Surgical site infection following pancreaticoduodenectomy in a referral cancer center in Mexico

Background: Pancreaticoduodenectomy is the standard treatment for resectable periampullary cancer. Surgical site infections(SSI) are common complications with increased morbidity. The study aimed to describe the prevalence, risk factors, microbiology, and outcomes of SSI among patients undergoing pancreaticoduodenectomy. Methods: We conducted a retrospective study in a referral cancer center between January 2015 and June 2021. We analyzed baseline patient characteristics and SSI occurrence. Culture results and susceptibility patterns were described. Multivariate logistic regression was used to determine risk factors, proportional hazards model to evaluate mortality, and Kaplan-Meier analysis to assess long-term survival. Results: A total of 219 patients were enrolled in the study;101(46%) developed SSI. Independent factors for SSI were diabetes mellitus, preoperative albumin level, biliary drainage, biliary prostheses, and clinically relevant postoperative pancreatic fistula. The main pathogens were Enterobacteria and Enterococci. Multidrug-resistance rate in SSI was high but not associated with increased mortality. Infected patients had higher odds of sepsis, longer hospital stay and intensive care unit stay, and readmission rate. Neither 30-day mortality nor long-term survival was significantly different between infected and non-infected patients. Conclusions: SSI prevalence among patients undergoing pancreaticoduodenectomy was high and largely caused by resistant microorganisms. Most risk factors were related to preoperative instrumentation of the biliary tree. SSI was associated with greater risk of unfavorable outcomes;however, survival was unaffected.

Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours worldwide.The mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related deaths.Systemic drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC treatment.Unfortunately,these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance.Thus,novel pharmacological alternatives are urgently needed.For instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune system.Furthermore,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients.In addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic alternatives.Here,we review the current and novel pharmacological approaches to fight HCC.Preclinical studies,as well as approved and ongoing clinical trials for liver cancer treatment,are discussed.The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

Cancer stem cell impact on clinical oncology

Cancer is a widespread worldwide chronic disease. In most cases, the high mortality rate from cancer correlates with a lack of clear symptoms, which results in late diagnosis for patients, and consequently, advanced tumor disease with poor probabilities for cure, since many patients will show chemo-and radio-resistance. Several mechanisms have been studied to explain chemo-and radio-resistance to anti-tumor therapies, including cell signaling pathways, anti-apoptotic mechanisms, stemness, metabolism, and cellular phenotypes. Interestingly, the presence of cancer stem cells(CSCs), which are a subset of cells within the tumors, has been related to therapy resistance. In this review, we focus on evaluating the presence of CSCs in different tumors such as breast cancer, gastric cancer, lung cancer, and hematological neoplasias, highlighting studies where CSCs were identified in patient samples. It is evident that there has been a great drive to identify the cell surface phenotypes of CSCs so that they can be used as a tool for anti-tumor therapy treatment design. We also review the potential effect of nanoparticles, drugs, natural compounds, aldehyde dehydrogenase inhibitors, cell signaling inhibitors, and antibodies to treat CSCs from specific tumors. Taken together, we present an overview of the role of CSCs in tumorigenesis and how research is advancing to target these highly tumorigenic cells to improve oncology patient outcomes.

Outcomes of critically ill cancer patients with Acinetobacter baumannii infection

AIM: To describe the intensive care unit(ICU) outcomes of critically ill cancer patients with Acinetobacter baumannii(AB) infection.METHODS: This was an observational study that included 23 consecutive cancer patients who acquired AB infections during their stay at ICU of the National Cancer Institute of Mexico(INCan), located in Mexico City. Data collection took place between January 2011, and December 2012. Patients who had AB infections before ICU admission, and infections that occurred during the first 2 d of ICU stay were excluded. Data were obtained by reviewing the electronic health record of each patient. This investigation was approved by the Scientific and Ethics Committees at INCan. Because of its observational nature, informed consent of the patients was not required.RESULTS: Throughout the study period, a total of 494 critically ill patients with cancer were admitted to the ICU of the INCan, 23(4.6%) of whom developed AB infections. Sixteen(60.9%) of these patients had hematologic malignancies. Most frequent reasons for ICU admission were severe sepsis or septic shock(56.2%) and postoperative care(21.7%). The respiratory tract was the most frequent site of AB infection(91.3%). The most common organ dysfunction observed in our group of patients were the respiratory(100%), cardiovascular(100%), hepatic(73.9%) and renal dysfunction(65.2%). The ICU mortality of patients with 3 or less organ system dysfunctions was 11.7%(2/17) compared with 66.6%(4/6) for the group of patients with 4 or more organ system dysfunctions(P = 0.021). Multivariate analysis identified blood lactate levels(BLL) as the only variable independently associated with inICU death(OR = 2.59, 95%CI: 1.04-6.43, P = 0.040). ICU and hospital mortality rates were 26.1% and 43.5%, respectively.CONCLUSION: The mortality rate in critically ill patients with both HM, and AB infections who are admitted to the ICU is high. The variable most associated with increased mortality was a BLL ≥ 2.6 mmol/L in the first day of stay in the ICU.

Opening the doors of the intensive care unit to cancer patients: A current perspective

The introduction of new treatments for cancer and advances in the intensive care of critically ill cancer patients has improved the prognosis and survival. In recent years, the classical intensive care unit(ICU) admission comorbidity criteria used for this group of patients have been discouraged since the risk factors for death that have been studied, mainly the number and severity of organic failures, allow us to understand the determinants of the prognosis inside the ICU. However, the availability of intensive care resources is dissimilar by country, and these differences are known to alter the indications for admission to critical care setting. Three to five days of ICU management is warranted before making a final decision(ICU trial) to consider keep down intensive management of critically ill cancer patients. Nowadays, taking into account only the diagnosis of cancer to consider ICU admission of patients who need full-supporting management is no longer justified.

Mismatch repair protein expression and intratumoral budding in rectal cancer are associated with an increased pathological complete response to preoperative chemoradiotherapy: A case-control study

AIM To determine whether the association of rectal adenocarcinoma with a defective-mismatch repair system(dMMR) was associated with a pathological complete response(pCR) to preoperative chemoradiotherapy.METHODS A case-control study was designed with the aim of determining if patients with rectal adenocarcinoma with dM MR had an associated high pCR rate in response to neoadjuvant chemoradiotherapy(nCRT).RESULTS Seventy-two cases with pCR were compared against 144 controls without pCR. Across 216 cases, the mean age was 56.8 years, 140(64.8%) were men, and 63(29.2%) demonstrated the dMMR system. The pCR was associated with G1 tumors, dMMR, the absence of vascular invasion, and low tumor budding in the pretreatment biopsy. In a multivariant analysis, the factors associated with pCR were dMMR(OR: 2.61; 95%CI: 1.355-5.040, P = 0.004) and a low degree of tumor budding(OR: 2.52; 95%CI: 1.366-4.894, P = 0.025).CONCLUSION We found an independent association between dMMR and a low rate of tumor budding, with a higher rate of pCR, in the basal biopsies of patients with rectal carcinoma subjected to nCRT.

A single dose of caffeic acid phenethyl ester prevents initiation in a medium-term rat hepatocarcinogenesis model

AIM： To study of the effect of caffeic acid phenethyl ester （CAPE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODS： Male Wistar rats were subjected to a carcinogenic treatment （CT） and sacrificed at 25^th d; altered hepatic foci （AHF） were generated efficiently. To a second group of rats a single 20 mg/kg doses of CAPE was given 12 h before initiation with CT and were sacrificed at 25^th d. We evaluated the expression of preneoplastic markers as Y-glutamyltranspeptidase （GGT） and glutathione S-transferase type pi protein （GSTp） by histochemistry, RT-PCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances （TBARS） in homogenates of liver and used Unscheduled DNA Synthesis （UDS） assay by incorporation of [^3H] thymidine （^3HdT） in primary hepatocyte cultures （PHC）. RESULTS： At 25^th d after CT CAPE reduced the observed increase of GGT^＋AHF by 84% and liver expression ofggt mRNA by 100%. In case of the GSTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine （DEN） 12 h after its administration, we detected a 68% increase of TBARS. When CAPE was administered before DEN, it completely protected from liver TBARS induction. To have an indication of the sole effect of CAPE on initiation, two carcinogens were tested in a UDS assay in PHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CAPE concentration. CONCLUSION： Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.

A 4-year retrospective study of add-on therapy to the fixed combination of dorzolamide/timolol for the treatment of POAG

AIM:To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma(POAG)and the addition of other intraocular pressure(IOP)lowering medications such as prostaglandin analogs and brimonidine.METHODS:A retrospective,non-randomized,and descriptive clinical study was performed with 182 eyes diagnosed with POAG.Patients were divided into three groups:a group with fixed combination of dorzolamide/timolol only,a second group with prostaglandin analogs plus fixed combination of dorzolamide/timolol,and a third group with the addition of brimonidine to the same fixed combination.IOP data were gathered retrospectively and the differences between groups were calculated.RESULTS:IOP was reduced satisfactorily in all three groups;however,a progressive IOP reduction was noted in the group with the fixed combination plus prostaglandin analogs.In this group,a progressive,significant and more homogeneous response of the reduction was noted in comparison with the other groups.CONCLUSION:IOP reduction was efficacious in all three groups.The addition of prostaglandin analogs showed progressive IOP reduction,progressive responseand absence of long-term drift.Brimonidine did not show a significant additive effect.

Ventilator-associated pneumonia in patients with cancer: Impact of multidrug resistant bacteria

BACKGROUND Patients with cancer have several risk factors for developing respiratory failure requiring mechanical ventilation(MV).The emergence of multidrug resistant bacteria(MDRB)has become a public health problem,creating a new burden on medical care in hospitals,particularly for patients admitted to the intensive care unit(ICU).AIM To describe risk factors for ventilator-acquired pneumonia(VAP)in patients with cancer and to evaluate the impact of MDRB.METHODS A retrospective study was performed from January 2016 to December 2018 at a cancer referral center in Mexico City,which included all patients who were admitted to the ICU and required MV≥48 h.They were classified as those who developed VAP versus those who did not;pathogens isolated,including MDRB.Clinical evolution at 60-d was assessed.Descriptive analysis was carried out;comparison was performed between VAP vs non-VAP and MDRB vs non-MDRB.RESULTS Two hundred sixty-three patients were included in the study;mean age was 51.9 years;52.1%were male;68.4%had solid tumors.There were 32 episodes of VAP with a rate of 12.2%;11.5 episodes/1000 ventilation-days.The most frequent bacteria isolated were the following:Klebsiella spp.[n=9,four were Extended-Spectrum Beta-Lactamase(ESBL)producers,one was Carbapenem-resistant(CR)];Escherichia coli(n=5,one was ESBL),and Pseudomonas aeruginosa(n=8,two were CR).One Methicillin-susceptible Staphylococcus aureus was identified.In multivariate analysis,the sole risk factor associated for VAP was length of ICU stay(OR=1.1;95%CI:1.03-1.17;P=0.003).Sixty-day mortality was 53%in VAP and 43%without VAP(P=0.342).There was not higher mortality in those patients with MDRB.CONCLUSION This study highlights the high percentage of Gram-negative bacteria,which allows the initiation of empiric antibiotic coverage for these pathogens.In this retrospective,single center,observational study,MDRB VAP was not directly linked to increased mortality at 60 days.

Synthesis and Radiation Dosimetry of [⁶⁸Ga]-Ga-Lys¹, Lys³-DOTA-Bombesin (1,14) Antagonist for PET-Imaging, as a Potential Theragnostic Tracer in Oncology

This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinomas, but not in advanced stages. Therefore, there is a need to develop effective tracers for the accurate and specific detection of this disease. The objective of this study was to evaluate Lys1, Lys3-DOTA-BBN (1,14) analog with the radiolabeled positron emitter [68Ga]-Ga-BBN for receptor imaging with PET, and to determine its biodistribution and radiation dosimetry using whole-body (WB) PET scans in healthy volunteers. The highest uptake was in the pancreas, followed by urinary bladder. The critical organ was pancreas with a mean absorbed dose of 206 ± 0.7, 210 ± 0.7, 120 ± 0.9, 390.23 ± 0.6 μGy/MBq and the effective doses were estimated as 73.2 ± 0.6, 49.8 ± 0.3 μGy/MBq (women and men, respectively).

Alterations in Retinoic Acid Receptors in Non-Small Cell Lung Cancer and Their Clinical Implications

The nuclear retinoic acid receptor may play a critical role in the process of lung carcinogenesis. Alteration or loss of nuclear retinoic acid receptors (RARs) has been associated with progression in premalignant and malignant tissues and it is associated with malignant transformation in human cells. Vitamin A derivates, such as retinoic acid, have emerged as adjuvant to therapy in several types of cancer with favorable effects. Retinoic acid regulates the expression of target genes through the binding and activation of RARs, inhibiting growth proliferation. Diverse studies have evaluated different retinoids alone or in combination with chemotherapy in lung cancer, from which results have been controversial with benefits observed only in the subpopulation with high levels of triglycerides. Additionally, several large randomized trials using retinoids to prevent tobacco-related cancer have failed;due to the latter the use of retinoids in clinical trials remains controversial. However they could reduce the risk of cancer development in non-smokers. There is evidence that retinoids have different effects on lung cancer;still the identification of biomarkers could determinate their benefits as preventive or therapy agents. This review describes the RAR alterations during the development of Non-Small Cell Lung Cancer and sets out the importance of several cancer treatments with retinoid compounds.

SAP Expression in Candida albicans Strains Isolated from Mexican Patients with Vaginal Candidosis

To determine the frequency and expression of the ten SAP (secreted aspartyl protease) genes in a group of Candida albicans strains isolated from Mexican women suffering from vaginal candidosis, a group of 264 women (age 18 - 57 years) with vaginal infections, predisposed by diabetes mellitus or contraceptive consumption, were evaluated. C. albicans was identified using PCR to amplify the rRNA internal transcribed spacer regions ITS1 and ITS2. The presence of the SAP genes was determined using conventional PCR, and their expression levels were determined using real-time PCR after the C. albicans strains had been grown in reconstituted human vaginal epithelium (RHVE). C. albicans was identified in the samples from 50 women (18.9%). The genotyping frequencies of the SAP genes were as follows: SAP1, 94%;SAP2, 98%;SAP3, 80%;SAP4, 100%;SAP5, 100%;SAP6, 100%;SAP7, 63%;SAP8, 96%;SAP9, 70%;and SAP10, 88%. The most frequently expressed genes in the strains harboring all of the genes were SAP1, 90%;SAP2, 90%;SAP3, 90%;SAP4, 100%;SAP5, 90%;SAP6, 90%;SAP7, 100%;SAP8, 90%;SAP9, 100%;and SAP10, 100%. SAP genes were expressed in the RHVE, suggesting that the Sap proteins play an important role in the pathogenesis of infection.

Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine

Latin-America (LATAM) is the second region in gastric cancer incidence;gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian;IL-10 in Chilean;IL-10 in Colombian;EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.