Stoma associated complications after diverting loop ileostomy, end ileostomy or split stoma formation after right sided colectomy-a retrospective cohort study (StoComSplit Analysis).

BACKGROUND: For high-risk patients receiving right-sided colectomy, stoma formation is a safety strategy. Options are anastomosis with loop ileostomy, end ileostomy, or split stoma. The aim is to compare the outcome of these three options. METHODS: This retrospective cohort study included all patients who underwent right sided colectomy and stoma formation between January 2008 and December 2021 at two tertial referral centers in Switzerland. The primary outcome was the stoma associated complication rate within one year. RESULTS: A total of 116 patients were included. A total of 20 patients (17%) underwent primary anastomosis with loop ileostomy (PA group), 29 (25%) received an end ileostomy (ES group) and 67 (58%) received a split stoma (SS group). Stoma associated complication rate was 43% (n = 21) in PA and in ES group and 50% (n = 34) in SS group (n.s.). A total of 30% (n = 6) of patients in PA group needed reoperations, whereas 59% (n = 17) in ES and 58% (n = 39) in SS group had reoperations (P = 0.07). Wound infections occurred in 15% (n = 3) in PA, in 10% (n = 3) in ES, and in 30% (n = 20) in SS group (P = 0.08). A total of 13 patients (65%) in PA, 7 (24%) in ES, and 29 (43%) in SS group achieved stoma closure (P = 0.02). A total of 5 patients (38%) in PA group, 2 (15%) in ES, and 22 patients (67%) in SS group had a stoma-associated rehospitalization (P < 0.01). CONCLUSION: Primary anastomosis and loop ileostomy may be an option for selected patients. Patients with end ileostomies have fewer stoma-related readmissions than those with a split stoma, but they have a lower rate of stoma closure. CLINICAL TRIAL REGISTRATION: Trial not registered.

Perianal block with ropivacaine as a supplement to anaesthesia in proctological surgery: double-blind randomized placebo-controlled trial (PERCEPT).

BACKGROUND: The benefit of a perianal block as an adjunct to general or regional anaesthesia is debated. This RCT aimed to compare pain at 24 h and up to 14 days after proctological surgery in patients with and without a perianal block. METHODS: Between January 2018 and April 2019, patients were allocated to receive a perianal block with ropivacaine or placebo as an adjunct to anaesthesia. Patients, surgeons and assessors were blinded. The primary outcome was pain measured on a numerical rating scale (NRS) after 24 h. Secondary outcomes were need for rescue analgesia, and pain after 1, 2, 3, 6 and 12 h. The mean, rest and maximum NRS scores were measured for 14 days. RESULTS: A total of 138 patients were included, of whom 46 and 44 received general anaesthesia with or without ropivacaine respectively, and 23 and 25 received spinal anaesthesia with or without ropivacaine respectively (P = 0·858). The mean NRS score differed significantly at 24 h (mean(s.d.) 1·1(0·1) versus 2·3(0·2); P < 0·001), but not at 1 h (1·4(0·2) versus 2·2(0·3); P = 0·051). The NRS score was lower with use of ropivacaine at 2 h (1·0(0·2) versus 1·6(0·2); P = 0·045), 3 h (0·9(0·2) versus 1·5(0·2); P = 0·022), 6 h (1·1(0·2) versus 1·8(0·2); P = 0·042) and 12 h (1·2(0·2) versus 1·8(0·2); P = 0·034). The use of oral morphine equivalents was 10·2(1·4) and 16·6(2·5) mg with and without ropivacaine respectively (P = 0·028). The mean and maximum NRS scores within 14 days were lower when ropivacaine was used (95 per cent c.i. for difference 0·14 to 0·49 (P = 0·002) and 0·39 to 0·63 (P < 0·001) respectively). There was no injection-associated morbidity. CONCLUSION: Perianal block as an adjunct to general or regional anaesthesia should be recommended for proctological surgery. It yields a reduction in pain, a reduced need for opioids, and a faster recovery with minimal risk of adverse events. Registration number: NCT03405922 ( http://www.clinicaltrials.gov).

ANTECEDENTES: Se discute el beneficio del bloqueo perianal asociado a la anestesia general o regional. Este ensayo clínico aleatorizado tuvo como objetivo comparar el dolor a las 24 horas y hasta los 14 días tras cirugía proctológica en pacientes con y sin bloqueo perianal. MÉTODOS: Entre enero de 2018 y abril de 2019 se asignaron los pacientes para recibir un bloqueo perianal con ropivacaína o placebo como complemento de la anestesia. Los pacientes, los cirujanos y los evaluadores desconocían el grupo al que habían sido aleatorizados los pacientes. La variable principal fue el dolor a las 24 horas medido en una escala de numérica (numeric rating scale, NRS). Las variables secundarias fueron la necesidad de analgesia de rescate y el dolor a las 1, 2, 3, 6 y 12 horas. También se obtuvieron las puntuaciones media, en reposo y máxima de NRS durante 14 días. RESULTADOS: Se incluyeron 138 pacientes, de los que 46 recibieron anestesia general con ropivacaína, 44 anestesia general sin ropivacaína, 23 anestesia raquídea con ropivacaína y 25 anestesia raquídea sin ropivacaína (P = 0,858). La puntuación media de NRS fue significativamente diferente a las 24 horas (1,1 ± 0,1 versus 2,3 ± 0,2; P < 0,001), pero no en la primera hora (1,4 ± 0,2 versus 2,2 ± 0,3; P = 0,051). La puntuación NRS fue inferior para la ropivacaína a las 2 horas (1,0 ± 0,2 versus 1,6 ± 0,2; P = 0,045), 3 horas (0,9 ± 0,2 versus 1,5 ± 0,2; P = 0,022), 6 horas (1,1 ± 0,2 versus 1,8 ± 0,2; P = 0,042) y 12 horas (1,2 ± 0,2 versus 1,8 ± 0,2; P = 0,034). El uso equivalentes de morfina por vía oral fue de 10,2 ± 1,4 mg y 16,6 ± 2,5 mg (P = 0,028). Las puntuaciones media y máxima de NRS en los 14 días fueron más bajas para la ropivacaína (i.c. del 95%: 0,14-0,49, P = 0,002 y de 0,39-0,63, P < 0,0001, respectivamente). No hubo morbididad asociada a la inyección. CONCLUSIÓN: Se recomienda asociar el bloqueo perianal a la anestesia general o regional en la cirugía proctológica. Este procedimiento conlleva una reducción del dolor, una menor necesidad de opioides y una recuperación más rápida con efectos adversos escasos.

Left lower transverse incision versus Pfannenstiel-Kerr incision for specimen extraction in laparoscopic sigmoidectomy: a match pair analysis.

OBJECTIVE: The ideal location of specimen extraction in laparoscopic-assisted colorectal surgery is still debatable. The aim of this study was to compare the incidence of incisional hernias and surgical site infections in patients undergoing elective laparoscopic resection for recurrent sigmoid diverticulitis by performing specimen extraction through left lower transverse incision or Pfannenstiel-Kerr incision. METHODS: A total of 269 patients operated between January 2014 and December 2017 were retrospectively screened for inclusion in the study. Patients with specimen extraction through left lower transverse incision (LLT) and patients with specimen extraction through Pfannenstiel-K incision (P-K) were matched in 1:1 proportion regarding age, sex, comorbidities, and previous abdominal surgery. The incidence of incisional hernias and surgical site infections were compared by using Fisher's exact test. RESULTS: After matching 77 patients in the LLT group and 77 patients in the P-K group, they were found to be homogenous regarding the above mentioned descriptive characteristics. No patients in the P-K group developed an incisional hernia compared with 10 patients (13%) in the LLT group (p = 0.001). All these patients required hernia repair with mesh augmentation. The rate of surgical site infections was 1/77 in the P-K group and 0/77 in the LLT group (p = 1.0). In the P-K group, a wound protector was used in 86% of patients whereas in the LLT group, 39% of the wounds were protected during specimen extraction (p < 0.0001). CONCLUSION: The Pfannenstiel-Kerr incision may be the preferred extraction site compared with the left lower transverse incision given the significant reduction of the risk of incisional hernias.

Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma.

Ataxia-oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive neurologic disorder. The phenotype is characterized by ataxia, oculomotor apraxia, peripheral neuropathy and dystonia. AOA4 is caused by biallelic pathogenic variants in the PNKP gene encoding a polynucleotide kinase 3'-phosphatase with an important function in DNA-damage repair. By whole exome sequencing, we identified 2 variants within the PNKP gene in a 27-year-old German woman with a clinical AOA phenotype combined with a cerebellar pilocytic astrocytoma diagnosed at 23 years of age. One variant, a duplication in exon 14 resulting in the frameshift c.1253_1269dup p.(Thr424fs*49), has previously been described as pathogenic, for example, in cases of AOA4. The second variant, representing a nonsense mutation in exon 17, c.1545C>G p.(Tyr515*), has not yet been described and is predicted to cause a loss of the 7 C-terminal amino acids. This is the first description of AOA4 in a patient with central European descent. Furthermore, the occurrence of a pilocytic astrocytoma has not been described before in an AOA4 patient. Our data demonstrate compound heterozygous PNKP germline variants in a German patient with AOA4 and provide evidence for a possible link with tumor predisposition. Localization of the 2 variants in human PNKP NP_009185.2. NM_007254.3:c.1253_1269dup p.(Thr424fs*49) is predicted to cause a frameshift within the kinase domain, NM_007254.3:c.1545C>G p.(Tyr515*) is predicted to cause loss of 2 C-terminal amino acids of the kinase domain and 5 additional C-terminal amino acids.

Feasibility and effectiveness of laparoscopic transgastric stapler-assisted circumferential esophageal mucosectomy and simultaneous fundoplication in a pig model.

Laparoscopic transgastric stapler-assisted mucosectomy (SAM) has been described for minimally invasive circumferential en bloc resection of Barrett's esophagus (BE). Conceivably long-term disease control might be achieved by adding antireflux surgery after resection of BE by SAM. The aim of this study was to assess the feasibility of combined SAM and fundoplication in one laparoscopic procedure in six pigs. Furthermore, the competence of the gastroesophageal junction (GEJ) was assessed at baseline, after SAM, and after subsequent laparoscopic fundoplication. At each measuring point reflux measurements were repeated 6 times in each pig. Blue-colored water was infused into the stomach to provoke reflux. Intragastric yield pressure and volume were recorded until drainage of blue solution (DBS) was noted. Time to reflux was measured by DBS and by multichannel intraluminal impedance (MII). In all animals SAM followed by laparoscopic fundoplication was feasible in a single session. A weakening of the GEJ was found after SAM, indicated by decreased yield pressure (11.5 mmHg vs. 8.5 mmHg; P < 0.001), time to DBS (90 seconds vs. 60 seconds; P = 0.008) and MII (80 seconds vs. 33 seconds; P < 0.001). After additional Nissen fundoplication the GEJ competence was restored, with measurements returning to baseline values (time to DBS 99 seconds; P = 0.15; MII 76 seconds; P = 0.84). The yield pressure increased from 11.5 mmHg at baseline to 19.7 mmHg after SAM and fundoplication (P < 0.001). Laparoscopic fundoplication and SAM may be combined in a single laparoscopic session. Although the GEJ was weakened after SAM, Nissen fundoplication restored the GEJ as an effective reflux barrier in this experiment. For clinical validation, the results need to be confirmed in a prospective human trial.

Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells.

Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes. Lentiviral vectors (LV) pseudotyped with vesicular stomatitis virus glycoprotein were superior to gammaretroviral and alpharetroviral vectors and other envelopes tested. The elongation factor 1α short (EFS) promoter mediated the most robust expression, whereas expression levels were lower from the potent but more silencing-prone spleen focus forming virus (SFFV) promoter. Both full-length (A2UCOE) and minimal (CBX3) UCOE juxtaposed to two physiological and one viral promoter reduced transgene silencing with equal efficiency. However, a promoter-specific decline in expression levels was not entirely prevented. Upon differentiation of transgene-positive iPSC into endothelial cells, A2UCOE.EFS and CBX3.EFS vectors maintained highest transgene expression in a larger fraction of cells as compared with all other constructs tested here. The function of UCOE diminished, but did not fully counteract, vector silencing and possibilities for improvements remain. Nevertheless, the CBX3.EFS in a LV background exhibited the most promising promoter and vector configuration for both high titer production and long-term genetic modification of human iPSC and their progeny.

Meta-analysis of hybrid natural-orifice transluminal endoscopic surgery versus laparoscopic surgery.

BACKGROUND: Hybrid natural-orifice transluminal endoscopic surgery (NOTES), combining access through a natural orifice with small-sized abdominal trocars, aims to reduce pain and enhance recovery. The objective of this systematic review and meta-analysis was to compare pain and morbidity in hybrid NOTES and standard laparoscopy. METHODS: A systematic literature search was performed to identify RCTs and non-RCTs comparing hybrid NOTES and standard laparoscopy. The main outcome was pain on postoperative day (POD) 1. Secondary outcomes were pain during the further postsurgical course, rescue analgesia, complications, and satisfaction with the cosmetic result. The results of meta-analysis in a random-effects model were presented as odds ratio (ORs) or standard mean differences (MDs) with 95 per cent confidence intervals. RESULTS: Six RCTs and 21 non-randomized trials including 2186 patients were identified. In hybrid NOTES the score on the numerical pain scale was lower on POD 1 (-0·75, 95 per cent c.i. -1·09 to -0·42; P = 0·001) and on POD 2-4 (-0·58, -0·91 to -0·26; P < 0·001) than that for standard laparoscopy. The need for rescue analgesia was reduced in hybrid NOTES (OR 0·36, 0·24 to 0·54; P < 0·001). The reduction in complications found for hybrid NOTES compared with standard laparoscopy (OR 0·52, 0·38 to 0·71; P < 0·001) was not significant when only RCTs were considered (OR 0·83, 0·43 to 1·60; P = 0·570). The score for cosmetic satisfaction was higher after NOTES (MD 1·14, 0·57 to 1·71; P < 0·001). CONCLUSION: Hybrid NOTES reduces postoperative pain and is associated with greater cosmetic satisfaction in selected patients.

Surgery is essential in squamous cell cancer of the rectum.

PURPOSE: Squamous cell cancer (SCC) is a rare histological subtype of rectal cancer. It is unclear whether SCC should be treated by multimodal therapy, including surgery, or by chemoradiation alone. The objective of the study was to define an optimal treatment strategy. METHODS: Patients with rectal cancer and SCC histology were identified in the Surveillance Epidemiology and End Results Database between 1990 and 2013. According to treatment, three groups were defined: radiotherapy and surgery (RT/SX), radiotherapy (RT), and surgery (SX). Overall survival (OS) and disease-specific survival (DSS) for localized, regional, and distant disease were assessed using a multivariable Cox regression model. RESULTS: Out of 856,435 colorectal cancer patients, 1747 with SCC of the rectum were eligible. Four hundred and fifty-five were treated with RT/SX, 994 with RT, and 298 with SX. Adjusted hazard ratios (HR) did not differ for OS and DSS in localized disease. In regional disease, OS and DSS were improved for RT/SX compared to RT (HR 0.751, 95% CI 0.566-0.997, P = 0.048 and HR 0.679, 95% CI 0.478-0.966, P = 0.031). In distant disease, OS and DSS were not different. CONCLUSIONS: Multimodal therapy including surgery improved OS and DSS compared to receiving a treatment without surgery for regional disease in rectal SCC. No difference was observed in localized and distant disease. The findings contradict with recent reports favoring definitive chemoradiation.

Hartmann's procedure and laparoscopic reversal versus primary anastomosis and ileostomy closure for left colonic perforation.

PURPOSE: Emergency surgical strategies for acute left-sided colonic perforation are evolving preferring primary anastomosis (PA) with ileostomy to Hartmann's procedure (HP) based on the morbidity and reversal rates. However, HP is still commonly performed. Hartmann's reversal is associated with considerable morbidity. It is of interest whether laparoscopic reversal results in a lower morbidity as retrospective data suggest. Here, we compared the combined morbidity rates for two surgical strategies: strategy A, HP followed by laparoscopic reversal, and strategy B, sigmoid resection with PA followed by ileostomy closure. METHODS: Prospectively collected data of all consecutive patients undergoing HP for benign left-sided colonic perforation between 2010 and 2014 were retrospectively compared to data of patients undergoing PA. Groups were matched for age and Charlson comorbidity index. Additionally, patients were analyzed for American Society of Anesthesiologists score, body mass index, and peritonitis stage. End points were morbidity, operation time, reversal rate, time to reversal, and length of hospital stay. RESULTS: The study included 32 patients for whom Hartmann's reversal was planned, along with 32 matched patients who underwent PA and diverting ileostomy. Median age was 75 and 72 years, Charlson score was 6 (4-9) and 6 (5-7), and patients classified by the American Society of Anesthesiologists (ASA) higher than III were 81 % in both groups. Combined major morbidity rates were 21 % for strategy A and 20 % for strategy B (p = 1.0). Combined comprehensive complication index was 16.4 ± 14.1 and 12.3 ± 19.1 (p = 0.08). HP reversal by laparoscopy was achieved in 71 %. The colostomy reversal rate was 75 % compared to ileostomy closure rate of 88 % (p = 0.34). CONCLUSIONS: Laparoscopic Hartmann's reversal is achievable in a high proportion of patients. Strategy B tends to have lower overall morbidity; meanwhile, major morbidity seems to be similar. Yet, in critically ill patients and in the absence of expertise of the surgeon on call, HP followed by elective laparoscopic reversal represents a viable alternative.

Improved retroviral episome transfer of transcription factors enables sustained cell fate modification.

Retroviral vectors are versatile gene transfer vehicles widely used in basic research and gene therapy. Mutation of retroviral integrase converts these vectors into transient, integration-deficient gene delivery vehicles associated with a high degree of biosafety. We explored the option to use integration-deficient retroviral vectors to achieve transient ectopic expression of transcription factors, which is considered an important tool for induced cell fate conversion. Stepwise optimization of the retroviral episome transfer as exemplified for the transcription factor Oct4 enabled to improve both expression magnitude and endurance. Long terminal repeat-driven γ-retroviral vectors were identified as the most suitable vector architecture. Episomal expression was enhanced by epigenetic modifiers, and Oct4 activity was increased following fusion to a minimal transactivation motif of herpes simplex virus VP16. Based on kinetic analyses, we identified optimal time intervals for repeated vector administration and established prolonged expression windows of choice. Providing proof-of-concept, episomal transfer of Oct4 was potent to mediate conversion of human fibroblasts stably expressing Klf4, Sox2 and c-Myc into induced pluripotent stem cells, which were mainly free of residual Oct4 vector integration. This study provides evidence for suitability of retroviral episome transfer of transcription factors for cell fate conversion, allowing the generation of distinct patient- or disease-specific cell types.

Human BRCA1-associated breast cancer: no increase in numerical chromosomal instability compared to sporadic tumors.

BRCA1 is a major gatekeeper of genomic stability. Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. In this study, we determined the extent of CIN in 32 breast cancer tumors of women with a BRCA1 germline mutation compared to 62 unselected breast cancers. We applied fluorescence in situ hybridization (FISH) with centromere-specific probes for the chromosomes 1, 7, 8, 10, 17, and X and locus-specific probes for 3q27 (BCL6), 5p15.2 (D5S23), 5q31 (EGR1), 10q23.3 (PTEN), and 14q32 (IGH@) on formalin-fixed paraffin-embedded tissue microarray sections. Our hypothesis of an increased level of CIN in BRCA1-associated breast cancer could not be confirmed by this approach. Surprisingly, we detected no significant difference in the extent of CIN in BRCA1-mutated versus sporadic tumors. The only exception was the CIN value for chromosome 1. Here, the extent of CIN was slightly higher in the group of sporadic tumors.

Genome-wide single-nucleotide polymorphism analysis in juvenile myelomonocytic leukemia identifies uniparental disomy surrounding the NF1 locus in cases associated with neurofibromatosis but not in cases with mutant RAS or PTPN11.

Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disorder whose proliferative component is a result of RAS pathway deregulation caused by somatic mutation in the RAS or PTPN11 oncogenes or in patients with underlying neurofibromatosis type 1 (NF-1), by loss of NF1 gene function. To search for potential collaborating genetic abnormalities, we used oligonucleotide arrays to analyse over 116 000 single-nucleotide polymorphisms across the genome in 16 JMML samples with normal karyotype. Evaluation of the SNP genotypes identified large regions of homozygosity on chromosome 17q, including the NF1 locus, in four of the five samples from patients with JMML and NF-1. The homozygous region was at least 55 million base pairs in each case. The genomic copy number was normal within the homozygous region, indicating uniparental disomy (UPD). In contrast, the array data provided no evidence for 17q UPD in any of the 11 JMML cases without NF-1. We used array-based comparative genomic hybridization to confirm 17q disomy, and microsatellite analysis was performed to verify homozygosity. Mutational analysis demonstrated that the inactivating NF1 lesion was present on both alleles in each case. In summary, our data indicate that a mitotic recombination event in a JMML-initiating cell led to 17q UPD with homozygous loss of normal NF1, provide confirmatory evidence that the NF1 gene is crucial for the increased incidence of JMML in NF-1 patients, and corroborate the concept that RAS pathway deregulation is central to JMML pathogenesis.

Chromosomal aberrations in congenital bone marrow failure disorders--an early indicator for leukemogenesis?

As chromosomal instability may contribute to leukemogenesis in patients with congenital bone marrow failure (CBMF) disorders, it was the aim of this study to characterize chromosomally aberrant clones that arise during the clinical course of disease by means of R-banding and fluorescence in situ hybridization (FISH) analyses. In addition, multicolor-FISH and array-comparative genomic hybridization (CGH) were applied to characterize clonal chromosome aberrations in more detail. Between January 2004 and December 2005, we prospectively analyzed 90 samples of 73 patients with proven or suspected CBMF disorders enrolled in a German Study Network of CBMF diseases. Clonal aberrations could be identified in four of 73 patients examined. In one child with congenital thrombocytopenia, Jacobsen syndrome [del(11)(q24)c] was diagnosed, and thus a CBMF could be excluded. In a girl with Shwachman-Diamond syndrome, two independent clones, one with an isochromosome i(7)(q10), another with a complex aberrant karyotype, were identified. Simultaneously, transition into a myelodysplastic syndrome (MDS) occurred. The brother, who was also afflicted with Shwachman-Diamond syndrome, showed an isochromosome i(7q) as a single aberration. In the fourth patient with severe congenital neutropenia, an add(21)(q22) marker containing a low-level amplification of the AML1 gene was identified at the time point of transition into acute myelogenous leukemia (AML). In summary, we suggest that follow-up of patients with CBMF using chromosome and FISH analyses will be helpful for the early detection of transition into MDS or AML and thus should be an integral part of the clinical management of these patients.

[Implementation of hybrid-NOTES sigmoidectomy for diverticular disease : In a center for minimally invasive surgery]. / Implementierung der Hybrid-NOTES-Sigmoidektomie bei Divertikelkrankheit : In einem Zentrum für minimalinvasive Chirurgie.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) describes surgical procedures through a natural orifice. In hybrid-NOTES small transabdominal trocars are combined with a NOTES access. OBJECTIVE: To evaluate hybrid-NOTES sigmoidectomy as a standard procedure for diverticulitis. MATERIAL AND METHODS: Elective laparoscopic sigmoidectomies performed between May 2011 and January 2016 were prospectively collated. Primary endpoint was the feasibility of hybrid-NOTES sigmoidectomy. The reasons for planning a laparoscopically-assisted sigmoidectomy (LAS), intraoperative change of treatment and reactive conversion were evaluated. Secondary endpoints were complications and operative time. RESULTS: Out of 130 laparoscopic sigmoidectomies 83% were planned for hybrid-NOTES and 8 out of 52 (15%) transvaginal (TVS) and 14 out of 56 (25%) transrectal (TRS) sigmoidectomies were intraoperatively changed to LAS. The reason for the change in 64% was that the specimen was too bulky and 80% of scheduled hybrid-NOTES procedures were carried out as planned. The operative time for TVS (146.8 ± 44.5 min) was shorter compared to LAS (173.2 ± 58.8 min, P = 0.016). The morbidities of TVS (15.3%) and TRS (14.9%) were not significantly different from LAS (23.9%, P = 0.501 and P = 0.537, respectively). CONCLUSION: Hybrid-NOTES for diverticular disease may be indicated in more than 80% of cases. In respect of intraoperative change of treatment, hybrid-NOTES is feasible in two thirds of patients. Given a high level of expertise, hybrid-NOTES can be provided as a standard procedure in sigmoidectomy for diverticular disease.

Different breakage-prone regions on chromosome 1 detected in t(11;14)-positive mantle cell lymphoma cell lines and multiple myeloma cell lines are associated with different tumor progression-related mechanisms.

To better define secondary aberrations that occur in addition to translocation t(11;14)(q13;q32) in mantle cell lymphomas (MCL) and in multiple myelomas (MM), seven t(11;14)-positive MCL cell lines and four t(11;14)-positive MM cell lines were analysed by fluorescence R-banding and spectral karyotyping (SKY). Compared with published data obtained by G-banding, most chromosome aberrations were redefined or further specified. Furthermore, several additional chromosome aberrations were identified. Thus, these cytogenetically well defined t(11;14)-positive MCL and MM cell lines may be useful tools for the identification and characterization of genes that might be involved in the pathogenesis of MCL and MM, respectively. Since MCL and MM were found to have different alterations of chromosome 1, these were investigated in more detail by fluorescence in situ hybridization (FISH) and multicolor banding (MCB) analyses. The most frequently altered and deletion-prone loci in MCL cell lines were regions 1p31 and 1p21. In contrast, breakpoints in MM cell lines most often involved the heterochromatic regions 1p12-->p11, and the subcentromeric regions 1q12 and 1q21. These data are in accordance with previously published data of primary lymphomas. Our findings may indicate that different pathways of clonal evolution are involved in these morphologically distinct lymphomas harboring an identical primary chromosome aberration, t(11;14).

[Laparoscopic versus open rectal cancer resection: oncologically equal?]. / Laparoskopische vs. offene Rektumresektion: onkologisch gleichwertig?

The oncological equivalence of laparoscopic and open rectal cancer resection was evaluated in four multicenter randomized controlled trials. The COLOR II and the COREAN trials demonstrated oncological equivalence; however, the ACOSOG and the ALaCaRT studies came to a different conclusion. In the latter two studies a composite endpoint that assessed the quality of the mesorectal specimen, the completeness of tumor-free circumferential and distal resection margins was chosen. In both trials a higher success rate for open surgery was shown; nevertheless, the validity of this composite endpoint has not been proven and no conclusions on solid oncological endpoints can be drawn. The COLOR II and the COREAN trial therefore remain the only available studies which investigated solid oncological endpoints, such as local recurrence and disease-free survival over an adequate follow-up time period of 3 years; however, the comparability of the study groups at least of the COLOR II trial needs to be called into question as only the experience of the laparoscopic surgeons was assessed. With a local recurrence rate of 5 % in both groups the oncological quality seems nevertheless to be good; therefore, a systematically inadequate control group should not be assumed. At this point it can be concluded that a good oncological outcome can be achieved with laparoscopic rectal resection in the hands of experts. For a final assessment the long-term results of the on-going trials needs to be awaited. If the promising results for laparoscopic surgery of the COLOR II trial are confirmed laparoscopic rectal resection should be preferred to open resection in the future. This conclusion is based on the generally known perioperative benefits of minimally invasive surgery.

Sequence of the gamma-subunit of Spirulina platensis: a new principle of thiol modulation of F0F1 ATP synthase?

The gene encoding the gamma subunit of Spirulina platensis F0F1, the relative of the chloroplast F1 subunit responsible for thiol activation, has been cloned and sequenced. As in other cyanobacteria, a specific couple of cysteines like those involved in thiol modulation of the chloroplast enzyme was not found. Instead, two cysteine residues were identified in the Spirulina subunit at positions unique amongst all so far sequenced gamma subunits. Involvement of these cysteines in the thiol-modulation of the Spirulina enzyme reported before (Hicks and Yocum (1986) Arch. Biochem. Biophys. 245, 230-237, and Lerma and Gomez-Lojero (1987) Photosynth. Res. 11, 265-277) would manifest a re-invention of a regulatory mechanism.

Mutagenesis of the b'-subunit of Synechocystis sp. PCC 6803 ATP-synthase.

We investigated the F0F1 ATP synthase of the cyanobacterium, Synechocystis sp. PCC 6803. The gene for the F0-subunit b', a peptide probably located at the interface between F0 and F1, has been partially or completely evicted from the bacterial genome. We found that the complete deletion of the subunit was lethal to the cells. However, the subunit could be truncated down to its hydrophobic N-terminal stretch without much harm. Since the gene for b' probably shares a common ancestor with the gene for subunit b and emerged by gene duplication, we propose that b' gathered a new role during evolution, perhaps in the regulation of photophosphorylation.