Morris Beshay

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.

There is growing evidence that cancer stem cells (CSCs), a small subpopulation of self-renewal cancer cells, are responsible for tumor growth, treatment resistance, and cancer relapse and are thus of enormous clinical interest. Here, we aimed to isolate new CSC-like cells derived from human primary non-small cell lung cancer (NSCLC) specimens and to analyze the influence of different inhibitors of NF-κB and MYC signaling on cell survival. CSC-like cells were established from three squamous cell carcinomas (SCC) and three adenocarcinomas (AC) of the lung and were shown to express common CSC markers such as Prominin-1, CD44-antigen, and Nestin. Further, cells gave rise to spherical cancer organoids. Inhibition of MYC and NF-κB signaling using KJ-Pyr-9, dexamethasone, and pyrrolidinedithiocarbamate resulted in significant reductions in cell survival for SCC- and AC-derived cells. However, inhibition of the protein–protein interaction of MYC/NMYC proto-oncogenes with Myc-associated factor X (MAX) using KJ-Pyr-9 revealed the most promising survival-decreasing effects. Next to the establishment of six novel in vitro models for studying NSCLC-derived CSC-like populations, the presented investigations might provide new insights into potential novel therapies targeting NF-κB/MYC to improve clinical outcomes in NSCLC patients. Nevertheless, the full picture of downstream signaling still remains elusive.

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term “NF-kB binding” was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

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.

Objectives: Thoracic trauma (TT) is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. Its management is still a very challenging task. The purpose of this study was to analyse the risk factors affecting the outcome in a high-volume trauma centre and the efficacy of a specialised trauma team in level 1 trauma centres. Patients and methods: Between January 2003 and December 2012, data of all patients admitted to the accident and emergency (A&E) department were prospectively collected at the German Trauma Registry (GTR) and thereafter retrospectively analysed. Patients with chest trauma, an Injury Severity Score (ISS) ≥ 18 and an Abbreviated Injury Scale (AIS) > 2 in more than one body region were included. Patients were divided into two groups: group I included patients presenting with thoracic trauma between January 2003 and December 2007. The results of this group were compared with the results of another group (group II) in a later 5-year period (Jan. 2008–Dec. 2012). Univariate and multivariate analyses were performed, and differences with p < 0.05 were considered statistically significant. Results: There were 630 patients (56%) with thoracic trauma. A total of 540 patients (48%) had associated extrathoracic injuries. Group I consisted of 285 patients (197 male, mean age 46 years). Group II consisted of 345 patients (251 male, mean age 49 years). Overall 90-day mortality was 17% (n = 48) in group I vs. 9% (n = 31) in group II (p = 0.024). Complication rates were higher in group I (p = 0.019). Higher Injury Severity Scores (ISSs) and higher Abbreviated Injury Acale (AIS) scores in the thoracic region yielded a higher rate of mortality (p < 0.0001). Young patients (< 40 years) were frequently exposed to severe thoracic injury but showed lower mortality rates (p = 0.014). Patients with severe lung contusions (n = 94) (15%) had higher morbidity and mortality (p < 0.001). Twenty-three (8%) patients underwent emergency thoracotomy in group I vs. 14 patients (4%) in group II (p = 0.041). Organ replacement procedures were needed in 18% of patients in group I vs. 31% of patients in group II (p = 0.038). Conclusions: The presence of severe lung contusion, a higher ISS and AIS_thoracic score and advanced age are independent risk factors that are directly related to a higher mortality rate. Management of blunt chest trauma with corrective chest tube insertion, optimal pain control and chest physiotherapy results in good outcomes in the majority of patients. Optimal management with better survival rates is achievable in specialised centres with multidisciplinary teamwork and the presence of thoracic surgical experience.

A 27-year-old male patient presented with cough and right-sided, light thoracic pain. His physical appearance showed typical features of gigantism. Subsequently, further diagnostic work-up showed elevated level of growth hormone and a huge tumor of the right lung, identifying a typical pulmonary carcinoid tumor (TPCT). Curative surgery was performed leading to normalization of the elevated growth hormone levels few days after surgery. Two- and five-year follow-up showed no signs of recurrence. Respected to tumor size, we determined the largest TPCT to be reported in medical literature history.

Objectives:Thoracic trauma (TT) is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. Its management is still a very challenging task. The purpose of this study was to analyse the epidemiological finding, risk factors affecting the outcome in a high volume trauma centre.Patients and methods:Between January 2003 and December 2012 data of all patients admitted to the Accident and Emergency (A&E) were prospectively collected at the German Trauma Registry (GTR) thereafter retrospectively analysed.Patients with chest trauma and Injury Severity Score (ISS) ≥18 and Abbreviated Injury Scale (AIS) >2 in more than one body region were included. Patients were divided into two groups; group I included patients with thoracic trauma between January 2003 to December 2007. The results of this group were compared with the results of other group (group II) in a later five years period (Jan. 2008-Dec. 2012). Univariate and multivariate analysis was done, Statistical difference with PResults:There were 630 patients (56%) with thoracic trauma. 540 patients (48%) had associated extra thoracic injuries. Group I consisted of 285 patients (197 male, mean age 46 years). Group II consisted of 345 patients (251 male, mean age 49 year). Overall 90 days mortality was 17% (n=48) in group I vs. 9% (n=31) in group II (p=0.024). Complication rates were higher in group I (p=0.019). Higher injury severity score (ISS), and higher abbreviated injury score (AIS) thoracic showed higher rate of mortality (pp=0.014). Patients with severe lung contusions (n=94) (15%) had higher morbidity and mortality (pp=0.041). Organ replacement procedures were needed in 18% in group I vs. 31% in group II (p=0.038).Conclusions:The presence of severe lung contusion, higher ISS and AIS_thoracic and advanced age are directly related to higher mortality rate. Instantly management of blunt chest trauma with corrected chest tube insertion, optimal pain control and chest physiotherapy resulted in good outcome in the majority of patients. Optimal management with better survival rates is achievable in specialized centre with a multidisciplinary teamwork and the presence of thoracic surgical experience.

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

Pain control after thoracotomy is an important issue that affects the outcome in thoracic surgery. Intercostal nerve preservation (ICNP) has increased interest in the outcomes of conventional thoracotomy. The current study critically evaluates the role of preservation of the intercostal nerve in early and late pain control and its benefit in patients undergoing thoracotomy. Data obtained prospectively between January 2006 and December 2010 by a study colleague at our division of General Thoracic Surgery were retrospectively analysed. There were 491 patients who underwent thoracotomy. Eighty-one patients were excluded from the study due to incompatible data. Patients were divided into two groups according to the intercostal nerve state: Group I consisted of patients with ICNP and Group II consisted of patients with intercostal nerve sacrifice. Group I consisted of 288 patients [206 male (71%), P < 0.001, mean age 66 years]. Group II consisted of 122 patients [79 male (64%), P = 0.001, mean age 66 years]. There was less use of opiate in Group I (P = 0.019). Early mobilization of the patients was significantly higher in Group I (P = 0.031). The rate of pneumonia and re-admission to the intensive care unit was higher in Group II (P = 0.017 and 0.023, respectively). The rate of pain-free patients at discharge was significantly higher in Group I (P = 0.028). A 2-week follow-up after hospital discharge showed parasternal hypoesthesia to be more in Group II (P = 0.034). Significant patient contentment in Group I was noticed (P = 0.014). Chronic post-thoracotomy pain (CPTP) was higher in Group II (P = 0.016). ICNP without harvesting an intercostal muscle flap achieves excellent outcomes in controlling acute post-thoracotomy pain and CPTP. ICNP is an effective, simple method to perform, and it should be considered as standard in performing thoracotomy.