Overall Survival Prediction by Tumor Microenvironment Lymphocyte Distribution in Hepatocellular Carcinoma After Liver Transplantation.

INTRODUCTION: Our previous research demonstrated that CD8+ cell density profiling using a hexagonal grid-based digital image analysis method provides predictors of patient outcomes after liver resection due to hepatocellular carcinoma (HCC). Continuing our study, we have further investigated the applicability of the methodology to patients receiving a liver transplant for HCC. METHODS: The retrospective study enrolled patients with HCC who underwent liver transplantation (LT) at the Vilnius University Hospital Santaros Clinics between 2007 and 2020. We determined the density profiles of CD8+ lymphocytes at the interface between HCC and stroma and the interface between the perineoplastic liver parenchyma and stroma. Both digital image analysis and the hexagonal grid-based immunogradient method were applied to CD8+ immunohistochemistry images. Survival statistics based on clinicopathological, peripheral blood analysis, and surgical data determined the prognostic value of these indicators. RESULTS: Univariate clinicopathological predictors of worse OS after LT included: patient's age at the time of the transplantation, a higher number of HCC nodules, lower platelet count, longer activated thromboplastin time, lower serum albumin, higher serum total bilirubin, and lower serum creatinine levels. The two independent predictors of overall survival were mean CD8+ cell density at the epithelial edge of the explanted liver parenchyma-stroma interface and peripheral blood platelet count. CONCLUSIONS: Our model discloses that preoperative peripheral blood platelet count and mean CD8+ cell density at the epithelial edge of nonmalignant interface in the explanted liver parenchyma are independent predictors of OS for HCC after LT.

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.

Primary Liver Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review.

A primary liver perivascular epithelioid cell tumor (PEComa) is an extremely rare entity. In this article, we present a case report with a review of the literature on the patients diagnosed with primary liver PEComa and an elaboration of diagnostic and treatment modalities. A systematic literature search was conducted using the terms "perivascular epithelioid cell tumor", "PEComa", "liver", and "hepatic". All articles describing patients diagnosed with primary liver PEComa were included. We identified a total of 224 patients of primary liver PEComa from 75 articles and a case from the present study with a significant preponderance of females (ratio 4:1) and with a mean age of 45.3 ± 12.1 years. Most of the patients (114 out of 224, 50.9%) were asymptomatic. A total of 183 (81.3%) patients underwent surgical hepatic resection at the time of diagnosis, while 19 (8.4%) underwent surveillance. Recurrence and metastases were detected in seven (3.1%) and six (2.7%) patients, respectively. In conclusion, surgical resection remains the cornerstone of therapy; however, the presence of nonspecific imaging features makes it difficult to reach a definite diagnosis preoperatively. Therefore, a multidisciplinary approach should be the gold standard in selecting the treatment modality.

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.

The academic impact and value of an international online surgery lecture series.

Due to the worldwide travel restrictions caused by the 2019 coronavirus disease pandemic, many universities and students lost opportunities to engage in international exchange over the past 2 years. Teleconferencing systems have thus been developed to compensate for severe travel restrictions. Kansai Medical University in Japan and Vilnius University in Lithuania have a collaborative research and academic relationship. The two universities have been conducting an online joint international surgery lecture series for the medical students of both universities. Fifteen lectures were given from October 2021 to May 2022. The lectures focused on gastrointestinal surgery, gastroenterology, radiology, pathology, genetics, laboratory medicine, and organ transplantation. A survey of the attendees indicated that they were generally interested in the content and satisfied with attending this lecture series. Our efforts were successful in providing Japanese and Lithuanian medical students with the opportunity to engage in international exchange through lectures held in each other's countries.

Vermiform Appendix within Post-Laparoscopic Incisional Hernia: A Unique Case Report and Literature Review.

Background: Appendicitis within incisional hernia is an extraordinarily rare postoperative complication with an incidence range from 0.08 to 1%. From the 14 cases that we found in the English literature, only three present appendixes vermiform in incisional hernia followed by laparoscopic surgery. Only two cases are treated minimally invasively by the laparoscopic approach. Case presentation: We introduce a 65-year-old man who had a laparoscopic sigmoid colon resection and had a lump found at the 12 mm trocar site in the right iliac area in the late postoperative phase. There were no complaints from the patient. A vermiform appendix was unexpectedly discovered in the sac of that incisional hernia during control CT scans performed by chemotherapists. Laparoscopic hernia repair without appendectomy was performed. Postoperative outcomes were excellent. Conclusions: Because of low incidence and a lack of distinctive clinical presentation of appendicitis within incisional hernia, there is a risk of delayed perioperative diagnosis and treatment. A CT scan might play an important role in verifying the diagnosis early. For better postoperative outcomes, if possible, laparoscopic surgery should be chosen.

Assessing Liver Fibrosis Using 2D-SWE Liver Ultrasound Elastography and Dynamic Liver Scintigraphy with 99mTc-mebrofenin: A Comparative Prospective Single-Center Study.

Background and Objectives: Many quantitative imaging modalities are available that quantify chronic liver disease, although only a few of them are included in clinical guidelines. Many more imaging options are still competing to find their place in the area of diagnosing chronic liver disease. We report our first prospective single-center study evaluating different imaging modalities that stratify viral hepatitis-associated liver fibrosis in a treatment-naïve patient group. Materials and Methods: The aim of our study is to compare and to combine already employed 2D shear wave elastography (2D-SWE) with dynamic liver scintigraphy with 99mTc-mebrofenin in chronic viral hepatitis patients for the staging of liver fibrosis. Results: Seventy-two patients were enrolled in the study. We found that both 2D-SWE ultrasound imaging, with dynamic liver scintigraphy with 99mTc-mebrofenin are able to stratify CLD patients into different liver fibrosis categories based on histological examination findings. We did not find any statistically significant difference between these imaging options, which means that dynamic liver scintigraphy with 99mTc-mebrofenin is not an inferior imaging technique. A combination of these imaging modalities showed increased accuracy in the non-invasive staging of liver cirrhosis. Conclusions: Our study presents that 2D-SWE and dynamic liver scintigraphy with 99mTc-mebrofenin could be used for staging liver fibrosis, both in singular application and in a combined way, adding a potential supplementary value that represents different aspects of liver fibrosis in CLD.

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.

Preventing hemorrhoids during pregnancy: a multicenter, randomized clinical trial.

BACKGROUND: To compare specific dietary and behavioral recommendations for hemorrhoids prevention during pregnancy. METHODS: This was a randomized, single-blind, multicenter trial conducted in three different clinical centers. Patients were randomly allocated into two groups in a ratio of 1:1. Intervention consisted of specific dietary and behavioral counseling. The primary outcome of this study was the rate of hemorrhoids at the time of discharge from the obstetrics unit. Categorical variables were compared by the Chi-Squared or Fisher exact tests, as appropriate. Continuous variables were compared using either the Student's t-test or the Mann-Whitney U test. Binary logistic regression model was used to identify independent predictors of hemorrhoids after delivery. This analysis was performed on factors with a p-value < 0.10 in univariate analysis. Statistical analysis was performed using IBM SPSS 23.0 and GraphPad Prism 9 software. A P-value of less than 0.05 was considered significant for all tests. RESULTS: We observed a significantly lower hemorrhoids rate in the intervention group at the time of discharge from the obstetrics unit after delivery (intention-to-treat (ITT) (the relative risk (RR) 0.38; 95% the confidence interval (CI) 0.24-0.59; p < 0.001) per-protocol (PP) (RR 0.42; 95% CI 0.27-0.64; p < 0.001). There was no significant difference in spontaneous miscarriage rate between the groups for both ITT and PP analysis. Additional binary logistic regression analysis revealed that the intervention applied in this study was the only protective factor. Both, the history of hemorrhoids before pregnancy and the increase of newborn height was associated with a higher risk of hemorrhoids. CONCLUSIONS: Our suggested intervention, aimed to modify dietary and behavioral habits, significantly reduces the rate of hemorrhoids after pregnancy and can be safely recommended to pregnant women. TRIAL REGISTRATION: Date of registration: 2016-05-09; Date of initial patient enrollment: 2016-06-02; Trial registration number: 158200-16-843-357; Trial registration site URL: https://www.mf.vu.lt/mokslas/vilniaus-regioninis-biomedicininiu-39tyrimu-etikos-komitetas#isduoti40vrbtek-leidimai .

Necroptosis in Solid Organ Transplantation: A Literature Overview.

Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the cycle of sterile inflammation during IRI is consistent among different organs, the underlying mechanisms are poorly understood. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be crucial in the implementation of necroptosis. Moreover, apart from "silent" apoptotic death, necrosis also causes sterile inflammation-necroinflammation, which is triggered by various damage-associated molecular patterns (DAMPs). Those DAMPs activate the innate immune system, causing local and systemic inflammatory responses, which can result in graft failure. In this overview we summarize knowledge on mechanisms of sterile inflammation processes during SOT with special focus on necroptosis and IRI and discuss protective strategies.

Probiotic Supplementation Suppresses Tumor Growth in an Experimental Colorectal Cancer Liver Metastasis Model.

Colorectal cancer (CRC) ranks third in incidence and second in mortality of all cancers worldwide. At the time of primary diagnosis, around 20% of patients already have metastatic CRC and only around 20% are candidates for radical resection. Thus, most of the patients have to undergo chemotherapy (CTx). Due to chemoresistance and side effects, novel treatment additives are crucial for controlling the disease and prolonging patient survival. The aim of this study was to evaluate probiotic supplementation and its antitumorigenic effects in an experimental CRC liver metastasis model. Six-week-old male Wistar rats received either a multispecies probiotic (1.2 × 109 CFU/daily) or placebo mixture. On day 14 of the experiment, rat CRC cells (CC531) were implanted under the liver capsule later treated by FOLFOX CTx. Change in tumor volume was measured by performing micro computed tomography (micro-CT) scanning on experimental days 28 and 34. Additionally, immunohistochemical staining with anti-MPO, anti-Ki67, and anti-CD31 were performed. Tumor apoptosis was evaluated using TUNEL staining. Micro-CT image analysis indicates that probiotic supplementation significantly inhibits tumor growth. No synergistic effects between probiotic supplementation and FOLFOX CTx was observed. Reduced tumor volume was achieved by inhibiting angiogenesis, as tumor microvascular density was significantly lower in rats receiving probiotic supplementation. This study shows that a multispecies probiotic mixture significantly reduces angiogenesis and inhibits CRC liver metastasis growth in an experimental rat model.

Relaxin and Erythropoietin Significantly Reduce Uterine Tissue Damage during Experimental Ischemia-Reperfusion Injury.

Successful uterus transplantation, a potential treatment method for women suffering from absolute uterine infertility, is negatively affected by ischemia-reperfusion injury (IRI). The aim of this study is to investigate the protective effect of relaxin (RLX) or/and erythropoietin (EPO) on experimental uterus IRI. Eighty rats, randomly assigned into eight groups (n = 10/group), were pretreated with either saline, 5 µg/kg human relaxin-2, 4000 IU/kg recombinant human erythropoietin or their combination. Ischemia was achieved by clamping the aorta and ovarian arteries for 60 min, following 120 min of reperfusion and tissue sampling. For sham animals, clamping was omitted during surgery. There were no differences in tissue histological score, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, myeloperoxidase (MPO) and TUNEL-positive cell count between all sham-operated rats. Pretreatment with RLX preserved normal tissue morphology, reduced MDA levels, MPO and TUNEL-positive cell count, preserved SOD activity and upregulated NICD and HES1 gene expression when compared to the control group. Pretreatment with EPO reduced MDA levels. In conclusion, pretreatment with RLX, EPO or a combination of both EPO and RLX significantly alleviates uterine tissue damage caused by IRI.

The Impact of Epithelial-Mesenchymal Transition and Metformin on Pancreatic Cancer Chemoresistance: A Pathway towards Individualized Therapy.

Globally, pancreatic ductal adenocarcinoma remains among the most aggressive forms of neoplastic diseases, having a dismal prognostic outcome. Recent findings elucidated that epithelial-mesenchymal transition (EMT) can play an important role in pancreatic tumorigenic processes, as it contributes to the manifestation of malignant proliferative masses, which impede adequate drug delivery. An organized literature search with PubMed, Scopus, Microsoft Academic and the Cochrane library was performed for articles published in English from 2011 to 2021 to review and summarize the latest updates and knowledge on the current understanding of EMT and its implications for tumorigenesis and chemoresistance. Furthermore, in the present paper, we investigate the recent findings on metformin as a possible neoadjuvant chemotherapy agent, which affects EMT progression and potentially provides superior oncological outcomes for PDAC patients. Our main conclusions indicate that selectively suppressing EMT in pancreatic cancer cells has a promising therapeutic utility by selectively targeting the chemotherapy-resistant sub-population of cancer stem cells, inhibiting tumor growth via EMT pathways and thereby improving remission in PDAC patients. Moreover, given that TGF-ß1-driven EMT generates the migration of tumor-initiating cells by directly linking the acquisition of abnormal cellular motility with the maintenance of tumor initiating potency, the chemoprevention of TGF-ß1-induced EMT may have promising clinical applications in the therapeutic management of PDAC outcomes.

Interdisciplinary Approach of Establishing PDAC Resectability: Biochemical, Radiological and NAT Regimen Prognostic Factors-Literature Review.

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal tumors, with a 5-year overall survival rate of less than 10%. To date, curative surgical resection remains the only favorable option for improving patients' survival. However, there is no consensus on which prognostic biochemical, radiological markers or neoadjuvant therapy regimens would benefit patients the most. Materials and Methods: A literature review was performed focusing on overall survival, R0 resection, 30-day mortality, adverse events (AEs), and elevated biomarkers. The electronic databases were searched from 2015 to 2020. Results: We reviewed 22 independent studies. In total, 20 studies were retrospective single- or multi-center reviews, while 2 studies were prospective Phase II trials. Conclusions: Patients with borderline resectable or locally advanced PDAC, who received neoadjuvant therapy (NAT) and surgery, have significantly better survival rates. The CA 19-9 biomarker levels in the neoadjuvant setting should be evaluated and considered as a specific biomarker for tumor resectability and overall survival.

Quantitative Assessment of Liver Impairment in Chronic Viral Hepatitis with [99mTc]Tc-Mebrofenin: A Noninvasive Attempt to Stage Viral Hepatitis-Associated Liver Fibrosis.

Background and objectives-Chronic viral hepatitis B and C infections are one of the leading causes of chronic liver impairment, resulting in liver fibrosis and liver cirrhosis. An early diagnosis with accurate liver fibrosis staging leads to a proper diagnosis, thus tailoring correct treatment. Both invasive and noninvasive techniques are used in the diagnosis and staging of chronic liver impairment. Those techniques include liver biopsy, multiple serological markers (as either single tests or combined panels), and imaging examinations, such as ultrasound or magnetic resonance elastography. Nuclear medicine probes may also be employed in staging liver fibrosis, although the literature scarcely reports this. The purpose of our study was to investigate whether a dynamic liver scintigraphy with [99mTc]Tc-mebrofenin has any value in staging or grading chronic liver damage. Materials and Methods-We prospectively enrolled patients with chronic viral hepatitis B and C infection referred for liver biopsy. All patient underwent dynamic liver scintigraphy with 99mTc-mebrofenin prior to liver biopsy. Dynamic liver scintigraphy was performed immediately after intravenous tracer injection for 30 min scanning time. Multiple scintigraphy parameters were calculated (whole liver lobe and focal area time to peak (TTP), 30 min to peak ratio (30/peak), whole lobe and focal area slope index in 350 s (slope_350). Liver biopsy took place shortly after imaging. Results-We found that many dynamic scintigraphic parameters are positively or negatively associated with different stages of liver fibrosis. The main parameters that showed most value are the ratio between 30 min and the peak of the dynamic curve (30/peak_dex (ratio)), and liver clearance corrected for body surface area and liver area (LCL_m2_dm2 (%/min/m2/dm2)). Conclusions-Our present study proves that conducting dynamic liver scintigraphies with [99mTc]Tc-mebrofenin has potential value in staging liver fibrosis. The benefits of this method, including whole liver imaging and direct imaging of the liver function, provide an advantage over presently used quantitative imaging modalities.

Predictors of Quality of Life Six Years after Curative Colorectal Cancer Surgery: Results of the Prospective Multicenter Study.

Background and objectives: Improving early diagnosis and advances in colorectal cancer (CRC) treatment leads to longer survival of these patients. The purpose of this study was to identify the main surgical factors affecting long-term Quality of life (QoL) among colorectal cancer patients after surgery. Materials and Methods: QoL was prospectively evaluated in patients undergoing elective colorectal cancer resection operations in three CRC surgery centers of Lithuania using EORTC generic (QLQC-30) and disease-specific (QLQ-CR29) questionnaires at the time of preoperative admission and 1, 24, and 72 months after surgery. QoL was evaluated among different patient groups, diagnostic and treatment modalities, disease, and postoperative complications. Non-parametric tests and multivariate logistic regression models were used for statistical analysis. Results: Eighty-eight consecutive CRC patients from three institutions were included in the study over a three-month inclusion period, 42 (47.73%) women and 46 (52.27%) men, mean age 64.2 ± 11.5 years. Most tumors were localized in the sigmoid colon and rectum. The largest number of patients had stage III cancer. Twenty-nine patients died-a 6-year survival rate was 67%. 50 of 59 live patients (84.8%) responded to the questionnaire 6 years after their operation. Evaluating changes in quality of life 72 months after surgery with assessments before surgery, both questionnaire responses revealed good long-term CRC surgical treatment results: improved general and functional scale estimates and decreased symptom scale ratings. The multivariate analysis found that age, stoma formation, and rectal cancer were independent risk factors for having worse QoL six years after surgical intervention. Conclusions: Six years after surgery, QoL returns to preoperative levels. Age, stoma formation, adjuvant treatment, and rectal cancer reduce long-term QoL.

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.