Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry

BACKGROUND: Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. METHODS: From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. RESULTS: Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P < 0.0001) and in the hospital (median 7 days [IQR 4–11] vs. 12 [10–18], 12 [8–19] or 12 [9–17]; P < 0.0001), and complications occurred less frequently (22/127 [17.3%] vs. 37/92 [40.2%], 29/65 [44.6%] or 48/105 [45.7%]; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien–Dindo grade ≥ IIIa) complications (OR 0.49 [95% CI 0.25–0.96], P = 0.037), whereas—compared to exploration only—biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 [1.48–8.64], P = 0.005; 3.50 [1.39–8.81], P = 0.008; 4.96 [2.15–11.43], P < 0.001). CONCLUSIONS: In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12893-022-01833-3

Accuracy of prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography

Objective: X-linked hypohidrotic ectodermal dysplasia (XLHED), a developmental disorder characterized by malformation of hair, teeth, and sweat glands, results from defective ectodysplasin A1 (EDA1) caused by EDA mutations. Inability to sweat, the major problem of XLHED which can lead to life-threatening hyperthermia, has been shown to be amenable to intrauterine therapy with recombinant EDA1. The aim of this retrospective study was to evaluate the diagnostic accuracy of tooth germ sonography to identify affected fetuses in pregnant women with EDA mutations. Methods: Tooth germ sonography was performed in 38 cases at 10 study sites between gestational weeks 18 and 28. XLHED was diagnosed if fewer than six tooth germs were detected in mandible and/or maxilla. In all subjects, diagnoses were verified postnatally by EDA sequencing and/or clinical findings (standardized clinical assessments of hair, sweating, and dentition; orthopantomograms). Estimated weights of 12 affected male fetuses and postnatal weight gain of 12 boys with XLHED were assessed using appropriate growth charts. Results: In 19 of 38 sonografic examinations of 23 male and 13 female fetuses, a prenatal diagnosis of XLHED was made. The diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counting by clinical assessment corresponded well with radiografic findings. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. Conclusions: Tooth germ sonography is highly specific and reliable in establishing a prenatal diagnosis of XLHED

Photosynthetic production of enantioselective biocatalysts

$\bf Background:$ Global resource depletion poses a dramatic threat to our society and creates a strong demand for alternative resources that do not compete with the production of food. Meeting this challenge requires a thorough rethinking of all steps of the value chain regarding their sustainability resource demand and the possibility to substitute current, petrol-based supply-chains with renewable resources. This regards also the production of catalysts for chemical synthesis. Phototrophic microorganisms have attracted considerable attention as a biomanufacturing platform for the sustainable production of chemicals and biofuels. They allow the direct utilization of carbon dioxide and do not compete with food production. Photosynthetic enzyme production of catalysts would be a sustainable supply of these important components of the biotechnological and chemical industries. This paper focuses on the usefulness of recombinant cyanobacteria for the photosynthetic expression of enantioselective catalysts. As a proof of concept, we used the cyanobacterium $\it Synechocystis$ sp. PCC 6803 for the heterologous expression of two highly enantioselective enzymes. $\bf Results:$ We investigated the expression yield and the usefulness of cyanobacterial cell extracts for conducting stereoselective reactions. The cyanobacterial enzyme expression achieved protein yields of 3% of total soluble protein (%TSP) while the expression in $\textit {E. coli}$ yielded 6-8% TSP. Cell-free extracts from a recombinant strain expressing the recombinant esterase ST0071 from the thermophilic organism $\textit {Sulfolobus tokodai}$ ST0071 and arylmalonate decarboxylase from $\textit {Bordetella bronchiseptica}$ showed excellent enantioselectivity (>99% ee) and yield (>91%) in the desymmetrisation of prochiral malonates. $\bf Conclusions:$ We were able to present the proof-of-concept of photoautotrophic enzyme expression as a viable alternative to heterotrophic expression hosts. Our results show that the introduction of foreign genes is straightforward. Cell components from $\it Synechocystis$ did not interfere with the stereoselective transformations, underlining the usability of photoautotrophic organisms for the production of enzymes. Given the considerable commercial value of recombinant biocatalysts, cyanobacterial enzyme expression has thus the potential to complement existing approaches to use phototrophic organisms for the production of chemicals and biofuels