Outcome Quality After Colorectal Cancer Resection in Certified Colorectal Cancer Centers­Patient-Reported and Short-Term Clinical Outcomes.

BACKGROUND: In this observational study, patient-reported outcomes and short-term clinical outcome parameters in patients with colorectal cancer were studied 12 months after the start of treatment. Outcomes were also compared across German Certified Colorectal Cancer Centres. METHODS: Data were collected from 4239 patients with colorectal cancer who had undergone elective tumor resection in one of 102 colorectal cancer centers and had responded to a quality-of-life questionnaire before treatment (EORTC QLQ-C30 and -CR29). 3142 (74.1%) of these patients completed a post-treatment questionnaire 12 months later. Correlation analyses were calculated and case-mix adjusted comparisons across centers were made for selected patient-reported outcomes, anastomotic insufficiency, and 30-day-mortality. RESULTS: At 12 months, mild improvements were seen in mean quality-of-life scores (66 vs. 62 points), constipation (16 vs. 19), and abdominal pain (15 vs. 17). Worsening was seen in physical function (75 vs. 82) and pain (22 vs. 19). Better patient-reported outcomes at 12 months were associated with better scores before treatment. Better results in at least three of the five scores were associated with male sex, higher educational level, higher age, and private health insurance. Major worsening of fecal incontinence was seen among patients with rectal cancer without a stoma. The largest differences across centers were found with respect to physical function. Anastomotic insufficiency was found in 4.3% of colon cancer patients and 8.2% of rectal cancer patients. 1.9% of patients died within 30 days after their resection. CONCLUSION: Clinicians can use these findings to identify patients at higher risk for poorer patient-reported outcomes. The differences among cancer centers that were found imply that measures for quality improvement would be desirable.

[Impact of the Nursing Personnel Strengthening Act on minimally invasive surgery exemplified by right-sided hemicolectomy from an economic perspective]. / Auswirkungen des Pflegepersonalstärkungsgesetzes auf die minimal-invasive Chirurgie am Beispiel der Hemikolektomie rechts aus ökonomischer Perspektive.

BACKGROUND: In the past, a reduced length of postoperative hospital stay was considered a sufficient trade-off to refinance the additional costs associated with minimally invasive surgery; however, with the implementation of the Nursing Personnel Strengthening Act and disincorporation of nursing costs, this argumentation needs to be fundamentally reevaluated. METHOD: Using right-sided hemicolectomy as an example, a retrospective case analysis was conducted. Cost reductions associated with the length of hospital stay were compared before and after the introduction of the revised German diagnosis-related groups (aG-DRG) and offset against the increased material and personnel costs. RESULTS: Among the analyzed cases, the utilization of minimally invasive surgical techniques led to a substantial cost reduction per case compared to conventional surgical treatment. After the introduction of the aG-DRGs the financial benefits of a shortened hospital stay are greatly diminished and cannot be used to refinance the expenses necessary to perform minimally invasive surgery. From a strictly economical perspective, there is a strong incentive to only perform open surgical procedures. CONCLUSION: Disincorporation of nursing costs has destabilized the fragile concept of indirect refinancing of advanced operative techniques by the financial incentives associated with a shorter hospital stay. In order to comply with statutory regulations to implicate a performance-based funding, there is an urgent necessity to adjust the grouping algorithms for minimally invasive surgical procedures to the corresponding flat rates.

Spermatic cord liposarcomas incidentally found during hernia surgery: is histology of any lipoma mandatory? A review of the literature.

Purpose: Liposarcomas found incidentally during open or laparoscopic inguinal hernia surgery are extremely rare. It is unclear, whether any adipose tissue being removed during inguinal hernia surgery must be sent for histology due to the potential risk of liposarcoma of the spermatic cord. This study aims to evaluate the frequency of liposarcomas incidentally found in the inguinal canal during hernia surgery and tries to derive evidence-based recommendations regarding the optimal management of any fatty tissue found in the inguinal canal.Methods: A literature review of the PubMed/Medline electronic databases between January 1980 and January 2019 was performed using the search terms 'inguinal hernia' and 'liposarcoma'. There was only one study available on this topic. Therefore, an additional literature review was performed analyzing all reports on patients with incidentally detected liposarcomas of the spermatic cord in the inguinal canal during hernia surgery.Results: There was only one retrospective study evaluating the frequency of inguinal liposarcoma found at hernia operations with a frequency of less than 0.1%. There were 18 cases of spermatic cord liposarcomas that were truly found incidentally during operation for an unsuspected symptomatic or incarcerated inguinal hernia. These included 16 case reports with a total of 18 patients and 19 liposarcomas. All patients were male with a median age of 62.5 years (range: 24-86 years) years. Median size of liposarcoma was 10.5 cm (range: 3-30 cm). In seven patients, the inguinal liposarcoma was an extension of a retroperitoneal sarcoma. Treatment consisted of radical orchidectomy during the primary operation in 12 patients. Three out of the seven patients with retroperitoneal extension of the tumor underwent a secondary operation with complete resection of the tumor.Conclusions: Currently, there is no evidence-based recommendation available regarding the management of lipomas detected during open or laparoscopic inguinal hernia surgery. Due to the extremely low risk of the presence of a liposarcoma, routine histologic examination cannot be recommended unless the diameter exceeds 10 cm.

Entorhinal denervation induces homeostatic synaptic scaling of excitatory postsynapses of dentate granule cells in mouse organotypic slice cultures.

Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥ 3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr(2+))-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3-4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro.

Increased dentate gyrus excitability in neuroligin-2-deficient mice in vivo.

The postsynaptic adhesion protein neuroligin-2 (NL2) is selectively localized at inhibitory synapses. Here, we studied network activity in the dentate gyrus of NL2-deficient mice following perforant path (PP) stimulation in vivo. We found a strong increase in granule cell (GC) excitability. Furthermore, paired-pulse inhibition (PPI) of the population spike, a measure for γ-aminobutyric acid (GABA)ergic network inhibition, was severely impaired and associated with reduced GABA(A) receptor (GABA(A)R)-mediated miniature inhibitory postsynaptic currents recorded from NL2-deficient GCs. In agreement with these functional data, the number of gephyrin and GABA(A)R clusters was significantly reduced in the absence of NL2, indicating a loss of synaptic GABA(A)Rs from the somata of GCs. Computer simulations of the dentate network showed that impairment of perisomatic inhibition is able to explain the electrophysiological changes observed in the dentate circuitry of NL2 knockout animals. Collectively, our data demonstrate for the first time that deletion of NL2 increases excitability of cortical neurons in the hippocampus of intact animals, most likely through impaired GABA(A)R clustering.

Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice in vivo.

The submembrane cytoskeletal meshwork of the axon contains the scaffolding protein betaIV-spectrin. It provides mechanical support for the axon and anchors membrane proteins. Quivering (qv(3j)) mice lack functional betaIV-spectrin and have reduced voltage-gated sodium channel (VGSC) immunoreactivity at the axon initial segment and nodes of Ranvier. Because VGSCs are critically involved in action potential generation and conduction, we hypothesized that qv(3j) mice should also show functional deficits at the network level. To test this hypothesis, we investigated granule cell function in the dentate gyrus of anesthetized qv(3j) mice after electrical stimulation of the perforant path in vivo. This revealed an impaired input-output relationship between stimulus intensity and granule cell population spikes and an enhanced paired-pulse inhibition of population spikes, indicating a reduced ability of granule cells to generate action potentials and decreased network excitability. In contrast, the input-output curve for evoked field excitatory postsynaptic potentials (fEPSPs) and paired-pulse facilitation of fEPSPs were unchanged, suggesting normal excitatory synaptic transmission at perforant path-granule cell synapses in qv(3j) mutants. To corroborate our findings, we analyzed the influence of VGSC density reduction on dentate network activity using an established computational model of the dentate gyrus network. This in silico approach confirmed that the loss of VGSCs is sufficient to explain the electrophysiological changes observed in qv(3j) mice. Taken together, our findings demonstrate that betaIV-spectrin is required for normal granule cell firing and for physiological levels of network excitability in the mouse dentate gyrus in vivo.

Impairment of in vivo theta-burst long-term potentiation and network excitability in the dentate gyrus of synaptopodin-deficient mice lacking the spine apparatus and the cisternal organelle.

The function of the spine apparatus in dendritic spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin -/- mice. Here, we used synaptopodin -/- mice to explore the role of the spine apparatus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation following theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the spine apparatus and the cisternal organelle leads to a defect in long-term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions.