A simple and effective technique for laparoscopic gastrorrhaphy: modified Graham's patch with barbed suture.

INTRODUCTION: Peptic ulcers are caused by unbalanced acid production, and proton pump inhibitors (PPIs) in recent decades have helped to treat peptic ulcers effectively. Meanwhile, the incidence of perforated peptic ulcer (PPU) persists and has a high mortality rate if there is no adequate management. Primary closure with a modified Graham's patch was well performed in early detected PPU with a small size < 2 cm. A laparoscopic approach for PPU was prescribed for decades with proven feasibility and safety. We introduced an effective technique combined with barbed suture and modified Graham's patch, which can significantly reduce the surgical time without significantly increasing morbidity and mortality compared with traditional interrupted suture. PATIENTS AND METHOD: We retrospectively collected data from January 2014 to December 2020 in Keelung Change Gung Memorial Hospital, and a total of 154 patients receiving laparoscopic repair of PPU were included. There were 59 patients in the V-loc group (V group) and 95 patients in the laparoscopic primary repair group (P group). RESULTS: The V group had a significantly shorter operation time than the P group (96.93 ± 22.14 min vs. 123.97 ± 42.14, P < 0.001). Ten patients suffered from morbidity greater than the Clavien‒Dindo classification 4 (5 from V group, and 5 from P group). Three patients with leakage were reported. Two patients were in the V group, and one patient was in the P group (p = 0.432). CONCLUSION: Laparoscopic repair with barbed suture and modified Graham's patch provides a simple and effective technique in the management of acute abdomen. This technique can be easily performed by experienced surgeons and trainees in minimally invasive surgery without affecting patient safety.

Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.

Treatment of infected abdominal aortic aneurysm caused by Salmonella.

BACKGROUND: We reviewed the outcomes of patients treated for nontyphoidal Salmonella-infected abdominal aortic aneurysm (AAA) treatment at a single center. METHODS: This was a retrospective chart review of 26 patients with nontyphoidal Salmonella-infected AAA. Four patients underwent medical therapy alone, while 22 patients underwent surgical therapy. Revascularization method selection was dependent on preoperative antibiotic response in the surgical therapy group. RESULTS: The in-hospital mortality rate for the surgical therapy group was 14%, while the rate for the medical therapy group was 100%. Overall survival for the surgical therapy group was 82%, while the reinfection rate was 9%. In the surgical therapy group, 2 patients had periaortic abscesses and underwent in situ prosthetic graft replacement; none developed graft-related complications or died in the hospital. Kaplan-Meier analysis and log-rank testing revealed no significant differences in graft-related complication and overall survival rates between in situ prosthetic graft group and extra-anatomic bypass group. Salmonella choleraesuis had a higher antimicrobial resistance rate than other isolates. The predictors of survival were clinical presentation of abdominal pain and receiving surgical therapy. CONCLUSIONS: If patients with Salmonella-infected AAAs have good responses to preoperative antibiotic therapy, in situ prosthetic graft replacement is a viable revascularization method, even in the situation of periaortic abscess presentation formation.

Astragalus polysaccharides improve adjuvant chemotherapy-induced fatigue for patients with early breast cancer.

This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.

Regulation of the cell cycle and P13K/AKT/mTOR signaling pathway by phthalates in normal human breast cells.

OBJECTIVE: To investigate the impact of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), in breast carcinogenesis. MATERIALS AND METHODS: MCF-10A normal breast cells were treated with phthalates (100 nM) and 17ß-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue adjacent to estrogen receptor positive primary breast cancers. Cell viability was determined using a 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell cycles were analyzed using flow cytometry. The proteins involving cell cycles and P13K/AKT/mTOR signaling pathway were then evaluated by Western blot analysis. RESULTS: MCF-10A co-cultured cells treated with E2, BBP, DBP, and DEHP exhibited a significant increase in cell viability using MTT assay. The expressions of P13K, p-AKT, and p-mTOR, as well as PDK1 expression, were significantly higher in MCF-10A cells treated with E2 and phthalates. E2, BBP, DBP, and DEHP significantly increased cell percentages in the S and G2/M phases. The significantly higher expression of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1 in MCF-10A co-cultured cells were induced by E2 and these three phthalates. CONCLUSION: These results provide consistent data regarding the potential role of phthalates exposure in the stimulating proliferation of normal breast cells, enhancing cell viability, and driving P13K/AKT/mTOR signaling pathway and cell cycle progression. These findings strongly support the hypothesis that phthalates may play a crucial role in breast tumorigenesis.

The no-observed-adverse-effect level of phthalates promotes proliferation and cell cycle progression in normal human breast cells.

OBJECTIVE: The data on the association between phthalates and breast cancer risk remains inconsistent. This study aimed to explore the possible mechanism of low-dose exposures of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP), on breast tumorigenesis. METHODS AND METHODS: MCF-10A normal breast cells were treated with phthalates (10 and 100 nM) and 17ß-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue. Cell viability, cycle, and apoptosis were detected by MTT assay, flow cytometry, and TUNEL assay respectively. The expression levels of related proteins were determined by Western blot. RESULTS: Like E2, both 10 nM and 100 nM phthalates exerted significantly higher cell viability, lower apoptosis, and increased cell numbers in the S and G2/M phases with up-regulation of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1, compared with the control group. Significant increase in PDK1, P13K, p-AKT, p-mTOR, and BCL-2 expression and a decrease in Bax protein, cytochrome C, caspase 8, and caspase 3 levels were noted in cells treated with 10 nM and 100 nM phthalates and E2, compared with the control group and MCF-10A cells co-cultured with fibroblasts. The effects of the three phthalates were noted to be dose-dependent. CONCLUSIONS: The results indicate that phthalates at a level below its no-observed-adverse-effect concentration, as defined by the current standards, still induce cell cycle progression and proliferation as well as inhibit apoptosis of normal breast cells. Thus, the possibility of breast tumorigenesis through chronic phthalate exposure should be considered.

Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw.

Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center retrospective study included denosumab-treated breast cancer patients with bone metastases. Kaplan-Meier survival curves assessed exposure, SREs, osteonecrosis of the jaw (ONJ), and death. 132 patients were enrolled. The median denosumab exposure was 28.3 months (range 1.0-84.9). In the first year, 11.1% experienced SREs. This increased to 18.6% in the second, 21% in the third, and 35.1% in the fourth year and beyond. The median time to first on-study SRE has not been reached. 10 denosumab users (7.6%) developed ONJ. ONJ incidence was 0.9% in the first year, 6.2% in the second, 13.6% in the third, and 16.2% in subsequent years. The median time to first on-study ONJ has not been reached yet. Seven patients resumed denosumab after careful management of ONJ. Our data suggest that long-term treatment with denosumab may further prevent or postpone SREs at the cost of an increased risk of ONJ. The majority of patients who resumed denosumab did not experience a recurrence of ONJ.

The effect of a helmet type, home-use low-level light therapy device for chemotherapy-induced alopecia: study protocol for a randomized controlled trial.

BACKGROUND: Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. METHODS: One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. DISCUSSION: This study improves cancer patients' quality of life and provides clinical evidence. TRIAL REGISTRATION: Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.

Allogeneic hematopoietic stem cell transplantation for B-cell lymphoma in Taiwan.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered for patients with high-risk B-cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long-term follow-up data of patients who underwent allo-HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo-HSCT because of high-risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty-five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow-up duration was 18.6 months. The probability of 3-year progression-free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1-year non-relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft-versus-host disease (GVHD) were factors associated with inferior OS. The probability of 3-year OS in patients with diffuse large B-cell lymphoma who underwent allo-HSCT and allo-HSCT after ASCT was 40.2% and 25.2%, respectively. Allo-HSCT could be a salvage therapeutic option for relapsed or refractory B-cell lymphoma. Complete remission at the time of allo-HSCT and the presence of GVHD are independent variables for overall survival.

Treatment of primary infected aortic aneurysm without aortic resection.

BACKGROUND: We sought to determine the safety and efficacy of two different treatment strategies for patients with primary infected aortic aneurysms, including antibiotic treatment alone and endovascular aneurysm repair (EVAR) with aggressive antibiotic treatment, as alternatives to the established treatment of open surgical repair. METHODS: We conducted a retrospective chart review of patients who were treated for infected aortic aneurysm without undergoing aortic resection from January 2000 to December 2010 at a single institution. RESULTS: A total of 40 patients underwent traditional open repair during the study period. Sixteen patients with infected aortic aneurysm (11 men; median age, 70; range, 44-80 years) were identified as not having undergone aortic resection during the 11 years reviewed in the study. Nine patients received antibiotic treatment only (group I) and seven patients underwent EVAR with aggressive antibiotic treatment (group II). Salmonella species were isolated from seven patients in group I, and oxacillin-resistant Staphylococcus aureus was isolated from the remaining two patients. In group II, six patients had blood culture results showing Salmonella species and one patient had a blood culture result showing Escherichia coli. Group I (7 of 9 patients; 78%) had a higher hospital mortality rate than group II (0%; P = .003). Mean follow-up among survivors was 10 ± 15 months (range, 1-37 months). One patient in group II developed a reinfection episode (14%). There was no significant difference between group I (67%; SE, 27.2%) and group II (86%; SE, 13.2%) in the 3-month survival rates (log-rank, P = .39). CONCLUSIONS: Our results support the premise that EVAR is beneficial for the patients with infected aortic aneurysm. Treating an infected aortic aneurysm with antibiotics alone could not stop aneurysm expansion and eradicate the aortic infection before the aneurysm ruptures. For the patients with infected aortic aneurysms who have limited life expectancy and multiple comorbidities, EVAR with aggressive antibiotic treatment should be considered preferentially over antibiotic treatment alone.

PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations.

The activation of the PI3K signaling pathway resulting from genetic alterations induces carcinogenesis and resistance to anticancer therapies. Breast cancer is a major malignancy that is associated with dysregulation of the PI3K signaling pathway. PIK3CA mutations and PTEN loss occur in every subtype of breast cancer. PI3K inhibitors are being evaluated in breast cancer after the success of an alpha isoform-specific PI3K inhibitor in estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer. Some preclinical data indicate the potential for PI3K/mTOR targeting in combination with trastuzumab for HER2-positive breast cancer with or without expression of the estrogen receptor. However, the role of this therapy in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss remains unclear. We examined three HER2-positive, ER-negative breast cancer cell lines to determine the efficacy of a novel alpha isoform-specific PI3K inhibitor in combination with trastuzumab. The results indicated that this combination was effective in PIK3CA-mutant or PTEN-deficient breast cancer cells by inducing apoptosis and inhibiting the expression of downstream proteins. PTEN loss by siRNA modulation in parental HER2-positive cancer cells with PI3K signaling pathway alterations could not confer resistance to alpelisib or GDC-0077 plus trastuzumab. We selected the CK-MB-1 cell line without alterations in the PI3K pathway to demonstrate that PI3K inhibitors plus trastuzumab represented a biomarker-specific treatment. In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.

Application of PLASMIC Score in Risk Prediction of Thrombotic Thrombocytopenic Purpura: Real-World Experience From a Tertiary Medical Center in Taiwan.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by severe ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency (activity <10%). Urgent intervention based on the timely evaluation of ADAMTS13 level is crucial to guide optimal therapy. The recently developed PLASMIC score based on seven items allows the rapid identification of patients at high risk for TTP due to severe ADAMTS13 deficiency. This retrospective study included 31 hospitalized patients with suspicious thrombotic microangiopathy in National Cheng Kung University Hospital from December 2016 to July 2021. Data on ADAMTS13 activity and medical and laboratory information were retrieved from medical records. The PLASMIC score could be calculated in 24 of the 31 patients with available data, and the final cohort was stratified according to the 7-point PLASMIC score. All patients with high PLASMIC score (6-7) exhibited severe ADAMTS13 deficiency (activity ≤10%). One patient with a brain tumor and a PLASMIC score of 6 did not have severe ADAMTS13 activity of ≤10%. The patients in the intermediate- and low risk groups (PLASMIC scores of 5 and 0-4, respectively) exhibited ADAMTS13 activities of above 10%. Given the role of prompt diagnosis in the timely delivery of appropriate therapy, these findings confirm and strengthen the predictive value of the PLASMIC score in patients at high risk for TTP due to severe ADAMTS13 deficiency.

Clinical outcomes of AngioJet rheolytic thrombectomy in the treatment of May-Thurner syndrome-related deep venous thrombosis.

OBJECTIVE: May-Thurner syndrome (MTS) is an anatomic stenotic variation associated with deep vein thrombosis (DVT) of the left leg. The classical DVT treatment strategy is medical treatment without thrombus removal. This study was performed to assess the clinical outcomes of the combination of AngioJet™ rheolytic thrombectomy and stenting for treatment of MTS-related DVT. METHODS: We conducted a retrospective cohort study of patients treated for MTS-related DVT from January 2017 to June 2020 at a single institution. RESULTS: Fourteen patients (nine women) underwent AngioJet™ rheolytic thrombectomy for MTS-related DVT during the study period. The median DVT onset time was 8 days (interquartile range (IQR), 3-21 days). The median procedure time was 130 minutes (IQR, 91-189 minutes), and the median hospital stay was 7 days (IQR, 5-26 days). One patient had a residual thrombus and occluded iliac stent and underwent adjuvant catheter-directed thrombolysis for revascularization. The primary patency rate for the iliac stent was 92.9% at 12 months. CONCLUSION: Concomitant AngioJet™ rheolytic thrombectomy and stenting of MTS-induced lesions may be beneficial for patients with MTS-related DVT.

Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer.

Background: This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer. Methods: Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed. Results: CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis. Conclusions: A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.

In situ versus extra-anatomic reconstruction for primary infected infrarenal abdominal aortic aneurysms.

BACKGROUND: There is no standard procedure for revascularization after infected infrarenal abdominal aortic aneurysm resection. This study examines the outcomes of two contemporary methods. METHODS: We retrospectively reviewed medical records for patients who underwent repair of infected infrarenal abdominal aortic aneurysms from January 1998 to December 2007 at a single institution. Patients with infected prosthetic aortic grafts were excluded. RESULTS: Twenty-eight patients (22 men; mean age, 65 ± 12) had in situ graft (group I, n = 13) or extra-anatomic bypass (group II, n = 15), with a mean follow-up of 22 months. Mean hospital lengths of stay were 36 ± 16 days for group I and 46 ± 17 days for group II. Overall perioperative mortality was 5 of 28 (18%), comprising 1 of 13 in group I (8%) and 4 of 15 in group II (27%; P = .333). No early or late vascular-related complications occurred in group I. In group II, three patients had early vascular-related complications, including, graft infection, graft occlusion and ischemia colitis, and five patients had late vascular-related complications, including graft infection and graft occlusion. One patient ultimately lost a limb. Group I had a 0% late complication rate vs 33% in group II (P = .044). For cumulative survival rates, Kaplan-Meier analysis and log-rank testing revealed no significant differences between groups I and II. CONCLUSION: In situ graft revascularization is viable in afebrile patients or patients who have good response to preoperative antibiotic therapy. Extra-anatomic bypass grafting for infected infrarenal abdominal aneurysm resection has a similar long-term survival rate and should be considered in patients who are unsuitable for in situ graft revascularization; however, the postoperative complication rate is higher. Further prospective study with large patient populations is needed to determine the selection criteria for using in situ revascularization as alternative methods for treatment of infected abdominal aneurysms.

Surgical outcome for mycotic aortic and iliac anuerysm.

BACKGROUND: The present study was designed to review surgical outcomes for mycotic aneurysm of the aortic or iliac arteries at a single center. METHODS: The study was based on retrospective chart review of patients undergoing operation for mycotic aneurysm. RESULTS: From January 1998 to December 2007, 56 patients received surgical treatment for mycotic aneurysm of the aortic or iliac arteries. Aneurysm sites included the aortic arch (n=5), proximal thoracic aorta (n=4), distal thoracic aorta (n=5), paravisceral aorta (n=5), juxtarenal aorta (n=4), infrarenal aorta (n=30), and iliac arteries (n=3). Salmonella was the leading pathogen (n=34). Nineteen patients with suprarenal lesions underwent in situ prosthetic graft replacement (n=17), extra-anatomic bypass (n=1), or endovascular aneurysm repair (EVAR) (n=1), and 37 patients with infrarenal lesions underwent the same procedures (n=16, 20, and 1, respectively). Overall in-hospital mortality was 23%. After discharge, four patients (7%) developed reinfection that led to fatal sepsis. Graft infection developed after three in situ prosthetic grafts (9%) and one extra-anatomic bypass (5%). Patients with suprarenal aortic lesions had poorer in-hospital (34%) and late (16%) mortality rates than those with infrarenal lesions (p=0.025). Those with suprarenal lesions also had a lower cumulative survival rate (p=0.016). CONCLUSIONS: The location of mycotic aneurysm was the determinant of mortality. Mycotic aneurysm of the suprarenal aorta has poor prognosis and requires alternative surgical treatment.

Subtle cardiac dysfunction in lymphoma patients receiving low to moderate dose chemotherapy.

Left ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04-9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.

A simple novel model to predict hospital mortality, surgical site infection, and pneumonia in elderly patients undergoing operation.

BACKGROUND/AIMS: Predicting models of operative morbidity and mortality in the geriatric population are important in the prevention of adverse surgical outcomes. METHODS: A retrospective review of medical records was performed for patients over 80 years of age who underwent gastrointestinal surgery from 1998 to 2008. RESULTS: 215 patients were identified with a mean age of 83.7 years. Overall morbidity and mortality rates were 48.8 and 14.4%, respectively. Multivariate logistic regression analysis revealed that serum albumin levels [odds ratio (OR) = 0.367, p = 0.0267], postoperative pneumonia (OR = 3.471, p = 0.0101), hollow organ perforation or anastomosis combined with leakage (OR = 7.600, p = 0.0126), and preoperative systemic inflammatory response syndrome (OR = 3.186, p = 0.0323) were significant predictors of hospital mortality. Moreover, albumin (OR = 0.270, p = 0.0002) and physical disability (OR = 3.802, p = 0.0009) were significant predictors of postoperative pneumonia, and albumin (OR = 0.491, p = 0.0212) and enterotomy (OR = 3.335, p = 0.0208) were significant predictors of surgical site infections. CONCLUSION: This study provides novel predicting models to identify the elderly surgical patients at high risk, who should receive more intensive preventive and perioperative care.

Comprehensive assessment of HER2 alteration in a colorectal cancer cohort: from next-generation sequencing to clinical significance.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencing (NGS)-based techniques for determining HER2 status in CRC has been limited. Here, we detail our experience regarding the assessment of HER2 alterations in a CRC cohort. MATERIALS AND METHODS: We prospectively enrolled 73 CRC patients who underwent surgery and received adjuvant oxaliplatin treatment. We then examined HER2 alterations using the Oncomine Comprehensive Assay version 1, as well as clinical outcomes, in this cohort. RESULTS: Using the NGS-based assay, HER2 copy number gains in 12 of 73 CRCs were determined to range from 2.74 to 92.62. Of these 12 tumors, 6 had HER2 high-level copy number gain (92.6, 57.9, 57.0, 52.0, 35.2, and 8.42) and were all defined as HER2-positive CRC using HERACLES Diagnostic Criteria. Nevertheless, other 6 patients with low-level copy number gain (ranging from 2.74 to 3.04) and the remaining 61 patients without increase in HER2 copy number were all HER2-negative. Among the 6 HER2-positive CRCs, KRAS and PIK3CA mutations were detected in 1 (17%; G13D) and 2 (33.3%; 1 Q546R and 1 H1047R) patients, respectively. Moreover, 2 of the 6 (33.3%) HER2-positive patients had recurrent disease, while one patient had a partial response after anti-HER2 therapy. CONCLUSION: NGS-based tools could assist in the simultaneous detection of HER2 and other genomic alterations in patients with CRC. Only CRCs with HER2 high-level copy number gain were HER2-postive by current diagnostic criteria.