Predictive factors of 90-day mortality after curative hepatic resection for hepatocellular carcinoma: a western single-center observational study.

PURPOSE: The aim of this study was to identify predictive risk factors associated with 90-day mortality after hepatic resection (HR) in hepatocellular carcinoma (HCC). METHODS: All patients undergoing elective resection for HCC from a single- institutional and prospectively maintained database were included. Multivariate regression analysis was conducted to identify pre- and intraoperative as well as histopathological predictive factors of 90-day mortality after elective HR. RESULTS: Between August 2004 and October 2021, 196 patients were enrolled (148 male /48 female). The median age of the study cohort was 68.5 years (range19-84 years). The rate of major hepatectomy (≥ 3 segments) was 43.88%. Multivariate analysis revealed patient age ≥ 70 years [HR 2.798; (95% CI 1.263-6.198); p = 0.011], preoperative chronic renal insufficiency [HR 3.673; (95% CI 1.598-8.443); p = 0.002], Child-Pugh Score [HR 2.240; (95% CI 1.188-4.224); p = 0.013], V-Stage [HR 2.420; (95% CI 1.187-4.936); p = 0.015], and resected segments ≥ 3 [HR 4.700; (95% 1.926-11.467); p = 0.001] as the major significant determinants of the 90-day mortality. CONCLUSION: Advanced patient age, pre-existing chronic renal insufficiency, Child-Pugh Score, extended hepatic resection, and vascular tumor involvement were identified as significant predictive factors of 90-day mortality. Proper patient selection and adjustment of treatment strategies could potentially reduce short-term mortality.

Which factors predict tumor recurrence and survival after curative hepatectomy in hepatocellular carcinoma? Results from a European institution.

BACKGROUND: High tumor recurrence and dismal survival rates after curative intended resection for hepatocellular carcinoma (HCC) are still concerning. The primary goal was to assess predictive factors associated with disease-free (DFS) and overall survival (OS) in a subset of patients with HCC undergoing hepatic resection (HR). METHODS: Between 08/2004-7/2021, HR for HCC was performed in 188 patients at our institution. Data allocation was conducted from a prospectively maintained database. The prognostic impact of clinico-pathological factors on DFS and OS was assessed by using uni- and multivariate Cox regression analyses. Survival curves were generated with the Kaplan Meier method. RESULTS: The postoperative 1-, 3- and 5- year overall DFS and OS rates were 77.9%, 49.7%, 41% and 72.7%, 54.7%, 38.8%, respectively. Tumor diameter ≥ 45 mm [HR 1.725; (95% CI 1.091-2.727); p = 0.020], intra-abdominal abscess [HR 3.812; (95% CI 1.859-7.815); p < 0.0001], and preoperative chronic alcohol abuse [HR 1.831; (95% CI 1.102-3.042); p = 0.020] were independently predictive for DFS while diabetes mellitus [HR 1.714; (95% CI 1.147-2.561); p = 0.009), M-Stage [HR 2.656; (95% CI 1.034-6.826); p = 0.042], V-Stage [HR 1.946; (95% CI 1.299-2.915); p = 0.001, Sepsis [HR 10.999; (95% CI 5.167-23.412); p < 0.0001], and ISGLS B/C [HR 2.008; (95% CI 1.273-3.168); p = 0.003] were significant determinants of OS. CONCLUSIONS: Despite high postoperative recurrence rates, an acceptable long-term survival in patients after curative HR could be achieved. The Identification of parameters related to OS and DFS improves patient-centered treatment and surveillance strategies.

Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy versus Chest Tube Drainage for Treatment of Secondary Spontaneous Pneumothorax-A Retrospective Single-Center Analysis.

Background and objective: Current guidelines recommend chest tube (CT) drainage as the initial treatment of secondary spontaneous pneumothorax (SSP). Surgery should be considered in cases of persistent air leak or recurrent disease. Video-assisted thoracoscopic surgery (VATS) is nowadays an established surgical treatment for complicated spontaneous pneumothorax. However, reports on VATS-bullectomy with partial pleurectomy (VBPP) for treatment of secondary spontaneous pneumothorax (SSP) are limited. The primary aim of this study was to evaluate and compare the clinical outcomes of patients with secondary pneumothorax treated either by VBPP or CT drainage in our institution. Secondly, we assessed underlying clinical parameters to identify potential risk factors for SSP recurrence. Materials and Methods: Eighty-two patients were included in this study. Long-term recurrence rates and potential risk factors for SSP recurrence were analyzed. Results: Thirty-six patients (43.9%) underwent VBPP, whereas 46 (56.1%) patients subsequently underwent CT treatment. During a median follow-up period of 76.5 months, VBPP patients experienced a significantly low recurrence rate compared to CT patients (VBPP vs. CT: 16.7% vs. 41.3%; p = 0.016). However, VBPP was associated with a higher complication rate and significantly longer length of hospital stay (LOS). Male sex (male vs. female: p = 0.021) and CT treatment (VBPP vs. CT: p < 0.001) were identified as potential risk factors for SSP recurrence. Conclusions: VBPP is a suitable surgical treatment for SSP. However, prolonged LOS and possible complications should be discussed prior to VBPP.

Two-port versus three-port video-assisted thoracoscopic surgery for primary spontaneous pneumothorax: feasibility, postoperative outcome and long-term recurrence rates.

BACKGROUND: Two-port VATS (2-P-VATS) and three-port VATS (3-P-VATS) are well-established techniques for surgical therapy of primary spontaneous pneumothorax (PSP). However, comparisons of both techniques in terms of postoperative outcome and recurrence are limited. METHODS: From January 2010 to March 2020, we retrospectively reviewed data of 58 PSP patients who underwent VATS in our institution. For statistical analysis, categorical and continuous variables were compared by chi-square test or Fisher's exact test and the Student´s t-test, respectively. Twenty-eight patients underwent 2-P-VATS and 30 were treated with 3-P-VATS. Operation time, length of hospital stay (LOS), total dose of analgesics per stay (opioids and non-opioids), duration of chest tube drainage, pleurectomy volume (PV), postoperative complications and recurrence rates were compared between both groups. RESULTS: Clinical and surgical characteristics including mean age, gender, Body-Mass-Index (BMI), pneumothorax size, smoking behaviour, history of contralateral pneumothorax, side of pneumothorax, pleurectomy volume and number of resected segments were similar in both groups. The mean operation time, LOS and total postoperative opioid and non-opioid dose was significantly higher in the 3-P-VATS group compared with the 2-P-VATS group. Despite not being statistically significant, duration of chest tube was longer in the 3-P-VATS group compared with the 2-P-VATS group. In terms of postoperative complications, the occurrence of hemothorax was significantly higher in the 3-P-VATS group (3-P-VATS vs. 2-P-VATS; p = 0.001). During a median follow-up period of 61.6 months, there was no significant statistical difference in recurrence rates in both groups (2/28 (16.7%) vs. 5/30 (7.1%); p = 0.274). CONCLUSION: Our data demonstrate that 2-P-VATS is safer and effective. It is associated with reduced length of hospital stay and decreased postoperative pain resulting in less analgesic use.

BRAFV600E mutation: A promising target in colorectal neuroendocrine carcinoma.

To determine the role of BRAFV600E mutation and MAPK signaling as well as the effects of BRAF and MEK directed therapy in gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN), with a focus on highly aggressive gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). Using Sanger sequencing of BRAF exon 15 we determined the frequency of BRAFV600E mutations in 71 primary GEP-NENs. MEK phosphorylation was examined by immunohistochemistry in corresponding tissue samples. To evaluate the biological relevance of BRAFV600E mutation and MAPK signaling in GEP-NECs, effects of a pharmacological BRAF and MEK inhibition were analyzed in NEC cell lines both in vitro and in vivo. BRAFV600E mutation was detected in 9.9% of all GEP-NENs. Interestingly, only NECs of the colon harbored BRAFV600E mutations, leading to a mutation frequency of 46.7% in this subgroup of patients. In addition, a BRAFV600E mutation was significantly associated with high levels of MEK phosphorylation (pMEK) and advanced tumor stages. Pharmacological inhibition of BRAF and MEK abrogated NEC cell growth, inducing G1 cell cycle arrest and apoptosis only in BRAFV600E mutated cells. BRAF inhibitor dabrafenib and MEK inhibitor trametinib prevented growth of BRAFV600E positive NEC xenografts. High frequencies of BRAFV600E mutation and elevated expression levels of pMEK were detected in biologically aggressive and highly proliferative colorectal NECs. We provide evidence that targeting BRAF oncogene may represent a therapeutic strategy for patients with BRAF mutant colorectal NECs.

Establishment and Characterization of a Novel Cell Line Derived from a Small Cell Neuroendocrine Carcinoma of the Anal Canal.

BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are biologically aggressive tumors, associated with a very poor survival. Due to their rarity, our knowledge on GEP-NEC biology is very limited. The aim of this study was to establish a GEP-NEC cell line model that might contribute to a better understanding of this rare malignant disease to further develop novel therapeutic approaches in preclinical studies. METHODS: Small cell neuroendocrine cancer cell line NEC-DUE3 was derived from a lymph node metastasis of a neuroendocrine carcinoma (NEC) located at the anal canal. Morphological characteristics and the expression of neuroendocrine markers were comprehensively investigated. For genetic profiling, NEC-DUE3 cells were analyzed by DNA fingerprinting. Chromosomal aberrations were mapped by array comparative genomic hybridization. NEC-DUE3 cell tumorigenicity was evaluated in vivo and the sensitivity to chemotherapeutic agents was assessed in vitro. RESULTS: NEC-DUE3 cells were characterized by the expression of molecular markers that are commonly observed in GEP-NECs, were sensitive to treatment with cisplatin, and able to form tumors in immunodeficient mice. CONCLUSION: We established and characterized the first small cell GEP-NEC cell line that may serve as a valuable tool to create a better understanding of the biology of these rare tumors and to develop novel treatment strategies.

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare and challenging endocrine malignancy. Once spread, the therapeutic options are limited and the outcome poor. For these patients, the identification of new druggable biological markers is of great importance. Here, we investigated the prognostic and biological role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in MTC. METHODS: Eighty-six MTC and corresponding non-neoplastic thyroid specimens were immunohistochemically stained for CXCR4/7 using tissue microarray technology and expression levels correlated with clinicopathological variables. Medullary thyroid carcinoma cell line TT was treated with recombinant human SDF1α/CXCL12 (rh-SDF1α) and CXCR4 antagonists AMD3100 and WZ811. Changes in cell cycle activation, tumour cell invasiveness as well as changes in mRNA expression levels of genes associated with epithelial-mesenchymal transition (EMT) were investigated. RESULTS: High CXCR4 expression was associated with large tumour size and metastatic disease. CXCR4 antagonists significantly reduced tumour cell invasiveness, while the treatment with rh-SDF1α stimulated invasive growth, caused cell cycle activation and induced EMT. CONCLUSIONS: The CXCR4/CXCR7/CXCL12 axis plays an important role in MTC. We provide first evidence that the chemokine receptors might serve as potential therapeutic targets in patients with advanced MTC and offer new valuable insight into the underlying molecular machinery of metastatic MTC.

Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

BACKGROUND: Chromosomal instability (CIN) has repeatedly been identified as a prognostic marker. Here we evaluated the percentage of aberrant genome per cell (PAG) as a measure of CIN in single disseminated tumour cells (DTC) isolated from patients with operable oesophageal adenocarcinoma (EAC), to assess the impact of CINhigh DTCs on prognosis. METHODS: We isolated CK18positive DTCs from bone marrow (BM) or lymph node (LN) preparations of operable EAC patients. After whole-genome amplification, single DTCs were analysed for chromosomal gains and losses using metaphase-based comparative genomic hybridisation (mCGH). We calculated the PAG for each DTC and determined the critical threshold value that identifies high-risk patients by STEPP (Subpopulation Treatment Effect Pattern Plot) analysis in two independent EAC patient cohorts (cohort #1, n=44; cohort #2; n=29). RESULTS: The most common chromosomal alterations observed among the DTCs were typical for EAC, but the DTCs showed a varying PAG between individual patients. Generally, LNDTCs displayed a significantly higher PAG than BMDTCs. STEPP analysis revealed an increasing PAG of DTCs to be correlated with an increased risk for short survival in two independent EAC cohorts as well as in the corresponding pooled analysis. In all three data sets (cohort #1, cohort #2 and pooled cohort), PAGhigh DTCs conferred an independent risk for a significantly decreased survival. CONCLUSIONS: The analysis of PAG/CIN in solitary marker-positive DTCs identifies operable EAC patients with poor prognosis, indicating a more aggressive minimal residual disease.

Survivin and XIAP: two valuable biomarkers in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) accounts for ∼5% of all thyroid malignancies. To date, surgery is the first-line therapy with curative intention. However, for advanced MTC, conventional chemotherapeutic agents do not provide convincing results. Therefore, the identification of biomarkers that can be antagonised by small-molecule therapeutics may lead to novel encouraging treatment options. METHODS: Seventy-nine patients with surgically resected and histologically confirmed MTC were included in this study. Tissue microarrays were constructed to assess the relationship between inhibitor of apoptosis proteins (IAPs) survivin or XIAP expression levels and clinicopathological variables as well as overall survival. RESULTS: High survivin or XIAP expression was associated with an advanced T-stage and metastatic disease. Whereas tissue expression levels of survivin correlated with serum calcitonin levels, XIAP was overexpressed in the subgroup of patients with sporadic MTC. Both IAPs were negatively associated with patient survival in the multivariate Cox regressions analysis (survivin: hazard ratio (HR) 1.62; 95% confidence interval (CI): 1.21-2.16; P=0.001; XIAP: HR 1.78; 95% CI: 1.16-2.72; P=0.008). CONCLUSIONS: Survivin and XIAP demonstrate distinct expression patterns in MTCs, which are associated with advanced disease and poor prognosis. We thus provide first evidence that both IAPs might serve as viable targets in patients with MTC.

Predictors of mortality for necrotizing soft-tissue infections: a retrospective analysis of 64 cases.

PURPOSE: Necrotizing soft-tissue infection (NSTI) is a rare, but rapidly progressive and life-threatening disease with a high morbidity and mortality. The aim of the present study was to evaluate predictors of mortality in a group of patients with NSTIs treated at a single center. METHODS: The medical records of all patients that were treated because of a NSTI at our department between 1996 and 2011 were retrospectively analyzed. To identify factors that were associated with patients' outcome variables including demographic, clinical, laboratory, and microbiologic parameters were compared between the group of survivors and non-survivors. RESULTS: Sixty-four patients with the diagnosis of a NSTI were identified. The overall mortality was 32.8 %. Multiple regression analyses identified the development of a renal failure during the hospital stay and more importantly, the presence of visible skin necrosis on the initial clinical examination as independent prognostic markers for NSTIs. CONCLUSION: In patients with NSTIs, skin necrosis may serve as an indicator for an advanced stage of the disease. Thus, the presence of visible skin necrosis as an independent predictor of mortality emphasizes the outstanding importance of early diagnosis and prompt treatment to improve the prognosis of patients with NSTIs.

Comparative study of short-and long-term results in patients with perihilar cholangiocarcinoma undergoing surgical resection: does the extent and side of resection really affect outcome?

BACKGROUND: The surgical management of perihilar carcinoma (pCCA) is still subject of ongoing debate. To provide more clarity, this study was conducted to evaluate outcomes related to the side and extent of heatectomy in patients with pCAA. METHODS: A total of 32 patients with curative resection for pCCA were identified from our prospective database. Short-and long-term clinical outcome data and histopathological results were compared between right-sided (R-H) and left-sided (L-H) hepatectomy. RESULTS: Nine patients (28.13%) underwent left-sided hepatectomy while a right-sided hepatectomy was accomplished in 23 patients (71.87%). In the R-H group hepatic conditioning of the future liver remnant (FLR) prior to extended resection was necessary in 13 cases (56.52%), and simultaneous pancreaticoduodenectomy was performed in 5 patients (21.74%). The arterial and portal venous reconstruction rates were 17.39% and 11.11% (P=1.00), and 60.87% and 33.33% (P=0.243) in the R-H and L-H groups, respectively. No statistically significant differences in short-term morbidity and mortality between both groups were observed. The rate of R0 resections was comparable (R-H: 78.26% versus L-H: 66.67%; P=0.654) resulting in similar long-term overall and disease-free survival rates after right-and left hepatectomy. CONCLUSIONS: In patients with pCCA, both right- and left-sided resections appear to be safe and feasible options with similar postoperative morbidity and oncologic outcomes. Consecutively, the ideal surgical approach should be patient-tailored based on anatomical considerations and the functional future liver capacity.

Snail1 expression in colorectal cancer and its correlation with clinical and pathological parameters.

BACKGROUND: Snail1 is a transcription regulator of E-cadherin. The loss of E-cadherin seems to be a crucial step in the process of Epithelial-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumours. Overexpression of Snail1 is known to be associated with poor outcome in several solid tumours. The aim of this study was to analyse its expression profile and prognostic significance in colorectal cancer. METHODS: Tissue microarrays (TMA) containing paraffin-embedded primary colorectal cancer (CRC) tissue samples from 251 patients were used in this study. The expression of Snail1 and E-cadherin was assessed by immunohistochemistry in different tumour compartments, corresponding lymph node metastases and normal colonic mucosa. Intensity of staining was classified according to the Remmele score (standardized scoring system) as well as the semiquantitative score established by Blechschmidt et al. RESULTS: Snail1 expression was observed in 76% of the CRC. Loss of E-cadherin was noted in 87% of the CRC. Snail1 positive tumours were significantly correlated with Snail1 positive lymph node metastases (p=0.03). There was no significant correlation between loss of E-cadherin and Snail1 expression, or between N-stage or grading and Snail1 expression. Kaplan-Meier survival analysis identified no prognostic impact of Snail1 expression on overall survival. CONCLUSION: Snail1 expression was detectable in most of the CRC but showed no significant association with E-cadherin loss, clinical pathological characteristics or overall survival. The observed loss of E-cadherin could be explained by effects of other important EMT pathways, such as the Wnt-signalling cascade.

Optimizing Growth of the Future Liver Remnant and Making In-Situ Liver Transsection Safe-A Standardized Approach to ISLT or ALPPS.

In-situ splitting of the liver before extended resection has gained broad attention. This two-step procedure requires several measures to make an effective and safe procedure. Although the procedure is performed in many institutions, there is no consensus on a uniform technique. The two steps can be divided into different parts and a standardized technique may render the procedure safer and the results will be easier to evaluate. In this paper, we describe a detailed approach to in-situ splitting that allows making both procedures safe, avoids liver necrosis, and is easily reproducible. In the first procedure the portal branches to segments I and IV to VIII are divided, the arterial branches and bile ducts to these segments are preserved and encircled and the parenchyma between segments II/III and IVa/b is divided. This avoids necrosis and bile leaks of segments I and IV and avoids urgent completion operations. In particular, the handling of vital structures close to the dissection line seems important to us. Complete splitting and securing the right and middle hepatic vein will make the second step of this procedure a minimal-risk procedure at a stage where the patient is still recovering from the more demanding first step.

Postoperative Pain and Clinical Outcome Following Two- and Three-Port Video-Assisted Thoracoscopic Surgery for Secondary Spontaneous Pneumothorax.

BACKGROUND: Two-port (2P) and three-port (3P) video-assisted thoracoscopic surgery (VATS) are well-established surgical methods for the treatment of complicated spontaneous pneumothorax (SP). However, a comparison between both techniques, in terms of clinical outcomes in patients with secondary spontaneous pneumothorax (SSP), is unreported. The aim of this study was to evaluate and compare postoperative pain, as well as clinical outcome, following 2P and 3P VATS for SSP in our institution. METHODS: Between January 2008 and December 2020, we retrospectively analyzed the data of 115 SSP patients treated by VATS in our institution. Fifty-two patients underwent 2P-VATS, while 63 patients were treated by 3P-VATS. The total dose of analgesic use per stay (opioid and non-opioid), length of hospital stay (LOS), operation time, total area of pleurectomy, recurrence rates and postoperative complications were compared between both groups. RESULTS: The 3P-VATS group had a significantly higher total dose of analgesic use compared with the 2P-VATS patients. The LOS and mean operation time were significantly shorter in the 2P-VATS group. A larger area of pleurectomy was resected using 3P-VATS compared to 2P-VATS. The postoperative complications and recurrence of SSP during a median follow-up period of 76.5 months were similar in both groups. CONCLUSION: 2P-VATS is a safe surgical technique. It is associated with a short LOS and less postoperative pain, and, thus, low analgesic use.

Targeting abundant survivin expression in liposarcoma: subtype dependent therapy responses to YM155 treatment.

PURPOSE: Liposarcoma (LPS) represent the largest group of malignant soft tissue tumours comprising a heterogeneous group of subtypes in which the degrees of chemoresistance and radiosensitivity strongly vary. Consequently, it is of utmost interest to establish novel therapeutic regimens based on molecular targets. METHODS: Immunohistochemical staining of survivin was performed in tissue microarrays comprising 49 primary LPS specimens. LPS cell lines were treated with survivin antagonist YM155 and doxorubicin or etoposide alone as well as in combination. Changes in cell viability were investigated and the synergistic effect of a combined therapy analysed. RESULTS: Immunohistochemistry revealed an abundant expression of survivin in LPS that significantly concurred with less-differentiated tumour subtypes and grading. In vitro, we demonstrated the impact of the survivin inhibitor YM155 on dedifferentiated LPS (DDLPS) and, even more imposing, pleomorphic LPS (PLS) tumour cell viability with a strong induction of apoptosis. A combined treatment of doxorubicin or etoposide with YM155 augmented the cytotoxic effects on DDLPS and PLS cells. CONCLUSION: These findings support the significant role of survivin in the oncogenesis and progression of LPS subtypes providing a rationale to target survivin in eligible in-vivo models and to pioneer clinical applications of survivin-specific substances unfolding their therapeutic potential in LPS patients prospectively.

Clinicopathological and Prognostic Value of Survivin Expression in Surgically Resected Pancreatic Ductal Adenocarcinoma.

Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p < 0.001) and high cytoplasmic (p < 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4−129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04−3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC.

Effectiveness of Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy in the Treatment of Primary Spontaneous Pneumothorax-A Retrospective Long-Term Single-Center Analysis.

Background: Video-assisted thoracoscopic surgery (VATS) with bullectomy and partial pleurectomy (VBPP) is an increasingly used and well-established surgical treatment for primary spontaneous pneumothorax (PSP). However, reports on its effectiveness and long-term outcomes are limited. The aim of this study was to assess and compare long-term recurrence rates following VBPP and chest tube (CT) treatment and to identify potential risk factors for disease recurrence in patients with PSP. Methods: A total of 116 patients treated either by VBPP or CT were included in this study. Long-term recurrence rates and associations between clinical parameters and recurrence of pneumothorax were analyzed. Results: Sixty-two patients (53.4%) underwent VBPP, whereas 54 (46.6%) patients underwent CT treatment only. During a median follow-up period of 76.5 months, VBPP patients experienced a significantly lower recurrence rate compared to CT patients (6/62 vs. 35/54; p < 0.0001). CT treatment (VBPP vs. CT; p < 0.001) and a large initial pneumothorax size (Collins < 4 vs. Collins ≥ 4; p = 0.018) were independent risk factors for pneumothorax recurrence. Conclusion: VBPP is an effective and safe surgical treatment for PSP. Therefore, patients with a large pneumothorax size might benefit from VBPP, as they are at high risk for disease recurrence.

Esophageal cancer proliferation is mediated by cytochrome P450 2C9 (CYP2C9).

Cytochrome P450 epoxygenases (CYP450) have been recently shown to promote malignant progression. Here we investigated the mRNA and protein expression and potential clinical relevance of CYP2C9 in esophageal cancer. Highest expression was detected in esophageal adenocarcinoma (EAC; n=78) and adjacent esophageal mucosa (NEM; n=79). Levels of CYP2C9 in EAC and NEM were significantly higher compared to esophageal squamous cell carcinoma (ESCC; n=105). Early tumor stages and well-differentiated tumors showed a significantly higher CYP2C9 expression compared to progressed tumors. Moreover, CYP2C9 expression was correlated to high Ki-67 labeling indices in EAC and Ki-67 positive tumor cells in EAC and ESCC. Selective inhibition of CYP2C9 decreased tumor cell proliferation (KYSE30, PT1590 and OE19) in vitro, which was abolished by 11,12-epoxyeicosatrienoic acid (11,12-EET). Cell-cycle analysis using FACS revealed that inhibition of CYP2C9 leads to a G0/G1 phase cell-cycle arrest. CYP2C9 seems to be relevant for early esophageal cancer development by promoting tumor cell proliferation. Pharmacological inhibition of CYP2C9 might contribute to a more efficient therapy in CYP2C9 highly expressing esophageal cancers.

Socioeconomic Impact of Recurrent Primary Spontaneous Pneumothorax: Should Video-Assisted Thoracoscopic Surgery Be Considered at First Episode of Primary Spontaneous Pneumothorax?

BACKGROUND: Current guidelines recommend video-assisted thoracoscopic surgery (VATS) for recurrent primary spontaneous pneumothorax (PSP) and for cases with persistent air leak after chest tube treatment. The socioeconomic impact of recurrent PSP on the healthcare system is insufficiently reported. METHODS: Ninety-six patients treated for PSP between 01/2010 and 01/2020 were included. Forty-eight patients underwent primary VATS, while the second group received chest tube (CT) treatment only. Length of hospital stay (LOS), duration of chest tube, prolonged air leak, postoperative complications, recurrences and treatment costs were analyzed. RESULTS: Prolonged air leaks were evident in 12.5% and 22.9% patients of the VATS and CT group, respectively. Ten (20.8%) patients in the CT group underwent VATS for persistent air leakage. During follow-up, the VATS group recurred at 8.3% compared to 52.1% in the CT group. The total cost of treatment per patient, including treatment cost due to recurrence, was EUR 1.501 in the VATS group and EUR 2.233 in the CT group. CONCLUSIONS: Primary treatment of PSP by CT is associated with an increased socioeconomic burden for patients and the healthcare system due to high recurrence rates. This burden may be reduced if VATS is considered at the first episode of PSP.

Does Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy for Primary Spontaneous Pneumothorax Impair Health-Related Quality of Life and Pulmonary Function?

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) with partial pleurectomy is an established treatment for primary spontaneous pneumothorax (PSP). However, postoperative pulmonary function and health-related quality of life (HR-QoL) after VATS-bullectomy with partial pleurectomy (VBPP) have not been elucidated. METHODS: Eligible patients were assessed for HR-QoL using the Short-Form 36 (SF-36) health survey. Pulmonary function (PF) was evaluated by spirometry. We compared the results of the VBPP cohort with the German national norms, and with a similar cohort of patients successfully treated by chest tube (CT) only. RESULTS: A total of 25 VBPP patients completed the SF-36 health survey, of whom 15 presented for PF assessment. Between the VBPP and CT groups, the mean forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratio were not statistically significantly different. However, in both groups, FVC, FEV1, and FEV1/FVC were above the lower limit of normal (LLN), suggesting no restrictive or obstructive patterns. Compared with the sex- and age-matched normal German population, patients who underwent VBPP displayed a similar physical component summary score and a significantly decreased mental component summary score. Interestingly, comparison of the SF-36 domains between the VBPP and CT groups showed no statistical difference. CONCLUSION: VBPP is a suitable surgical treatment for PSP, with no apparent adverse impacts on pulmonary or physical function. However, psychological distress and measures to counteract its impact should be considered.