Radical versus Local Surgical Excision for Early Rectal Cancer: A Systematic Review and Meta-Analysis.

Background: Radical excision (RE) for rectal cancer carries a higher risk of mortality and morbidity, while local excision (LE) could decrease these postoperative risks. However, the long-term benefit of LE is still debatable. Aim: To study the effectiveness of LE versus RE in T1 and T2 rectal cancer. Methods: A systematic review and meta-analysis was conducted using key databases like PubMed and ClinicalTrials.gov. Only cohort studies and randomized controlled trials were included. RevMan 5.4 tool was used for data analysis. Both clinical and statistical heterogeneity of the studies were assessed, and I2 >75% was considered as highly heterogeneous. The primary outcomes being measured were 5-year overall survival (OS) and 5-year disease free survival (DFS). A subgroup analysis of patients with T1-only was also conducted, without adjuvant chemo/radiotherapy. Results: A total of 18 studies were included for final meta-analysis. Four were RCTs, while the other 15 were retrospective cohort studies. One included study had data from both RCT and non-RCT study groups. Nine studies were multicentered or national studies while nine were unicentral.There was no difference in risk ratio (RR) between OS: RR 0.95, 95% Confidence Interval (CI) [0.91, 0.99] and DFS: RR 0.93, 95% CI [0.87, 1.01]. There were lower hazards ratios in OS: RR 1.41, 95% CI [1.14, 1.74] and DFS: RR 1.95, 95% CI [1.36, 2.78] with radical, as compared to LE. Lower recurrence rate was associated with RE. Random effect model was used due to clinical heterogeneity between studies (different surgical procedures, tumor staging, adjuvant chemo or radiotherapy). Conclusions: LE for early-stage rectal cancer has lower 5-year OS and DFS than RE, with higher local recurrence rate. However, LE is associated with lower early postoperative mortality, morbidity and length of stay as compared to RE.

Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

The Incidence of Venous Thromboembolism and Practice of Deep Venous Thrombosis Prophylaxis Among Hospitalized Cirrhotic Patients.

Background: Patients with liver cirrhosis have altered hepatic synthetic functions which theoretically result in reduced levels of pro-and anti-coagulant factors as well as thrombocytopenia. Initially, cirrhotic patients were thought to be at an increased risk of bleeding and a reduced risk of thrombosis. Several studies have recently reported an increased occurrence of venous thromboembolism (VTE) in cirrhotic patients. In this study, we aimed to assess the current practice of deep venous thrombosis (DVT) prophylaxis, the incidence and predictors of VTE, and the associated bleeding sequelae in patients with liver cirrhosis. Methods: A retrospective cohort study was performed. We included all adult patients with a diagnosis of liver cirrhosis from January 2010 to June 2019 admitted to the hospital. Our cohort patients were divided into two groups, cirrhotic patients with pharmacological VTE prophylaxis and those with mechanical or no VTE prophylaxis. Results: We included 601 cirrhotic patients in our study. The incidence of VTE occurring within the first 6 months of their admission was 1.5%. Seven patients (1.49%) developed VTE with the majority being DVTs while not on pharmacologic prophylaxis, and two patients developed VTE despite being on pharmacologic prophylaxis; however, there was no statistical difference. Alcohol use was the most common underlying cause of liver cirrhosis (40.4%), followed by chronic hepatitis C (21.1%), and nonalcoholic steatohepatitis (11.3%). Out of the 601 patients included, 69 patients received neither pharmacologic nor mechanical VTE prophylactic agent (11.48%), while the remaining majority received either pharmacological or mechanical prophylaxis (88.52%). Conclusions: Our study did not show a statistically significant association between the use of pharmacological VTE prophylactic agents and a reduction in the risk of VTE in cirrhotic patients. The rates of usage of DVT prophylactic agents among our Northwell hospitals during the study period appeared to be no longer suboptimal when compared to prior studies. Low albumin appears to be a predictor factor to develop VTE. There was a statistically significant increase in bleeding risk and transfusion requirement in cirrhotic patients receiving no pharmacological VTE prophylactic agents. Further prospective trials are needed to shed more light on this subject and identify the group of cirrhotic patients who could safely benefit from pharmacologic VTE prophylaxis.

Upper GI Bleeding Secondary to Radiation Gastritis in a Patient with Preexisting Portal Hypertensive Gastropathy.

We commonly see patients presenting with either portal hypertensive gastropathy (PHG) or radiation gastritis. Radiation-induced hemorrhagic gastritis is an unusual lethal complication postradiation. Patients with preexisting PHG have very friable mucosa that can easily bleed after radiation for cancer treatment. There is an increased risk of bleeding with both entities present together. Our aim is to focus on treatment and possible prevention of gastrointestinal bleeding in patients with preexisting PHG undergoing radiation therapy for newly diagnosed cancer. Several therapies like prednisolone, argon plasma coagulation, laser coagulation have been proposed. There are no set guidelines for treatment. In these patients, if radiation therapy is indicated either for hepatic or gastrointestinal malignancy, it is suggested to premedicate with proton pump inhibitors or sucralfate. We describe a case of 73-year-old female who presented with upper gastrointestinal bleeding. She had liver cirrhosis secondary to nonalcoholic fatty liver disease and diagnosed with pancreatic cancer, for which she received chemoradiation. She was found to have both radiation gastritis and PHG with diffuse erythematous, edematous, congested mucosa with diffuse oozing blood in the antrum making it very challenging to treat.

Guillain-Barré Syndrome as a Presenting Symptom in Breast Cancer: The Importance of Considering Paraneoplastic Neurologic Syndrome.

Paraneoplastic neurological syndromes (PNS) are a group of rare immune-mediated disorders with neurological sequela in cancer patients. It usually occurs when an immune response against a systemic tumor is incorrectly directed to the nervous system. Compared to other reported manifestations of PNS in breast cancer, Guillain Barre syndrome (GBS) is exceedingly rare. There is only one other reported case in the literature of GBS that was diagnosed in a breast cancer patient. We report the second recorded case of a 61-year-old female with a history of early-stage breast cancer, who presented with symptoms of lower extremity weakness initially suspected to be GBS but later found to have been recurrent breast cancer. No specific guidelines are available for the treatment of PNS. Treatment of underlying malignancy with chemotherapy and immunotherapies are usually recommended.

Delayed anaphylaxis due to gadolinium- A rare clinical scenario.

Acute respiratory distress syndrome is a sudden in onset, diffuse inflammatory form of lung injury which may be associated with a variety of etiologies such as pneumonia, sepsis, aspiration, and severe trauma. Prompt recognition and treatment of acute respiratory distress syndrome is critical to reduce the associated high mortality. Severe lung injury presenting as acute respiratory distress syndrome secondary to gadolinium contrast media (gadobutrol) is rarely reported. We describe an interesting case of a 47-year-old woman who presented to the emergency department with acute respiratory failure after gadolinium administration. She was diagnosed with acute respiratory distress syndrome, was admitted to the intensive care unit due to requiring mechanical ventilation. Her condition improved with epinephrine and steroids and she was successfully extubated and discharged from the hospital in one week.

Is COVID-19 an Independent Risk Factor for Heparin-Induced Thrombocytopenia?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral respiratory illness initially described in Wuhan, China, and was declared a pandemic by World Health Organization (WHO) in 2020, and the disease is named coronavirus disease (COVID-19). SARS-CoV2 is known to cause fever, cough, fatigue, and acute respiratory distress syndrome. As more patients become infected, extrapulmonary manifestations came to rise and hypercoagulability is one among those. COVID-19 could predispose patients to both venous and arterial thromboembolic events which are commonly treated with unfractionated heparin or low molecular weight heparin (LMWH). The treatment of patients who develop heparin-induced thrombocytopenia (HIT) while being treated with heparin or LMWH for COVID-induced thromboembolic complications is challenging. We describe a patient admitted to the hospital with COVID-19 pneumonia, found to have a cerebrovascular event treated with unfractionated heparin. She also received therapeutic LMWH for anticoagulation on day 1 of presentation due to atrial fibrillation. She was diagnosed with HIT and was found to have a pulmonary embolism, aortic arch mural thrombus, and arterial thrombi in the lower extremities. As more recent studies showed HIT antibodies in COVID-19 patients who are naive for heparin-based products, COVID-19 may be an independent risk factor for the development of HIT. The role of COVID-19 in the development of HIT is uncertain. High vigilance is required to diagnose and initiate treatment for HIT early in the disease course as it can be life-threatening.

Coinfection of Helicobacter pylori and Hepatitis C Virus in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) and hepatocellular carcinoma (HCC) was firstly proposed in 1994 after Ward et al demonstrated the role of Helicobacter hepaticus in the development of HCC in mice. Studies also investigated the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) coexisting with H. pylori in causing HCC. A causal relationship was never confirmed, and the relationship remains controversial. This meta-analysis aimed to summarize the research on this topic and investigate if a relationship exists between H. pylori infection and the development of HCC and if the presence of HCV and HBV along with H. pylori plays a role in liver carcinogenesis. METHODS: Following PRISMA guidelines, we performed a systematic review of all relevant studies published in the literature using the keywords "Helicobacter pylori" and "hepatocellular carcinoma" on major literature databases, including PubMed, EMBASE, Web of Science, and Cochrane controlled trials register. A total of 656 research studies were identified between 1994 and 2020. Of those, 26 qualified under our selection criteria. Patients who were positive for HCC were classified as cases and those who did not have HCC were classified as controls. The H. pylori status and HCV status, if available, were identified for both groups. Statistical analysis was carried out by a biostatistician according to the Cochrane reviewer's handbook. RESULTS: Out of the 26 studies included in the final analysis, 13 were retrospective case-control studies, 11 were cross-sectional studies, and two were prospective case-control and cohort studies. Overall, the prevalence of H. pylori infection was 64.78% (561 of 866) amongst HCC cases and 47.92% (1,718 of 3,585) in the non-HCC control group. The summary odds ratio (OR) for the association of H. pylori infection with the risk for HCC (using the random-effects model, which accounted for the heterogeneity across the 26 studies) was determined to be 4.75 (95% confidence interval (CI): 3.06 - 7.37, I2 = 63%). We also performed a subgroup analysis to determine the odds of developing HCC in the presence of H. pylori and HCV coinfection. The summary OR of it was 12.76 (95% CI: 4.13 - 39.41, I2 = 78%). The summary OR for the risk of developing HCC in the presence of HCV infection without H. pylori infection was 2.21 (95% CI: 0.70 - 6.94, I2 = 79%). Whereas, the odds of developing HCC in the presence of only H. pylori infection without HCV was found to be 0.54 (95% CI: 0.11 - 2.63, I2 = 80%). There was inconsistency in the data presented in some studies regarding HCV infection status. Since data were extracted from different study designs, subgroup analysis by study design was performed which showed no significant difference between the study groups (P = 0.5705). CONCLUSION: This meta-analysis demonstrates a positive association between H. pylori infection and the development of HCC. There is a significantly higher risk of developing HCC in the presence of HCV infection along with H. pylori. Further prospective cohort studies are needed to prove the causal relationship, especially in cases of HBV and HCV coinfection, and cirrhotic patients.

An Emphasis on Screening to Detect Liver Cirrhosis and Hepatocellular Carcinoma in Patients Having Undergone the Fontan Procedure in Early Childhood.

The Fontan procedure is a surgical procedure for patients with single-ventricle anatomy that results in the flow of systemic venous blood to the lungs without passing through a ventricle. Before the 1970s, most children with single-ventricle anatomy failed to survive into adulthood. With the introduction of the Fontan procedure, and its many modifications, the survival rate of these patients improved exponentially. With patients surviving longer, complications from this procedure are being documented for the first time. Cardiovascular complications are expected early on and are well studied. More serious are the non-cardiovascular complications in patients who survive into adulthood. The biggest entity is Fontan-associated liver disease (FALD) which needs thorough monitoring to screen for hepatocellular carcinoma (HCC). FALD includes chronic passive congestion, liver cirrhosis, and HCC. Once cirrhosis develops, monitoring with annual liver function tests, AFP, and abdominal ultrasonography need to occur to screen for HCC. Patients may need to be evaluated for combined heart-liver transplantation. Strict guidelines need to be developed for monitoring and surveillance of these patients to prevent late-stage complications. Herein, we report a unique case of FALD in a young female presenting two decades after the procedure with variceal bleeding.