Restoration of nerve agent inhibited muscle force production in human intercostal muscle strips with HI 6.

An important factor for successful therapy of poisoning with organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Unfortunately, clinically used oximes, e.g. obidoxime and pralidoxime, are of limited effectiveness in poisoning with different OP nerve agents requiring the search for alternative oximes, e.g. HI 6. In view of substantial species differences regarding reactivation properties of oximes, the effect of HI 6 was investigated with sarin, tabun and soman exposed human intercostal muscle. Muscle force production by indirect field stimulation and the activity of the human muscle AChE was assessed. 30 µM HI 6 resulted in an almost complete recovery of sarin blocked muscle force and in an increase of completely inhibited muscle AChE activity to approx. 30% of control. In soman or tabun exposed human intercostal muscle HI 6 (50 and 100 µM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition, HI 6 up to 1000 µM had no effect on soman blocked muscle force indicating that this oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial therapeutic effect on nerve agent blocked neuromuscular transmission.

Combined spontaneous contralateral pneumothorax and post-pneumonectomy mediastinal shift-associated dextrocardia.

We report here on an unusual late postoperative presentation of extreme post-pneumonectomy dextrocardia and spontaneous contralateral pneumothorax presenting as late complications occurring approximately 2 years after right-sided pneumonectomy. Computed tomography is the diagnostic modality of choice to obtain information on anatomical changes within the post-pneumonectomy space. Knowledge of the spectrum of cardiopulmonary, pleural, and other complications after lung resection is important to properly manage complications in post-pneumonectomy patients.

[Rare occurrence of fulminant acid burn of the esophagus]. / Seltene Ursache einer fulminanten Säureverätzung des Osophagus.

Peptic ulcer due to Zollinger-Ellison syndrome is a rare entity. In this case report a 55-year-old man had a medical history of esophageal reflux, vomiting, and diarrhea for 10 years. Despite continuous medication with a proton pump inhibitor, no complete recovery from symptoms was achieved. A diagnosis of gastrinoma was at first not considered. After discontinuation of the proton pump inhibitor for only a few days, the strong stimulation of the gastrinoma led to fulminant hydrochloric acid burn of the distal esophagus with iatrogenic or spontaneous perforation at the esophagogastral junction. We describe the operative treatment as a two-stage reconstruction with colon interposition and resection of the primary tumor in the duodenum.

["Good advice is precious." The second opinion from the point of view of an interdisciplinary cancer therapy center]. / "Guter Rat ist teuer". Die Zweitmeinung aus Sicht eines interdisziplinären Tumortherapiezentrums.

BACKGROUND AND OBJECTIVE: The setting up of an interdisciplinary tumor treatment center together with a "tumor board" has resulted in early specialty-bridging assessment and therapeutic decisions of cancers, some of them complex, in hospitalized patients with visceral tumors. It was the aim of this study to compare the use and value of the decisions of the tumor board ("second opinion") with those of the original assessment made elsewhere after primary surgical treatment. PATIENTS AND METHODS: Information on the tumor board's database, recorded explicitly as "external comments" or "second opinion" were accessed. The data were then classified according to organs or organ systems and further divided into those cases in which the primary tumor had not been treated, those with tumor recurrence and those with metastases or recurrence of metastases. RESULTS: 8298 cases were evaluated during a five-year period. There were 373 "second opinions" (4.5%), most of the referrals relating to tumors of the upper gastrointestinal tract, corresponding to the focus of our institution. Previously untreated primary tumors amounted to 53.6% of cases, local recurrences in 14.7% and initial evidence of metastases of a visceral tumor in 9.9%. In 21.7% progression of a known metastasizing tumor was the main reason for requesting a second opinion. The second opinion agreed with the external decision for surgery alone in 16.4% of all enquiries. Minor modifications of the external therapeutic decisions were recommended in 5.9% of referred cases, while in 47.2% major changes were recommended. 28,7% of enquiries could not be evaluated because essential data were not available. CONCLUSIONS: Requests for a second opinion in the treatment of visceral tumors are still rare in Germany. Good and current findings are requisites for giving a reliable second opinion. In fewer than a fifth of cases was there agreement with regard to a primarily surgical intervention. The concept of multimodal forms of treatment are usually given priority, which underlines the need for establishing interdisciplinary advisory panels.

Colorectal cancer patients before resection of hepatic metastases. Impact of (18)F-FDG PET on detecting extrahepatic disease.

AIM: Evaluation of the role of FDG-PET in comparison to conventional staging methods for detecting extrahepatic tumour deposits prior to resection of liver metastases. PATIENTS, METHODS: In our prospective study, 58 patients (24 women, 34 men; age 33-81 years) with liver metastases of colorectal carcinoma underwent FDG-PET. Images were acquired in 3D-mode including transmission scans and reconstructed iteratively. For conventional staging all patients underwent abdominal ultrasound, helical computed tomography (CT) of the thorax and abdomen, and colonoscopy/rectoscopy. A preliminary therapeutic decision was established without knowledge of the FDG-PET findings. Thereafter, it was revised or confirmed according to the results of FDG-PET. RESULTS: In 3/58 patients extrahepatic tumour deposits were concordantly identified with both conventional staging methods and FDG-PET. However, in one case, both conventional methods and FDG-PET were false positive regarding pulmonary metastases. In 12/58 patients, nothing but FDG-PET detected extrahepatic tumour masses, which were later confirmed either by histology or follow-up. CONCLUSION: Our study suggests that in 21% of patients exclusively FDG-PET is an appropriate diagnostic tool to reveal extrahepatic metastases or local recurrence of colorectal carcinoma. Our results demonstrate that FDG-PET provides relevant additional information for accurate therapeutic planning as compared to the conventional combination of staging methods. Therefore, FDG-PET has to exert a decisive influence on the decision for resection of hepatic metastases.

[Quality management and experiences with the "cancer center"]. / Qualitätsmanagement und Erfahrungen mit dem "Cancer Center".

BACKGROUND: The goal of quality management in oncology is to achieve the best possible therapeutic outcome. Improved diagnostic methods, more sophisticated therapies in various fields of specialisation and the increased implementation of multimodal therapies have led to considerable advances in the treatment of certain tumors in recent years. However, these advances depend on an interdisciplinary approach necessitating an increased division of labour. These in turn, because of the more complex organizational requirements within hospitals, make greater demands on quality management. METHODS: In October 1999 first steps were taken in the Klinikum rechts der Isar der TU München to organisationally integrate the various institutions involved in the treatment of patients with gastro-intestinal tumors. All the oncologic competence available was bundled in a Cancer Center thus creating the structural prerequisites for interdisciplinary quality management. A daily multidisciplinary Tumor Board, a computer-supported interdisciplinary information and communications system, an interdisciplinary Disease Management Team, an outpatients department and a study centre were all called into life. RESULTS: By the time the outpatients department went into service in November 2001 all the other structural innovations underlying interdisciplinary quality management had already been implemented. Since October 1999 2438 patients had been presented to the Tumor Board, 74% of them with primarily curative intent. CONCLUSIONS: The disease-oriented structure of the Cancer Center has proved worthwhile. The impact of the structure on the quality of processes and results, however, has yet to be evaluated.

[Necessary prerequisites for the function of an oncological competence center. Information technology, documentation of findings and telecommunication]. / Notwendige Voraussetzungen für die Funktion eines onkologischen Kompetenzzentrums. Infomationstechnologie, Befunddokumentation und Telekommunikation.

INTRODUCTION: The organisation of an interdisciplinary cancer center, especially the establishment of a daily tumorboard requires adequate hardware and intelligent software, which is not available in most hospitals and described here with concepts, realisation and first clinical results. MATERIALS AND METHODS: Based on a TCP/IP network and several inhomogeneous department subsystems we developed an intranet-based oncological documentation- and conference software (oncofile), which can be easily operated and administered in a web browser. Common digital media can be imported and the concept allows for paperless organisation of the daily tumor board. The expert decisions are documented online during tumor board runtime together with selected clinical images and the consensus of the decisionmakers. Local therapeutic guidelines as well as trial information can be accessed over the intranet, and interfaces for internet- and telecommunication are used for second opinion and integration of external expertise. RESULTS: Between 10/99 and 2/2002 3298 presentations of 2438 cases were made in the daily tumor board. 74% of the patients had a curative oncological treatment concept, and 24% of the patients received neoadjuvant treatment. 49% of the patients were scheduled for primary resection. Six patients can be effectively handled in a 30 minute tumorboard. CONCLUSION: The establishment of a daily tumorboard is possible by help of intranet-technology, a central database with web clients and moderate hardware investments. The composition of the patient cohort as well as all decisions ever made to a particular patient are transparent at all times. Prospective quality control studies are under way.

[Clinic communication and disease-oriented centers]. / Klinikkommunikation und krankheitsorientierte Zentren.

German hospitals and surgical clinics/departments are facing far-reaching changes. One triggering factor is the imminent reorganization of hospital financing to a system of compensation, which is universally based on diagnosis-related groups (DRGs) and entails a market-economy orientation in the hospital sector. Digital technologies, which facilitate making the necessary adjustments to clinic structures to meet forthcoming challenges, represent another element. The "digital transformation" of the hospital of the future takes place on three levels. The restructuring of the surgical realm runs rather a traditional course by increasing use of information technology, mostly to optimize documentation and existing procedures or to reduce costs. The second sphere reaches substantially further, encompassing reorganization of disease-oriented cooperation between the different medical specialties and enabling the establishment of suitably structured disease-oriented medical centers. This is followed by the third phase, which involves networking clinics or medical centers with private practitioners, aftercare and rehabilitation services, and other disease-oriented care providers.

[Organizational prerequisites for multimodality therapy concepts]. / Organisatorische Voraussetzungen für die Durchführung multimodaler Therapiekonzepte.

The increasing use of multimodal therapies confronts clinics with the need to create new organisational structures. The high degree of specialisation necessitates that the separate disciplines seek ways of working closer together. This is particularly the case when staging results have to be evaluated and a multimodal therapy course chosen or when quality management issues and the coordination of different steps of a treatment are being considered. By establishing disease-oriented organisational structures and by institutionalizing interdisciplinary cooperation, e.g. in daily tumor board meetings and in fixed disease management teams, the organisational prerequisites for implementing multimodal therapies are created.

[The situation of oncological surgery in Germany in 1998: results of a current survey]. / Die Situation der onkologischen Chirurgie in Deutschland 1998: Aktuelle Umfrageergebnisse.

The situation of oncological surgery in Germany was evaluated by sending a questionnaire in January 1998 to 1979 registered surgical clinics. A total of 938 responded and stated that they are involved in that field. In 72% of the departments oncological surgery adds up to 10-30% of their overall work. The proportion of oncological surgery correlated to hospital size and is highest in university clinics. Colorectal surgery is 93% and is the leading topographical field in oncological surgery. 73% of the hospitals regularly perform gastric tumor surgery. The proportion of hospitals with breast surgery is surprisingly high (45%). Many hospitals (54.6%) report neoadjuvant treatment regimens. Together with adjuvant therapy this rate amounts to 85.2%. The diagnostic spectrum of the hospitals involved in the inquiry is satisfactory. However, the modern possibilities of network and telecommunication are not sufficiently used. A second opinion is required predominantly in their own department or clinic, but not between centers. The surgeon's position concerning the speciality "surgical oncology" is ambivalent: only 35.3% of the department chiefs support this speciality--and over 90% of the departments reject the structural independence of "surgical oncology" from "visceral surgery".

[Responsibilities of the surgeon for therapy planning in solid tumors]. / Die Aufgaben der Chirurgen in der Therapieplanung bei soliden Tumoren.

Surgery is still the primary domain for patients suffering from solid cancers, although in many cases multimodal treatment will be required. If the surgeons want to retain this status, the interdisciplinary dialogue must be intensified, as treatment strategies are developed today in an interdisciplinary context. There is a unique chance for future surgeons to establish and lead "tumor boards" within their infrastructure. Tumor boards should be built up in almost every hospital to deal with surgical oncology throughout the entire country. If necessary, specialists from other hospitals or cancer centers must be involved, and modern information technology such as telecommunications should be used to obtain second opinions. Using this technique, smaller hospitals in the area can adapt to the progress and standards of dedicated cancer centers. Modern techniques of telecommunication allow for case presentations and discussions on treatment strategies over long distances, as well as virtual teleconferences in tumor boards meetings. The future role of surgeons in the treatment of solid cancers will depend largely on their ability to resolve the problems outlined here. The surgeon himself must become the modulatory core factor within this evolutionary process.

[Der Chirurg and Langenbecks Archiv für Chirurgie--2 different directions by surgical publications]. / DER CHIRURG und das LANGENBECKS ARCHIV FUR CHIRURGIE--zwei verschiedene Stossrichtungen chirurgischer Publikationen.

DER CHIRURG is the most successful German surgical journal and, reaches with a circulation of more than 8400 copies approx. 60% (including secondary readers approx. 80%) of active surgeons in Germany. DER CHIRURG covers scientific information by highly qualified reviews (30%-35% of the content) as well as peer-reviewed original papers (60%). The rejection rate of original papers is currently 55%. Topics of the reviews are as follows: oncology (20%), benign gastrointestinal surgery (20%), traumatology (15%) and general topics (20%). The thematic spectrum of the original papers is similar. The current problems for this journal are quality control, the issue of double publication, the assurance of an adequate impact factor, and the recruitment of local and international experts for highly qualified reviews.

Radical transhiatal esophagectomy with two-field lymphadenectomy and endodissection for distal esophageal adenocarcinoma.

Distal adenocarcinoma of the esophagus is defined as a tumor originating from an endobrachyesophagus or a tumor with its main tumor mass (more than two-thirds) located in the distal tubular esophagus. Controversy exists about the optimal mode of surgical resection. Some favor transthoracic esophagectomy, whereas others prefer transhiatal (blunt) esophagectomy. A radical transhiatal esophagectomy (RTE) combined with two-field lymphadenectomy and mediastinoscopic dissection of the upper thoracic esophagus (endodissection) is described herein. We assessed the short- and long-term results of this technique and compared them to a historical group of patients undergoing conventional transhiatal esophagectomy (THE) for adenocarcinoma of the distal esophagus. Altogether 124 patients underwent transmediastinal esophagectomy because of adenocarcinoma of the distal esophagus in our department between January 1986 and May 1995. Thirteen of these patients were excluded from this analysis because of preoperative chemotherapy. The remaining 109 patients were divided into two groups: 62 patients who underwent THE between January 1986 and March 1991 (51 men, 11 women; mean age 65.3 years, range 31-83 years) and 47 patients who had RTE between April 1991 and May 1995 (44 men, 3 women; mean age 63.4 years, range 41-84 years). To compare the long-term results of RTE and THE, we used a matched-pairs analysis considering tumor stage and age. The hospital (30-day) mortality was marginally lower in the RTE group (4.3% versus 6.4%), resulting in an overall mortality of 5.5%. The rate of pulmonary complications was insignificantly lower in the RTE group [19.1% RTE versus 25.8% THE; not significant (NS), and the rate of postoperative cardiac abnormalities significantly decreased after RTE (2.6% RTE versus 19.3% THE; p < 0.05). The overall rate of R0 resections was 87.2% (82.2% RTE, 87.1% THE). Overall survival was similar within the two study groups. Complete tumor removal, T and N stages, and the lymph node ratio were identified as prognostic factors for long-term survival. Overall survival was better after RTE than after conventional THE in patients with involved lymph nodes. The mean number of resected lymph nodes per patient in the RTE group was 26.7. Positive lymph nodes were most common in the paracardial region and at the lesser curvature (72%/10.8% of all invaded abdominal nodes). In the mediastinum positive nodes were most common in the paraesophageal and paraaortal region (48%/27% of all mediastinal nodes). Patients with positive abdominal and mediastinal lymph nodes had a poor long-term prognosis. Distal adenocarcinoma of the esophagus can be safely resected by RTE with two-field lymphadenectomy and endodissection. This technique allows radical "enbloc" resection of the tumor-bearing distal third of the esophagus, which includes the primary area of lymph node metastasis of adenocarcinoma of the distal esophagus: the lower mediastinum and paracardial region. The analysis showed that RTE incurred fewer cardiac complications and a better overall survival in N1-positive patients when compared retrospectively to THE. Intraoperative mediastinoscopy allows controlled dissection of the upper mediastinum and biopsy of several mediastinal lymph nodes, with the advantage of providing additional staging information.

[Concept and realization of nationally applicable clinic guidelines in the intra- and internet--a quality assurance measure in the health care system?]. / Konzeption und Realisierung überregional nutzbarer Klinikrichtlinien im Intra- und im Internet--eine Qualitätssicherungsmassnahme im Gesundheitssystem?

This project aimed at the realisation of a database for clinical guidelines in abdominal surgery and oncology, which can be used within a hospital network as well as from the internet. The "Klinikmanual Chirurgie" (currently in German only) can be accessed via http://nt1.chir.med.tu-muenchen.de/manual.h tm worldwide and free of charge. An English version is in preparation.

Prognostic factors of resected adenocarcinoma of the esophagus.

BACKGROUND: The main purpose of this study was to determine prognostic factors in patients with surgical treatment of adenocarcinoma of the esophagus. METHODS: Within a 12.5-year period, esophageal adenocarcinoma was resected in 165 patients by radical transhiatal esophagectomy (n = 134) or transthoracic en bloc esophagectomy (n = 31). Tumors were analyzed according to the 1992 UICC classification with respect to pTNM stage, residual tumor (R) status, grading, and ratio of infiltrated to resected lymph nodes (lymph node ratio); both univariate and multivariate analysis of prognostic factors were performed. RESULTS: The 30-day mortality rate was 6.1%. A complete removal of the tumor was achieved in 83% of the patients. Lymph node metastases were not detected in mucosal cancer (pT1a) but were detected in 18% of submucosal cancer (pT1b), 77% of pT2, 83% of pT3, and 96% of pT4. The overall 5-year survival rate was 34%; for patients without postoperative residual tumor (R0) it was 41%, and for those without lymph node metastases (pN0, R0) 63%. The 5-year survival rate for patients (pN1) with less than 30% invaded lymph nodes was 45%, compared with 0% for more than 30% invaded nodes. Independent prognostic factors for R0 resected patients excluding postoperative fatal outcome were pT and lymph node ratio. CONCLUSIONS: Long-term survival after resection of esophageal adenocarcinoma is mainly associated with complete tumor removal, limited esophageal wall penetration, and ratio of infiltrated to removed lymph nodes of less than 0.3.

Results of transmediastinal endoscopic oesophageal dissection.

A theoretical benefit of transhiatal oesophagectomy (THOE), the avoidance of thoracotomy, is counteracted by the fact that mediastinal dissection of the oesophagus is performed bluntly by hand and without direct vision. To overcome these difficulties, we have described a technique of oesophageal endodissection and evaluated its clinical results. This method allows for mediastinal dissection of the thoracic oesophagus by the use of a mediastinoscope, videoendoscopy and dedicated instruments. Structures such as the trachea, both main bronchi, the vagal trunks, the parietal pleura and mediastinal lymph nodes can be regularly identified. From April/91 until October/93 57 patients underwent endodissection for THOE because of adenocarcinoma of the oesophagus; most of these patients were included in a separate prospective analysis. We found that endodissection was helpful intraoperatively because mediastinal dissection can be performed simultaneously with the abdominal approach; main anatomic structures as well as tumor staging information can be determined even before the hiatus is opened by the abdominal team. Major intraoperative complications were rare (n = 3, 5.3%) and all but one (lesion of the right main bronchus) were managed without thoracotomy. 30-day mortality of all patients was 5.3% (n = 3). Comparative data from a previous prospective study revealed that the main clinical advantage of endodissection over conventional THOE was the lower rate of postoperative pulmonary complications and a low rate of recurrent nerve palsy. Thus, we believe that endodissection is a technical improvement; the method, however, does not solve the problem of the limited dissection of THOE because a systematic lymphadenectomy cannot be performed.

Endodissection of the thoracic esophagus. Technique and clinical results in transhiatal esophagectomy.

OBJECTIVE: Transhiatal esophagectomy (THE), mostly performed in patients with adenocarcinoma of the esophagus, bears the risk of damage to mediastinal structures because the physician's vision is poor during esophageal dissection. The authors report a new endoscopic technique, which enables microsurgical dissection of the esophagus under visual control, that can be performed simultaneously to the abdominal approach. The clinical results in unselected patients with malignant esophageal disease were compared with those of patients undergoing conventional THE. METHODS: Thirty unselected patients (24 men and 6 women; median age, 60 years; age range, 35 to 80 years), mostly with adenocarcinoma of the esophagus, underwent endodissection between April 1991 and July 1992. Thirty patients, who underwent conventional THE between January 1986 and December 1990, were selected using a matched pair algorithm. RESULT: Three significant intraoperative complications were recorded during endodissection (one case of mediastinal bleeding; one case of postoperative bleeding; and one case of a lesion of the right main bronchus), and all were managed without further patient morbidity. The mortality rate (30 days) was 6.6% in the endodissection group (vs. 9.9% THE; not significant [NS]). The frequency of postoperative severe pulmonary complications was 13.3% in the endodissection group (vs. 30% in THE; p < 0.05). The rate of recurrent nerve palsy was only 6.6% in the endodissection group (vs. 13.3% in THE; NS). CONCLUSIONS: Endodissection is especially helpful during esophageal dissection at or above the trachea. It allows identification of mediastinal structures and controlled biopsy of mediastinal lymph nodes. This study showed that endodissection eliminates the "blind angle" during conventional THE, prevents recurrent nerve damage, and reduces pulmonary distress during transhiatal esophagectomy.

The role of esophageal motility in gastroesophageal reflux disease: technique and clinical results of ambulatory 24-hour mano/-pH-metry.

The interplay between esophageal motility and gastroesophageal reflux (GER) was investigated with a new ambulatory system of 24-h monitoring of intraesophageal pressures and pH (MP24). The technique allows for simultaneous digital recordings and off-line data analysis. Both computer-aided and visual analyses were used, and algorithms for intercorrelation of mano- and pH-metry were developed. In a group of normal volunteers the physiological response of esophageal motility on GER was defined. In unselected patients suffering from GER disease, the esophageal motility prior to and during GER events were analyzed. In healthy people, most GER episodes occurred spontaneously and were cleared from the distal esophagus by peristaltic contractions. In GER patients, reflux episodes were often preceded by irregular contractions; during GER, esophageal motility was less often peristaltic compared with controls. Therefore, we conclude that MP24 gives relevant information in GER disease which might help in selecting patients for medical or surgical therapy.

Interaction of gastroesophageal reflux and esophageal motility. Evaluation by ambulatory 24-hour manometry and pH-metry.

The present study addresses the question of whether esophageal motility shortly before, during, and after gastroesophageal reflux (GER) is different in patients with GER disease and healthy controls. Twenty-four-hour continuous recordings of intraesophageal pressures and pH were performed in 12 unselected patients with clinically proven GER disease and in 11 volunteers using a new ambulatory and digital recording device. All GER episodes in each studied subject were classified according to their associated motility pattern shortly before (induction period) and during (response period) GER. More GER episodes were analyzed in patients than in volunteers (median: 41 vs 26, P less than 0.05), and a total of 917 GER episodes (593 in patients, 324 in volunteers) was recorded. During the induction period patients more often had irregular esophageal contractions (median: 23% vs 13%, P less than 0.05) and less often had a peristaltic sequence (median: 6% vs 21%) than normals. No difference between patients and controls existed when comparing the frequency of negative pressure peaks or common cavity phenomena shortly before GER. During the response period peristaltic motility in patients was decreased (median: 10% vs 47%, P less than 0.05). We conclude that: (1) GER events in GER patients are more often associated with irregular esophageal contractions than in healthy controls; (2) GER patients present with a diminished, if any, esophageal peristalsis during GER; and (3) combined ambulatory manometry and pH-metry provides clinically useful information on the individual pathogenesis of GER disease, which is superior to the information retrieved by pH-metry alone.