Mitochondrial respiration in peripheral arterial disease depends on stage severity.

Peripheral arterial disease (PAD) is an increasing cause of morbidity and its severity is graded based on clinical manifestation. To investigate the influence of the different stages on myopathy of ischemic muscle we analysed severity-dependent effects of mitochondrial respiration in PAD. Eighteen patients with severe PAD, defined as chronic limb-threatening ischemia, 47 patients with intermittent claudication (IC) and 22 non-ischemic controls were analysed. High-resolution respirometry (HRR) was performed on muscle biopsies of gastrocnemius and vastus lateralis muscle of patients in different PAD stages to investigate different respiratory states. Results from HRR are given as median and interquartile range and were normalized to citrate synthase activity (CSA), a marker for mitochondrial content. In order to account for inter-individual differences between patients and controls, we calculated the ratio of O2-flux in gastrocnemius muscle over vastus muscle ('GV ratio'). CSA of the gastrocnemius muscle as a proxy for mitochondrial content was significantly lower in critical ischemia compared to controls. Mitochondrial respiration normalized to CSA was higher in IC compared to controls. Likewise, the GV ratio was significantly higher in IC compared to control. Mitochondrial respiration and CSA of PAD patients showed stage-dependent modifications with greater changes in the mild PAD stage group (IC).

Influence of the COVID-19 pandemic on the timing of surgical triage, tumor stage, and therapy of patients with colon carcinoma.

PURPOSE: With the onset of the COVID pandemic in Germany in March 2020, far-reaching restrictions were imposed that limited medical access for patients. Screening examinations such as colonoscopies were greatly reduced in number. As rapid surgical triage after diagnosis is prognostic, our hypothesis was that pandemic-related delays would increase the proportion of advanced colon cancers with an overall sicker patient population. METHODS: A total of 204 patients with initial diagnosis of colon cancer were analyzed in this retrospective single-center study between 03/01/2018 and 03/01/2022. Control group (111 patients, pre-COVID-19) and the study group (93 patients, during COVID-19) were compared in terms of tumor stages, surgical therapy, complications, and delays in the clinical setting. The data were presented either as absolute numbers or as median for constant data. RESULTS: A trend towards more advanced tumor stages (T4a p = 0.067) and a significant increase of emergency surgeries (p = 0.016) with higher rates of ileus and perforation (p = 0.004) as well as discontinuity resections (p = 0.049) during the pandemic could be observed. Delays in surgical triage after endoscopic diagnosis were seen during the 2nd lockdown (02/11/20-26/12/20; p = 0.031). CONCLUSION: In summary, the results suggest delayed treatment during the COVID-19 pandemic, with the infection pattern of COVID appearing to have a major impact on the time between endoscopic diagnosis and surgical triage/surgery. Adequate care of colon cancer patients is possible even during a pandemic, but it is important to focus on structured screening and tight diagnosis to treatment schedules in order to prevent secondary pandemic victims.

The effect of revascularization on recovery of mitochondrial respiration in peripheral artery disease: a case control study.

BACKGROUND: Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle. METHODS: Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB). RESULTS: Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10-1.64) vs. non-ischemic 0.93 (IQR 0.69-1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46-0.82) vs non-ischemic 1.16 (IQR 0.77-1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47-0.76) vs. non-ischemic 1.02 (IQR 0.64-1.40) p = 0.010). CONCLUSIONS: Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery.

Survival rates and prognostic factors in right- and left-sided colon cancer stage I-IV: an unselected retrospective single-center trial.

PURPOSE: Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. METHODS: In total, 417 patients with colon cancer stage I-IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan-Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. RESULTS: Our study showed no significant difference of the overall survival between rCC and lCC stage I-IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1-123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2-9.0), increased lymph node ratio of 0.6-1.0 (HR: 5.3; CI 95%: 1.7-16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7-2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9-91.9), CEA blood level 20.1-100 µg/l (HR: 5.4; CI 95%: 2.4-12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0-49.0), and severe surgical complications (Clavien-Dindo III-IV) (HR: 2.9; CI 95%: 1.5-5.5) were identified as predictors of a diminished overall survival. CONCLUSION: Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.

Reduction of Postoperative Wound Infections by Antiseptica (RECIPE)?: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether intraoperative subcutaneous wound irrigation with 0.04% polyhexanide can reduce surgical site infection (SSI) in elective laparotomies compared to saline. BACKGROUND: SSI is a common complication after gastrointestinal surgery. To date, there is a lack of evidence whether subcutaneous wound irrigation is beneficial in terms of reduction of SSI. METHODS: The RECIPE trial was an investigator initiated single-center, single-blind prospective, randomized controlled trial with 2 parallel treatment groups, comparing wound irrigation with 0.9% saline to antiseptic 0.04% polyhexanide solution in elective laparotomies. Primary endpoint was the rate of SSI within 30 days postoperatively according to Centers for Disease Control and Prevention criteria. RESULTS: Between February 02, 2015, and May 23, 2018, 456 patients were randomly assigned to saline (n = 228) or polyhexanide (n = 228). Final cohort for analysis comprised 393 patients (202 in the saline and 191 in the polyhexanide group). Overall rate of SSI was 28.2%, n = 111. Simple analysis with cross tabulation revealed that significantly fewer SSIs occurred in the polyhexanide group: n = 70 (34.7%) versus n = 41 (21.5%); P = 0.004. In a multiple logistic regression model the factor wound irrigation with polyhexanide [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.27-0.72; P = 0.001) was associated with risk reduction of SSI. Preoperative anemia (OR 2.08; 95% CI 1.27-3.40; P = 0.004) and more than 5 prior abdominal operations compared to none (OR 8.51; 95% CI 2.57-28.21; P < 0.001) were associated with SSI. CONCLUSIONS: Intraoperative subcutaneous wound irrigation with antiseptic 0.04% polyhexanide solution is effective in reducing SSI after elective laparotomies.

Regeneration of Mitochondrial Function in Gastrocnemius Muscle in Peripheral Arterial Disease After Successful Revascularisation.

OBJECTIVE: Myopathy, characterised by altered mitochondrial function, is a central part of the pathophysiology of peripheral arterial disease and the aim of this study was to investigate the effect of revascularisation on mitochondrial function. METHODS: High resolution respirometry was used to investigate mitochondrial respiration and the results were normalised to citrate synthase activity (CSA), a marker of mitochondrial content. Ten patients with symptomatic peripheral arterial disease (study group) and 10 subjects without ischaemia (control group) were included. Ankle brachial index and ultrasound imaging were performed before and after vascular intervention to confirm technically successful revascularisation. Within the study group, muscle biopsies from the gastrocnemius muscle were taken before vascular intervention and six weeks after revascularisation. Within the control group, tissue was harvested once. RESULTS: There were no significant group differences regarding anthropometric data. CSA showed a significant increase after successful revascularisation (CSA pre-operative 281.4 (252.4-391.8) nmol/min/mg protein vs. CSA post-operative 438.5 (361.4-471.3) nmol/min/mg protein; p = .01) with post-operative return of values to the range of control subjects (CSA control 396.6 (308.2-435.9)). Mitochondrial respiration normalised to CSA in oxidative phosphorylation (P) as well as in electron transfer (E) capacity were significantly reduced post-operatively when compared with pre-operative values (P pre-operative 0.218 (0.196-0.266) pmol/(sec×mg) per CSA vs. post-operative 0.132 (0.116-0.150) pmol/(sec×mg) per CSA, p = .007; E pre-operative 0.230 (0.195-0.279) pmol/(sec×mg) per CSA vs. post-operative 0.129 (0.120-0.154) pmol/(sec×mg) per CSA, p = .005) meaning a post-operative return of values to within the range of control subjects (P control 0.124 (0.080-0.155) pmol/(sec×mg) per CSA; E control 0.121 (0.079-0.125) pmol/(sec×mg) per CSA). CONCLUSION: With these results, it has been shown that the initially impaired mitochondrial function and content can normalise after revascularisation.

Synergy of Fluorescence and Near-Infrared Spectroscopy in Detection of Colorectal Cancer.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide. There is an urgent need for simple and fast methods to improve tumor detection in the diagnostic and intraoperative setting to avoid complications and provide objective information in distinguishing malignant and benign colorectal tissue. Optical spectroscopy methods have recently shown a great potential for this discrimination in different organs. MATERIALS AND METHODS: In this pilot study, fluorescence emission spectra (excitation: 473 nm) and diffuse reflectance spectra (DRS) of normal and tumor tissues from resected colorectal cancer specimen were measured using fiber optical probes in an ex vivo setting, and the data were subjected to multivariate analysis. RESULTS: Substantial spectral differences were found in the fluorescence and DRS spectra of colorectal cancer tissue in comparison to benign tissue. The diagnostic potential of a multimode optical system combining both spectroscopic methods was investigated by mathematical combination. Compared with the individual techniques, a higher sensitivity of the joint DRS-fluorescence optical system in the discrimination between malignant and benign colorectal tissue could be observed. CONCLUSIONS: In the pilot study presented herein, a quick and reliable method to differentiate malignant and benign colorectal tissue ex vivo with different spectroscopic techniques using spectral fiber probes could be established. Joint fluorescence and near-infrared spectroscopy had a higher sensitivity in tissue discrimination and showed to be a promising combination of two spectroscopic methods. Further studies using the synergic effect of fluorescence and DRS spectroscopy are needed to transfer these findings into the in vivo situation.

Influence of the COVID-19 Pandemic on Patients with Rectal Cancer.

Objectives: The COVID-19 pandemic and its associated restrictions have resulted in delayed diagnoses across various tumor entities, including rectal cancer. Our hypothesis was based on the expectation of a reduced number of primary operations due to higher tumor stages compared to the control group. Methods: In a single-center retrospective study conducted from 1 March 2018 to 1 March 2022, we analyzed 120 patients with an initial diagnosis of rectal cancer. Among them, 65 patients were part of the control group (pre-COVID-19), while 55 patients were included in the study group (during the COVID-19 pandemic). We compared tumor stages, treatment methods, and complications, presenting data as absolute numbers or mean values. Results: Fewer primary tumor resections during the COVID-19 pandemic (p = 0.010), as well as a significantly lower overall number of tumor resections (p = 0.025) were seen compared to the control group. Twenty percent of patients in the COVID-19 group received their diagnosis during lockdown periods. These patients presented significantly higher tumor stages (T4b: 27.3% vs. 6.2%, p = 0.025) compared to the control group prior to the pandemic. In addition, more patients with angiolymphatic invasion (ALI) were identified in the COVID-19 group following neoadjuvant treatment compared to the control group (p = 0.027). No differences were noted between the groups regarding complications, stoma placement, or conversion rates. Conclusions: The COVID-19 pandemic, particularly during lockdown, appears to have contributed to delayed diagnoses, resulting in higher tumor stages and a decreased number of surgeries. The quality of rectal cancer treatment can be maintained under pandemic conditions.

A Modified Run-Off Resistance Score from Cross-Sectional Imaging Discriminates Chronic Critical Limb Ischemia from Intermittent Claudication in Peripheral Arterial Disease.

Atherosclerotic peripheral arterial disease (PAD) leads to intermittent claudication (IC) and may progress into chronic limb-threatening ischemia (CLTI). Scoring systems to determine the atherosclerotic burden of a diseased extremity have been developed. This study aimed to evaluate a modification of the run-off resistance (mROR) score for its usability in cross-sectional imaging. The mROR was determined from preoperative imaging of patients undergoing revascularization for PAD. A total of 20 patients with IC and 20 patients with CLTI were consecutively included. A subgroup analysis for diabetic patients was conducted. The mROR was evaluated for its correlation with disease severity and clinical covariates. Patients with CLTI were older; cardiovascular risk factors, diabetes, and ASA 4 were more frequent. The mROR scores were higher in CLTI than in IC. In diabetic patients, no difference was detected between CLTI and IC. In CLTI, non-diabetic patients had a higher mROR. The mROR score is positively correlated with the severity of PAD and can discriminate CLTI from IC. In diabetic patients with CLTI, the mROR is lower than in non-diabetic patients. The mROR score can be determined from cross-sectional imaging angiographies. It may be useful for clinicians helping with vascular case planning, as well as for scientific purposes.

Rethinking the TNM Classification Regarding Direct Lymph Node Invasion in Pancreatic Ductal Adenocarcinoma.

Mechanisms of lymph node invasion seem to play a prognostic role in pancreatic ductal adenocarcinoma (PDAC) after resection. However, the 8th edition of the TNM classification of the American Joint Committee on Cancer (AJCC) does not consider this. The aim of this study was to analyse the prognostic role of different mechanisms of lymph node invasion on PDAC. One hundred and twenty-two patients with resected PDAC were examined. We distinguished three groups: direct (per continuitatem, Nc) from the main tumour, metastasis (Nm) without any contact to the main tumour, and a mixed mechanism (Ncm). Afterwards, the prognostic power of the different groups was analysed concerning overall survival (OS). In total, 20 patients displayed direct lymph node invasion (Nc = 16.4%), 44 were classed as Nm (36.1%), and 21 were classed as Ncm (17.2%). The difference in OS was not statistically significant between N0 (no lymph node metastasis, n = 37) and Nc (p = 0.134), while Nm had worse OS than N0 (p < 0.001). Direct invasion alone had no statistically significant effect on OS (p = 0.885). Redefining the N0 stage by including Nc patients showed a more precise OS prediction among N stages (p = 0.001 vs. p = 0.002). Nc was more similar to N0 than to Nm; hence, we suggest a rethinking of TNM classification based on the mechanisms of lymph node metastases in PDAC. Overall, this novel classification is more precise.