Textbook outcomes of hepatocellular carcinoma patients with sarcopenia: A multicenter analysis

BackgroundThe impact of sarcopenia on textbook outcome (TO) after hepatectomy in hepatocellular carcinoma (HCC) patients remains unclear. This study aimed to investigate the association between sarcopenia and TO, to clarify its long and short-term prognostic value, and to develop a nomogram model based on sarcopenia and TO for survival prediction.MethodsPatients who underwent HCC resection between January 2012 and March 2017 in three large hospitals in Fujian were retrospectively recruited and divided into sarcopenia and non-sarcopenia groups based on skeletal muscle index (SMI) values. TO was defined as no 30-day morality, no 30-day readmission, negative margins, no prolonged hospital stay, and no major complications. Multivariate regression was used to screen for clinical factors associated with TO. Nomograms of overall survival (OS) and recurrence-free survival (RFS) after hepatectomy for HCC were developed.ResultsA total of 1172 patients were included in the study. The TO rates were 28.74% (121/421 patients) in the sarcopenia group and 43.4% (326/751 patients) in the non-sarcopenia group. The results showed that sarcopenia was an independent predictor of TO (p < 0.001), TO was an independent predictor of perioperative treatment-related sarcopenia (PTRS)(p = 0.002), and TO was an independent predictor of OS and RFS (p < 0.001). Nomogram models based on sarcopenia and TO were generated and accurately predicted OS and RFS at 1, 3, and 5 years.ConclusionBoth sarcopenia and TO are independent predictors of OS and RFS after HCC resection. Sarcopenia was an independent predictor of TO. Sarcopenia influenced long-term survival by affecting short-term postoperative outcomes.     

Textbook outcome,chemotherapy compliance,and prognosis after radical gastrectomy for gastric cancer: A large sample analysis

BackgroundThis study aims to analyze the effect of textbook outcome (TO) on the long-term prognosis and adjuvant chemotherapy (AC) compliance of patients with gastric cancer (GC) in a single institute.Materials and methodsConsecutive patients who underwent radical gastrectomy with pathological stage I-III at Union Hospital of Fujian Medical University from January 2010 to June 2017 were included. TO was defined as receiving a complete-potentially curative status, ≥15 lymph nodes examined, hospital stay ≤21 days, and freedom from intraoperative and postoperative complications, re-intervention in 30 days, 30-day readmission to the hospital or intensive care unit, and 30-day postoperative mortality.ResultsTotally 3993 patients were included, of which 3361 (84.2%) patients achieved TO. The overall, disease-specific, and recurrence-free survival of patients achieving TO were significantly better than those of patients without achieving TO (all P < 0.05). The total number of AC cycles was greater and the interval from surgery to first AC was shorter in the TO group compared with the Non-TO group. Age >65 years old, open surgery, pT3-4 stage, and total radical gastrectomy (TG) were identified as related high-risk factors for failure to achieve TO. Laparoscopic surgery facilitated TO achievement in high-risk groups.ConclusionTO is a reliable indicator of favorable prognosis of patients with GC and contributes to postoperative chemotherapy compliance. Age ≤65 years old, non-TG, pT1-2 stage, and laparoscopic surgery may promote the achievement of TO.     

A multi-institutional analysis of Textbook Outcomes among patients undergoing cytoreductive surgery for peritoneal surface malignancies

BackgroundWhile recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM).Study designAll patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction >1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay >75th percentile, and non-home discharge.ResultsAmong 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age <65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time <7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p < 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p < 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p < 0.01).ConclusionAmong patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.     

Textbook outcome and survival after gastric cancer resection with curative intent: A population-based analysis

BackgroundThe concept of textbook outcome (TO) has been proposed for analyzing quality of surgical care. This study assessed the incidence of TO among patients undergoing curative gastric cancer resection, predictors for TO achievement, and the association of TO with survival.MethodAll patients with gastric and gastroesophageal junction cancers undergoing curative gastrectomy between January 2014–December 2017 were identified from a population-based database (Spanish EURECCA Registry). TO included: macroscopically complete resection at the time of operation, R0 resection, ≥15 lymph nodes removed and examined, no serious postoperative complications (Clavien-Dindo ≥II), no re-intervention, hospital stay ≤14 days, no 30-day readmissions and no 90-day mortality. Logistic regression was used to assess the adjusted achievement of TO. Cox survival regression was used to compare conditional adjusted survival across groups.ResultsIn total, 1293 patients were included, and TO was achieved in 541 patients (41.1%). Among the criteria, “macroscopically complete resection” had the highest compliance (96.5%) while “no serious complications” had the lowest compliance (63.7%). Age (OR 0.53 for the 65–74 years and OR 0.34 for the ≥75 years age group), Charlson comorbidity index ≥3 (OR 0.53, 95%CI 0.34–0.82), neoadjuvant chemoradiotherapy (OR 0.24, 95%CI 0.08–0.70), multivisceral resection (OR 0.55, 95%CI 0.33–0.91), and surgery performed in a community hospital (OR 0.65, CI95% 0.46–0.91) were independently associated with not achieving TO. TO was independently associated with conditional survival (HR 0.67, 95%CI 0.55–0.83).ConclusionTO was achieved in 41.1% of patients who underwent gastric cancer resection with curative intent and was associated with longer survival.     

Defining Textbook Outcome in liver surgery and assessment of hospital variation: A nationwide population-based study

IntroductionTextbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery.MethodsThis was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment.Results2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score ≥3 (aOR 0.70, CI 0.51–0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44–0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34–0.94, p = 0.02), Charlson Comorbidity Index ≥2 (aOR 0.73, CI 0.54–0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36–0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed.ConclusionTO differs between indications for liver resection and can be used to assess between hospital and network differences.     

Immunohistochemically demonstrated suppressed expression of tryptophan oxygenase, a marker for liver differentiation, within putative preneoplastic rat liver lesions

The behaviour of rat liver putative preneoplastic lesions withrespect to the enzyme tryptophan oxygenase (TO), a liver-specificdifferentiation marker, and a possible growth-related marker,glucose-6-phosphate dehydrogenase (G6PD) was investigated duringand after their induction by diethylnitros-amine initiationand subsequent ‘selection pressure’. Using specificantibodies to rat liver TO and G6PD and the avidin-biotin complexmethod for immunohistochemical staining it was demonstratedthat all of the nodular lesions showing increased expressionof G6PD during the induction phase were also negative or deficientin TO enzyme protein. With the onset of ‘phenotypic instability’or loss of marker enzymes, a gradual return to normal expressionof TO activity was evident. Administration of dexamethasoneand L-tryptophan 11 weeks after cessation of carcinogen treatmentallowed differentiation between morphologically altered, apparentlypersisting lesions in which no, or little, enzyme inductionwas apparent and instable lesions showing a strong increasein levels of TO protein. Thus, persisting nodular lesions sharea common lack of response to normal homeostatic physiologicalcontrol.     

宫颈癌三维近距离治疗中两种常用施源器的剂量学比较

目的 对比研究环形施源器(Nucletron#090.617)和三管施源器(Nucletron#189.730)对宫颈癌患者三维近距离治疗受照剂量的影响。 方法 选取已完成治疗的根治性宫颈癌Ⅱ_B—Ⅳ_A期患者 40例,20例采用环形施源器,另外 20例采用三管施源器,分别统计三维近距离治疗计划中靶区 V_150% 、D₁₀₀和膀胱、直肠、小肠 D_{2 cc}。采用立独样本t检验方法对比分析两种施源器在宫颈癌三维近距离治疗中CTV和OAR的剂量。 结果 环形施源器和三管施源器的靶体积分别为(66.04±13.86) cm³、(65.67±15.08) cm³(P=0.052)。环形施源器中 D₁₀₀、V_150%分别为(3.71±0.34) Gy、0.54±0.02;三管施源器中 D₁₀₀、V_150%分别为(3.37±0.49) Gy、0.56±0.04(P=0.016、0.034)。环形施源器中膀胱、直肠、小肠 D_{2 cc}分别为(4.33±0.39)、(3.38±0.30)、(3.04±1.02) Gy,三管施源器的分别为(2.93±1.27)、(2.95±0.80)、(3.41±0.57) Gy (P=0.000、0.037、0.171)。 结论 宫颈癌三维近距离治疗中环形施源器靶区的覆盖度优于三管施源器,而膀胱、直肠受量同时也高于三管施源器,但小肠受量无差异。临床治疗中主要还是根据肿瘤的位置、侵犯范围以及阴道的条件来选择施源器。     

Textbook Outcome as a measure of surgical quality assessment and prognosis in gastric neuroendocrine carcinoma: A large multicenter sample analysis

ObjectiveQuality assurance is crucial for oncological surgical treatment assessment. For rare diseases, single-quality indicators are not enough. We aim to develop a comprehensive and reproducible measurement, called the “Textbook Outcome” (TO), to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma (G-NEC) patients.MethodsData from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed. TO included receiving a curative resection, ≥15 lymph nodes examined, no severe postoperative complications, hospital stay ≤21 d, and no hospital readmission ≤30 d after discharge. Hospital variation in TO was analyzed using a case mix-adjusted funnel plot. Prognostic factors of survival and risk factors for non-Textbook Outcome (non-TO) were analyzed using Cox and logistic models, respectively.ResultsTO was achieved in 56.6% of 860 G-NEC patients. TO patients had better overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) than non-TO patients (P<0.05). Moreover, TO patients accounted for 60.3% of patients without recurrence. Multivariate Cox analysis revealed non-TO as an independent risk factor for OS, DFS, and RFS of G-NEC patients (P<0.05). Increasing TO rates were associated with improved OS for G-NEC patients, but not hospital volume. Multivariate logistic regression revealed that non-lower tumors, open surgery, and >200 mL blood loss were independent risk factors for non-TO patients (P<0.05).ConclusionsTO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients. Factors predicting non-TO are identified, which may help guide strategies to optimize G-NEC outcomes.     

Assignment of two Japanese xeroderma pigmentosum patients to complementation group D and their characteristics

Japanese xeroderma pigmentosum sib patients XP58TO and XP59TO were assigned to complementation group D on the basis of cell hybridization studies. Ultraviolet and 4-nitroquinoline-1-oxide hypersensitivity and reduced unscheduled DNA synthesis of cells of these XP patients were also characteristic of authentic group-D cells. The patients have not yet developed either apparent neuromental abnormalities or skin cancers.     

Tumor subpopulation interactions affecting melphalan sensitivity in palpable mouse mammary tumors

Paired mixtures of melphalan-sensitive and relatively insensitive tumor cell subpopulation lines, originally derived from the same mammary tumor, were injected s.c. into syngeneic mice. When tumors were palpable, the mice were treated with melphalan at doses shown to be effective against the melphalan-sensitive subpopulations. Sensitivity was assessed by the loss of colony-forming ability of tumor cells harvested 1 to 14 days after treatment. When growing in tumors mixed with melphalan-sensitive line 4TO7 cells, line 66 (less sensitive) appeared much more sensitive than when it was grown alone. Line 66 tumors growing on the opposite sides of mice bearing line 4TO7 tumors were not more sensitive than when grown alone, indicating the lack of a systemic mechanism in the transfer of sensitivity from 4TO7 to 66. Furthermore, line 66 was not more sensitive when mixed with line 168TFAR (another melphalan-sensitive subpopulation) than when alone. The "transfer of sensitivity" from line 4TO7 to line 66 could be reproduced in collagen gel cultures but not in monolayer. Interestingly, line 4TO7, unlike line 168TFAR, is more sensitive to melphalan in collagen culture than in monolayer. This difference in sensitivity does not appear to be influenced by differences in cell density between the two culture systems. In collagen culture, the increased sensitivity of line 66 in the presence of line 4TO7 did not require cell contact and so appeared to act through diffusible factors(s). Collectively, these data suggest that the transfer of sensitivity is not dependent upon host factors or upon drug sensitivity per se but rather upon some mechanism requiring tumor cell-tumor cell interaction between specific subpopulation pairs. In additional studies, pH was ruled out as a factor in the transfer of sensitivity.     

Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells

Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents.     

Use of diagnostic tests by dermatologists, podiatrists and family practitioners in the United States: pilot data from a cross-sectional survey

Before treating onychomycosis, it is important to exclude other conditions such as lichen planus and psoriasis. The purpose of this study was to evaluate physician preferences and uses of diagnostic tests for toenail onychomycosis (TO) by surveying dermatologists (D), podiatrists (P) and family practitioners (FP) in the United States. Surveys were mailed to approximately 1000 randomly sampled physicians from each of the three specialities. The questionnaire consisted of 15 items regarding physician and practice characteristics, number of patients with TO seen and treated, tests used to diagnose TO and reasons for using the tests. Results were analysed using several statistical methods. Response rates were low (D33.7%; P16.6%; FP28.4%). Ds and Ps (75.2%) and FPs (43.4%) reported feeling 'very confident' at diagnosing onychomycosis. KOH was the preferred diagnostic test for all three specialities. More Ds (75.4%) felt 'very confident' interpreting potassium hydroxide (KOH) exams than Ps (24.9%) and FPs (18.5%). Use of KOH exams was statistically associated with confidence interpreting exams (P P = 0.04092; D & FP P < 0.0001). Some FPs (46.6%) and Ps (21.6%) did not obtain a confirmatory diagnostic test prior to the treatment of onychomycosis while 63.6% of Ds 'almost always/always' did. While limited by low-response rate, this study provides pilot information on the diagnostic preferences for TO by American D, P and FP.     

Anti-estrogens enhance the therapeutic effect of lymphokine-activated killer cells on the P815 murine mastocytoma

Tamoxifen (TX) and toremifene (TO) enhanced the lysis of P815 mastocytoma cells in vitro by syngeneic DBA2 spleen cells that have been activated by human recombinant interleukin-2 (IL-2) for 6 days (lymphokine-activated killer [LAK] cells). Similarly, enhanced tumor suppression occurred when TX- or TO-treated P815 cells were mixed with LAK cells and injected s.c. into normal DBA2 recipients. Tumor suppression could be increased further by treating such recipients orally with TX or TO and by the repeated injections of LAK cells into the tumor site. The treatment of animals bearing tumors (5 mm in diameter) orally with TX or TO or with LAK cells i.p. resulted in tumor suppression. When the drug treatment was combined with LAK cells, tumor suppression was more pronounced, and complete tumor regression was induced in a significant number of the animals so treated. Our results indicate that the immunotherapeutic effect of LAK cells can be significantly amplified by combined treatment with the anti-estrogens TX or TO. © 1996 Wiley-Liss, Inc.     

Vincristine-resistant human leukemia cell line: new monoclonal antibodies to a 65kDa membrane protein.

A vincristine-resistant human myelomonocytic leukemic cell line (KY-VCR) was established. KY-VCR exhibited approximately a 2.5 x 10(6)-fold increase in resistance to vincristine compared to the parental cell line. KY-VCR showed a decreased uptake and, an increased efflux of vincristine, and cross-resistance to Adriamycin and Actinomycin D. The M(r) 200,000 membrane glycoprotein was overexpressed in KY-VCR. Furthermore, two antibodies, designated TO73 and TO77, preferentially reacting with KY-VCR were obtained. Enzyme linked immunosorbent study indicated that both antibodies recognized the same epitope and TO77 the wide portion. Immunoprecipitation analysis demonstrated that the antibodies recognized M(r) 65,000 membrane protein, which was distinct from overexpressed glycoprotein in KY-VCR. The induction of membrane protein identified by the antibodies may play a role in drug resistance. KY-VCR cells and two antibodies to them may be very useful for the study of drug resistance and prediction of drug efficacy.     

Inhibition of repairable DNA-damage in Escherichia coli K-12 cells recovered from various organs of nitrosamine-treated mice by vitamin A, phenethylisothiocyanate, oleic acid and triolein.

The influence of various dietary constituents--phenethylisothiocyanate (PEITC), oleic acid (OA), triolein (TO), and vitamin A (ROL)--on the genotoxic activity of nitrosamines (NDMA, NDELA, NPYR) was investigated. For this purpose differential DNA repair assays with Escherichia coli K-12 strains were performed in vitro and in vivo with mice. Under in vitro conditions (liquid holding), all compounds reduced nitrosamine induced DNA-damage in the indicator bacteria in the dose range 1-10 micrograms/ml, the ranking order of efficiency being PEITC greater than OA greater than ROL greater than or equal to TO. In animal-mediated assays, acute oral treatment with PEITC (17-150 mg/kg), 2 h before nitrosamine administration, resulted in a marked decrease of nitrosamine genotoxicity in liver, kidneys, lungs and in the blood. Also in other organs (spleen, testes) an increase in differential survival (which serves as a measure for repairable DNA damage) occurred. With ROL only a comparatively moderate antigenotoxic effect was obtained at a high dose level (250 mg/kg) under identical experimental conditions. OA (2000 mg/kg) and TO (16,000 mg/kg) were completely inactive. Upon repeated treatment (consecutive oral administration of the putative antigenotoxins over 4 days, a final treatment 24 h before nitrosamine administration) PEITC (150 mg/kg/day), ROL (80 mg/kg/day) and OA (2000 mg/kg/day) had no influence on the genotoxic effects of the nitrosamines. Repeated treatment with TO (4000-16,000 mg/kg/day) resulted in a moderate dose-dependent reduction of NDMA-induced DNA-damage in the indicator bacteria, whereas in combination with NPYR only a marginal effect was observed. Biochemical experiments indicated that the antigenotoxic effects of PEITC seen under in vivo conditions were due to inhibition of alpha-hydroxylation of the nitrosamines, whereas ROL and TO appeared not to interfere strongly with this metabolic activation step. Our results indicate that in vitro assays do only partly reflect the antigenotoxic properties of the different food constituents in vivo and that animal-mediated DNA repair assays with E. coli strains are an appropriate approach to study the effects of modifiers of nitrosamine genotoxicity in the living animal.     

Clinical analysis of 276 cases of non-palpable TO breast cancer

Objective Discussion of diagnosis, treatment and prognosis of non-palpable TO breast cancer. Methods Between 1978 and 1997, 9,980 female patients with operable breast cancer were treated surgically, of which 276 were determined to have TO breast cancer. Most TO breast cancers could be detected promptly with careful examination of presenting symptoms, such as nipple discharge, local thickening of the breast, nipple erosion, nipple retraction and postmenopausal mastalgia, while 12 cases were detected by routine mammography of the contralateral breast. Results All patients were treated surgically and their tissue subjected to histopathological examination. Most cases (73.0%) were noninvasive or early invasive carcinoma. Axillary lymph nodes metastases were found in 7.69% of 234 mastectomy cases. Conclusion The survival rate was significantly increased if the tumor was in an early stage. The 5-, 10-, 15-years survival rates were 98.1%, 94.6% and 90.3%, respectively.     

Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade?

British Journal of Cancer (2002) 86, 1662–1663. DOI: 10.1038/sj/bjc/6600313 www.bjcancer.com© 2002 Cancer Research UK     

Strain-specific tumorigenesis in mouse skin induced by the carcinogen, 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one, and its relation to DNA adduct formation and persistence

The incidence of skin tumors has been studied in three strains of mice, namely, TO, C57BL, and DBA/2, after treatment with the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one. After either a single dose followed by croton oil promotion or a continual dose of the carcinogen, tumors were observed in the TO and C57BL strains, with the TO mice having the shorter mean latent period. The DBA/2 mice, however, appeared to be resistant to tumor formation by either treatment. To understand the mechanism of resistance, several criteria have been investigated. Metabolism of the carcinogen was assessed in terms of the total DNA adduct formation and the pattern of individual adducts after separation by high-pressure liquid chromatography, and no major differences between the three strains was found. Similarly, the rates of disappearance of the individual adducts when measured over 14 days posttreatment were not strain specific. Persistent binding of the carcinogen after 2 months was found in all three strains and could be reduced markedly if croton oil was administered throughout this period. The ability of the phorbol esters to cause biochemical changes in both sensitive and resistant strains was indicated by the induction of ornithine decarboxylase in each of the three strains after treatment with either croton oil or its active component, 12-O-tetradecanoylphorbol-13-acetate.