Outcomes of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma: A tertiary center experience.

Objective: To assess the overall survival in patients with intermediate stage hepatocellular carcinoma following transarterial chemoembolization. Methods: It is a retrospective descriptive study carried out in the Department of Radiology of Liaquat National Hospital Karachi, Pakistan. Seventy-two patients were enrolled from July 2014 to December 2021 and had chemoembolization therapy. Patients were followed till their demise. Mean and Median survivals were calculated. Results: A total of 72 patients had a median survival of 15 months with 95% confidence interval (11 months was lower bound and 18 months was upper bound), 19 months was the mean survival time with 95% confidence interval (14.7 months was lower limit and 22.6 months the upper limit). The factors which had a significant impact on the median survival time were Child-Pugh classification, average size of tumor and embolization pattern. Conclusion: Transarterial chemoembolization (TACE) increases the median survival time effectively and safely in patients with hepatocellular carcinoma. However complete resolution of disease is not possible with TACE, with most patient eventually succumbing to the disease. The overall survival for TACE in this study correlates well with other studies. Child Pugh Class, tumor size and embolization pattern have significant effect on survival of patients.

One-Hour Bundle Protocols for Surgical Sepsis and Septic Shock in Surgical Intensive Care Unit: Clinical Outcome Aspects in the Thai Context.

BACKGROUND: Surgical sepsis is a syndrome occurring during the perioperative period with a high mortality rate. Since the one-hour bundle protocol was recommended to decrease sepsis-related morbidity and mortality in clinical practice, the protocol has been applied to surgical patients with sepsis and septic shock. However, clinical outcomes in these surgical patients remain unknown. Thus, this study aimed to compare survival outcomes in patients before and after the implementation of one-hour bundle care in clinical practice. METHODS: In this prospective cohort study, 401 surgical patients with sepsis were divided into two groups, with 195 patients undergoing the one-hour bundle from December 25, 2021, to March 31, 2024, and 206 patients undergoing usual care from January 1, 2018, to December 24, 2021, before the one-hour bundle protocol was implemented by the Surviving Sepsis Campaign (SSC). Demographic data, treatment processes, and clinical outcomes were recorded. RESULTS: After the one-hour bundle protocol was applied in surgical practice, the median survival time was significantly increased in surgical patients who underwent one-hour bundle care (95% confidence interval (CI): 12.32-19.68) (p= 0.016). Factors influencing the increase in the mortality rate were delays in fluid resuscitation of >2 hours, vasopressor initiation of >2 hours, and empirical antibiotics of >5 hours (p= 0.017, 0.028, and 0.008, respectively). CONCLUSION: One-hour bundle care for surgical patients with sepsis resulted in an increased median survival time. Delays in fluid resuscitation (>2 hours), vasopressor initiation (>2 hours), and empirical antibiotics (>5 hours) were factors associated with mortality.

Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.

BACKGROUND: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). OBJECTIVE: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA. METHODS: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites. RESULTS: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037). CONCLUSION: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.

Debulking Hepatectomy for Colorectal Liver Metastasis Conveys Survival Benefit.

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan-Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial.

Mortality in French people with polyhandicap/profound intellectual and multiple disabilities.

BACKGROUND: In recent decades, progress has been made in the care of people with polyhandicap/profound intellectual and multiple disabilities (PIMD) through a better understanding of the pathophysiology and the development of new care management and rehabilitation strategies adapted to these extreme pathologies. Although there is a lack of knowledge about the health status and care management of the oldest people, a better understanding of the natural course of life of people with polyhandicap/PIMD would consequently allow the optimisation of preventive and curative care management strategies. Few robust data on mortality and life expectancy have been documented for this population in France. Our aims are to estimate the median survival time and assess the factors associated with mortality in people with polyhandicap/PIMD receiving care in France. METHODS: This study included people with polyhandicap/PIMD, followed by the French national cohort 'Eval-PLH' since 2015. These individuals were included in specialised rehabilitation centres and residential institutions. The people included in the first wave of the cohort (2015-2016) were eligible for the present study. Vital status on 1 January 2022 (censoring date) was collected in two ways: (1) spontaneous reporting by the participating centre to the coordinating team and (2) systematic checking on the French national death platform. According to the vital status, survival was calculated in years from the date of birth to the date of death or from the date of birth to the censoring date. The factors associated with mortality were evaluated using the Cox proportional regression hazards model. RESULTS: Data from 780 individuals aged between 3 and 67 years were analysed. At the censoring date, 176 (22.6%) had died, and the mean survival was 52.8 years (95% confidence interval: 51.1-54.5). Mortality was significantly associated with a progressive aetiology, recurrent pulmonary infections, drug-resistant epilepsy and a higher number of medical devices. CONCLUSIONS: This study shows for the first time the survival and impact of factors associated with mortality in people with polyhandicap/PIMD in France.

Improvement of Midpoint Imputation for Estimation of Median Survival Time for Interval-Censored Time-to-Event Data.

BACKGROUND: Progression-free survival (PFS) is used to evaluate treatment effects in cancer clinical trials. Disease progression (DP) in patients is typically determined by radiological testing at several scheduled tumor-assessment time points. This produces a discrepancy between the true progression time and the observed progression time. When the observed progression time is considered as the true progression time, a positively biased PFS is obtained for some patients, and the estimated survival function derived by the Kaplan-Meier method is also biased. METHODS: While the midpoint imputation method is available and replaces interval-censored data with midpoint data, it unrealistically assumes that several DPs occur at the same time point when several DPs are observed within the same tumor-assessment interval. We enhanced the midpoint imputation method by replacing interval-censored data with equally spaced timepoint data based on the number of observed interval-censored data within the same tumor-assessment interval. RESULTS: The root mean square error of the median of the enhanced method is almost always smaller than that of the midpoint imputation regardless of the tumor-assessment frequency. The coverage probability of the enhanced method is close to the nominal confidence level of 95% in most scenarios. CONCLUSION: We believe that the enhanced method, which builds upon the midpoint imputation method, is more effective than the midpoint imputation method itself.

Colorectal cancer metastasis to the thyroid: A case report and review of the literature.

Metastatic thyroid cancer is rare. Here, the case of a patient with colon cancer that metastasized to the thyroid is described. The patient underwent radical rectal cancer surgery in August 2017 and received six cycles of chemotherapy with oxaliplatin and capecitabine postoperatively. On August 4, 2018, the patient was admitted to the hospital due to the discovery of thyroid nodules on ultrasound and carcinoembryonic antigen levels within the normal range. The biopsy from the fine needle aspiration suggested a malignant tumor. The patient underwent radical thyroid cancer surgery. Using intraoperative rapid frozen pathology, medullary carcinoma was diagnosed. Using postoperative routine pathology combined with immunohistochemistry results, thyroid metastasis from colorectal adenocarcinoma was diagnosed. After surgery, the patient regularly visited the outpatient clinic for chemotherapy with capecitabine. As of May 2023, the patient is still alive with no recurrence.

A Preliminary Study Indicating Improvement in the Median Survival Time of Glioblastoma Multiforme Patients by the Application of Deuterium Depletion in Combination with Conventional Therapy.

Glioblastoma multiforme (GBM) and malignant gliomas are the most common primary malignant brain tumors. Temozolomide (TMZ) chemotherapy plus radiation therapy (RT), admi-mistered after debulking surgery, increased the median survival time (MST) from 12.1 months with RT alone merely to 14.6 months, respectively. In this study, the actions of deuterium-depleted water (DDW) on the survival of GBM patients who also received conventional therapies was investigated. Without changing the conventional treatment, the daily fluid intake of the patients was wholly replaced with DDW in 1.5-2 L per day volume to reduce the D concentration in their bodies. The primary endpoint was the MST. The 55 patients involved in this study, who received conventional treatment and consumed DDW, showed a longer MST (30 months) compared to the historical control (12.1-14.6 months). There was a massive difference between the two genders in the calculated MST values; it was 25 months in the male subgroup (n = 33) and 42 months in the female subgroup (n = 22), respectively. The MST was 27 months without TMZ treatment (38 patients) and 42 months in the TMZ-treated group (17 patients), respectively. For the selected 31 patients, who consumed DDW in the correct way in addition to their conventional treatments, their MST was calculated as 30 months. Within this group, the 20 subjects who had relapsed before DDW treatment had 30 months of MST, but in those 10 subjects who were in remission when DDW treatment started, their MST was 47 months. In the subgroup of patients who began their DDW treatment parallel with radiotherapy, their MST was again 47 months, and it was 25 months when their DDW treatment was started at 8 weeks or later after the completion of radiotherapy. Altogether, these survival times were substantially prolonged compared to the prospective clinical data of patients with primary GBM. Consequently, if conventional therapies are supplemented with D depletion, better survival can be achieved in the advanced stage of GBM than with the known targeted or combination therapies. Application of DDW is recommended in all stages of the disease before surgery and in parallel with radiotherapy, and repeated DDW courses are advised when remission has been achieved.

Effect of surgical treatment on patients with stage T3 or T4 triple-negative breast cancer: a SEER-based retrospective observational study.

Background: The use of surgery is controversial in patients with stage T3 or T4 triple-negative breast cancer (TNBC). We aimed to explore the effect of surgical treatment on overall survival (OS) of these patients. Methods: A total of 2,041 patients were selected and divided into the surgical and non-surgical groups based on the Surveillance, Epidemiology, and End Results database from 2010 to 2018. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to balance covariates between different groups. The OS of the two groups were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression models. Results: A total of 2,041 patients were included in the study. After PSM and IPTW, baseline characteristics of the matched variables were fully balanced. Kaplan-Meier survival curves showed that the median survival time and OS of TNBC patients with stage T3 or T4 in the surgical group were significantly improved compared with those in the non-surgical group. Multivariate Cox proportional hazards regression analysis showed that surgery was a protective factor for prognosis. Conclusion: Our study found that surgery prolonged the median survival and improved OS compared with the non-surgical group of TNBC patients with stage T3 or T4.

Resectability and prognosis of gallbladder cancer: a cross-sectional study of 100 cases from a tertiary care centre of Eastern Nepal.

Gallbladder cancer (GBC) is the fifth most common neoplasm of the digestive tract and has an overall incidence of 3 per 100 000 people. Only 15-47% of the preoperatively known GBC are suitable for resection. The objective of the study was to investigate the resectability and prognosis of GBC patients. Materials and methods: It is a prospective observational study including all cases of primary cancers of the gallbladder in the Department of Surgical Gastroenterology at a tertiary care center over the period from January 2014 to December 2019. The primary endpoint was resectability and overall survival. Results: During the study period, 100 patients with GBC were reported. The mean age at the time of diagnosis was 52.5 years, with a female predominance (67%). The curative intent resection (radical cholecystectomy) was possible in 30 (30%) patients; while 18 (18%) required palliative surgical treatment. The overall survival of the entire group was 9 months; while those patients who underwent surgery with curative intent had a median overall survival of 28 months after a median follow-up of 42 months. Conclusion: This study found that only one-third of patients achieve radical surgery with curative intent. Overall, the prognosis of patients is poor with a median survival of less than a year due to the advanced stage disease. Multimodality treatment, screening ultrasound, and neo-/adjuvant therapy may improve survival.

Therapeutic response and prognostic factors of 14 dogs undergoing transcatheter arterial embolization for hepatocellular masses: A retrospective study.

BACKGROUND: Information regarding the therapeutic effect and outcome of transcatheter arterial embolization (TAE) for hepatic masses is limited in veterinary medicine. HYPOTHESIS/OBJECTIVES: To analyze the therapeutic response, outcome (overall survival), and their predictors in dogs that underwent TAE for primary hepatocellular masses. We hypothesized that larger pre-TAE tumors would be associated with worse outcomes. ANIMALS: Fourteen client-owned dogs. METHODS: Retrospective study. Medical records between 1 September 2016 and 30 April 2022 were reviewed to identify dogs treated with TAE for hepatic masses diagnosed as hepatocellular origin by cytological or histopathological examination. Computed tomography images were compared before and after TAE. The univariate Cox proportional hazards test was performed to assess the associations between variables and survival. Univariate linear regression analysis was performed to assess the associations between variables and the tumor reduction percentage: ([post-TAE volume - pre-TAE volume]/pre-TAE volume) × 100. RESULTS: The median survival time was 419 days (95% confidence interval, 82-474). History of intra-abdominal hemorrhage (P = .03) and pre-TAE tumor volume/body weight (P = .009) were significantly associated with overall survival. The mean reduction percentage was -51% ± 40%. Pre-TAE tumor volume/body weight ratio (cm3 /kg; P = .02, correlation coefficient = 0.704) was significantly correlated with the volume reduction percentage. CONCLUSIONS: History of intra-abdominal hemorrhage and large pre-TAE tumor volume/body weight ratio could be predictive factors for adverse outcomes after TAE. Pre-TAE tumor volume/body weight ratio could be a predictive factor for therapeutic effect.

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism.

BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

Comparison of hepatitis B virus reactivation in hepatocellular carcinoma patients who received tyrosine kinase inhibitor alone or together with programmed cell death protein-1 inhibitors.

BACKGROUND AND AIMS: Programmed cell death protein-1 (PD-1) inhibitors plus tyrosine kinase inhibitor (TKI) have dramatically improved survival of patients with advanced hepatocellular carcinoma (HCC). However, the risk of hepatitis B virus (HBV) reactivation from these antitumor medications remains unclear. METHODS: Patients receiving TKI monotherapy (TKI group) or TKI combined with PD-1 inhibitors (combination group) were included. The primary endpoint was HBV reactivation as defined by an increase in HBV DNA titer by at least 1 log (tenfold) from baseline. The secondary endpoints included tumor progression and overall survival. RESULTS: Four hundred and ninety-nine patients met the inclusion criteria, including 296 patients in the TKI group and 203 patients in the combination group. The 3-, 6- and 12-month cumulative incidence rates of HBV reactivation in the TKI group vs. combination group were 7.8%, 12.8% and 21.3% vs. 9.9%, 19.2% and 30.0%, respectively (p = 0.02). The Cox proportional hazard model indicated that combination therapy (HR 1.41, 95% CI 1.00-1.99, p = 0.05), ALT > 40 U/ml (HR 1.50, 95% CI 1.05-2.16, p = 0.03), and tumor size > 5 cm (HR 1.58, 95% CI 1.10-2.28, p = 0.01) were independent risk factors for HBV reactivation. Compared with the HBV reactivation group, the progression-free survival and overall survival of patients in the HBV non-reactivation group were significantly prolonged (p < 0.001 and p = 0.001). CONCLUSIONS: Patients who received TKI combined with PD-1 inhibitors had a greater risk for HBV reactivation, and those with HBV reactivation had a higher rate of tumor progression and shorter survival time, than those receiving TKI alone.

Treatment effect measures under nonproportional hazards.

In a clinical trial with a time-to-event endpoint the treatment effect can be measured in various ways. Under proportional hazards all reasonable measures (such as the hazard ratio and the difference in restricted mean survival time) are consistent in the following sense: Take any control group survival distribution such that the hazard rate remains above zero; if there is no benefit by any measure there is no benefit by all measures, and as the magnitude of treatment benefit increases by any measure it increases by all measures. Under nonproportional hazards, however, survival curves can cross, and the direction of the effect for any pair of measures can be inconsistent. In this paper we critically evaluate a variety of treatment effect measures in common use and identify flaws with them. In particular, we demonstrate that a treatment's benefit has two distinct and independent dimensions which can be measured by the difference in the survival rate at the end of follow-up and the difference in restricted mean survival time, and that commonly used measures do not adequately capture both dimensions. We demonstrate that a generalized hazard difference, which can be estimated by the difference in exposure-adjusted subject incidence rates, captures both dimensions, and that its inverse, the number of patient-years of follow-up that results in one fewer event (the NYNT), is an easily interpretable measure of the magnitude of clinical benefit.

Toxic evaluation of Proclaim Fit® on adult and larval worker honey bees.

Impacts to honey bees due to exposure to agricultural pesticides is one of the most serious threats to the beekeeping industry. Our research evaluated toxicity of the formulated insecticides Lufenuron+Emamectin benzoate (Proclaim Fit®) on the European honey bee Apis mellifera L. at field-realistic concentration (worst-case scenario). Newly emerged (≤24-h old) and forager (unknown age) worker bees were treated with the field recommended concentration of Proclaim Fit® using three routes of exposure including residual contact, oral, and spray within the laboratory. We also assessed the effects of Proclaim Fit® on the specific activity of some well-known detoxifying enzymes including α-esterase, ß-esterase, and Glutathione S-transferase (GST) in the honey bees. In addition, toxicity of the formulation was tested on 4th instar larvae within the hive. Based on estimated median survival times (MSTs), Proclaim Fit® was highly toxic to the bees, especially when applied as spray. According to our estimated relative median potency (RMP) values, newly emerged bees were 1.72× more susceptible than foragers to Proclaim Fit® applied orally. Enzyme assays revealed the considerable involvement of the enzymes, especially GST and α-esterase, in detoxification of the Proclaim Fit®, but their activities were significantly influenced by route of exposure and age of bee. Notably, Proclaim Fit® was highly toxic to 4th instar honey bee larvae. Our results generally indicate a potent toxicity of Proclaim Fit® toward honey bees. Therefore, its application requires serious consideration and adherence to strict guidelines, especially during the flowering time of crops.

Five-lipoxygenase-activating protein-mediated CYLD attenuation is a candidate driver in hepatic malignant lesion.

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer. However, the lipid pro-inflammatory mediators have only been seldom investigated in HCC pathogenesis. Cylindromatosis (CYLD) attenuation is involved in hepatocarcinogenesis. Here, we aimed to evaluate the significance of hepatic lipid pro-inflammatory metabolites of arachidonate-affected CYLD expression via the 5-lipoxygenase (5-LO) pathway. Resection liver tissues from HCC patients or donors were evaluated for the correlation of 5-LO/cysteinyl leukotrienes (CysLTs) signaling to the expression of CYLD. The impact of functional components in 5-LO/CysLTs cascade on survival of HCC patients was subsequently assessed. Both livers from canines, a preponderant animal for cancer research, and genetic-modified human HCC cells treated with hepatocarcinogen aristolochic acid I (AAI) were further used to reveal the possible relevance between 5-LO pathway activation and CYLD suppression. Five-LO-activating protein (FLAP), an essential partner of 5-LO, was significantly overexpressed and was parallel to CYLD depression, CD34 neovascular localization, and high Ki-67 expression in the resection tissues from HCC patients. Importantly, high hepatic FLAP transcription markedly shortened the median survival time of HCC patients after surgical resection. In the livers of AAI-treated canines, FLAP overexpression was parallel to enhanced CysLTs contents and the simultaneous attenuation of CYLD. Moreover, knock-in FLAP significantly diminished the expression of CYLD in AAI-treated human HCC cells. In summary, the hepatic FLAP/CysLTs axis is a crucial suppressor of CYLD in HCC pathogenesis, which highlights a novel mechanism in hepatocarcinogenesis and progression. FLAP therefore can be explored for the early HCC detection and a target of anti-HCC therapy.

Prognostic factors of 112 elderly patients with advanced non-small cell lung cancer.

Objectives: In this study we retrospectively analyzed the prognostic factors of patients with advanced non-small cell lung cancer (NSCLC). Methods: Clinical data of 112 patients with advanced NSCLC treated in the tumor center of our hospital from January 2016 to December 2017 were analyzed retrospectively, follow up the survival of patients, the effects of gender, age, tumor stage, pathological type, performance status (PS) score, smoking history and treatment on the survival of elderly patients with advanced NSCLC were analyzed. Results: The median survival time was 12.0 months, and the median age was 74 years. The 3-year survival rate after confirmation of advanced lung cancer was 6.25%. Kaplan Meier univariate analysis showed that age, PS score, smoking status and treatment correlated with the prognosis(P<0.05). Cox multivariate analysis showed that age >70 years, PS score>2, smoking and no targeted therapy were independent adverse prognostic factors for elderly patients with advanced NSCLC(P<0.05). Conclusions: Age, PS score, smoking and treatment mode affect the prognosis and survival of elderly patients with advanced NSCLC. Effective treatment should be given according to the principle of evidence-based medicine.

Management and Outcomes in Anal Canal Adenocarcinomas-A Systematic Review.

(1) Background: Anal canal adenocarcinomas constitute 1% of all gastrointestinal tract cancers. There is a current lack of consensus and NICE guidelines in the United Kingdom regarding the management of this disease. The overall objective was to perform a systematic review on the multitude of practice and subsequent outcomes in this group. (2) Methods: The MEDLINE, EMBASE, EMCARE and CINAHL databases were interrogated between 2011 to 2021. PRISMA guidelines were used to select relevant studies. The primary outcome measure was 5-year overall survival (OS). Secondary outcome measures included both local recurrences (LR) and distant metastases (DM). The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies retrieved. The study was registered on PROSPERO (338286). (3) Results: Fifteen studies were included. Overall, there were 11,967 participants who were demographically matched. There were 2090 subjects in the largest study and five subjects in the smallest study. Treatment modalities varied from neoadjuvant chemoradiotherapy (CRT), CRT and surgery (CRT + S), surgery then CRT (S + CRT) and surgery only (S). Five-year OS ranged from 30.2% to 91% across the literature. LR rates ranged from 22% to 29%; DM ranged from 6% to 60%. Study heterogeneity precluded meta-analysis. (4) Conclusions: Trimodality treatment with neoadjuvant chemoradiotherapy (CRT) followed by radical surgery of abdominoperineal excision of rectum (APER) appeared to be the most effective approach, giving the best survival outcomes according to the current data.

G-CSF-producing left lung squamous cell carcinoma positive for ROS1 rearrangements completely resected after neoadjuvant radiation chemotherapy: A case report.

Granulocyte colony-stimulating factor (G-CSF) promotes neutrophil production. G-CSF-producing tumors have a feature of neutrophilia without infection, and most patients with G-CSF-producing tumors show an aggressive clinical course and poor prognosis. A 71-year-old woman was diagnosed with left lung cancer, cT4N1M0, stage IIIA. Severe neutrophilia and bone marrow uptake in 18-fluorodeoxyglucose-positron emission tomography suggested the possibility of G-CSF-producing lung cancer. Following neoadjuvant radiation chemotherapy, left lower lobectomy and left upper lobe partial resection were performed. According to pathology findings of the resected specimen, the patient was diagnosed with G-CSF-producing left lung squamous cell carcinoma. Moreover, genetic tests showed that the tumor cells were positive for c-ros oncogene 1 (ROS1) rearrangements. To our knowledge, this is the first reported case of G-CSF-producing lung cancer with ROS1 rearrangements, and complete resection was performed successfully after neoadjuvant radiation chemotherapy.

Correlation of HBV DNA and Hepatitis B Surface Antigen Levels With Tumor Response, Liver Function and Immunological Indicators in Liver Cancer Patients With HBV Infection Undergoing PD-1 Inhibition Combinational Therapy.

Background: Thus far, few studies have investigated the safety and efficacy of programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) antibodies in patients with hepatitis B virus (HBV)-related liver cancer. Objective: To investigate the effect of combination therapy with programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) on HBV-related liver cancer. Methods: Until January 31, 2022, liver cancer patients with hepatitis B surface antigen (HBsAg) or HBV DNA positivity, treated with PD-1 ICIs and TKIs combined with nucleoside analogs (NAs), were retrospectively reviewed. The correlation between the change in HBV DNA and HBsAg levels and tumor response was analyzed using the χ2 test. Cox univariate and multivariate survival analyses and Kaplan-Meier curves were used to identify and compare risk factors and overall survival (OS). Results: A total of 48 patients were enrolled in the study, with an objective response rate (ORR) of 31.3%, a disease control rate (DCR) of 66.7%; the incidence of adverse events was mostly mild. A significant decrease in HBV DNA and HBsAg levels was observed at 12 and 24 weeks compared with the baseline (p < 0.05). Compared to patients with progressive disease (PD), patients with disease control showed a more significant decrease in HBV DNA and HBsAg levels at 12 and 24 weeks (p < 0.001). Eleven patients showed elevations in HBV DNA level and one of them showed HBV reactivation; however, the reactivation was not associated hepatitis. Moreover, eight patients showed elevation in HBsAg. Elevation in HBV DNA level was associated with poor tumor response (P=0.001, OR=18.643 [95% CI: 3.271-106.253]). Cox survival analysis suggested that HBV DNA increase (P=0.011, HR=4.816, 95% CI: 1.439-16.117) and HBsAg increase (P=0.022, HR=4.161, 95% CI: 1.224-16.144) were independent risk factors associated with survival time. Kaplan-Meier curves suggested that patients who exhibited an increase in HBV DNA (6.87 months vs undefined, log-rank test: p= 0.004) and HBsAg (8.07 months vs undefined, log-rank test: p= 0.004) levels had a shorter median survival time (MST). Patients without increased HBsAg showed better baseline liver function and routine blood tests (p<0.05) than patients with increased HBsAg. An increase in C-reactive protein (CRP) and interleukin-6 (IL-6), and a decrease in T lymphocytes, CD4+ T lymphocytes, and B lymphocytes at 1-week post-treatment associated with HBsAg well-controlled. Conclusion: HBV-related liver cancer patients treated with combination therapy showed improved efficacy and safety profiles. Combination therapy has some effect on HBV infection, and a correlation between tumor response and antiviral efficacy was found. Elevation of HBV DNA and HBsAg levels may indicate poorer tumor response and survival time. Better baseline liver function and early immune activation may be associated with decline in HBsAg levels.