Epigenetic age oscillates during the day.

Since their introduction, epigenetic clocks have been extensively used in aging, human disease, and rejuvenation studies. In this article, we report an intriguing pattern: epigenetic age predictions display a 24-h periodicity. We tested a circadian blood sample collection using 17 epigenetic clocks addressing different aspects of aging. Thirteen clocks exhibited significant oscillations with the youngest and oldest age estimates around midnight and noon, respectively. In addition, daily oscillations were consistent with the changes of epigenetic age across different times of day observed in an independant populational dataset. While these oscillations can in part be attributed to variations in white blood cell type composition, cell count correction methods might not fully resolve the issue. Furthermore, some epigenetic clocks exhibited 24-h periodicity even in the purified fraction of neutrophils pointing at plausible contributions of intracellular epigenomic oscillations. Evidence for circadian variation in epigenetic clocks emphasizes the importance of the time-of-day for obtaining accurate estimates of epigenetic age.

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).

Changes of Colorectal Cancer Diagnostics and Hospitalizations during First Wave of COVID-19 Pandemic in Lithuania.

Purpose: Our aim was to see the possible effect of the first COVID pandemic wave in Lithuania on colorectal cancer (CRC) preventive, diagnostic and treatment procedures. Methods: A retrospective analysis was performed using the database of the National Cancer Institute, Lithuania. We have divided patients into two groups: group 1 - patients treated during the nonpandemic period (2019 January 1 to 2019 July 31) and group 2 - the pandemic period (2020 January 1 to 2020 July 31). We analyzed numbers of screening, therapeutic colonoscopies performed, and treated patients for CRC during two periods. Results: In general, 1318 lower gastrointestinal endoscopic procedures were performed in the first group and 862 procedures in the second group, which was 34.6% less compared to the first group. The first group included 672 (51%) colonoscopies, 172 (13%) day surgeries and 474 (36%) CRC screening programmes. In group 2, 456 (34.6%) less patients underwent CRC diagnostics and treatment: 141 (21%) less colonoscopies, 93 (54%) less day surgeries, 222 (47%) less CRC screening programmes, and 26 (13%) less patients were hospitalized for surgical treatment (196 vs 170). Conclusion: Our study reveals worrying changes in the timely access to diagnostic procedures during the COVID-19 pandemic that possibly provoked rise in cases with the advanced stage CRC. However, despite numerical difference between groups existed, the difference between groups do not reach statistical significant level.

The 2022 European Society of Coloproctology (ESCP) global snapshot audit of faecal incontinence: Study protocol.

AIM: Faecal incontinence (FI) is a common problem, affecting about 9% of Western populations. However, only a few patients seek consultation and the number of such patients reaching hospital care is unknown. Current treatment pathways are poorly evidence based and are thought to vary greatly between different countries. This audit will study the incidence of patients presenting to coloproctologists with FI, current practice including diagnostics, conservative and surgical techniques across different units in Europe and worldwide. The aim is to explore the incidence of FI in patients attending colorectal surgical clinics, treatment choices and accessibility to diagnostic tools/advanced treatments across the international cohort. Outcomes to be measured include the volume of FI patients consulting clinical practice per surgeon, patient demographics, and diagnostics and intervention details. METHOD: An international multicentre snapshot audit will be performed. During the study period all consecutive eligible patients will be included over an 8-week period between 9 January and 28 February. Data will be entered and saved in a Research Electronic Data Capture secured database. Moreover, two short physician and centre-level surveys will be filled for current practice evaluation. The results will be published in international journals and will be prepared in accordance with guidelines set by the STROBE (strengthening the reporting of observational studies in epidemiology) statement for observational studies. DISCUSSION: This multicentre, global prospective audit will be delivered by consultant colorectal and general surgeons as well as trainees. The data obtained will lead to a better understanding of the incidence of FI and treatment and diagnostic possibilities. This snapshot audit will be hypothesis generating and inform areas that need future prospective study.

Primary tumor resection in colorectal cancer patients with unresectable distant metastases: a minireview.

Colorectal cancer (CRC) is the second most common cause of cancer-related death among both men and women worldwide and the third most common cancer overall. About 20% of patients diagnosed with CRC were discovered to have distant metastatic lesions, the majority of which were located in the liver. For the optimum treatment of CRC patients with hepatic metastases, interventional radiologists, medical oncologists, and surgeons must all collaborate. The surgical excision of the primary tumor is an important part of CRC treatment since it has been found to be curative in cases of CRC with minimal metastases. However, given the evidence to date was gathered from retrospective data, there is still controversy over the effectiveness of primary tumor resection (PTR) in improving the median overall survival (OS) and quality of life. Patients who have hepatic metastases make up a very tiny fraction of those who are candidates for resection. With a focus on the PTR, this minireview attempted to review the current advancements in the treatment options for hepatic colorectal metastatic illness. This evaluation also included information on PTR's risks when performed on individuals with stage IV CRC.

Incidence, Mortality, and Survival Trends in Cancer of the Gallbladder and Extrahepatic Bile Ducts in Lithuania.

Background and Objectives: Gallbladder cancer is a rare type of cancer, with aggressive clinical behavior. Limited treatment options provide poor survival prognosis. We aimed to investigate the incidence, mortality trends, and survival of gallbladder and extrahepatic bile duct cancer in Lithuania between 1998 and 2017. Materials and Methods: The study was based on the Lithuanian Cancer Registry database. The study included all cases of cancer of the gallbladder and extrahepatic bile ducts reported to the Registry in the period 1998-2017. Age-specific and age-standardized incidence rates were calculated. In addition, 95% confidence intervals for APC (Annual Percent Change) were calculated. Changes were considered statistically significant if p was <0.05. Relative survival estimates were calculated using period analysis according to the Ederer II method. Results: Age-standardized rates for gallbladder cancer and extrahepatic bile duct cancer among females decreased from 3.91 to 1.93 cases per 100.000 individuals between 1998 and 2017, and from 2.32 to 1.59 cases per 100.000 individuals between 1998 and 2017 among males. The highest incidence rates were found in the 85+ group with 27.5/100,000 individuals in females and 26.8/100,000 individuals in males. The 1-year as well as 5-year relative survival rates of both genders were 34.29% (95% CI 32.12-36.48) and 16.29% (95% CI 14.40-18.27), respectively. Conclusions: Incidence and mortality from gallbladder and extrahepatic bile duct cancer decreased in both sexes in Lithuania. Incidence and mortality rates were higher in females than in males. Relative 1-year and 5-year survival rates showed a steady increase during the study period among males and females.

Evaluation, management and future perspectives of anal pruritus: a narrative review.

PURPOSE: The without a time limitation. Most recent search was performed on 1st June 2022. RESULTS: Thorough history and physical examination are very important in view of multiple possible causes of anal pruritus. Most of the focus during examination is drawn on to the perianal region. A digital rectal examination and an anoscopy are essential. It is necessary aim of this narrative review is to overview the classification, diagnostics, possible treatment options and future perspective of anal pruritus. METHODS: The search was performed by two authors (AD and MJ) independently in the following electronic databases: PubMed, EMBASE, Web of Science, Cochrane Library, CENTRAL and the Allied and Complementary Medicine Databases (AMED). Search was restricted to English language only to avoid moisture and the use of soaps in the perianal region. Furthermore, the patient should avoid certain foods and increase the intake of fiber. If the symptoms do not resolve, topical steroids, capsaicin (0.006%) and tacrolimus (0.1%) ointments may be used. For intractable cases, intradermal methylene blue injection might give a long-lasting symptom relief. CONCLUSION: Anal pruritus is a long-term deteriorating quality of life issue. Most of the time it is a symptom with a difficult diagnosis. Thorough history and examination should be performed for the best possible treatment.

International Society of University Colon and Rectal Surgeons survey of surgeons' preference on rectal cancer treatment.

PURPOSE: Rectal cancer treatment has a wide range of possible approaches from radical extirpative surgery to nonoperative watchful waiting following chemoradiotherapy, with or without, additional chemotherapy. Our goal was to assess the personal opinion of active practicing surgeons on rectal cancer treatment if he/she was the patient. METHODS: A panel of the International Society of University Colon and Rectal Surgeons (ISUCRS) selected 10 questions that were included in a questionnaire that included other items including demographics. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in our database and remained open from April 16 to 28, 2020. RESULTS: One hundred sixty-three specialists completed the survey. The majority of surgeons (n=65, 39.9%) chose the minimally invasive (laparoscopic) surgery for their personal treatment of rectal cancer. For low-lying rectal cancer T1 and T2, the treatment choice was standard chemoradiation+local excision (n=60, 36.8%) followed by local excision±chemoradiotherapy if needed (n=55, 33.7%). In regards to locally advanced low rectal cancer T3 or greater, the preference of the responders was for laparoscopic surgery (n=65, 39.9%). We found a statistically significant relationship between surgeons' age and their preference for minimally invasive techniques demonstrating an age-based bias on senior surgeons' inclination toward open approach. CONCLUSION: Our survey reveals an age-based preference by surgeons for minimally invasive surgical techniques as well as organ-preserving techniques for personal treatment of treating rectal cancer. Only 1/4 of specialists do adhere to the international guidelines for treating early rectal cancer.

Surviving rectal cancer at the cost of a colostomy: global survey of long-term health-related quality of life in 10 countries.

BACKGROUND: Colorectal cancer management may require an ostomy formation; however, a stoma may negatively impact health-related quality of life (HRQoL). This study aimed to compare generic and stoma-specific HRQoL in patients with a permanent colostomy after rectal cancer across different countries. METHOD: A cross-sectional cohorts of patients with a colostomy after rectal cancer in Denmark, Sweden, Spain, the Netherlands, China, Portugal, Australia, Lithuania, Egypt, and Israel were invited to complete questionnaires regarding demographic and socioeconomic factors along with the Colostomy Impact (CI) score, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and five anchor questions assessing colostomy impact on HRQoL. The background characteristics of the cohorts from each country were compared and generic HRQoL was measured with the EORTC QLQ-C30 presented for the total cohort. Results were compared with normative data of reference European populations. The predictors of reduced HRQoL were investigated by multivariable logistic regression, including demographic and socioeconomic factors and stoma-related problems. RESULTS: A total of 2557 patients were included. Response rates varied between 51-93 per cent. Mean time from stoma creation was 2.5-6.2 (range 1.1-39.2) years. A total of 25.8 per cent of patients reported that their colostomy impairs their HRQoL 'some'/'a lot'. This group had significantly unfavourable scores across all EORTC subscales compared with patients reporting 'no'/'a little' impaired HRQoL. Generic HRQoL differed significantly between countries, but resembled the HRQoL of reference populations. Multivariable logistic regression showed that stoma dysfunction, including high CI score (OR 3.32), financial burden from the stoma (OR 1.98), unemployment (OR 2.74), being single/widowed (OR 1.35) and young age (OR 1.01 per year) predicted reduced stoma-related HRQoL. CONCLUSION: Overall HRQoL is preserved in patients with a colostomy after rectal cancer, but a quarter of the patients interviewed reported impaired HRQoL. Differences among several countries were reported and socioeconomic factors correlated with reduced quality of life.

Imaging standardisation in metastatic colorectal cancer: A joint EORTC-ESOI-ESGAR expert consensus recommendation.

BACKGROUND: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points. PATIENTS AND METHODS: Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. RESULTS: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. CONCLUSION: This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.

The Effect of comprehensive rehabilitation on Lithuanian adolescent's nonspecific low back pain, depending on the duration: Nonrandomized single-arm trial.

OBJECTIVE: To determine pain and functional changes during comprehensive rehabilitation (CR) in adolescents with nonspecific low back pain (NLBP), and to determine the optimal CR duration. METHODS: The study included 106 adolescents (39 boys [36.8%], 67 girls [63.2%]), 14 to17 years old, with the following inclusion criteria: duration of NLBP for at least 12 weeks; conservative NLBP treatment was effectless; pain intensity using the visual analogue pain scale (VAS) ≤ 7 points; disrupted daily activities; ability to understand and answer the questions; written consent to participate voluntarily in the study. The pain was assessed using the VAS scale, functional changes were assessed using the Oswestry Disability Index (ODI), 12-Item Short Form Survey, Hospital Anxiety and Depression Scale (HAD), and physical functional capacity and proprioception (Proprio) were assessed using an isokinetic dynamometer. The participants performed a comprehensive pain rehabilitation program consisting of physiotherapy, TENS, magnetotherapy, lumbar massage, and relaxing vibroacoustic therapy. The active CR cycle lasted for 22 sessions (with intermediate measurements after 5 and 16 sessions), after which we performed passive observation for another half a year. Five measurements were performed. RESULTS: Pain, functional assessment, and physical capacity were improved with CR. Statistically significant improvement became apparent after 5 CR sessions, but statistical and clinical significance became apparent after 16 CR sessions. In the distant period, after the completion of CR, neither statistical nor clinical changes occurred. CONCLUSIONS: CR is effective in reducing pain, and improving functional state and physical capacity quickly and reliably in 16 CR sessions, which is sufficient to obtain clinically satisfactory CR results. Good results were achieved during CR and neither improved nor deteriorated spontaneously in the distant period. This study shows a possible mismatch between NLBP intensity and impaired functional state in adolescents.

Cutaneous Melanoma with Tonsillar Metastasis: Treatment with Cryoablation.

Metastasis of cutaneous melanoma to the oral cavity is a rare condition. Male patient with cutaneous melanoma metastasis to right tonsil 2 years after radical skin lesion resection was treated with surgery: tonsillectomy and later resection of soft palate were performed. Two years later the patient was diagnosed with progressive disease to right tonsil and soft palate. Rapid inoperable relapse was detected six months later. The patient underwent two procedures of palliative cryoablation of the metastasis. Postoperative course was uneventful. Patient died 7 months later due to progression of the disease. Cryoablation alone or together with surgery may be a relatively safe option for treatment of inoperable disease of head and neck tumours.

Anastomotic Leak Impact on Long-Term Survival after Right Colectomy for Cancer: A Propensity-Score-Matched Analysis.

Our goal was to assess the impact of anastomotic leaks (ALs) on oncologic outcomes using a case-matched analysis. Patients undergoing right hemicolectomy for cancer between 2014 and 2018 were included. The main variables were the risk factor of anastomotic leak, overall survival and disease-free survival. Propensity score matching was performed according to the patient's age, co-morbidities and TNM staging as well as the type of procedure. Oncologic outcomes were analyzed. We included 488 patients and performed final analysis on 69 patients. The AL rate was 4.71% (23 patients). Intrahospital mortality was significantly higher in the AL group, at 1.3% (6 of 465) vs. 8.7% (2 of 23), p = 0.05. Three-year overall survival (OS) in the non-AL group was higher, although the difference could not be considered significant (71.5% vs. 37.3%, p = 0.082); similarly, the likelihood for impaired 3-year progression-free survival (PFS) was lower, but the difference here could also not be considered significant (69.3% vs. 37.3%, p = 0.106). Age, advanced tumor stage, lymph node metastases and distant metastases were associated with higher probability of death or recurrence of disease. In contrast, minimally invasive surgery was associated with lower probability of death (HR (95% CI): 0.99 (0.14-0.72); p = 0.023) and recurrence of disease (HR (95% CI): 0.94 (0.13-0.68); p = 0.020). In an adjusted Cox regression analysis, AL, age and distant metastases were associated with poor long-term survival. Moreover, AL, age and distant metastases were associated with higher probability of recurrence of disease. Based on our results, AL is a significant factor for worse oncologic outcomes. Simple summary: we aimed to assess patients with anastomotic leaks following right hemicolectomy for cancer. These patients were matched to patients without leaks. Propensity score analysis demonstrated that anastomotic leak was a marker of worse oncologic outcomes.

Low Anterior Resection Syndrome: What Have We Learned Assessing a Large Population?

Our goal was to assess the rate of symptoms commonly included in LARS score in a large general population. The study was based on a population-based design. We disseminated LARS scores through community online platforms and general practitioners throughout Lithuania. We received 8183 responses to the questionnaire. There were 142 (1.74%) participants who were excluded for lack of information. There were 6100 (75.9%) females and 1941 (24.1%) males. After adjusting for sex and age, male participants had a significant average score of 18.4 (SD ± 10.35) and female 20.3 (SD ± 9.74) p < 0.001. There were 36.4% of participants who had minor LARS symptoms, and 14.2% who had major LARS symptoms. Overall, major LARS-related symptoms were significantly related to previous operations: 863 participants in the operated group (71.7%), and 340 in the non-operated group (28.3%; p0.001). In 51−75-year-old patients, major LARS was significantly more prevalent with 22.7% (p < 0.001) and increasing with age, with a higher incidence of females after the age of 75. After excluding colorectal and perineal procedures, the results of multivariate logistic regression analysis indicated the use of neurological drugs and gynaecological operations were independent risk factors for major LARS−odd ratio of 1.6 (p = 0.018, SI 1.2−2.1) and 1.28 (p = 0.018, SI 1.07−1.53), respectively. The symptoms included in the LARS score are common in the general population, and there is a variety of factors that influence this, including previous surgeries, age, sex, comorbidities, and medication. These factors should be considered when interpreting the LARS score following low anterior resection and when considering treatment options preoperatively.

Hand Assisted Laparoscopic Surgery for Colorectal Cancer: Surgical and Oncological Outcomes from a Single Tertiary Referral Centre.

The aim of this study was to report overall experience, perioperative and long-term survival results in a single tertiary referral center in Lithuania with hand assisted laparoscopic surgery (HALS) for colorectal cancer. A prospectively maintained database included 467 patients who underwent HALS for left-sided colon and rectal cancer, from April 2006 to October 2016. All those operations were performed by three consultant surgeons and nine surgical residents, in all cases assisted by one of the same consultant surgeons. There were 230 (49.25%) females, with an average age of 64 ± 9.7 years (range, 26-91 years). The procedures performed included 170 (36.4%) anterior rectal resections with partial mesorectal excision, 160 (34.26%) sigmoid colectomies, 81 (17.35%) left hemicolectomies, 45 (9.64%) low anterior rectal resections with total mesorectal excision, and 11 (2.25%) other procedures. Stage I colorectal cancer was found in 140 (29.98%) patients, 139 (29.76%) stage II, 152 (32.55%) stage III and 36 (7.71%) stage IV. There were five conversions to open surgery (1.1%). The mean postoperative hospital stay was 6.9 ± 3.4 days (range, 1-30 days). In total, 33 (7.06%) patients developed postoperative complications. The most common complications were small bowel obstruction (n = 6), anastomotic leakage (n = 5), intraabdominal abscess (n = 4) and dysuria (n = 4). There were two postoperative deaths (0.43%). Overall, 5-year survival for all TNM stages was 85.7%, 93.2% for stage I, 88.5% for stage II and 76.3% for stage III. Hand assisted colorectal surgery for left-sided colon and rectal cancer in a single tertiary referral center was feasible and safe, having all the advantages of minimally invasive surgery, with good perioperative parameters, adequate oncological quality and excellent survival.

Tissue-Based Markers as a Tool to Assess Response to Neoadjuvant Radiotherapy in Rectal Cancer-Systematic Review.

According to current guidelines, the current treatment for locally advanced rectal cancer is neoadjuvant therapy, followed by a total mesorectal excision. However, radiosensitivity tends to differ among patients due to tumor heterogeneity, making it difficult to predict the possible outcomes of the neoadjuvant therapy. This review aims to investigate different types of tissue-based biomarkers and their capability of predicting tumor response to neoadjuvant therapy in patients with locally advanced rectal cancer. We identified 169 abstracts in NCBI PubMed, selected 48 reports considered to meet inclusion criteria and performed this systematic review. Multiple classes of molecular biomarkers, such as proteins, DNA, micro-RNA or tumor immune microenvironment, were studied as potential predictors for rectal cancer response; nonetheless, no literature to date has provided enough sufficient evidence for any of them to be introduced into clinical practice.

A Case Report and Review of the Literature of Penile Metastasis From Rectal Cancer.

Background: Metastatic involvement of the penis in cases of rectal cancer is exceptionally rare condition. Our clinical case report and review of the literature will contribute in complementing currently limited data on penile metastasis from rectal cancer. Case report: We report a case of a 64-year-old male diagnosed with penile metastasis from rectal cancer. The patient was treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME). However, penile metastasis developed 3 years later, clinically presenting as penile pain and solid formations along the entire length of the penis with visible tumor in the head of the penis. The amputation of penis was performed, and adjuvant chemotherapy was prescribed. The patient survived only 6 months. Conclusion: Penile metastasis from rectal cancer in most cases is a lethal pathology that indicates wide dissemination of oncological disease and has a very poor prognosis. Aggressive surgical treatment is doubtful in metastatic disease as this will negatively affect the quality of life.