Impact of mechanical bowel preparation on the gut microbiome of patients undergoing left-sided colorectal cancer surgery: randomized clinical trial.

BACKGROUND: Postoperative complications after colorectal cancer surgery have been linked to the gut microbiome. However, the impact of mechanical bowel preparation using oral preparation agents or rectal enema on postoperative infections remains poorly understood. This study aimed to compare the impact of oral preparation and rectal enema on the gut microbiome and postoperative complications. METHODS: This open-label pilot RCT was conducted at the National Cancer Institute, Vilnius, Lithuania. Patients with left-side colorectal cancer scheduled for elective resection with primary anastomosis were randomized 1 : 1 to preoperative mechanical bowel preparation with either oral preparation or rectal enema. Stool samples were collected before surgery, and on postoperative day 6 and 30 for 16S rRNA gene sequencing analysis. The primary outcome was difference in ß-diversity between groups on postoperative day 6. RESULTS: Forty participants were randomized to oral preparation (20) or rectal enema (20). The two groups had similar changes in microbiome composition, and there was no difference in ß-diversity on postoperative day 6. Postoperative infections occurred in 12 patients (32%), without differences between the study groups. Patients with infections had an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. CONCLUSION: Mechanical bowel preparation with oral preparation or rectal enema resulted in similar dysbiosis. Patients who experienced postoperative infections exhibited distinct gut microbiome compositions on postoperative day 6, characterized by an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. REGISTRATION NUMBER: NCT04013841 (http://www.clinicaltrials.gov).

Short- and long-term outcome differences between patients undergoing left and right colon cancer surgery: cohort study.

PURPOSE: Since the literature currently provides controversial data on the postoperative outcomes following right and left hemicolectomies, we carried out this study to examine the short- and long-term treatment outcomes. METHODS: This study included consecutive patients who underwent right or left-sided colonic resections from year 2014 to 2018 and then they were followed up. The short-term outcomes such as postoperative morbidity and mortality according to Clavien-Dindo score, duration of hospital stay, and 90-day readmission rate were evaluated as well as long-term outcomes of overall survival and disease-free survival. Multivariable Cox regression analysis was performed of overall and progression-free survival. RESULTS: In total, 1107 patients with colon tumors were included in the study, 525 patients with right-sided tumors (RCC) and 582 cases with tumors in the left part of the colon (LCC). RCC group patients were older (P < 0.001), with a higher ASA score (P < 0.001), and with more cardiovascular comorbidities (P < 0.001). No differences were observed between groups in terms of postoperative outcomes such as morbidity and mortality, except 90-day readmission which was more frequent in the RCC group. Upon histopathological analysis, the RCC group's patients had more removed lymph nodes (29 ± 14 vs 20 ± 11, P = 0.001) and more locally progressed (pT3-4) tumors (85.4% versus 73.4%, P = 0.001). Significantly greater 5-year overall survival and disease-free survival (P = 0.001) were observed for patients in the LCC group, according to univariate Kaplan-Meier analysis. CONCLUSIONS: Patients with right-sided colon cancer were older and had more advanced disease. Short-term surgical outcomes were similar, but patients in the LCC group resulted in better long-term outcomes.

Effect of home-based prehabilitation on postoperative complications after surgery for gastric cancer: randomized clinical trial.

BACKGROUND: Recent studies have demonstrated that prehabilitation improves patients' physical fitness but its impact on postoperative morbidity remains unclear. This study aimed to assess the effect of personalized, multimodal, semisupervised, home-based prehabilitation on postoperative complications after surgery for gastric cancer. METHODS: This RCT was conducted at two centres in Lithuania. Patients (aged at least18 years) with gastric cancer scheduled to undergo elective primary surgery or surgery after neoadjuvant chemotherapy for gastric cancer were randomized (1 : 1) to prehabilitation or standard care. Prehabilitation included exercise interventions focused on endurance, respiratory muscle strength, stretching, and resistance training as well as nutritional and psychological support. The primary outcome was the proportion of patients with postoperative complications within 90 days after surgery. Secondary outcomes included 90-day mortality rate, physical condition, fitness level, nutritional status, quality of life, anxiety and depression level, and proportion of patients completing neoadjuvant chemotherapy. RESULTS: Between February 2020 and September 2022, 128 participants were randomized to prehabilitation (64) or standard care (64), and 122 (prehabilitation 61, control 61) were analysed. The prehabilitation group had increased physical capacity before the operation compared with baseline (mean 6-min walk test change +31 (95 per cent c.i. 14 to 48) m; P = 0.001). The prehabilitation group had a decreased rate of non-compliance with neoadjuvant treatment (risk ratio (RR) 0.20, 95 per cent c.i. 0.20 to 0.56), a 60 per cent reduction in the number of patients with postoperative complications at 90 days after surgery (RR 0.40, 0.24 to 0.66), and improved quality of life compared with the control group. CONCLUSION: Prehabilitation reduced morbidity in patients who underwent gastrectomy for gastric cancer. REGISTRATION NUMBER: NCT04223401 (http://www.clinicaltrials.gov).

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in combination with FOLFOX chemotherapy as a first-line treatment for gastric cancer patients with peritoneal metastases: single-arm phase II study.

BACKGROUND: Gastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment. METHODS: This study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6-7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228-47) in a CT scan performed 7 days after the 4th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity. DISCUSSION: This study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM. TRIAL REGISTRATION: NCT05644249. Registered on December 9, 2022.

Comprehensive testing of colorectal anastomosis: results of prospective observational cohort study.

BACKGROUND: Anastomotic leakage remains one of the most threatening complications in colorectal surgery. Intraoperative testing of anastomosis may reduce the postoperative anastomotic leakage rates. This study aimed to investigate a novel comprehensive intraoperative colorectal anastomosis testing technique to detect the failure of the anastomosis construction and to reduce the risk of postoperative leak. METHODS: This multi-centre prospective cohort pilot study included 60 patients who underwent colorectal resection with an anastomosis at or below 15 cm from the anal verge. Comprehensive trimodal testing consisted of indocyanine green fluorescence angiography, tension testing, air-leak, and methylene blue leak tests to evaluate the perfusion, tension, and mechanical integrity of the anastomosis. RESULTS: Ten (16.7%) patients developed an anastomotic leakage. Trimodal test was positive in 16 (26.6%) patients and the operative plan was changed for all of them. Diverting ileostomy was performed in 14 (87.5%) patients. However, two (12.5%) patients still developed clinically significant anastomotic leakage (Grade B). Forty-four (73.4%) patients had a negative trimodal test, preventive ileostomy was performed in 19 (43.2%), and five (11.4%) patients had clinically significant anastomotic leakage (Grade B and C). CONCLUSION: Trimodal testing identifies anastomoses with initial technical failure where reinforcement of anastomosis or diversion can lead to an acceptable rate of anastomotic leakage. Identification of well-performed anastomosis could allow a reduction of ileostomy rate by two-fold. However, anastomotic leakage rate remains high in technically well-performed anastomoses.

Distal Gastrectomy with Billroth II Reconstruction is Associated with Oralization of Gut Microbiome and Intestinal Inflammation: A Proof-of-Concept Study.

BACKGROUND: Subtotal gastrectomy with Billroth II reconstruction (SGB2) results in increased gastric pH and diminished gastric barrier. Increased gastric pH following PPI therapy has an impact on the gut microbiome, intestinal inflammation, and possibly patient health. If similar changes are present after SGB2, these can be relevant for patient health and long-term outcomes after surgery. The aim of the study is to investigate whether SGB2 is associated with specific changes in gut microbiome composition and intestinal inflammation. PATIENTS AND METHODS: This cross-sectional proof-of-concept study includes patients after SGB2 (n = 14) for early gastric cancer and their nongastrectomized in-house relatives as controls (n = 8). Fecal microbiome composition, intestinal inflammation (fecal calprotectin), gut permeability (DAO, LBP, sCD14), systemic inflammation (CRP) markers, and gastrointestinal symptoms are investigated. This study is registered at ClinicalTrials.gov (NCT03418428). RESULTS: Microbiome oralization following SGB2 was defined by an increase in Escherichia-Shigella, Enterococcus, Streptococcus, and other typical oral cavity bacteria (Veillonella, Oribacterium, and Mogibacterium) abundance. The fecal calprotectin was increased in the SGB2 group [100.9 (52.1; 292) vs. 25.8 (17; 66.5); p = 0.014], and calprotectin levels positively correlated with the abundance of Streptococcus (rs = 0.639; padj = 0.023). Gastrointestinal symptoms in SGB2 patients were associated with distinct taxonomic changes of the gut microbiome. CONCLUSIONS: SGB2 is associated with oralization of the gut microbiome; intestinal inflammation and microbiome changes were associated with gastrointestinal symptoms. These novel findings may open gut microbiome as a new target for therapy to improve quality of life and general patient health in long-term survivors after SGB2.

Impact of the Interval Between Neoadjuvant Chemotherapy and Gastrectomy on Short- and Long-Term Outcomes for Patients with Advanced Gastric Cancer.

BACKGROUND: The optimal time between neoadjuvant chemotherapy (NAC) and gastrectomy for gastric cancer (GC) remains unknown. This study aimed to investigate the association between the time-to-surgery (TTS) interval and the major pathologic response (mPR). METHODS: In this study, 280 consecutive GC patients who underwent NAC followed by gastrectomy between 2014 and 2018 were retrospectively analyzed by the use of prospectively collected databases from three major GC treatment centers in Lithuania and Estonia. Based on TTS, they were grouped into three interval categories: the early-surgery group (ESG: ≤ 30 days; n = 70), the standard-surgery group (SSG: 31-43 days; n = 138), and the delayed-surgery group (DSG: ≥ 44 days, n = 72). The primary outcome of the study was the mPR rate. The secondary end points were postoperative morbidity, mortality, oncologic safety (measured as the number of resected lymph nodes and radicality), and long-term outcomes. RESULTS: The mPR rate for the ESG group (32.9%) was significantly higher than for the SSG group (20.3%) or the DSG group (16.7%) (p = 0.047). Furthermore, after adjustment for patient, tumor, and treatment characteristics, the odds for achievement of mPR were twofold higher for the patients undergoing early surgery (odds ratio [OR] 2.09; 95% conflidence interval [CI] 1.01-4.34; p = 0.047). Overall morbidity, severe complications, 30-day mortality, R0 resection, and retrieval of at least 15 lymph nodes rates were similar across the study groups. In addition, the long-term outcomes did not differ between the study groups. CONCLUSIONS: This study suggests that an interval of more than 30 days between the end of NAC and gastrectomy is associated with a higher mPR rate, the same oncologic safety of surgery, and similar morbidity and mortality.

Short and long-term outcomes of elderly patients undergoing left-sided colorectal resection with primary anastomosis for cancer.

BACKGROUND: The proportion of elderly colorectal cancer (CRC) patients requiring surgery is increasing. Colorectal resection for left-sided cancers is the most controversial as the primary anastomosis or end-colostomy and open or minimally invasive approaches are available. Therefore, this study was conducted to investigate the short- and long-term outcomes in elderly patients after resection with primary anastomosis for left-sided CRC. METHODS: The cohort study included left-sided colorectal cancer patients who underwent resection with primary anastomosis. The participants were divided into non-elderly (≤75 years) and elderly (> 75 years) groups. Short- and long-term postoperative outcomes were investigated. RESULTS: In total 738 (82%) and 162 (18%) patients were allocated to non-elderly and elderly groups, respectively. Minimally invasive surgery (MIS) was less prevalent in the elderly (42.6% vs 52.7%, p = 0.024) and a higher proportion of these suffered severe or lethal complications (15.4% vs 9.8%, p = 0.040). MIS decreased the odds for postoperative complications (OR: 0.41; 95% CI: 0.19-0.89, p = 0.038). The rate of anastomotic leakage was similar (8.5% vs 11.7%, p = 0.201), although, in the case of leakage 21.1% of elderly patients died within 90-days after surgery. Overall- and disease-free survival was impaired in the elderly. MIS increased the odds for long-term survival. CONCLUSIONS: Elderly patients suffer more severe complications after resection with primary anastomosis for left-sided CRC. The risk of anastomotic leakage in the elderly and non-elderly is similar, although, leakages in the elderly seem to be associated with a higher 90-day mortality rate. Minimally invasive surgery is associated with decreased morbidity in the elderly.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal malignancy: initial experience of the first program in the Baltic countries.

BACKGROUND: Peritoneal malignancies include primary and metastatic cancer of the peritoneal cavity. The most common origin for peritoneal metastasis is ovarian, gastric, and colorectal cancers. Irrespective of the origin, peritoneal metastases represent the advanced disease and are associated with poor long-term outcomes. The minimally invasive approach of pressurized intraperitoneal aerosol chemotherapy (PIPAC) allows repeated applications and objective assessment of tumor response by comparing histological samples. This study aimed to investigate the initial experience with PIPAC in the Baltic region. METHODS: All patients who underwent PIPAC at Vilnius University Hospital Santaros Klinikos between 2015 and 2020 were included in this retrospective study. The primary outcome of the study was overall survival (OS) in patients with peritoneal carcinomatosis treated by PIPAC. The secondary outcomes included postoperative morbidity; peritoneal carcinomatosis index (PCI) and ascites reduction after treatment by PIPAC. RESULTS: In total, 15 patients underwent 34 PIPAC procedures. PIPAC-related intraoperative and postoperative morbidity occurred in 3 (8.8%) of 34 procedures. Following PIPAC, the median PCI decreased from 8 (4; 15) to 5 (1; 16) in GC patients, although, the difference failed for significance, p = 0.581. In OC patients, PCI after PIPAC remained stable. Median overall survival after PIPAC procedure was 25 (95% CI 5-44) months. Ovarian cancer patients (22; 95% CI 12-44 months) had significantly higher OS, compared to gastric cancer patients (8; 95% CI 4-16 months), p = 0.018. CONCLUSIONS: PIPAC is safe and feasible for patients with gastric and ovarian cancers peritoneal metastases.

Custodiol® Supplemented with Synthetic Human Relaxin Decreases Ischemia-Reperfusion Injury after Porcine Kidney Transplantation.

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI.

Short- and long-term outcomes of surgery for colorectal and non-colorectal liver metastasis: a report from a single center in the Baltic country.

BACKGROUND: The liver is a major target organ for metastases of various types of cancers. Surgery is a well-established option for colorectal liver metastases (CRLM). Regarding the improved surgical and anesthetic techniques, the safety of liver resection has increased. Consequently, the interest in the surgical management of non-colorectal liver metastases (non-CRLM) has gained significant attention. Therefore, this study was designed to investigate the surgical treatment outcomes for non-CRLM and to compare it with an outcome of CRLM in a tertiary care center in the Baltic country-Lithuania. METHODS: We retrospectively analyzed data from all patients who underwent liver resection for CRLM or non-CRLM between 2010 and 2017 in a tertiary care center-Vilnius University hospital Santaros Clinics. Demographic and metastasis characteristics, as well as disease-free and overall survival, were compared between the study groups. RESULTS: In total, 149 patients were included in the study. Patients in the CRLM group were older (63.2 ± 1.01 vs 54.1 ± 1.8 years, p < 0.001) and mainly predominant by males. Overall postoperative morbidity rate (16.3% vs 9.8%, p = 0.402) and major complications rate (10% vs 7.8%, p = 0.704) after liver resection for CRLM and non-CRLM was similar. Kaplan-Meier analysis showed higher disease-free survival in the CRLM group with 89.4% vs 76.5% and 64.9% vs 31.4% survival rates at 1 and 3 years, respectively (p = 0.042), although overall survival was not different between the CRLM and non-CRLM groups with 89.4% vs 78.4% and 72.0% vs 46.1% survival rates at 1 and 3 years, respectively (p = 0.300). CONCLUSIONS: In this study, we confirmed comparable short- and long-term outcomes after liver resection for CRLM and non-CRLM. Surgical resection should be encouraged as an option in well-selected patients with non-CRLM.

Risk factors for anastomotic leakage and its impact on long-term survival in left-sided colorectal cancer surgery.

BACKGROUND: Anastomotic leakage (AL) significantly impairs short-term outcomes. The impact on the long-term outcomes remains unclear. This study aimed to identify the risk factors for AL and the impact on long-term survival in patients with left-sided colorectal cancer. METHODS: Nine-hundred patients with left-sided colorectal carcinoma who underwent sigmoid or rectal resection were enrolled in the study. Risk factors for AL after sigmoid or rectal resection were identified, and long-term outcomes of patients with and without AL were compared. RESULTS: AL rates following sigmoid and rectal resection were 5.1% and 10.7%, respectively. Higher ASA score (III-IV; OR = 10.54, p = 0.007) was associated with AL in patients undergoing sigmoid surgery on multivariable analysis. Male sex (OR = 2.40, p = 0.004), CCI score > 5 (OR = 1.72, p = 0.025), and T3/T4 stage tumors (OR = 2.25, p = 0.017) were risk factors for AL after rectal resection on multivariable analysis. AL impaired disease-free and overall survival in patients undergoing sigmoid (p = 0.009 and p = 0.001) and rectal (p = 0.003 and p = 0.014) surgery. CONCLUSION: ASA score of III-IV is an independent risk factor for AL after sigmoid surgery, and male sex, higher CCI score, and advanced T stage are risk factors for AL after rectal surgery. AL impairs the long-term survival in patients undergoing left-sided colorectal surgery.

Early versus standard closure of temporary ileostomy in patients with rectal cancer: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: A significant proportion of patients undergoing rectal cancer surgery receive a temporary ileostomy because of its benefits in case of anastomotic dehiscence. However, the best timing for closure remains unclear. METHODS: Early closure (EC; 30 days after creation) and standard closure (SC; 90 days after creation) of ileostomy were compared in a single-center randomized controlled trial conducted at National Cancer Institute (Vilnius, Lithuania). Patients with a temporary ileostomy who underwent rectal cancer surgery and did not have anastomotic leakage or other serious complications were randomized to early or standard ileostomy closure groups. Thirty days postoperative morbidity following ileostomy closure was the primary outcome of the study. RESULTS: The trial was prematurely terminated due to the safety reason after 86 patients were randomized to EC (43 patients) and SC (43 patients) groups. The overall 30 days postoperative morbidity rate was dramatically higher in the EC group (27.9% vs 7.9%; P = 0.024). Moreover, severe complications (Clavien-Dindo ≥3) were present only after EC of ileostomy in five (11.6%) patients. CONCULSION: Early closure of ileostomy at 30 days after radical rectal resection is not safe and should not be performed.

Surgical treatment outcomes of patients with T1-T2 gastric cancer: does the age matter when excellent treatment results are expected?

BACKGROUND: The proportion of early gastric cancer stages is increasing, as is the incidence of gastric cancer among the elderly population. Therefore, this study was designed to analyze surgical treatment outcomes of T1-T2 gastric cancer in elderly patients. METHODS: A total of 457 patients with T1-T2 gastric cancer who underwent gastrectomy between 2005 and 2015 were enrolled in this retrospective study. Patients were classified into two groups according to age (< 70 years versus ≥ 70 years). Clinicopathological features, surgical treatment results, and clinical outcomes were compared between the groups. RESULTS: Higher ASA score (ASA 3/4), differentiated cancer, and intestinal-type tumors were more common in elderly patients. Postoperative complication rates were similar between the two groups; however, postoperative mortality rates were significantly higher in the elderly group. Higher ASA score was independently associated with postoperative complications in the elderly group. Furthermore, severe postoperative complications were found as an independent factor associated with higher 90-day mortality rate. Elderly patients had a significantly poorer 5-year overall survival rate. Two surgery-related factors-total gastrectomy and complicated postoperative course-were revealed as independent prognostic factors for poor overall survival in the elderly group. CONCLUSIONS: Despite higher postoperative mortality rate and poorer overall survival results, elderly patients with gastric cancer should be considered for radical surgery. ASA score may be useful for predicting surgical treatment outcomes in elderly patients undergoing surgery for GC and hence assists clinicians in planning treatment strategies for each individual patient.

Safety of expanded criteria for endoscopic resection of early gastric cancer in a Western cohort.

BACKGROUND: Endoscopic resection is widely accepted treatment option for early gastric cancer if tumors meet the standard or expanded indications. However, the safety of expanded criteria is still under investigation. Furthermore, discussion, if any additional treatment is necessary for patients who underwent endoscopic resection but exceeded expanded criteria, is rising. This study aimed to evaluate the safety of extended indications for endoscopic resection of early gastric cancer in a Western cohort. Also, we aimed to analyze the lymph node metastasis rate in tumors which exceeds the extended criteria. METHODS: Two hundred eighteen patients who underwent surgery for early gastric cancer at National Cancer Institute, Vilnius, Lithuania between 2005 and 2015 were identified from a prospective database. Lymph node status was examined in 197 patients who met or exceeded extended indications for endoscopic resection. RESULTS: Lymph node metastasis was detected in 1.7% of cancers who met extended indications and in 30.2% of cancers who exceeded expanded indications. Lymphovascular invasion and deeper tumor invasion is associated with lymph node metastasis in cancers exceeding expanded indications. CONCLUSIONS: Expanded criteria for endoscopic resection of early gastric cancer in Western settings is not entirely safe because these tumors carry the risk of lymph node metastasis.

Impact of Melatonin in Solid Organ Transplantation-Is It Time for Clinical Trials? A Comprehensive Review.

Solid organ transplantation is the "gold standard" for patients with end-stage organ disease. However, the supply of donor organs is critical, with an increased organ shortage over the last few years resulting in a significant mortality of patients on waiting lists. New strategies to overcome the shortage of organs are urgently needed. Some experimental studies focus on melatonin to improve the donor pool and to protect the graft; however, current research has not reached the clinical level. Therefore, this review provides a comprehensive overview of the data available, indicating that clinical evaluation is warranted.

Risk factors for lymph node metastasis in early gastric cancer patients: Report from Eastern Europe country- Lithuania.

BACKGROUND: Current risk factors for lymph node metastasis in early gastric cancer have been primarily determined in Asian countries; however their applicability to Western nations is under discussion. The aim of our study was to identify risk factors associated with lymph node metastasis in Western cohort patients from the Eastern European country - Lithuania. METHODS: A total of 218 patients who underwent open gastrectomy for early gastric cancer were included in this retrospective study. After histolopathological examination, risk factors for lymph node metastasis were evaluated. Overall survival was evaluated and factors associated with long-term outcomes were analyzed. RESULTS: Lymph node metastases were present in 19.7% of early gastric cancer cases. The rates were 5/99 (4.95%) for pT1a tumors and 38/119 (31.9%) for pT1b tumors. Submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation were identified as independent risk factors for lymph node metastasis. Submucosal tumor invasion and lymphovascular invasion were also associated with worse 5-year survival results. CONCLUSION: Our study established submucosal tumor invasion, lymphovascular invasion, and high grade tumor differentiation as risk factors for lymph node metastasis.