Marcel André Schneider

High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients’ Perceptions on Initiation, Reasons for Use, and Obtainment

Background High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated. Methods We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group’s views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring’s qualitative content analysis was used to evaluate our data. Results In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination. Conclusions Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients’ motives for long-term, high-dose BZD use when formulating treatment plans for this patient group, especially since it is known that individuals are more compliant with approaches they perceive to be manageable, tolerable, and effective.

How much liver needs to be transected in ALPPS? A translational study investigating the concept of less invasiveness.

BACKGROUND ALPPS induces rapid liver hypertrophy after stage‐1 operation, enabling safe, extended resections (stage‐2) after a short period. Recent studies have suggested that partial transection at stage‐1 might be associated with a better safety profile. The aim of this study was to assess the amount of liver parenchyma that needs to be divided to achieve sufficient liver hypertrophy in ALPPS. METHODS In a bi‐institutional, prospective cohort study, nonfibrotic patients who underwent ALPPS with complete (n = 22) or partial (n = 23) transection for colorectal liver metastases were analyzed and compared with an external ALPPS cohort (n = 23). A radiologic tool was developed to quantify the amount of parenchymal transection. Liver hypertrophy and clinical outcome were compared between both techniques. The relationship of partial transection and hypertrophy was investigated further in an experimental murine model of partial ALPPS. RESULT The median amount of parenchymal transection in partial ALPPS was 61% (range, 34–86%). The radiologic method correlated poorly with the intraoperative surgeons estimation (rS = 0.258). Liver hypertrophy was equivalent for the partial ALPPS, ALPPS, and external ALPPS cohort (64% vs 60% vs. 64%). Experimental data demonstrated that partial transection of at least 50% induced comparable hypertrophy (137% vs 156%) and hepatocyte proliferation compared to complete transection. CONCLUSION The study provides clinical and experimental evidence that partial liver partition of at least 50% seems to be equally effective in triggering volume hypertrophy as observed with complete transection and can be re recommended as less invasive alternative to ALPPS.

Perfusion settings and additives in liver normothermic machine perfusion with red blood cells as oxygen carrier. A systematic review of human and porcine perfusion protocols

Liver machine perfusion (MP) at normothermic temperature (NMP) is a promising way to preserve and evaluate extended criteria donor livers. Currently, no consensus exists in methodology and perfusion protocols. Here, the authors performed a systematic literature search to identify human and porcine studies reporting on liver NMP with red blood cells. A qualitative synthesis was performed concerning technical aspects of MP, fluid composition, gas supply, and liver positioning. Thirty‐seven publications including 11 human and 26 porcine studies were considered for qualitative synthesis. Control mode, pressure, flow, perfusate additives, and targeted blood gas parameters varied across human as well as porcine studies. For future analyses, it is advisable to report flow adjusted to liver weight and exact pressure parameters including mean, systolic, and diastolic pressure. Parenteral nutrition and insulin addition was common. Parenteral nutrition included amino acids and/or glucose without lipids. Taurocholic acid derivatives were used as bile flow promoters. However, short‐term human NMP without taurocholic acid derivatives seems to be possible. This finding is relevant due to the lack of clinical grade bile salts. Near physiological oxygen tension in the perfusate is doable by adjusting gas flows, while blood gas parameters regulation needs more detailed description.

Impact of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) on growth of colorectal liver metastases

Background Associating liver partition and portal vein ligation for staged hepatectomy induces an unprecedented liver hypertrophy and enables resection of otherwise unresectable liver tumors. The effect of associating liver partition and portal vein ligation for staged hepatectomy on tumor proliferation, however, remains a concern. This study investigated the impact of associating liver partition and portal vein ligation for staged hepatectomy on growth of colorectal metastases in mice and in humans. Methods The effect of associating liver partition and portal vein ligation for staged hepatectomy and 90% portal vein ligation on colorectal liver and lung metastases was investigated in mice. In vivo tumor progression was assessed by magnetic resonance imaging, histology, and survival experiments. The effects of associating liver partition and portal vein ligation for staged hepatectomy, portal vein ligation, and control sera on cultures of several colorectal cancer cell lines (MC38 and CT26) were tested in vitro. Additionally, the international associating liver partition and portal vein ligation for staged hepatectomy registry enabled us to identify patients with remaining tumor in the future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy stage 1. Results Two and 3 weeks after associating liver partition and portal vein ligation for staged hepatectomy stage 1, portal vein ligation, or sham surgery, liver magnetic resonance images showed similar numbers (P = .14/0.82), sizes (P = .45/0.98), and growth kinetics (P = .58/0.68) of intrahepatic tumor. Tumor growth was not different between the associating liver partition and portal vein ligation for staged hepatectomy and portal vein ligation groups after completion of stage 2. Median survival after tumor cell injection was similar after sham surgery (36 days; 95% confidence interval; 27–57 days), completion of associating liver partition and portal vein ligation for staged hepatectomy (42 days; 95% confidence interval; 35–49 days), and portal vein ligation (39 days; 95% confidence interval; 34–43 days, P = .237). Progression of pulmonary metastases and in vitro cell proliferation were comparable among groups. Observations in humans failed to identify any accelerated tumor growth in the future liver remnant within the regenerative phase after associating liver partition and portal vein ligation for staged hepatectomy stage 1. Conclusion The accelerated regeneration process associated with associating liver partition and portal vein ligation for staged hepatectomy does not appear to enhance growth of colorectal metastases.

Reply to “Ex situ normothermic machine perfusion of donor livers using a haemoglobin-based oxygen carrier: a viable alternative to red blood cells”

We highly appreciate the interest expressed in the letter by de Vries et all concerning our recent systematic review (1, 2), and congratulate for the successful transplantation using HBOC during normothermic perfusion. We agree, that ex situ normothermic and also subnormothermic liver perfusion using HBOC is per se an interesting option to spare red blood cells as oxygen carrier. This article is protected by copyright. All rights reserved.

Insurance status does not affect short-term outcomes after oncological colorectal surgery in Europe, but influences the use of minimally invasive techniques: a propensity score-matched analysis

Background and PurposeControversy exists whether surgical treatment is influenced by insurance status. American studies suggest higher morbidity and decreased survival in uninsured patients with colorectal cancer (CRC). It remains elusive, however, whether these findings apply to European countries with mandatory, government-driven insurance systems. We aimed to analyze whether operative techniques, quality of surgery, and complication rates differ among patients covered by statutory (SI) versus private (PI) healthcare insurance.MethodsBased on a prospective national surgical quality database, patients undergoing elective resection for CRC during 2007–2015 were identified. A propensity score match of eligible patients with SI and PI yielded 765 patients per group.ResultsHierarchical status of the operating surgeon differed substantially (p = 0.001): junior surgeons operated on > 50% of patients with SI, whereas over 80% of patients with PI were operated by senior surgeons. Minimally invasive techniques were used more frequently in patients with PI (p = 0.001) and patients with SI undergoing colonic resection showed an increased conversion rate (OR 2.44). Median duration of surgery (p = 0.001) and blood loss (p = 0.002) were higher in patients with SI; however, length of hospital stay was equal. Neither the rate of positive resection margins nor the number of resected lymph nodes differed among groups. Complications and mortality occurred with similar frequencies for patients undergoing colon (p = 0.140) and rectal (p = 0.335) resection.ConclusionThe use of minimally invasive techniques was favored in patients with PI; however, the quality of oncological resection was not affected by insurance status and only minor differences in perioperative complications observed.

The Allosteric Hemoglobin Effector Itpp Inhibits Metastatic Colon Cancer in Mice

Objective: To test the effects of enhanced intracellular oxygen contents on the metastatic potential of colon cancer. Background: Colorectal cancer is the commonest gastrointestinal carcinoma. Distant metastases occur in half of patients and are responsible for most cancer-related deaths. Tumor hypoxia is central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP), a nontoxic, antihypoxic compound, has recently shown significant benefits in experimental cancer, particularly when combined with standard chemotherapy. Whether ITPP protects from distant metastases in primary colon cancer is unknown. Methods: ITPP alone or combined with FOLFOX was tested in a mouse model with cecal implantation of green fluorescent protein-labeled syngeneic colorectal cancer cells. Tumor development was monitored through longitudinal magnetic resonance imaging-based morphometric analysis and survival. Established serum markers of tumor spread were measured serially and circulating tumor cells were detected via fluorescence measurements. Results: ITPP significantly reduced the occurrence of metastases as well as other indicators of tumor aggressiveness. Less circulating tumor cells along with reduction in malignant serum markers (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary cancer site. Importantly, animals treated with ITPP had a significant survival benefit compared with respective controls, while a combination of FOLFOX with ITPP conferred the maximum benefits, including dramatic improvements in survival (mean 86 vs 188 d). Conclusions: Restoring oxygen in metastatic colon cancer through ITPP inhibits tumor spread and markedly improves animal survival; an effect that is enhanced through the application of subsequent chemotherapy. These promising novel findings call for a clinical trial on ITPP in patients with colorectal cancer, which is under way.