Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer.

PURPOSE: Pancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes. METHODS: A retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan-Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival. RESULTS: 4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4-7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8-7.8) vs. 6.7 months (95% CI 6.4-7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7-11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5-8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9-22%) and 14.8% (95% CI 11.1-19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2-4.4%). CONCLUSION: Our results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

Surgical Skill Decay as a Result of the COVID-19 Pandemic.

BACKGROUND: This study aimed to objectively evaluate the impact of the gap in surgical practice caused by COVID-19 on surgical skill decay. METHODS: This retrospective cohort study enrolled 148 cases of adult patients who were qualified for elective or urgent laparoscopic cholecystectomy. This study compared the period of nine months before the pandemic outbreak and nine months after the end of the pandemic. We analyzed the duration of surgery, the number of intraoperative adverse events (IAEs), postoperative complications (PCs), and differences between the surgeries performed by residents and those performed by specialists. RESULTS: The number of IAEs did not differ significantly between groups (after COVID-19 (AC) and before COVID-19 (BC)). A difficult gallbladder (DGB) was associated with an increased risk of IAEs during surgery in both groups (BC:OR = 2.94, p = 0.049; AC:OR = 2.81, p = 0.35). The multivariate analyses showed no significant differences in IAEs or PCs when the residents performed surgeries compared to specialists. The average duration of surgery was significantly longer in the post-pandemic group (BC-102.4 min vs. AC-119.9 min, p = 0.024). CONCLUSIONS: Measurable determinants of surgical skills are the duration of surgery and the number of intraoperative adverse events. By defining this indicators, our study objectively shows that the reduction in the volume of surgeries during COVID-19 resulted in a phenomenon known as surgical skill decay.

Malnutrition as an unfavorable prognostic factor after surgical treatment for metastatic colorectal cancer.

<b><br>Introduction:</b> Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. Distant metastases are usually located in the liver and are present in 50% of patients.</br> <b><br>Aim:</b> The aim of this study is to evaluate changes in body composition and phase angle before and after surgical treatment of CRC liver metastases, as well as survival time and treatment costs.</br> <b><br>Material and methods:</b> The study included 134 patients who received 174 surgeries for CRC liver metastases. Bioelectrical impedance analysis (BIA) was performed using an AKERN BIA 101 analyzer.</br> <b><br>Results:</b> BIA was performed before and after surgery. The results of tests (total body water content [TBW], body cell mass [BCM], and phase angle) showed a reduction in BCM by 2.21 kg and a statistically significant decrease in phase angle values after surgery (from 5.06 to 4.25 in women and from 5.34 to 4.76 in men). These values are below the reference range for both sexes. There was a correlation between phase angle values and muscle mass, both before (R = 0.528, p<0001) and after surgery (R = 0.634, p<000.1). Preoperative levels of the tumor marker CEA were elevated in more than half of the patients. The median survival time after resection of liver metastases was 37.6 months.</br> <b><br>Discussion:</b> A significant factor that increases complications, mortality, and treatment costs of cancer patients is malnutrition, which could be the earliest symptom of malignant disease.</br> <b><br>Conclusions:</b> Successful treatment of CRC requires the patients to participate in follow-up examinations and to be aware of early signs associated with recurrence (e.g., blood in the stool or weight loss). The patients' nutritional status should be monitored and recorded in a DILO card.</br>.

Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma.

Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer.

Recommendations for modern perioperative care for elective surgery: consensus of panel of exerts.

INTRODUCTION: Correct surgical technique and perioperative care are two factors that can reduce the number of complications, improve treatment outcomes and shorten the length of hospital stay. The introduction of enhanced recovery protocols has changed the approach to patient care in some centers. However, there are significant differences among centers, and in some the standard of care has remained unchanged. AIM: the goal of the panel was to develop recommendations for modern perioperative care in accordance with current medical knowledge in order to reduce the number of complications associated with surgical treatment. An additional goal was to optimize and standardize perioperative care among Polish centers. MATERIALS AND METHODS: the development of these recommendations was based on a review of the available literature from the PubMed, Medline and Cochrane Library databases from January 1, 1985 to March 31, 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and were assessed using the Delphi method. RESULTS AND CONCLUSIONS: 34 recommendations for perioperative care were presented. They cover aspects of pre-, intra- and post-operative care. Implementation of the presented rules allows to improve the results of surgical treatment.

The complication rate, but not the mortality rate, lower after percutaneous endoscopic gastrostomy than after open surgical gastrostomy: comparison of two methods in a high volume group of patients.

Introduction: Percutaneous endoscopic gastrostomy (PEG) has become the primary procedure for long-term enteral nutrition of most, but not all patients with dysphagia. Still in some patients gastrostomy may only be performed with open surgical technique (SG). Finally, in some patients due to relative contraindications to both methods, surgeons have to choose one of them. Aim: To compare PEG with SG in terms of effectiveness and safety. Material and methods: A retrospective study of 612 patients with dysphagia, who underwent PEG (573) or SG (39) was conducted. Authors analysed effectiveness of PEG and SG procedures as well as the type, frequency and treatment methods of complications classified according to Clavien-Dindo Classification. Results: The rate of all complications was significantly lower for PEG than for SG and a significant effect of the treatment type on the probability of serious complications was observed - notably lower after PEG (OR = 0.21, 95% CI: 0.05-0.8, p = 0.02). The 30-day mortality rate was 1.74% for PEG and 0% for SG. PEG patients who required laparotomy were over 30 times more likely to die than others. No significant effect of the nutrition status on the probability of serious complications was observed (OR = 0.83, 95% CI: 0.51-1.34, p = 0.46). Conclusions: A significant effect of the treatment type on the probability of serious complications was confirmed. This result was robust to the preoperative patients' nutrition status which was found to be insignificant. A lower risk of postoperative complications, a relatively easy procedure make PEG a procedure of choice in patients with dysphagia.

Simultaneous surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava and ischemic heart disease own research and literature review.

<b> Introduction:</b> Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Tumor penetration into the inferior vena cava/right atrium is rare, as it occurs only in 34% of HCC patients. There are no clear guidelines for the management of this stage of disease. </br></br> <b>Aim:</b> This is a case report of a patient with HCC and tumor thrombus in the inferior vena cava and with advanced coronary artery disease. </br></br> <b> Materials and methods:</b> The patient was qualified for a simultaneous cardiac surgery and liver resection with removal of the tumor thrombus from the inferior vena cava due to a high risk of sudden cardiac death. The first stage involved aortocoronary bypass followed by a right-sided hemihepatectomy with removal of the tumor thrombus from the inferior vena cava (this part of the operation was performed by extracorporeal circulation). The postoperative period was uneventful. Surgical treatment is one of the therapeutic options that offers a chance to radically remove the tumor and extend the patient's life. From a standpoint, these operations are extremely difficult and carry a high risk of perioperative complications (up to 40%). At the same time, the patient is at risk of complications due to cancer, such as pulmonary embolism, tricuspid stenosis, and congestive heart failure, which should be considered when choosing a treatment method. A significant number of patients also suffer from chronic conditions that worsen the prognosis. Cardiac diseases combined with tumor thrombus in the inferior vena cava may cause sudden cardiac death. </br></br> <b>Conclusions:</b> Surgical treatment should be considered in patients with HCC and tumor thrombus in the inferior vena cava, especially in patients with cardiovascular disease burden, as it is not only a chance to prolong life, but also to protect them against life-threatening cardiac complications.

Kidney stones are common in patients with short-bowel syndrome receiving long-term parenteral nutrition: A predictive model for urolithiasis.

BACKGROUND: In short-bowel syndrome (SBS) treated with parenteral nutrition (PN), multiple complications can occur. The etiology of kidney stones may be linked to the underlying disease thrombosis, surgical complications, complications of therapy for cancer, Crohn's disease, metabolic abnormalities resulting from morphological and functional changes in the gastrointestinal tract, and to treatment used. We analyzed all these parameters in a large cohort of patients receiving home PN (HPN), to define the incidence of stones and groups of patients particularly at risk of stone formation. One of the objectiveswas to develop a predictive model of urolithiasis. METHODS: This observational retrospective study included 459 patients with SBS recieving HPN in a single center. Patient records were evaluated for demographics, SBS etiology, and underlying disease, anatomy of the gastrointestinal tract, intestinal failure classification, nutrition regimen, and presence of urolithiasis. RESULTS: Kidney stones were diagnosed in 24% of patients. Nodifferences in incidence were noted between the various etiologic groups. The incidence in patients with a colon in continuity and those with an end stoma was similar. The length of residual small bowel did not play a role in stone formation. There were no differences between patients according to the severity of intestinal failure. In patients treated with PN and limited oral feeding, the risk of urolithiasis was twice as high as in patients receiving PN only. CONCLUSIONS: Patients developed urolithiasis with no relation to the SBS etiology. The risk of kidney stone formation was higher in patients recieving PN with oral feeding.

The Relationship between Nutritional Status and Body Composition with Clinical Parameters, Tumor Stage, CA19-9, CEA Levels in Patients with Pancreatic and Periampullary Tumors.

Recent studies have obtained inadequate data on the association between nutritional status, body composition, clinical parameters and tumor stage in patients withpancreatic and periampullary tumors. The purpose of this study was to assess the relationship between nutritional status (NS), body composition (BC) and selected clinical parameters in patients with pancreatic and periampullary cancer, as well as describe the differences between resection and non-resection groups. This is a prospective study of 76 patients with pancreatic and periampullary tumors. We evaluated NS, BMI, body mass loss (BML) and albumin, total protein, CRP, CEA, CA19-9, lipase, amylase, tumor stage, and BC using bioelectrical impedance (BIA). All subjects were divided into resection (n = 59) and non-resection (n = 17) groups. The non-resection group had a worse NS, as well as increased amylase and WBC, compared to the resection. The selected parameters of BC corresponded to BML albumin, TP, NS, age, BMI, Karnofsky, RBC, HCT and HGB. No associations were found between BC with tumor size, CRP, CA19-9, and CEA. We recorded the relationship between metastasis and NRS, as well as tumor size with SGA. The percentage of BML was positively correlated with age and CRP but negatively correlated with RBC, HGB, HCT and anthropometric measurements. We found many statistical correlations with NS and selected parameters, as well as differences between the resection and non-resection group. The detection of early prognostic factors of nutritional impairments would improve the quality of life and reduce the rate of postoperative complications.

Brain-derived neurotrophic factor in gastroenterology oncology - short review of current literature.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophins group which plays a crucial role in brain development and neurogenesis. In the hypothalamus it is described as playing a role in energy metabolism and feeding behaviour. The hippocampal concentration of BDNF is believed to play an important role in learning and memory, it has a protective role in neurodegeneration and stress responses. BDNF is also known to take part in many other processes, e.g. angiogenesis, proliferation, cell migration and apoptosis. With its receptor TrkB, neurotrophins are important agents that playa role in neural diseases, as well as in cardiovascular and metabolic disorders, such as diabetes mellitus or acute coronary syndrome. Over the last few years, BDNF interaction with TrkB has also been found to be involved in cancer development, including brain, breast, urinary and gastrointestinal cancer. TrkB expression itself has been described as an aggressive neural tumour. BDNF/TrkB signalling takes part in promoting tumour growth and metastasis. The presented review focuses on gastrointestinal cancer and presents the current literature concerning influence of BDNF and TrkB receptor in cancer progression. Special attention is also paid to data confirming the possible role of BDNF/TrkB interaction in chemotherapy resistance. This might present the opportunity to assess the BDNF and TrkB pathway as a possible novel target for anticancer therapies.