Robotic and laparoscopic liver resection-comparative experiences at a high-volume German academic center.

PURPOSE: Minimally invasive liver surgery (MILS) is a feasible and safe procedure for benign and malignant tumors. There has been an ongoing debate on whether conventional laparoscopic liver resection (LLR) or robotic liver resection (RLR) is superior and if one approach should be favored over the other. We started using LLR in 2010, and introduced RLR in 2013. In the present paper, we report on our experiences with these two techniques as early adopters in Germany. METHODS: The data of patients who underwent MILS between 2010 and 2020 were collected prospectively in the Magdeburg Registry for Minimally Invasive Liver Surgery (MD-MILS). A retrospective analysis was performed regarding patient demographics, tumor characteristics, and perioperative parameters. RESULTS: We identified 155 patients fulfilling the inclusion criteria. Of these, 111 (71.6%) underwent LLR and 44 (29.4%) received RLR. After excluding cystic lesions, 113 cases were used for the analysis of perioperative parameters. Resected specimens were significantly bigger in the RLR vs. the LLR group (405 g vs. 169 g, p = 0.002); in addition, the tumor diameter was significantly larger in the RLR vs. the LLR group (5.6 cm vs. 3.7 cm, p = 0.001). Hence, the amount of major liver resections (three or more segments) was significantly higher in the RLR vs. the LLR group (39.0% vs. 16.7%, p = 0.005). The mean operative time was significantly longer in the RLR vs. the LLR group (331 min vs. 181 min, p = 0.0001). The postoperative hospital stay was significantly longer in the RLR vs. the LLR group (13.4 vs. LLR 8.7 days, p = 0.03). The R0 resection rate for solid tumors was higher in the RLR vs. the LLR group but without statistical significance (93.8% vs. 87.9%, p = 0.48). The postoperative morbidity ≥ Clavien-Dindo grade 3 was 5.6% in the LLR vs. 17.1% in the RLR group (p = 0.1). No patient died in the RLR but two patients (2.8%) died in the LLR group, 30 and 90 days after surgery (p = 0.53). CONCLUSION: Minimally invasive liver surgery is safe and feasible. Robotic and laparoscopic liver surgery shows similar and adequate perioperative oncological results for selected patients. RLR might be advantageous for more advanced and technically challenging procedures.

Mesothelial cyst of the round ligament.

Mesothelial cyst of the round ligament is a rare finding in females, with only a few cases reported so far. A case of a 25 year old female patient presenting with a palpable mass in her right inguinal region is presented. The preoperative investigation through ultrasound (U/S), computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of an intraabdominal cystic lobular mass in the inguinal canal, in contact with the femoral vessels. The mass was excised and the diagnosis of a benign mesothelial cyst was made through pathological examination. Even though it is a rare condition, it is advisable that clinicians consider in the differential diagnosis when evaluating a non-reducible mass in the inguinal region of a female patient.

[Robotic-Assisted Liver Surgery]. / Roboterassistierte Leberchirurgie.

BACKGROUND: The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of ≤ 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria. RESULTS: Malignant liver tumours were removed in 10 patients (71%) and benign symptomatic liver tumors in 3 patients (21%), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7%) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21%) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14%). One patient (7%) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively. CONCLUSION: Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.

[Results of surgical treatment of hiatal hernia]. / Ergebnisse der operativen Therapie großer Hiatushernien.

BACKGROUND: Hiatus hernias are considered as the most prominent form of diaphragmatic hernias. The passage is defined through the oesophageal hiatus, resulting in a superdiaphragmatic displacement of parts of the stomach or the complete stomach, respectively. In our work we investigated the treatment of partial thoracic stomach with both open and minimally invasive surgical procedures emphasising the view on operating data, the success of the surgery and recurrence rates. Patients with mesh insertion for hernia defect closures were considered separately. MATERIAL AND METHOD: 94 Patients were treated in the period from 01.01.2003 to 01.06.2010. The ratio male/female was 2 : 1. The median age was 66 years. All data were prospectively collected by means of surgical protocols and data from the central patient records and analysed retrospectively. The statistical analyses were performed with SPSS 18.0 (SPSS Inc., Chicago, IL, USA). Any existing significances were determined using the T-test. RESULTS: Of the 94 patients, 65 were operated laparoscopically. In the case of nine patients an initial laparoscopic surgery had to be changed to an open procedure. The reasons for switching surgical procedures were splenic bleeding in the case of 2 patients, intestinal injury due to perforation by the trocar in one case and unclear surgical situs in 6 cases. The postoperative complication rate was 24 %. The main reasons were a delayed achievement of passage. The mortality rate was 0 %. The comparison between laparoscopic and open groups showed, by comparable complication and recurrence rates, a shorter recovery time in favour of patients operated on laparoscopically. Additionally it can be stated that a bridge closure with mesh (ePTFE) had no significant influence on the postoperative outcome. Therefore we cannot confirm the postulated poor postoperative results of other groups. CONCLUSION: In summary, the clear trend in the surgical treatment of hiatus hernias is to minimally invasive surgery. Only for patients with multiple previous operations, who are expected to have strong adhesions, the operation with comparable morbidity and mortality rates can also be planned primarily as open. In this case, however, longer postoperative recovery times must be expected. Large defects can be treated with comparable complication and recurrence rates by mesh insertion (ePTFE).

Conserved proline residues prevent dimerization and aggregation in the ß-lactamase BlaC.

Evolution leads to conservation of amino acid residues in protein families. Conserved proline residues are usually considered to ensure the correct folding and to stabilize the three-dimensional structure. Surprisingly, proline residues that are highly conserved in class A ß-lactamases were found to tolerate various substitutions without large losses in enzyme activity. We investigated the roles of three conserved prolines at positions 107, 226, and 258 in the ß-lactamase BlaC from Mycobacterium tuberculosis and found that mutations can lead to dimerization of the enzyme and an overall less stable protein that is prone to aggregate over time. For the variant Pro107Thr, the crystal structure shows dimer formation resembling domain swapping. It is concluded that the proline substitutions loosen the structure, enhancing multimerization. Even though the enzyme does not lose its properties without the conserved proline residues, the prolines ensure the long-term structural integrity of the enzyme.

The training pathway for residents: 'Robotic Curriculum for young Surgeons' (RoCS) does not impair patient outcome during implementation into clinical routine.

The "Robotic Curriculum for young Surgeons" (RoCS) was launched 03/2020 to address the increasing importance of robotics in surgical training. It aims to provide residents with foundational robotic skills by involving them early in their training. This study evaluated the impact of RoCS' integration into clinical routine on patient outcomes. Two cohorts were compared regarding the implementation of RoCS: Cohort 1 (before RoCS) included all robot-assisted procedures between 2017 and 03/2020 (n = 174 adults) retrospectively; Cohort 2 (after RoCS) included all adults (n = 177) who underwent robotic procedures between 03/2020 and 2021 prospectively. Statistical analysis covered demographics, perioperative parameters, and follow-up data, including mortality and morbidity. Subgroup analysis for both cohorts was organ-related (upper gastrointestinal tract (UGI), colorectal (CR), hepatopancreaticobiliary system (HPB)). Sixteen procedures were excluded due to heterogeneity. In-hospital, 30-, 90-day morbidity and mortality showed no significant differences between both cohorts, including organ-related subgroups. For UGI, no significant intraoperative parameter changes were observed. Surgery duration decreased significantly in CR and HPB procedures (p = 0.018 and p < 0.001). Estimated blood loss significantly decreased for CR operations (p = 0.001). The conversion rate decreased for HPB operations (p = 0.005). Length of hospitalization decreased for CR (p = 0.015) and HPB (p = 0.006) procedures. Oncologic quality, measured by histopathologic R0-resections, showed no significant changes. RoCS can be safely integrated into clinical practice without compromising patient safety or oncologic quality. It serves as an effective training pathway to guide robotic novices through their first steps in robotic surgery, offering promising potential for skill acquisition and career advancement.

Is there a disadvantage to radical lymph node dissection in colon cancer?

BACKGROUND: The necessity for radical lymph node dissection for solid tumours was discussed in the past controversially. The aim of this study was to correlate the oncologic results of radical surgery for colon cancer with potential complications. METHODS: A total of 1,453 patients with R0-resected colon cancer operated on between 1978 and 2004 were analysed in a prospective database. The follow-up was at least 5 years. Rates of survival, locoregional and distant recurrences and complications were calculated. RESULTS: To compare the oncological outcome, the time frame was divided into five periods. In the last cohort (2000-2004), we observed in stage I-III tumours a 5-year cancer-related survival rate of 90.1 %, compared to 82.1 % in the first cohort (1978-1984) (p = 0.061). The local recurrence rate could be reduced from 6.5 to 3.2 % in the same cohorts (p = 0.059). It reached the level of significance in the multivariate analysis. The rates of distant metastases did not change. For patients with stage III, the 5-year cancer survival rates increased from 62.0 to 81.8 % (p = 0.005). Morbidity and mortality were comparable to other studies even to those with limited lymph node dissections. CONCLUSION: Radical lymph node dissection in colon cancer is not associated with obvious disadvantages to the patient. Specific considerable side effects were not observed when the preparation is performed in embryonic planes preserving the autonomous nerves. The complication rates were not increased compared to other studies, even to those with limited lymphatic dissection. In addition, radical lymph node dissection in colon cancer may improve survival.

[Consultations by senior physicians in general and abdominal surgery for other medical disciplines over 10 years at a tertiary center-Is a fast time-consuming processing necessary? : Spectrum of clinical findings, diagnoses and treatment decision making]. / Allgemein- und viszeralchirurgische Oberarztkonsile für andere medizinische Disziplinen über 10 Jahre an einem tertiären Zentrum ­ ist eine schnelle, zeitaufwendige Abarbeitung notwendig? : Klinisches Befund­, Diagnose- und therapeutisches Entscheidungsspektrum.

BACKGROUND: The challenges of an adequate, efficient and rational medical treatment and care of patients are always associated with an interprofessional activity of several specialist disciplines. AIM: The spectrum of variable diagnoses and the profile of surgical decision-making with further surgical measures within the framework of senior physician consultation in general and visceral surgery for neighboring medical disciplines were analyzed on a representative patient cohort over a defined observational time period. PATIENTS AND METHODS: All consecutive patients (n = 549 cases) were documented as part of a clinical systematic prospective single center observational study at a tertiary center using a computer-based patient registry over 10 years (1 October 2006-30 September 2016). The data were analyzed with respect to the spectrum of clinical findings, diagnoses, treatment decisions and the influencing factors as well as gender and age differences and time-dependent developmental trends using χ2-tests and U­tests. RESULTS (KEY POINTS): The predominant discipline for requests for surgical consultation was cardiology (19.9%) followed by surgical disciplines (11.8%) and gastroenterology (11.3%). Disorders of wound healing (7.1%) and acute abdomen (7.1%) were predominant in the diagnostic profile. In 11.7% of the patients the indications for immediate surgery were derived, whereas in 12.9% elective surgery was recommended. The conformity rate of suspected and definitive diagnoses was only 58.4%. CONCLUSION: The surgical consultation work is an important mainstay of a sufficient and especially timely clarification of surgically relevant questions in nearly all medical institutions and especially in a center. This serves i) the quality assurance of surgery in the clinical care of patients with need of additional interdisciplinary needs for surgical treatment in the daily practice of general and abdominal surgery in research on clinical care, ii) clinical marketing and monetary aspects in the sense of patient recruitment and iii) last but not least to provide emergency care of patients. Due to the high proportion of 12% of subsequent emergency operations, which were derived from requests for general and visceral surgical consultations, such requests must be processed promptly during working hours.

Outcome of operative therapy of hepatic metastatic stomach carcinoma: a retrospective analysis.

BACKGROUND: In general, hepatic metastasis from stomach carcinoma has an unfavorable prognosis. In addition, there are often further metastases in other organs, such as peritoneal carcinomatosis. The major aim of the present study was to investigate a potential curative surgical approach in these patients. MATERIAL AND METHODS: Thirty-one patients with hepatic metastases from stomach cancer were treated in the University Clinic Erlangen-Nürnberg. The data were collected retrospectively from 1972 to 1977 and prospectively since 1978 at the Erlangen Cancer Registry. The time frame of this retrospective analysis from patients who had surgical resection of hepatic metatases from gastric cancer was from 1972 to 2008. The median age of the patients was 65 years, and the ratio of men to women was 2:1. RESULTS: Atypical or anatomical resections of segments were possible in 21 cases. Larger operations, such as hemihepatectomy (right/left), were performed in 10 patients. The postoperative complication rate was 29%, and the hospital mortality was 6%. The five-year survival rate was 13%; R0 resection was achieved in 23 patients. We also found a significant difference in the 5-year survival rate between synchronous and metachronous metastases (0 vs. 29%; p < 0.001) and R0 resected patients (p = 0.002). Patients with solitary metastases had a significantly better median survival than patients with multiple metastases (21 vs. 4 months; p < 0.005.) CONCLUSIONS: The overall survival in our study was 13%; therefore gastric cancer with liver metastases is not in every case a palliative situation. It seems that patients with liver metastases benefit from resection, especially if the metastases are metachronous (p < 0.001) and solitary, provided that a curative R0 resection has been achieved. An interdisciplinary approach with neoadjuvant chemotherapy appears useful. Additional controlled studies should be conducted.

Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence.

FoxM1 is a member of the Forkhead family of transcription factors and is implicated in inducing cell proliferation and some forms of tumorigenesis. It binds promoter regions with a preference for tandem repeats of a consensus 'TAAACA' recognition sequence. The affinity of the isolated FoxM1 DNA-binding domain for this site is in the micromolar range, lower than observed for other Forkhead proteins. To explain these FoxM1 features, we determined the crystal structure of its DNA-binding domain in complex with a tandem recognition sequence. FoxM1 adopts the winged-helix fold, typical of the Forkhead family. Neither 'wing' of the fold however, makes significant contacts with the DNA, while the second, C-terminal, wing adopts an unusual ordered conformation across the back of the molecule. The lack of standard DNA-'wing' interactions may be a reason for FoxM1's relatively low affinity. The role of the 'wings' is possibly undertaken by other FoxM1 regions outside the DBD, that could interact with the target DNA directly or mediate interactions with other binding partners. Finally, we were unable to show a clear preference for tandem consensus site recognition in DNA-binding, transcription activation or bioinformatics analysis; FoxM1's moniker, 'Trident', is not supported by our data.

Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing.

All organisms need to ensure that no DNA segments are rereplicated in a single cell cycle. Eukaryotes achieve this through a process called origin licensing, which involves tight spatiotemporal control of the assembly of prereplicative complexes (pre-RCs) onto chromatin. Cdt1 is a key component and crucial regulator of pre-RC assembly. In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent DNA rereplication. Here, we address the mechanism of DNA licensing inhibition by Geminin, by combining X-ray crystallography, small-angle X-ray scattering, and functional studies in Xenopus and mammalian cells. Our findings show that the Cdt1:Geminin complex can exist in two distinct forms, a "permissive" heterotrimer and an "inhibitory" heterohexamer. Specific Cdt1 residues, buried in the heterohexamer, are important for licensing. We postulate that the transition between the heterotrimer and the heterohexamer represents a molecular switch between licensing-competent and licensing-defective states.

Oncological outcome after hyperthermic isolated limb perfusion for primarily unresectable versus locally recurrent soft tissue sarcoma of extremities.

INTRODUCTION: The management of locally advanced extremity soft tissue sarcomas, particularly in terms of a limb salvage strategy, represents a challenge, especially in recurrent tumors. In the context of a patient-tailored multimodal therapy, hyperthermic isolated limb perfusion (ILP) is a promising limb-saving treatment option. We report the outcome of patients with primarily irresectable and locally recurrent soft tissue sarcoma (STS) treated by ILP. PATIENTS AND METHODS: Data about patient demographics, clinical und histopathological characteristics, tumor response, morbidity and oncological outcome of all patients with STS, who underwent an ILP at our institution in a 10-year period, were retrospectively detected and analyzed. RESULTS: The cohort comprised 30 patients. Two patients were treated with ILP for palliative tumor control, 13 patients because of a local recurrent soft tissue sarcoma (rSTS) and 15 patients because of primarily unresectable soft tissue sarcoma (puSTS). 25 of the 28 patients with curative intention received surgery after ILP (11 pts with rSTS and 14 pts with puSTS). Histopathologically we observed complete response in 6 patients (24%) and partial responses in 19 patients (76%) with a significant better remission in patients with puSTS (p = 0,043). Limb salvage rate was 75%. Mean follow-up was 69 months [range 13-142 months]. Seven (7/11; 64%) patients with rSTS and one (1/14; 7%) patient with puSTS developed local recurrence after ILP and surgery, whereas eight (8/13; 62%) rSTS patients and seven (7/15; 47%) puSTS patients developed distant metastasis. During follow-up, eight patients (28.5%) died of disease (5/13; 38%) rSTS and 3/15 (20%) puSTS. ILP in the group of previously irradiated sarcoma patients (n = 13) resulted in a limb salvage rate of 69% and was not associated in an increased risk for adverse events. DISCUSSION: ILP for advanced extremity STS is a treatment option for both puSTS and rSTS resulting in good local control and should be considered in multimodal management. ILP is also a good option for patients after radiation history.

A falciform ligament flap surface sealing technique for laparoscopic and robotic-assisted liver surgery.

Whether sealing the hepatic resection surface after liver surgery decreases morbidity is still unclear. Nevertheless, various methods and materials are currently in use for this procedure. Here, we describe our experience with a simple technique using a mobilized falciform ligament flap in minimally invasive liver surgery (MILS). We retrospectively analyzed the charts from 46 patients who received minor MILS between 2011 and 2019 from the same surgical team in a university hospital setting in Germany. Twenty-four patients underwent laparoscopic liver resection, and 22 patients received robotic-assisted liver resection. Sixteen patients in the laparoscopic group and fourteen in the robotic group received a falciform ligament flap (FLF) to cover the resection surface after liver surgery. Our cohort was thus divided into two groups: laparoscopic and robotic patients with (MILS + FLF) and without an FLF (MILS-FLF). Twenty-eight patients (60.9%) in our cohort were male. The overall mean age was 56.8 years (SD 16.8). The mean operating time was 249 min in the MILS + FLF group vs. 235 min in the MILS-FLF group (p = 0.682). The mean blood loss was 301 ml in the MILS + FLF group vs. 318 ml in the MILS-FLF group (p = 0.859). Overall morbidity was 3.3% in the MILS + FLF group vs. 18.8% in the MILS-FLF group (p = 0.114). One patient in the MILS-FLF group (overall 2.2%), who underwent robotic liver surgery, developed bile leakage, but this did not occur in the MILS + FLF group. Covering the resection surface of the liver after minor minimally invasive liver resection with an FLF is a simple and cost-effective technique that does not prolong surgical time or negatively affect other perioperative parameters. In fact, it is a safe add-on step during MILS that may reduce postoperative morbidity. Further studies with larger cohorts will be needed to substantiate our proof of concept and results.

Structure of cyanase reveals that a novel dimeric and decameric arrangement of subunits is required for formation of the enzyme active site.

BACKGROUND: Cyanase is an enzyme found in bacteria and plants that catalyzes the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide. In Escherichia coli, cyanase is induced from the cyn operon in response to extracellular cyanate. The enzyme is functionally active as a homodecamer of 17 kDa subunits, and displays half-site binding of substrates or substrate analogs. The enzyme shows no significant amino acid sequence homology with other proteins. RESULTS: We have determined the crystal structure of cyanase at 1.65 A resolution using the multiwavelength anomalous diffraction (MAD) method. Cyanase crystals are triclinic and contain one homodecamer in the asymmetric unit. Selenomethionine-labeled protein offers 40 selenium atoms for use in phasing. Structures of cyanase with bound chloride or oxalate anions, inhibitors of the enzyme, allowed identification of the active site. CONCLUSIONS: The cyanase monomer is composed of two domains. The N-terminal domain shows structural similarity to the DNA-binding alpha-helix bundle motif. The C-terminal domain has an 'open fold' with no structural homology to other proteins. The subunits of cyanase are arranged in a novel manner both at the dimer and decamer level. The dimer structure reveals the C-terminal domains to be intertwined, and the decamer is formed by a pentamer of these dimers. The active site of the enzyme is located between dimers and is comprised of residues from four adjacent subunits of the homodecamer. The structural data allow a conceivable reaction mechanism to be proposed.

The X-ray crystal structure of neuronal Sec1 from squid sheds new light on the role of this protein in exocytosis.

BACKGROUND: Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis. They regulate vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought to prevent SNARE complex formation, a protein complex required for membrane fusion. Whereas Sec1 molecules are essential for neurotransmitter release and other secretory events, their interaction with syntaxin molecules seems to represent a negative regulatory step in secretion. RESULTS: Here we report the X-ray crystal structure of a neuronal Sec1 homologue from squid, s-Sec1, at 2.4 A resolution. Neuronal s-Sec1 is a modular protein that folds into a V-shaped three-domain assembly. Peptide and mutagenesis studies are discussed with respect to the mechanism of Sec1 regulation. Comparison of the structure of squid s-Sec1 with the previously determined structure of rat neuronal Sec1 (n-Sec1) bound to syntaxin-1a indicates conformational rearrangements in domain III induced by syntaxin binding. CONCLUSIONS: The crystal structure of s-Sec1 provides the molecular scaffold for a number of molecular interactions that have been reported to affect Sec1 function. The structural differences observed between s-Sec1 and the structure of a rat n-Sec1-syntaxin-1a complex suggest that local conformational changes are sufficient to release syntaxin-1a from neuronal Sec1, an active process that is thought to involve additional effector molecule(s).

Crystal structure of UDP-N-acetylglucosamine enolpyruvyltransferase, the target of the antibiotic fosfomycin.

BACKGROUND: The ever increasing number of antibiotic resistant bacteria has fuelled interest in the development of new antibiotics and other antibacterial agents. The major structural element of the bacterial cell wall is the heteropolymer peptidoglycan and the enzymes of peptidoglycan biosynthesis are potential targets for antibacterial agents. One such enzyme is UDP-N-acetylglucosamine enolpyruvyltransferase (EPT) which catalyzes the first committed step in peptidoglycan biosynthesis: the transfer of the enolpyruvyl moiety of phosphoenolpyruvate (PEP) to the 3-hydroxyl of UDP-N-acetylglucosamine (UDPGlcNAc). EPT is of potential pharmaceutical interest because it is inhibited by the broad spectrum antibiotic fosfomycin. RESULTS: The crystal structure of substrate-free EPT has been determined at 2.0 A resolution. The structure reveals a two-domain protein with an unusual fold (inside out alpha/beta barrel) which is built up from the sixfold repetition of one folding unit. The only repetitive element in the amino acid sequence is a short motif, Leu-X3-Gly(Ala), which is responsible for the formation of hydrogen-bond interactions between the folding units. An enzyme which catalyzes a similar reaction to EPT, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), has a very similar structure despite an amino acid sequence identity of only 25%. To date, only these two enzymes appear to display this characteristic fold. CONCLUSIONS: The present structure reflects the open conformation of the enzyme which is probably stabilized through two residues, a lysine and an arginine, located in the cleft between the domains. Binding of the negatively charged UDPGlcNAc to these residues could neutralize the repulsive force between the two domains, thereby allowing the movement of a catalytically active cysteine residue towards the cleft.

Crystal structure of a bacterial chitinase at 2.3 A resolution.

BACKGROUND: Chitinases cleave the beta-1-4-glycosidic bond between the N-acetyl-D-glucosamine units of which chitin is comprised. Chitinases are present in plants, bacteria and fungi, but whereas structures are available for two prototypic plant enzymes, no structure is available for a bacterial or fungal chitinase. RESULTS: To redress this imbalance, the structure of native chitinase A from Serratia marcescens has been solved by multiple isomorphous replacement and refined at 2.3 A resolution, resulting in a crystallographic R-factor of 16.2%. The enzyme comprises three domains: an all beta-strand amino-terminal domain, a catalytic alpha/beta-barrel domain, and a small alpha+beta-fold domain. There are several residues with unusual geometries in the structure. Structure determination of chitinase A in complex with N,N',N",N"'-tetra-acetylo-chitotetraose, together with biochemical and sequence analysis data, enabled the positions of the active-site and catalytic residues to be proposed. CONCLUSIONS: The reaction mechanism seems to be similar to that of lysozyme and most other glycosylhydrolases, i.e. general acid-base catalysis. The role of the amino-terminal domain could not be identified, but it has similarities to the fibronectin III domain. This domain may possibly facilitate the interaction of chitinase A with chitin.

[Surgery for metastases, anatomical and ethical limits. Special aspect: oligometastases]. / Metastasenchirurgie - anatomische und ethische Grenzen. Besonderer Aspekt: Oligometastasierung.

The surgical resection of metastases is nowadays feasible in selected patients with multifocal metastatic disease due to the implementation of interdisciplinary multimodal therapeutic options. Anatomical limitations do not seem to represent obstacles which cannot be overcome because of the development of new surgical techniques. The cornerstone of the selection of patients is the correct staging diagnosis achieved through modern diagnostic tools; however, surgery alone does not always offer acceptable survival and recurrence-free rates. Furthermore, in every complex surgical procedure there is the risk of morbidity and mortality; therefore, parameters such as alternative therapeutic modalities, the individual situation of the patient and tumor biology have to be considered in order to make the correct selection of patients. This is one of the major future challenges and should never be driven by unfounded hopes and expectations of the patients. The same principle also applies for brain metastases, which represent the most common brain tumors. Approximately 70 % of patients with brain metastases have 1-3 lesions (oligometastases). Treatment is now individualized and the goal of therapy has shifted towards long-term survival (≥ 24 months) and improved quality of life. Under this aspect surgery is one of the important treatment options, particularly in patients with a single metastasis or oligometastases. Furthermore, approximately 20 % of patients who have recurrent brain metastases, successfully undergo a complete resection of tumors and with a Karnofsky performance status (KPS) score > 70 show a long-term survival of ≥ 24 months.

Molecular, crystal and solution structure of a beta-cyclodextrin complex with the bromide salt of 2-(3-dimethylaminopropyl)tricyclo[3.3.1.1(3,7)]decan-2-ol, a potent antimicrobial drug.

The pharmacological properties of a cyclomaltoheptaose (beta-cyclodextrin) series of adamantane-group-bearing compounds that exhibit potent antibacterial activity have been studied, both isolated and in complex with beta-cyclodextrins (betaCDs). In this work, the structure of the bromide salt of 2-(3-dimethylaminopropyl)-tricyclo[3.3.1.1(3,7)]decan-2-ol(A DM-10) complexed with betaCD and ten water molecules was studied in the solid state by X-ray crystallography and in solution by NMR spectroscopy. X-ray crystallographic studies of the complex were performed both at room and cryogenic temperatures. The long aliphatic chain of ADM-10 adopts a single conformation at low temperature in contrast to what is observed at room temperature, where two side chain conformations are seen. Both NMR and X-ray crystallography studies indicate that the adamantane moiety of ADM-10 is buried in the betaCD cavity. Chemical shifts in NMR experiments can be explained on the basis of the crystal structure of the complex.