Quality of life, distress and psychological adjustment in patients with colon cancer.

PURPOSE: The purpose of this study was to investigate the relationships between distress, psychological adjustment, and quality of life in patients with colon cancer. METHOD: This study employed a cross-sectional design and included 104 colon cancer patients treated at AHEPA Hospital, Thessaloniki, Greece. The assessment tools used encompassed the Distress Thermometer, MINI-MAC scale, and FACT-C to evaluate distress, psychological adjustment, and quality of life. Statistical analysis, conducted in SPSS software, encompassed correlation tests and linear regression to explore the interplay between these variables in colon cancer patients. RESULTS: Correlation tests revealed that patients' quality of life is positively correlated with a fighting spirit (r = 0.719, p < 0.001), cognitive avoidance (r = 0.634, p < 0.001), and fatalism (r = 0.518, p < 0.001), and negatively with helplessness and hopelessness (r = -0.756, p < 0.001), and anxious preoccupation (r = -0.679, p < 0.001). OLS regression findings verified these results partially for a significance level of 5% but indicated no statistically significant effect of cognitive avoidance and fatalism on quality of life, which was further found unaffected by total distress. CONCLUSIONS: The intricate links between quality of life, distress, and psychological adjustment in colon cancer patients call for deeper investigation. A personalized approach in psycho-oncology care is essential for comprehensive treatment. These findings highlight the significance of addressing the psychological and emotional needs of colon cancer patients, as observed in the study's results.

Mental health well-being and functional adjustment in colorectal cancer patients: a prospective cohort study.

BACKGROUND: Colorectal cancer significantly affects the quality of life of patients, while at the same time contributing to the development of symptoms of psychopathology. The aim of this prospective study, is to investigate the role of the disease in the quality of life of patients with colon cancer and in the appearance of symptoms of anxiety and depression, as well as the connection of the above characteristics during the recovery process, given the distress symptoms experienced by the patients. METHODS: In the present study, HADS, FACT - C, well as the DT are use, in a sample of 118 patients of an average age of 70.5 ± 8.5 years, which were submitted to partial or total colectomy surgery. RESULTS: Moderate levels of anxiety (M = 8.25, SD = 3.87) and low levels of depression (M = 6.90, SD = 2.97) and distress (M = 5.84, SD = 2.60) emerged preoperatively, while the improvement was significant of patients' quality of life level 6 months after surgery. At the same time, a significant negative effect of the patients' distress level preoperatively on their quality of life, during the recovery process was observed. CONCLUSION: Preoperative anxiety is not considered to be an element that affects the functionality and the psychological and physical adaptation to the disease of patients with colon cancer. On the contrary, the feelings of distress they experience can be a predictive factor of their quality of life after the partial or total colectomy surgery.

Romidepsin hepatocellular carcinoma suppression in mice is associated with deregulated gene expression of bone morphogenetic protein and Notch signaling pathway components.

Recently, our group showed that Romidepsin, a histone deacetylase inhibitor (HDACi), suppressed diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in mice. In the present study, we investigated the effect of Romidepsin-treatment on gene expression levels of components of Bmp and Notch signaling pathways, which are both known to be aberrantly regulated in hepatocarcinogenesis. Total RNA from liver tissue samples and paraffin-embedded livers were retrieved from a recent experiment where C57BL/6 mice were treated with Romidepsin 10 months after DEN challenge and sacrificed 2 months later. RT qPCR was used for quantification of gene expression and immunohistochemistry for in situ protein detection. Regarding Bmp pathway, Romidepsin HCC-suppression was found to correlate significantly with Bmp2 and Bmp7 ligand up- and down-regulation, respectively. Intracellularly, Romidepsin-treated HCC mice exhibited a significant elevation of Bmp-inhibitor Smurf2 and Bmp-target gene Id3, as compared to the HCC untreated controls. Concerning Notch signaling, higher expression levels of ligands Jag1/Dll4, accompanied by a decreased expression of receptor Notch2, were identified in the Romidepsin-treated group. Τhe anti-oncogenic effect of Romidepsin, also correlated significantly with an increased expression of Hes1 target, as well as an up- and down-regulation of Klf4 and Sox9 transcription factors, respectively. Moreover, the cancer-related genes Snai2 and p21, known to be involved in many signaling pathways, including Bmp and Notch, were also found to be downregulated in Romidepsin-treated mice. Romidepsin HCC suppression is associated with gene expression deregulation of selective components of both Bmp and Notch signaling cascades.

HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice.

BACKGROUND: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC. MATERIALS AND METHODS: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR. RESULTS: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC. CONCLUSION: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.

Contemporary management of borderline resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive tumors, with a low rate of survival, likely due to the tendency of the tumor for early local and distant spread. Pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all cancer deaths. Surgical resection still represents the best curative treatment for PDAC, although only 10-20% of patients are upfront resectable at diagnosis, 50% has metastatic disease and 35% locally advanced cancer. The 5-year overall survival (OS) after curative resection is limited to 20%. Moreover among patients who undergo surgery, 30% develop early recurrence while most of them will eventually relapse. The risk of early failure after surgery could be associated with inadequate preoperative radiological staging, lack of radical surgery and differences in tumor aggressiveness. In recent years, more accurate patient categorization due to sophisticated imaging tools and techniques increase the survival rate while neoadjuvant treatment can help surgeons select patients who will benefit most from surgery. Neoadjuvant therapy includes chemotherapy alone, chemoradiotherapy, chemotherapy with chemoradiation and targeted therapies. The aim of this review is to present the available data concerning the management of patients with borderline PDAC.

Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase inhibitor Danusertib.

Background: To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods: Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, ß-catenin. Hepatocyte growth factor receptor (C-MET/HGFR) and Bcl-2 antagonist of cell death (BAD) serum levels were determined using a quantitative sandwich enzyme immunoassay technique. Results: Inhibition of AURK reduced the number of DEN-induced liver tumours. Apoptosis and proliferation was very low in both DEN-induced and anti- AURK groups respectively. The hepatocellular adenoma cells of DEN-treated mice uniformly had ample nuclear INCENP whereas in anti- AURK markedly decreased. Expression of ß-catenin, NF-kB and c-Jun did not differ in liver tumors of both AURK -depleted and non-depleted mice. Conclusions: Depletion of AURK reduced the number of DEN-induced hepatic tumours. However, their size did not differ significantly between the groups.

Effects of Wnt-1 blockade in DEN-induced hepatocellular adenomas of mice.

Recent evidence has suggested that downregulation of the Wnt/ß-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN-treated mice had multiple variably-sized hepatic cell adenomas. Anti-Wnt-1 was particularly potent in suppressing the expression of critical elements of the Wnt/ß-catenin signaling pathway, such as ß-catenin and Frizzled-1 receptor, however, not Dickkopf-related protein 1. This effect co-existed with the suppression of Cyclin D1, FOXM1, NF-κΒ and c-Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl-2 and c-Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

Primary gigantic leiomyosarcoma of the liver treated with portal vein embolization and liver resection.

Primary hepatic leiomyosarcoma (PHL) is an extremely rare tumor. The tumor has no specific presentations and often diagnosis is delayed until it reaches a significant size. We report the case of a 69-year-old female presented with a huge PHL. Due to size of the tumor and to be operable, the patient subjected to right portal vein embolization (PVE) and selective embolization of segment V. Four weeks after the PVE, liver resection was conducted (Segments V+VI bisegmentectomy plus resection of IVA). The patient had an uncomplicated post-operative course, and discharged at the 8th post-operative day. Diagnosis of PHL was confirmed by histopathological and immunohistochemical examinations. The patient refused to receive adjuvant chemotherapy, and revealed evidence of recurrence six months after the operation, and finally died 12 months after the operation and 16 months after initial diagnosis. PHL is an extremely rare tumor and often in first presentation has significant size. Radical surgery with adjuvant chemotherapy is key feature for prolonged survival.

Jejunojejunal Intussusception due to Metastatic Melanoma Seven Years after the Primer.

Intestinal intussusception in adults is a rare medical condition accounting for less than 5% of all intussusceptions. Herein we present a 45-year-old patient with a history of abdominal pain and loss of weight. CT scan revealed jejunojejunal intussusceptions. The patient was subjected to exploratory operation and small intestine resection due to a mass causing intestinal intussusception. Pathology confirmed suspected diagnosis of metastatic melanoma to small intestine secondary to melanoma, 7 years after the initial manifestation. Postoperative evaluation with 18FDG-PET/CT revealed increased uptake in the thyroid gland. Subsequent total thyroidectomy revealed severe Hashimoto thyroiditis and no signs of metastasis. The patient received adjuvant immunotherapy and is healthy with no signs of recurrence 3 years after the initial diagnosis and treatment.

Immunosuppression strategies in liver transplantation patient; patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) consists the main primary malignant tumor of the liver. There is an underlining liver cirrhosis mainly attributed to chronic hepatitis B virus or hepatitis C virus, alcoholic liver disease, nonalcoholic steatohepatitis and other pathologic conditions. Liver transplantation consists a radical management, treating both cancer and cirrhosis. By introducing the Milan Criteria for liver transplantation in HCC patients there was a 5-year survival escalation. Even though there is a careful selection of patients with HCC for transplantation, recurrent disease is still high. The role of immusuppression therapy is of paramount importance, in order to avoid acute and chronic graft rejection while protecting the patient from tumor recurrence. In recent years newer immunosuppressive agents such as the mTOR inhibitors are proposed, having dual properties, as both immunosuppressive and antitumors agents.

Toll-like receptors in liver ischemia reperfusion injury: a novel target for therapeutic modulation?

BACKGROUND: There is increasing evidence that Toll-like receptors (TLRs) sense host tissue damage by engaging with endogenous ligands. TLRs are considered to be involved in many primarily non-immune-related diseases. Hepatic ischemia reperfusion injury (IRI) represents one of these disorders. OBJECTIVE: To present the latest findings supporting the involvement of TLRs in liver IRI and to explore their role as potential targets for therapeutic intervention. METHODS: A review of the literature summarizing the latest advances in TLR signaling, the role of TLRs in each hepatic cell population and the involvement of TLRs in the pathophysiology of hepatic IRI. The potential role of TLR-targeting treatment strategies in liver IRI is discussed. CONCLUSIONS: Recent experimental evidence suggests that TLR activation on Kupffer cells provides the triggering signal for pro-inflammatory responses that lead to liver IRI. Modulating TLR signaling could have a beneficial effect in patients with liver IRI.

Bilateral Morgagni Hernia: Primary Repair without a Mesh.

We present a case of bilateral Morgagni hernia in a 68-year-old male with an intermittent history of progressive onset of breath shortness and occasional cardiac arrhythmias. Diagnosis was made by clinical examination and the findings in a plain chest radiograph and was confirmed by computed tomography scan. The patient was operated electively and subjected to a transabdominal approach. A bilateral subcostal incision revealed a large right side anterior diaphragmatic defect with a hernia containing the ascending colon, the majority of the transverse colon and a huge amount of omentum. Also a second smaller defect was found on the left side with no hernia inside. After large bowel and omentum had been taken down to the peritoneal cavity, both defects were primarily closed using interrupted nylon sutures without the use of a mesh. The patient recovered very well, had an uneventful postoperative course and was released on the 5th postoperative day. 15-month follow-up failed to reveal any signs of recurrence.