FAK, Src and p-Paxillin expression is decreased in liver metastasis of colorectal carcinoma patients.

PURPOSE: The FAK/Src/Paxillin (PXN) axis has been implicated in malignant transformation, tumor growth, progression and metastasis. The present study aimed to assess FAK/Src/PXN protein expression in both primary and liver metastatic sites of colorectal adenocarcinoma (CRC). METHODS: FAK, Src and p-PXN expression was assessed immunohistochemically on 32 primary CRCs and their corresponding liver metastases, being also analyzed in relation with clinicopathological characteristics and patient survival. RESULTS: FAK, Src and p-PXN expression was significantly decreased in liver metastasis compared to matched paired primary CRCs (p<0.01). Increased FAK expression in primary CRCs was significantly associated with poor histological grade and advanced disease stage (p=0.0330 and p=0.0204, respectively). Increased Src expression in primary colorectal tumors was significantly associated with the presence of lymph node metastasis (p=0.0325), while elevated p-PXN expression with poor histological grade (p=0.0284). CONCLUSIONS: FAK, Src and p-PXN appear to play a role in the pathophysiological aspects of CRC. The lower expression of these proteins in liver metastasis compared to the primary CRC could significantly impact the choice of a novel therapeutic agent according to the disease stage.

Assessing the clinical utility of Wnt pathway markers in colorectal cancer.

PURPOSE: ß-catenin and AXIN2 play an important role in the Wnt signaling pathway. The aim of this study was to investigate ß-catenin and AXIN2 expression in colorectal cancer (CRC) and relate these findings with patients' clinicopathological features and prognosis. METHODS: 57 consecutive patients with surgically treated CRC were included in this study. Quantitative PCR and immunohistochemistry (IHC) analyses were performed to characterize the expression of the aforementioned markers in CRC tissues. RESULTS: ß-catenin overexpression in the nucleus was associated with advanced N stage CRCs (p=0.04). Multivariate Cox regression analysis showed that ß-catenin overexpression is an independent prognostic factor for overall survival (OS). A positive correlation between ß-catenin location and AXIN2 mRNA was observed. CONCLUSIONS: Nuclear ß-catenin is a valuable prognostic factor. AXIN2 is a component of the "Destruction Complex" and also a Wnt target gene. However, the clinical importance of AXIN2 expression in CRC remains unclear.

Systemic treatment and primary tumor location in patients with metastatic colorectal cancer.

PURPOSE: Tumor location (right-sided vs. left-sided) is known to exert a significant influence on the prognosis of primary colorectal cancer (CRC). Given the genetic continuity between primary and metastatic lesions, we aimed to summarize the existing literature on the prognostic implications of primary tumor site as well as to examine the response to chemotherapy by primary tumor location in patients with metastatic CRC (mCRC). METHODS: A structured review of the literature was performed between 6/1/2016-7/1/2016 using the Pubmed database. Original research articles published between 1/1/2000- 07/01/2016 were considered eligible. The primary endpoints were overall survival (OS)/ progression free survival (PFS) and response to systemic treatment in patients with mCRC. RESULTS: Eleven studies were included. Tumor site was a strong independent predictor of worse OS/PFS in 9 studies, with right-sided tumors having worse prognosis in all cases. Furthermore, 6 studies demonstrated an inferior response to systemic treatment or worse prognosis following the administration of specific regimens among patients with right-sided cancers. As such, there is significant evidence that right-sided lesions are associated with poor outcomes and resistance to systemic treatment. CONCLUSION: Consequently, primary tumor location should be a consideration, when the administration of systemic therapy is contemplated in mCRC.

Combined ultrasonic aspiration and saline-linked radiofrequency precoagulation: a step toward bloodless liver resection without the need of liver inflow occlusion: analysis of 313 consecutive patients.

BACKGROUND: Hemorrhage is undoubtedly one of the main factors contributing to morbidity and mortality in liver resections. Vascular occlusion techniques are effective in controlling intraoperative bleeding, but they cause liver damage due to ischemia. We evaluated the effectiveness and safety of using a combined technique for hepatic parenchymal transection without liver inflow occlusion. METHODS: Three hundred and thirteen consecutive patients who underwent liver resection in four hepato-pancreato-biliary units. Hepatic parenchymal transection was carried out using a combined technique of saline-linked radiofrequency precoagulation and ultrasonic aspiration without liver inflow occlusion. RESULTS: During the study period 114 minor and 199 major hepatic resections were performed. The mean amount of intraoperative blood loss was 377 ml (SD 335 ml, range 50 to 2,400 ml) and the blood transfusion rate was 10.5%. The median amount of blood loss during parenchymal transection and parenchymal transection time was 222 ml (SD 224 ml, range 40 to 2,100 ml) and 61 minutes (range 12 to 150 minutes) respectively. There were two postoperative deaths (0.6%). Complications occurred in 84 patients (26.8%) and most complications were minor. CONCLUSIONS: Combined technique of saline-linked radiofrequency ablation and ultrasonic aspiration for liver resection is a safe method for both major and minor liver resections. The method is associated with decreased blood loss, reduced postoperative morbidity, and minimal mortality rates. We believe that this combined technique is comparable to other techniques and should be considered as an alternative.

Rescue medical activities among sea migrants and refugees in the Mediterranean region: lessons to be learned from the 2014-2020 period.

BACKGROUND: Since 2014, the number of migrants and refugees crossing the Mediterranean towards Europe has risen significantly due to various reasons. Both state agencies and non-governmental organizations (NGOs) have launched rescue missions in the Central Mediterranean in accordance with international legal obligations for search and rescue (SAR) operations for those under distress at sea. Our aim is to summarise the specific qualifications needed for maritime SAR in the Mediterranean both in terms of the population at risk, the equipment and the medical support required, especially during the coronavirus disease 2019 (COVID-19) pandemic and the operational legal framework. MATERIALS AND METHODS: This article aims to summarise the key points of SAR efforts from a medical perspective as depicted in the relevant literature during a specific timeline period (2014-2020) in a specific part of the Mediterranean Sea (Central Mediterranean route). Only papers published in English and whose full text was available were included in this study. The inclusion criteria were: a) articles referring to sea rescue operations between 2014 and 2020, b) research that focused on medical preparedness and assistance during rescue operations in the Central Mediterranean route, c) studies concerning demographic and clinical features of the rescue population, d) guidelines on the rule of conduct of persons and states participating in rescue activities. The exclusion criteria were: a) studies describing SAR operations in different regions of the world and b) studies focusing on routes, demographics and medical support of migrants/refugees on land. RESULTS: Three major themes were identified: a) characteristics of the population in distress at sea: country of origin, age groups, presence of communicable and non-communicable diseases were identified in the relevant literature. Our research shows that dermatological and respiratory issues were the major concerns among sea migrants, coming from different countries of both Africa and Asia, being relatively young and mostly males; b) medical preparedness and equipment needed for rescue: according to current guidelines, revised during the COVID-19 pandemic, infrastructure needed during SAR operations includes both equipment for resuscitation, personal protective equipment, deck adjustments, medical personnel trained to function in an austere setting and able to handle vulnerable patient groups such as children and pregnant women; c) medico-legal implications of SAR operations: knowledge of the legal framework encompassing SAR operations seems necessary, as European Union and state led initiatives seem to withdraw from proactive SAR, while criminalising NGO led rescue efforts. Operating with the imperative to save lives seems to be the only way of respecting international law and human values, thus, a summary of what the law dictates was made in an effort to keep medical workers participating in such operations updated. CONCLUSIONS: Investigation aims to shed light on the special clinical features of sea migrants, the skills, equipment and organizational structure needed by medical workers participating in SAR operations as well as the legal framework under which they will be asked to operate. Special consideration will be given to the difficulties that emerged due to the COVD-19 pandemic.

Irreversible electroporation and sarcomas: where do we stand?

Sarcomas arise from uncontrolled cell growth in tissues of mesodermal origins, such as connective tissue, bone, cartilage, fat or muscle. Surgical resection is still considered the cornerstone in the treatment of sarcomas. However, in many cases where tumor is adjacent to vital structures like major vessels, other treatment modalities may be implemented. Irreversible electroporation (IRE), a new form of ablative technique has been introduced lately in the treatment of several types of sarcomas. Irreversible electroporation has shown promising results and survival improvement in primarily inoperable solid tumors and locally advanced cancers, including prostate, kidney, liver, bone and pancreatic cancers in close proximity to important structures. The aim of this review was to sum up the current knowledge and the future perspectives of the usage of IRE in the management of sarcomas. Our study indicates that IRE could possibly represent a potential therapeutic option in patients with advanced or metastatic sarcoma, when surgery is not indicated.

Circadian variation in expression of G1 phase cyclins D1 and E and cyclin-dependent kinase inhibitors p16 and p21 in human bowel mucosa.

AIM: To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS: Between January 2003 and December 2004, twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism, underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalin-fixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours (00:00, 06:00, 12:00, 18:00 and 24:00), we studied the expression of G(1) phase cyclins (D(1) and E) as well as the expression of the G(1) phase cyclin-dependent kinase (CDK) inhibitors p16 and p21 as indicators of cell cycle progression in colonic epithelial cells using immunohistochemical methods. RESULTS: The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00:00 and 18:00, respectively (P<0.001). A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12:00 and 18:00 (P<0.001), respectively. When the complexes cyclins D(1) -p21 and E-p21 were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D(1) -p16 and E-p16 were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00:00, 06:00 and 24:00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18:00. CONCLUSION: Colonic epithelial cells seem to enter the G(1) phase of the cell cycle during afternoon (between 12:00 and 18:00) with the highest rates obtained at 18:00. From a clinical point of view, the present results suggest that G(1) -phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.

Increased incidence of papillary thyroid cancer detection among thyroidectomies in Greece between 1991 and 2006.

OBJECTIVE: To examine existing evidence, trends and possible factors that may have affected the incidence of papillary thyroid cancer (PTC) among patients undergoing thyroidectomies in an iodine-sufficient population of Greece. STUDY DESIGN: All histology records from the patients who had undergone thyroid surgery at the Department of Surgery Laiko Hospital, Athens, Greece from January 1991 to December 2006 were retrospectively analyzed. Records were placed in a database which included patients' demographics, history, and medical condition, clinical and surgical parameters. PATIENTS AND METHODS: One thousand four hundred and twenty-six patients (265 males and 1161 females) had undergone thyroidectomy during the above period of time. All surgeons favoured total thyroidectomy with resection of pro- and paratracheal lymph nodes. Thyroid tumors were classified according to the WHO classification system and were staged according to the TNM staging system. RESULTS: In 278 patients, PTC was histologically diagnosed. From 1999 onwards, thyroid surgery shifted towards total thyroidectomy, while statistically significantly increased incidence of PTC and papillary microcarcinoma detection and decreased incidence of PTC greater than 10 mm detection in the whole population were noticed. Moreover, from 1999 onwards, smaller size of primary tumors, higher incidence of T1 tumors, lower incidence of T4 tumors, lower incidence of metastatically infiltrated peritracheal lymph nodes, higher incidence of stage I tumors and lower incidence of stage IV tumors were documented. Finally, a higher incidence of PTC in males, females and the whole population aged 51-70 years compared to the other age groups since 2003 was noticed. CONCLUSION: The increased incidence of PTC clearly correlated to the increased incidence of papillary microcarcinoma detection, reflecting the proportion for total thyroidectomy as well as changes in the diagnostic approach boosted by more careful pathological examination, rather than the effect of environmental factors such as the Chernobyl accident. Whether the Chernobyl accident has any predisposing effect on the increased incidence of PTC remains to be proven.