Current status of indocyanine green fluorescent angiography in assessing perfusion of gastric conduit and oesophago-gastric anastomosis.

Anastomotic leak (AL) remains a significant complication after esophagectomy. Indocyanine green fluorescent angiography (ICG-FA) is a promising and safe technique for assessing gastric conduit (GC) perfusion intraoperatively. It provides detailed visualization of tissue perfusion and has demonstrated usefulness in oesophageal surgery. GC perfusion analysis by ICG-FA is crucial in constructing the conduit and selecting the anastomotic site and enables surgeons to make necessary adjustments during surgery to potentially reduce ALs. However, anastomotic integrity involves multiple factors, and ICG-FA must be combined with optimization of patient and procedural factors to decrease AL rates. This review summarizes ICG-FA's current applications in assessing esophago-gastric anastomosis perfusion, including qualitative and quantitative analysis and different imaging systems. It also explores how fluorescent imaging could decrease ALs and aid clinicians in utilizing ICG-FA to improve esophagectomy outcomes.

Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer.

Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted.

COVID-19: Asymptomatic Carrier: An Autopsy Case Report.

The severe acute respiratory syndrome (SARS)-coronavirus- 2 (CoV-2) outbreak in Wuhan, China has now spread to many countries across the world including the India with an increasing death toll. On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Owing to its infectivity, high risk of transmission, and limited handling of dead bodies, published data on the course of diseases has been limited. Most patients with COVID-19 have a mild disease course and remain as asymptomatic carrier; however, few patients of older age and with co-morbidites develop severe disease leading on to fatality. If due to COVID-19 infection death occurs, an autopsy is unlikely. However in unnatural deaths the legal duty impels the proper performance of a full autopsy, to find out the cause and manner of death. The detailed autopsy examination along with histo-pathological findings in the organs of asymptomatic patient of COVID-19 and its comparison with microscopic findings in Aluminium Phosphide poisoning are discussed below. This will summarizes the research status for COVID-19 deaths, which will be important for evaluation of cause of death, prevention, control and clinical strategies of COVID-19.

Prognostic impact of perineural, blood and lymph vessel invasion for esophageal cancer.

BACKGROUND: With a median survival of ⟨22 months esophageal cancer is one of the most aggressive tumors, up to 20% of node negative patients develop systemic relapse. Studies investigating the prognostic impact of tumor-micro-invasion in blood (AI) and lymphatic vessels (LVI) as well as perineural invasion (PNI) have shown inconsistent results. The aim of the present study was to investigate the prognostic value of the aforementioned factors in a large homogenously treated cohort of patients with esophageal cancer. METHODS: Data from 695 patients with surgically treated esophageal cancer were analyzed. AI, LVI and PNI were determined and data were statistically correlated with clinico-pathological parameters and survival of the patients. RESULTS: Thirteen percent of all specimens showed an AI, 35% a LVI and 5% a PNI. The invasion factors were mostly significantly correlated with the established prognostic parameter, including bone marrow micro-metastases. Kaplan-Meier analysis revealed a prognostic impact for LVI in both cancer subtypes, while AI and PNI were significant factors in adenocarcinoma only. In multivariate analysis, none showed statistical significance. However, sub-analysis of completely resected, node negative and non-metastasized patients showed a significant prognostic impact of LVI. CONCLUSION: The prognostic significance of AI, LVI and PNI seems to be limited compared to the established prognostic parameters of the UICC staging system. In completely resected, node negative and non-metastasized patients, LVI is an independent prognostic parameter for a worse outcome. Those patients might benfit from additional treatment or more intensive follow up.

Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain.

Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research.

C-X-C motif receptor 2, endostatin and proteinase-activated receptor 1 polymorphisms as prognostic factors in NSCLC.

The progress of non-small cell lung cancer (NSCLC) is dependent on sufficient angiogenesis. Thrombin induced activation of proteinase-activated receptor 1 (PAR-1) on platelets leads to platelet secretion and aggregation. This influences cell survival, apoptosis and angiogenesis by the release of VEGF and Endostatin (ES), a potent angiogenesis inhibitor. Interleukin-8 (IL-8) induces tumor angiogenesis independent of the VEGF pathway through the chemokine C-X-C motif receptor 2 (CXCR-2). Our purpose was to evaluate germline polymorphisms of these potential therapy targets as prognostic markers for disease free survival (DFS) and overall survival (OS) in surgically treated NSCLC patients. In total 209 Caucasian patients, treated between 1996 and 2011, were included in this study. Genomic DNA was extracted from peripheral blood leucocytes. Genotyping of CXCR-2 +1208 C > T and +785 C > T, PAR-1 -506 Ins/del and -14 Ivs A > T and ES +4349 G > A was performed by TaqMan(®) genotyping assays or by polymerase chain reaction (PCR) followed by capillary electrophoresis. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of selected polymorphisms. The PAR-1 -14 Ivs A/A genotype was associated with advanced tumor stages (p = 0.024) and, in univariate analysis, with shorter median OS in squamous cell lung carcinoma (SqCC, p = 0.035). The CXCR-2 + 1208T/T genotype was associated with aggressive tumor biology (p = 0.038), and shorter DFS and OS (p = 0.018, p = 0.021) in NSCLC and especially in SqCC a negative predictor for DFS and OS (p = 0.045, p = 0.041). Genotyping of the CXCR-2 +1208 C >T polymorphism could be a useful tool to identify high-risk SqCC subgroups.

The T393C polymorphism of GNAS1 is a predictor for relapse and survival in resectable non-small cell lung cancer.

INTRODUCTION: The GNAS1 T393C single nucleotide polymorphism (T393C-SNP) correlates with Gαs mRNA stability and protein expression and augmented apoptosis. Genetic germ line variations as stable and reproducible markers potentially serve as prognostic marker in oncology. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In total 163 Caucasian patients, who had been surgically treated for NSCLC between 1998 and 2010, were included in this study. Genotyping of peripheral blood cells was performed by polymerase chain reaction and digestion using the restriction enzyme FokI. The T393C-SNP was correlated with clinic-pathological parameters and survival. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of the T393C-SNP. RESULTS: C-allele carriers had a higher recurrence rate (p=0.018) and a shorter disease-free survival compared to homozygous T-allele carriers (12.26 months vs. 44.65 months, p=0.009). The overall survival in homozygous C allele carriers was shorter (19.10 months vs. 53.95 months, p=0.019). Multivariate Cox regression identified the CC genotype as a negative independent prognostic factor for recurrence (hazard ratio 2.36, p=0.007) and survival (hazard ratio 2.51, p=0.008). CONCLUSION: Determination of T393C-SNP preoperatively potentially allows allocation of NSCLC patients into different risk profiles and may influence the therapeutic strategy.

LigaSure™ vs. conventional dissection techniques in pancreatic surgery--a prospective randomised single-centre trial.

BACKGROUND: Surgical procedures in pancreatic surgery are well established, but still involve time-consuming manual dissection. We compared the use of LigaSure with conventional dissection techniques in pancreatic surgery in a prospective randomised single-centre trial (registration number: NCT00850291). METHODS: Patients with tumours of the pancreatic head that were assumed to be technically resectable were randomised to LigaSure or conventional surgery. The primary endpoint of this study was overall operation time. Secondary endpoints were preparation time until tumour resection, intraoperative blood loss, number of given units of packed red blood cells, costs of surgery, postoperative morbidity, length of hospital stay and mortality. RESULTS: There was no difference in overall operation time between the two groups (P = 0.227). Median costs for pancreatic surgery were significantly less in the conventional group with €3,047 (range 2,004-5,543) vs. €3,527 (range 2,516-5,056, P = 0.009). Preparation time, intraoperative blood loss, number of units of packed red blood cells, postoperative morbidity, length of hospital stay and mortality did not differ between the two groups. CONCLUSION: Our data indicate that the LigaSure device is equivalent to conventional dissection modalities in pancreatic surgery.

The GNAS1 T393C single nucleotide polymorphism predicts the natural postoperative course of complete resected esophageal cancer.

BACKGROUND: Genetic variations in cancer patients may serve as important prognostic indicators of clinical outcome. The GNAS1 T393C single nucleotide polymorphism (SNP) diversely correlates with the clinical outcome in cancer. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected only surgically treated esophageal cancer (EC). METHODS: Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent only complete surgical resection for EC. T393C-SNP was correlated with clinic-pathological parameters, tumor cell dissemination in bone marrow (DTC) and clinical outcome. RESULTS: T-allele carriers had more advanced disease due to presence of lymph node metastasis (P < 0.0001) and DTC (P = 0.01) and higher recurrence rate (P = 0.01) compared to CC genotype. The disease-free (P < 0.001) and overall survival (P < 0.001) was better in CC compared to TT and TC patients. In the multivariate Cox regression disease-stage adjusted analysis the T393C-SNP was identified as a strong independent prognostic factor for recurrence (hazard ratio 1.8, P = 0.01) and survival (hazard ratio 2.5, P < 0.001) in EC patients. CONCLUSION: Determination of T393C-SNP preoperatively will allow allocation of EC patients into different risk profiles which may help to stratify patients eligible for neoadjuvant and or adjuvant therapy.