Minimally-Invasive Diaphragmatic Plication in Patients with Unilateral Diaphragmatic Paralysis.

Background: Diaphragm eventration (DE) represents a frequent problem with consecutive major impacts on respiratory function and the quality of life of the patients. The role of diaphragmatic plication (DP) is still underestimated. The aim of the present study is to evaluate the efficacy of minimally-invasive surgical diaphragmatic plication for the management of unilateral diaphragmatic eventration, to the best of our knowledge, this is the largest series reported in the literature using a non-resectional technique. Methods: All patients with unilateral diaphragmatic paralysis admitted for diaphragmatic plication (DP) between January 2008 and December 2022 formed the cohort of this retrospective analysis. DP procedure was done to plicate the diaphragm without resection or replacement with synthetic materials. Patients were divided into two groups: Group I included patients who underwent DP through an open thoracotomy, and Group II included patients who underwent DP through video-assisted thoracoscopic surgery (VATS). Data from all patients were collected prospectively and subsequently analyzed retrospectively. Patients' characteristics, lung function tests, radiological findings, type of surgical procedures, complications, and postoperative follow-up were compared. The primary outcome measure was the postoperative result (deeper position of the paralyzed diaphragm) and improvement of dyspnea. The secondary outcome was lung function values over a long-term follow-up. Results: The study included a total of 134 patients who underwent diaphragmatic plication during the study period. 94 (71.7%) were males, mean age of 64 (SD ± 14.0). Group I (thoracotomy group) consisted of 46 patients (35 male). Group II (VATS-group) consisted of 88 patients (69 male). The majority of patients demonstrated impaired lung functions (n = 126). The mean length of diaphragmatic displacement was 8 cm (SD ± 113.8 cm). The mean duration of the entire procedure, including placement of the epidural catheter (EDC), was longer in group I than in group II (p = 0.016). This was also observed for the mean length of the surgical procedure itself (p = 0.031). Most patients in group I had EDC (n = 38) (p = 0.001). Patients in group I required more medication for pain control (p = 0.022). A lower position of the diaphragm was achieved in all patients (p < 0.001). The length of hospital stay was 7 (SD ± 4.5) days in group I vs. 4.5 (SD ± 3.2) days in group II (p = 0.036). Minor complications occurred in 3% (n = 4) in group I vs. 2% (n = 3) in group II. No mortality was observed in any of the groups. Postoperative follow-up of patients at 6, 12, and 24 months showed a significant increase in forced vital capacity (FVC) up to 25% (SD ± 10%-35%) (p = 0.019), in forced expiratory volume in 1 s (FEV1) up to 20% (SD ± 12%-38%) in both groups (p = 0.026), also in the diffusion capacity of carbon monoxide (DLCO) up to 15% (SD ± 10%-20%) was noticed in both groups. Chronic pain symptoms were noted in 13% (n = 6) in group I vs. 2% (n = 2) in group II (p = 0.014). Except for one patient in group II, no recurrence of DE was observed. Conclusions: Diaphragm plication is an effective procedure to reduce debilitating dyspnea and improve lung function in patients suffering from diaphragm eventration. Minimally invasive diaphragmatic plication using VATS procedures is a safe and feasible procedure for the management of unilateral diaphragmatic paralysis. VATS-DP is superior to open procedure in terms of pain management and length of hospital stay, hence, accelerated recovery is more likely. Careful patient selection is crucial to achieving optimal outcomes. Prospective studies are needed to validate these results.

Structure and Dynamics of Human Chemokine CCL16-Implications for Biological Activity.

Human C-C motif ligand 16 (CCL16) is a chemokine that is distinguished by a large cleavable C-terminal extension of unknown significance. Conflicting data have been reported concerning its tissue distribution and modulation of expression, rendering the biological function of CCL16 enigmatic. Here, we report an integrated approach to the characterisation of this chemokine, including a re-assessment of its expression characteristics as well as a biophysical investigation with respect to its structure and dynamics. Our data indicate that CCL16 is chiefly synthesised by hepatocytes, without an appreciable response to mediators of inflammation, and circulates in the blood as a full-length protein. While the crystal structure of CCL16 confirms the presence of a canonical chemokine domain, molecular dynamics simulations support the view that the C-terminal extension impairs the accessibility of the glycosaminoglycan binding sites and may thus serve as an intrinsic modulator of biological activity.

Women's Perception of Transgastric and Transvaginal Natural Orifice Transluminal Endoscopic Surgery (NOTES) - Impact of Medical Education, Stage of Life and Cross-Cultural Aspects.

Introduction: Despite that NOTES produces at least matchable clinical long-term results when compared to laparoscopy, still a restraint within the medical community and among patients is evident. Consequently, it might be meaningful to evaluate factors of patient's NOTES perception to promote its acceptance. NOTES is still quite novel and questionnaires regarding its perception by the public is still lacking even so in the Middle East. Aim of our survey is to investigate the viewpoint of female healthcare staff on NOTES. Materials and Methods: A total of 350 questionnaires along with written information about Minimally Invasive Surgery and NOTES were distributed among the female staff in a Tertiary-care Hospital in Abu Dhabi, 257 were returned completely anonymously and voluntarily and entered into a database with a response rate of 73%. We surveyed factors like religion, medical background, age as well as history of previous laparoscopy, endoscopy, birth and other aspects that may impact a woman's perception of both transgastric and transvaginal NOTES for cholecystectomy and ovariectomy, respectively. Results: Univariate analyses revealed the majority of Muslim women to be more receptive to NOTES as a choice of surgical technique for cholecystectomy and for ovariectomy, respectively, when compared to Christians and Hindus. However, when compared to Muslims, Christian and Hindu groups had a larger share of medical professions. Women with a medical background would opt significantly less for NOTES. Among younger women, NOTES cholecystectomy was refused due to anxiety concerning future pregnancies and sexual dysfunction. Multinomial logistic regression analysis determined medical background and with independent predictive value for the overall choice of interventional technique (p<0.001). Marital status played a significant role only in the comparison of laparoscopy vs transgastric NOTES when performing cholecystectomy and ovariectomy (p<0.01). Conclusion: In this first study emanating from the Middle East, medical education and partly life stage rather than cross-cultural differences seem to influence NOTES perception in women.

Dual color DMD-SIM by temperature-controlled laser wavelength matching.

Structured illumination microscopy (SIM) is a fast and gentle super-resolution fluorescence imaging technique, featuring live-cell compatible excitation light levels and high imaging speeds. To achieve SIM, spatial modulation of the fluorescence excitation light is employed. This is typically achieved by interfering coherent laser beams in the sample plane, which are often created by spatial light modulators (SLMs). Digital micromirror devices (DMDs) are a form of SLMs with certain advantages, such as high speed, low cost and wide availability, which present certain hurdles in their implementation, mainly the blazed grating effect caused by the jagged surface structure of the tilted mirrors. Recent works have studied this effect through modelling, simulations and experiments, and laid out possible implementations of multi-color SIM imaging based on DMDs. Here, we present an implementation of a dual-color DMD based SIM microscope using temperature-controlled wavelength matching. By carefully controlling the output wavelength of a diode laser by temperature, we can tune two laser wavelengths in such a way that no opto-mechanical realignment of the SIM setup is necessary when switching between both wavelengths. This reduces system complexity and increases imaging speed. With measurements on nano-bead reference samples, as well as the actin skeleton and membrane of fixed U2OS cells, we demonstrate the capabilities of the setup.

Technical aspects of paediatric robotic pancreatic enucleation based on a case of an insulinoma.

BACKGROUND: Insulinomas are rare insulin-producing pancreatic neuroendocrine tumours leading to severe episodes of hypoglycaemia. Surgery is the predominant curative therapy. METHODS: We report here the first paediatric case of an insulinoma of the pancreatic body resected completely robotically under ultrasound guidance in a 10-year-old male with multiple endocrine neoplasia type 1. The port set-up was adapted for the narrowed dimensions of the paediatric peritoneal space. We comment on technical key steps for the organ-preserving procedure that was performed in close proximity to critical anatomic structures, with supporting video. Preoperative diagnostics, including endoscopic ultrasound, to determine surgical management are highlighted. RESULTS: Following an uneventful post-operative course, the boy was discharged on day 11 with normalised glucose-metabolism. A pseudocyst developing after 4 weeks was treated with endoscopic stenting. CONCLUSIONS: The applicability of a robotic surgical system in limited space conditions such as found in the paediatric abdominal cavity is demonstrated here for pancreatic surgery.

Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies.

The liver as the largest organ in the human body is composed of a complex macroscopic and microscopic architecture that supports its indispensable function to maintain physiological homeostasis. Optical imaging of the human liver is particularly challenging because of the need to cover length scales across 7 orders of magnitude (from the centimeter scale to the nanometer scale) in order to fully assess the ultrastructure of the entire organ down to the subcellular scale and probe its physiological function. This task becomes even more challenging the deeper within the organ one hopes to image, because of the strong absorption and scattering of visible light by the liver. Here, we demonstrate how optical imaging methods utilizing highly specific fluorescent labels, as well as label-free optical methods can seamlessly cover this entire size range in excised, fixed human liver tissue and we exemplify this by reconstructing the biliary tree in three-dimensional space. Imaging of tissue beyond approximately 0.5 mm length requires optical clearing of the human liver. We present the successful use of optical projection tomography and light-sheet fluorescence microscopy to derive information about the liver architecture on the millimeter scale. The intermediate size range is covered using label-free structural and chemically sensitive methods, such as second harmonic generation and coherent anti-Stokes Raman scattering microscopy. Laser-scanning confocal microscopy extends the resolution to the nanoscale, allowing us to ultimately image individual liver sinusoidal endothelial cells and their fenestrations by super-resolution structured illumination microscopy. This allowed us to visualize the human hepatobiliary system in 3D down to the cellular level, which indicates that reticular biliary networks communicate with portal bile ducts via single or a few ductuli. Non-linear optical microscopy enabled us to identify fibrotic regions extending from the portal field to the parenchyma, along with microvesicular steatosis in liver biopsies from an older patient. Lastly, super-resolution microscopy allowed us to visualize and determine the size distribution of fenestrations in human liver sinusoidal endothelial cells for the first time under aqueous conditions. Thus, this proof-of-concept study allows us to demonstrate, how, in combination, these techniques open up a new chapter in liver biopsy analysis.

Grave thoraco-intestinal complication secondary to an undetected traumatic rupture of the diaphragm: a case report.

BACKGROUND: Diaphragmatic lesions as a result of blunt or penetrating trauma are challenging to detect in the initial trauma setting. This is especially true when diaphragmatic trauma is part of a polytrauma. Complications of undetected diaphragmatic defects with incarcerating bowel are rare, but as in our patient can be serious. CASE PRESENTATION: A 57-year-old female presented to the Emergency Room of our Hospital in a critical condition with 3 days of increasing abdominal pain. The initial clinical examination showed peritonism with tinkling peristaltic bowel sounds of mechanical obstruction. A thoraco-abdominal CT scan demonstrated colon prolapsed through the left diaphragmatic center with a large sero-pneumothorax under tension. As the patient was hemodynamically increasingly unstable with developing septic shock, an emergency laparotomy was performed. After retraction of the left colon, which had herniated through a defect of the tendinous center of the left diaphragm and was perforated due to transmural ischemia, large amounts of feces and gas discharged from the left thorax. A left hemicolectomy resulting in a Hartmann-type procedure was performed. A fully established pleural empyema required meticulous debridement and lavage conducted via the 7-10 cm in diameter phrenic opening followed by a diaphragmatic defect reconstruction. Due to pneumonia and recurring pleural empyema redo-debridement of the left pleural space via thoracotomy were required. The patient was discharged on day 56. A thorough history of possible trauma revealed a bicycle-fall trauma 7 months prior to this hospitalization with a surgically stabilized fracture of the left femur and conservatively treated fractures of ribs 3-9 on the left side. CONCLUSION: This is the first report on a primarily established empyema at the time of first surgical intervention for feco-pneumothorax secondary to delayed diagnosed diaphragmatic rupture following abdomino-thoracic blunt trauma with colic perforation into the pleural space, requiring repetitive surgical debridement in order to control local and systemic sepsis. Thorough investigation should always be undertaken in cases of blunt abdominal and thoracic trauma to exclude diaphragmatic injury in order to avoid post-traumatic complications.

Hepatic Vasculopathy and Regenerative Responses of the Liver in Fatal Cases of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects the nasopharynx and lungs and causes coronavirus disease-2019 (COVID-19). It may impact the heart, brain, kidney, and liver.1 Although functional impairment of the liver has been correlated with worse clinical outcomes, little is known about the pathophysiology of hepatic injury and repair in COVID-19.2,3 Histologic evaluation has been limited to small numbers of COVID-19 cases with no control subjects2,4 and demonstrated largely heterogeneous patterns of pathology.2,3.

Platelets Boost Recruitment of CD133+ Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions.

We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair.

Impact of ASA-score, age and learning curve on early outcome in the initiation phase of an oncological robotic colorectal program.

The ASA score is known to be an independent predictor of complications and mortality following colorectal surgery. We evaluated early outcome in the initiation phase of a robotic oncological colorectal resection program in dependence of comorbidity and learning curve. 43 consecutive colorectal cancer patients (median age: 74 years) who underwent robotic surgery were firstly analysed defined by physical status (group A = ASA1 + 2; group B = ASA3). Secondly, outcome was evaluated relating to surgery date (group E: early phase; group L: late phase). There were no differences among groups A and B with regard to gender, BMI, skin-to-skin operative times (STS), N- and M-status, hospital-stay as well as overall rate of complications according to Dindo-Clavien and no one-year mortality. GroupA when compared to group B demonstrated significantly lower mean age (65.5 years ± 11.4 years vs 75.8 years ± 8.9 years), T-stage and ICU-stay. When separately analyzed for patients age ICU-stay was comparable (> 75 years vs. < 75 years). Group E and L demonstrated comparable characteristics and early outcome except more frequent lymphatic fistulas in group E. STS was reduced in group L compared to group E. Beyond learning curve aspects in our series, we could demonstrate that patient's physical condition according to ASA rather than age may have an impact on early outcome in the initial phase of a robotic oncological colorectal program.

Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition.

Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial-mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (NMYC) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential.

Management of Complex Facial Injuries: Cutting Traumas by Angle Grinders.

The use of angle grinders can lead to complex facial injuries. The most frequent sites affected are within the head and face region. Anatomical boundaries or structures are not respected by the high-speed disc of angle grinders, and thus, injuries can be mutilating, permanently disabling, or even lethal. Functional and aesthetical satisfying results can be reached through debridement, excision of wound edges, and meticulous layered functional closure after appropriate reconstruction of additional facial bony defects. The management and short-term outcome of a complex facial cutting trauma by an angle grinder are presented and discussed.

In situ split plus portal vein ligation (ISLT) - a salvage procedure following inefficient portal vein embolization to gain adequate future liver remnant volume prior to extended liver resection.

BACKGROUND: Right extended liver resection is frequently required to achieve tumor-free margins. Portal venous embolization (PVE) of the prospective resected hepatic segments for conditioning segments II/III does not always induce adequate hypertrophy in segments II and III (future liver remnant volume (FLRV)) for extended right-resection. Here, we present the technique of in situ split dissection along segments II/III plus portal disruption to segments IV-VIII (ISLT) as a salvage procedure to overcome inadequate gain of FLRV after PVE. METHODS: In eight patients, FLRV was further pre-conditioned following failed PVE prior to hepatectomy (ISLT-group). We compared FLRV changes in the ISLT group with patients receiving extended right hepatectomy following sufficient PVE (PVEres-group). Survival of the ISLT-group was compared to PVEres patients and PVE patients with insufficient FLRV gain or tumor progress who did not receive further surgery (PVEnores-group). RESULTS: Patient characteristics and surgical outcome were comparable in both groups. The mean FLRV-to-body-weight ratio in the ISLT group was smaller than in the PVEres-group pre- and post-PVE. One intraoperative mortality due to a coronary infarction was observed for an ISLT patient. ISLT was successfully completed in the remaining seven ISLT patients. Liver function and 2-year survival of ~ 50% was comparable to patients with extended right hepatectomy after efficient PVE. Patients who received a PVE but who were not subsequently resected (PVEnores) demonstrated no survival beyond 4 months. CONCLUSION: Despite extended embolization of segments I and IV-VIII, ISLT should be considered if hypertrophy was not adequate. Liver function and overall survival after ISLT was comparable to patients with trisectionectomy after efficient PVE.

A typical carcinoid of the lung - a case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression.

RATIONALE: Neuroendocrine tumors (NETs) of the lung account for 5% of all cases of lung cancer, which itself is the leading cause of cancer-related death worldwide. In accordance to its rarity, only few cell lines of NETs exist, which even often lack key characteristics of the primary tumor, making it difficult to study underlying molecular mechanisms. PATIENT CONCERNS: The patient reported in this case is a 71-year old woman, which never smoked but suffered under dry cough. DIAGNOSES: Chest CT-scan showed a paracardiac nodule of the lingula with 2 × 1.8 cm in diameter. INTERVENTIONS: The detected paracardiac nodule of the lingula was anatomically resected using video assisted thoracic surgery. OUTCOMES: Histopathological diagnostic of the removed tissue identified the tumor as a well-differentiated typical carcinoid (TC), which represents one of the four subgroups of pulmonary NETs. Next to the successful treatment of the patient, we were able to propagate cancer stem cells (CSCs) out of the resected tumor tissue. To the best of our knowledge, we firstly isolated CSCs of a typical carcinoid, which were positive for the prominent CSC markers CD44, CD133 and nestin, confirming their stem cell properties. Additionally, CSCs, further referred as BKZ1, expressed the neuroendocrine marker synaptophysin, verifying their neuroendocrine origin. However, nuclear synaptophysin protein was also present in other stem cell populations, suggesting a role as general stem cell marker. LESSON: In line with the importance of CSCs in cancer treatment and the lack of CSC-models for neuroendocrine neoplasms, the here described BKZ1 cancer stem cell line of a typical carcinoid represents a promising new model to study pulmonary carcinoids and particular NETs.

A standardized suprapubic bottom-to-up approach in robotic right colectomy: technical and oncological advances for complete mesocolic excision (CME).

BACKROUND: Several studies have demonstrated a direct correlation between lymph node yield and survival after colectomy for cancer. Complete mesocolic excision (CME) in right colectomy (RC) reduces local recurrence but is technically demanding. Here we report our early single center experience with robotic right colectomy comparing our standardized bottom-to-up (BTU) approach of robotic RC with CME and central vessel ligation (CVL) facilitated by a suprapubic access with the "classical" medial-to-lateral (MTL) strategy. METHODS: A 4-step BTU approach of robotic RC guided by embryonal planes in the process of retrocolic mobilization with suprapubic port placement was performed in the BTU-group (n = 24; all with intention to treat cancer). In step 1 CME was initiated with caudolateral mobilization of the right colon guided by the fascia of Toldt across the duodenum and up to the Trunk of Henle. Subsequently, dissection was performed BTU right of the middle supramesenteric vessels with central ileocolic vessel ligation in step 2. Subsequent to separation of the transverse retromesenteric space and completion of mobilization the hepatic flexure in step 3, the transverse mesocolon was then transected right of the middle colic vessels in step 4. An extracorporeal side to side anastomosis was performed. We compared the outcome of the BTU-group with a MTL-group (n = 7). RESULTS: Patient characteristics like age, gender, BMI, comorbidity (ASA) and M-status were comparable among groups. There was no conversion. Overall complication rate was 35.5%. We experienced no anastomoses insufficiency, grade Dindo/Clavien III/IV complication or mortality in this study. Type I and II complications and surgical characteristics incl. OR-time, ICU- and hospital-stay were comparable between the two groups. However, the lymph node yield was superior in the BTU-group (mean 40.2 ± 17.1) when compared with the MTL-group (16,3 nodes ±8.5; p <  0,001). CONCLUSIONS: Compared to the classical MTL approach, robotic suprapubic BTU RC changes from a search of the layers bordering the oncological dissection to a consequent utilization of the planes as a retro-mesocolic guide during CME. The BTU strategy could bear the potential to increase the lymph node yield. Robotic systems may provide the technical requirements to combine advantages of both open and minimally invasive RC.