69%, and 51% ( P=0.039). The overall 5-year survival rates were 29%, 31%, and 14% ( P=0.068), respectively; in R(0)-resected patients, they were 40%, 41%, and 27% ( P=0.771). In univariate analysis, the TNM classification ( P<0.001), R classification ( P<0.001), and tumor stage ( P<0.001) were relevant prognostic factors. In multivariate analysis, only the R classification ( P=0.003), LN ratio ( P=0.012), and N stage ( P=0.027) were independent prognostic factors. In 35 of 177 patients resected with curative intent, R(0) resections could not be achieved, mainly because of residual tumor in the circumferential plane (22/35=63%). Only in 37% of cases (13/35) was the R(1) situation due to exclusive positive oral or aboral resection margins. Therefore, in only 7% of all patients resected with curative intent (13/177) did the question arise of whether the R(1) resection could have been avoided by a different surgical approach. Surgical, pulmonary, and cardiac complications were found in 33%, 26%, and 10%, respectively. The mortality within 30 days was 4%. CONCLUSIONS: Failure of R(0) resection in patients treated with curative intent is mostly caused by residual tumor in the circumferential plane. Therefore, different surgical approaches with varying oral and aboral resection margins are of minor importance for reducing the frequency of R(1) resections. Downstaging of tumors by neoadjuvant treatment may increase the R(0) resection rate.

Pheochromocytoma during pregnancy: laparoscopic and conventional surgical treatment of two cases.

Pheochromocytoma is a rare entity. When it presents during pregnancy, rapid recognition and diagnosis are crucial in order to avoid the maternal and fetal morbidity and mortality associated with severe, uncontrolled hypertension. Difficulties arise from the differential diagnosis of pre-eclampsia. We report two patients operated on for pheochromocytoma during pregnancy. The first patient developed new-onset hypertension in early pregnancy. Prior to presentation, there had been non-specific signs of endocrine disorder, namely a mild diabetes, but no hypertension requiring medication. The second patient sought medical care for irregular heartbeat, shortness of breath, and fatigue during the 6th week of pregnancy. She was found to be hypertensive; diagnostic evaluation revealed substantially increased catecholamine levels. The diagnosis was made by elevated urinary catecholamines and by MRI scan as well as ultrasonography, both of which demonstrated an adrenal mass. Both patients underwent surgical extirpation of the affected adrenal gland. The procedure was performed laparoscopically in the case of the second patient. Pre-operatively, both patients were pre-treated with alpha-blockade followed by secondary beta-blockade. Patient two also received methyldopa for control of hypertension. Both patients were readily weaned from antihypertensive medications post-operatively, with complete resolution of hypertension within a few hours. Each pregnancy progressed normally to term.

[Endoscopic ultrasound in routine clinical practice for staging adenocarcinomas of the stomach and distal esophagus]. / Endosonographie in der klinischen Routine beim Adenokarzinom des distalen Osophagus und Magens. Eine ernüchternde Bilanz.

PROBLEM: Endoscopic ultrasound (EUS) is an important diagnostic tool for determining the best therapeutic strategy (primary resection, neoadjuvant therapy or palliation only) to offer esophageal or gastric cancer patients. PATIENTS AND METHODS: In the present study (1992-2001),we evaluated the accuracy of EUS in adenocarcinomas of the distal esophagus and stomach and compared our results with pathologists findings as the gold standard. RESULTS: Of the 222 patients studied, the precise examination of 11% EUS was not completely possible due to severe tumor stenosis. The accuracy of EUS with respect to T, N+/- and TN+/- amounted to 51%, 65% and 34% in 131 patients with adenocarcinomas of the esophageal gastric junction and to 50%, 66% and 37% in 91 patients with adenocarcinomas located in the fundus, corpus or antrum of the stomach respectively. With respect to T-stage, the overstaging of tumors was more common than understaging, especially in pT2b-carcinomas. The subgroup analysis of the 131 EGJ adenocarcinoma patients showed that the results obtained by EUS were slightly better in type I (distal esophageal cancer) than in type II and III cardia carcinomas (proximal gastric cancer).When comparing two observation periods (1992-1996 and 1997-2001), the accuracy of endoscopic ultrasound staging was very similar in both periods for T-category (51% vs 49%) and N-category (63% vs 64%) as well as for combined TN-staging (36% vs 35%) respectively. CONCLUSIONS: In clinical routine examinations of adenocarcinomas of the stomach and the distal esophagus, the accuracy of EUS is not as good as the excellent results in the past--mostly obtained under study conditions--may suggest.

Operative treatment of renal autonomous hyperparathyroidism: cause of persistent or recurrent disease in 304 patients.

BACKGROUND: Subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX and AT) are standard procedures in the treatment of renal autonomous hyperparathyroidism. In contrast to primary hyperparathyroidism, the persistence/recurrence rate is reported of up to 12.0%. PATIENTS AND METHODS: Between 1986 and 2000 we operated on 304 patients with renal autonomous hyperparathyroidism including 14 patients who were admitted after a primary operation in an outside hospital. Mean observation period was 51.4+/-38.9 months. RESULTS: The overall persistence/recurrence rate in our patients was 9.0% (26/290). After SPTX, excluding patients with an incomplete operation, it was 3.7%, and after TPTX and AT it was 6.0%. Reasons for developing recurrent or persistent disease in these patients were removal of less than 3.5 glands ( n=12), hyperplastic autograft ( n=5), and supernumerary gland ( n=4). After the first reoperation 7 patients (26.9%) had persistent or recurrent disease. CONCLUSIONS: An incomplete primary operation caused by missed cervical glands was the major reason for persistent ( n=8) or recurrent ( n=4) disease after different operative strategies in renal autonomous hyperparathyroidism.

The actual role of classic bilateral cervicotomic approach for primary hyperparathyroidism in the era of minimally invasive surgery.

UNLABELLED: Recent advances in preoperative localisation of parathyroid adenomas and intraoperative prove of complete removal of hyperfunctioning parathyroid tissue have fostered less invasive operative procedures which directly target the diseased gland. Such strategies have partially replaced the previous gold standard procedure of bilateral neck exploration. We herein report on our own series of 1099 consecutive operations for primary hyperparathyroidism performed in a 16 year period and provide information and arguments for primary bilateral exploration in selected cases. 97.1% of patients were cured by the primary operation. From 1999 through 2001, 200 patients underwent bilateral neck exploration, whereas 63 unilateral operations were performed (33 patients were treated by minimally invasive video-assisted parathyroidectomy (MIVAP) and 30 by minimally invasive open parathyroidectomy (MIOP). In the remaining 200 patients minimally invasive unilateral parathyroid surgery was not feasible due to concomitant goiter (n = 102), lack of preoperative localisation (n = 30), previous thyroid surgery (n = 10), suspected multiglandular disease (n = 10), or other reasons (n = 8). In 40 patients the decision for bilateral neck exploration was made despite feasibility of a unilateral approach. CONCLUSION: Whereas unilateral exploration produced excellent cure rates in older patients, it is not recommended in patients with a high likelihood of multiglandular disease, presence of a large or multinodular goitre, high PTH levels, giant adenoma, unclear MIBI scans or an unreliable OPTH assay. Contrasting recent reports on a dramatic shift of technique towards minimally invasive procedures unilateral parathyroid surgery may not be preferably advisable in a majority of patients from countries with insufficient iodine supplementation.

[Standards in diagnosis of diverticulitis]. / Standards in der Diagnostik der Divertikulitis.

The diagnostic procedure is determined by the severity of the diverticulitis. In complicated cases of diverticulitis, it is necessary to detect those patients with obstructive ileus, perforation, and peritonitis who require instant emergency surgery. In all other cases, diagnostic procedures serve as a tool to determine the best therapeutic options. The CT scan of the abdomen seems to have the highest reliability for determining therapy. Other investigations such as barium enema and coloscopy are not indicated in emergency cases or cannot exactly describe the stage of the diverticular disease. Many surgeons still prefer an enema with water-soluble contrast medium in emergency cases to visualize a perforation. CT scans have the same ability to answer this question, but they are more expensive and are not available everywhere at any given time.

Neurogenic appendicopathy: a clinical disease entity?

BACKGROUND AND AIMS: This study compared two histopathological examinations for the diagnosis of neurogenic appendicopathy (NA), assessed the frequency of NA, and evaluated whether it is a clinical disease entity distinct from acute appendicitis. PATIENTS AND METHODS: In a prospective observational multicenter study (surgical departments of five hospitals with one reference pathology) we evaluated 282 patients who underwent appendectomy for suspected appendicitis; we examined the frequency of NA in acute appendicitis and in the negative appendectomy group. For the diagnosis two staining methods were compared. We also attempted to determine clinical features of NA. RESULTS: We observed 93% accuracy for hematoxylin-eosin staining compared with S-100 staining (reference standard) in the diagnosis of NA. There was NA in 3.8% of patients with acute appendicitis and in 47% of those with negative appendectomy. We observed significant differences between the three groups (NA without appendicitis, acute appendicitis, and negative appendectomy without neurogenic appendicopathy) only for sex, age, vomiting, similar previous complaints, rebound tenderness, guarding, rigidity, leukocytes (univariate analysis) and sex (multivariate analysis). CONCLUSION: Neurogenic appendicopathy is a histopathological entity that can be identified by hematoxylin-eosin staining. History and clinical examination do not enable us preoperatively to differentiate between acute appendicitis, NA, and negative appendectomy.

Clinical impact of retinoids in redifferentiation therapy of advanced thyroid cancer: final results of a pilot study.

Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.

Neurogenic appendicopathy in children.

BACKGROUND: In a prospective multicenter study, we could show that neurogenic appendicopathy is a histological entity. This study compares the general and the pediatric population with respect to clinical presentation and incidence of neurogenic appendicopathy (NA). METHODS: Included were patients that underwent appendectomy for suspected appendicitis, excluded were patients younger than 6 years and patients with missing data. Neurogenic appendicopathy was diagnosed by S-100 immunochemistry and/or haematoxylineosin (H.E.) staining. Two age groups (< or = 14 y and > 14 y) were compared with respect to the frequency of NA. RESULTS: In only four cases out of 84 children (4.8%) did we find neurogenic appendicopathy compared to 48 patients (24.2 %) out of 198 adolescents and adults. In the subgroup with negative appendectomy, the frequency of NA was 16.7% (< or = 14 years) and 56.6% (> 14 years). A clinical differentiation between neurogenic appendicopathy and acute appendicitis was not possible because of the small sample size. CONCLUSION: Neurogenic appendicopathy is a very rare histopathological entity in children. History and clinical examination do not make it possible for us to differentiate preoperatively between acute appendicitis and neurogenic appendicopathy.

Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus.

BACKGROUND: The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. METHODS: From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. RESULTS: Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 +/- 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. CONCLUSIONS: NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival.

Genetic determinants of IL-6 expression levels do not influence bone loss in inflammatory bowel disease.

Bone loss in inflammatory bowel disease (IBD) is presumed to be mediated by inflammation. Increased levels of the multifunctional cytokine IL-6 in inflammatory diseases have been proposed to be the link in such "inflammation-mediated osteopenia." A recently described G/C polymorphism with an effect on transcription rate and plasma levels of IL-6 suggests a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. This study aimed to assess the frequency of genotypes and haplotypes of the G/C polymorphism of IL-6 in IBD patients. A further aim was to assess whether carriage of the potentially protective CC genotype is favorable with respect to the development of bone disease in IBD. The IL-6 polymorphism was typed in 105 IBD patients and 113 healthy controls. Bone mineral density was evaluated at baseline and after a prospective 2-year-follow-up. The favorable CC genotype with decreased IL-6 release was not underrepresented in IBD patients compared to healthy controls. Carriage of this genotype was not protective with respect to the development of bone disease, either for the bone mineral density at baseline or for the prospectively observed bone loss. Within the subgroup of patients who did not receive steroids during follow-up, the prospectively observed bone loss was even slightly higher in CC carriers, but differences did not reach significance. Genetically determined differences in the degree of the IL-6 response to stressful stimuli are no major predictors for the degree of bone disease in IBD patients.

The microbiology of postoperative peritonitis.

Postoperative peritonitis carries a higher risk of complications and mortality than does community-acquired disease. Little, however, is known about the specific microbiology of this condition. To gain insight into this problem, the microbiological findings of 67 patients with postoperative peritonitis were compared with those of 68 patients with community-acquired peritonitis. In a comparison of postoperative peritonitis with community-acquired disease, the number of isolates of enterococci (23 versus 6) and Enterobacter species (13 versus 4) were increased and the number of isolates of Escherichia coli (21 versus 42) were reduced. Antibiotic therapy before reintervention increased the number of resistant organisms at relaparotomy (33% versus 8%). The in vitro efficacy of the primary antibiotic or combination of drugs did not affect mortality rates (40% versus 38% after effective and ineffective treatment, respectively). Thus, the microbiology of postoperative peritonitis differs significantly from that of community-acquired disease, and specific antibiotic therapy is required, despite the doubtful impact on survival.