Label-free ultra-sensitive colorimetric detection of hepatitis E virus based on oxidase-like activity of MnO2 nanosheets.

Hepatitis E virus (HEV) is an evolving infectious entity that causes viral hepatitis infections worldwide. Current routine methods of identifying and diagnosing HEV are someway laborious and costly. Based on the biomimicking oxidase-like activity of MnO2 nanosheets, we designed a label-free, highly sensitive colorimetric sensing technique for HEV detection. The prepared MnO2 catalyst displays intrinsic biomimicking oxidase-like catalytic activity and efficiently oxidizes the 3,3',5,5'-tetramethylbenzidine (TMB) substrate from colorless to blue colored oxidized TMB (oxTMB) product which can be measured at 652 nm by UV-visible spectrum. When the HEV-DNA was added, DNA adsorbed easily on MnO2 surface through physical adsorption and electrostatic interaction which hinders the oxidase-like catalytic activity of MnO2. Upon the introduction of target, the HEV target DNA binds with its complementary ssDNA on the surface of MnO2, the hybridized DNA releases from the surface of MnO2, which leads to recovery of oxidase-like catalytic activity of MnO2. This strategy was applied to construct a colorimetric technique for HEV detection. The approach works in the linear range of 1 fM-100 nM DNA concentration with the limit of detection (LOD) of 3.26 fM (S/N = 3) and quantitative limit (LOQ) of 36.08 fM. The TMB-MnO2 platform was highly selective for HEV target DNA detection when compared with potential interferences. Result of serum sample analysis demonstrates that this sensing system can be used for clinical diagnostic applications.

Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH.

The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification.

Diaqua-bis-(nitrato-κO)bis-(pyridine-κN)manganese(II).

The structure of the title manganese complex, [Mn(NO3)2(C5H5N)2(H2O)2], consists of discrete monomeric entities with Mn(2+) ions located on centres of inversion. The metal cation is octahedrally coordinated by a trans-N2O4 donor set with the pyridine N atoms located in the apical positions. Discrete mol-ecules are linked by O-H⋯O hydrogen bonds into one-dimensional supra-molecular infinite chains along the b and c axes.

Lung neuroendocrine neoplasms: a single centre surgical series and analysis of staging.

BACKGROUND: To review the outcomes of surgically resected lung neuroendocrine neoplasms (LNEN) at a tertiary referral centre and to validate a previously published LNEN-specific staging system (NETL). METHODS: All patients who were identified on histopathology to have LNEN were included. Pre-, intra- and post-operative outcomes were collected, including long-term survival. Patients were staged by both the TNM (seventh and eighth edition) and NETL staging (seventh and eighth edition definitions). Kaplan-Meier (KM) survival analysis was performed according to histopathology and stage, along with uni- and multivariate analyses. RESULT: A total of 132 patients were included in the study, with a median age of 65 years; 55% were female. Typical carcinoid (TC) was the most common pathology (53.4%) followed by large cell neuroendocrine carcinoma (LCNEC - 23.5%), atypical carcinoid (AC - 20.5%) and small cell carcinoma (3.0%). The most common operation performed was a lobectomy (55.3%). Overall survival at 5 years was 80% (100% TC, 78.2% AC, LCNEC 40.9%) and 5-year disease free survival was 76.8% (TC 94.3%, AC 56.8%, LCNEC 56.4%). KM curves showed a trend towards NETL performing better than TNM, however, in multivariate analysis only the histological subtype was found to be significant in our study. CONCLUSION: This is the largest known Australian series of LNEN to date, showing survival comparable to international outcomes. We have demonstrated large variations in outcome, driven by histological grade. The TNM system does not correlate with survival and we have not been able to show that currently proposed NETL staging is superior.

Novel Schiff bases of Vanillin: potent inhibitors of macrophage harbored Leishmania tropica.

Due to limited chemotherapeutic options for leishmaniasis, novel synthetic compounds are gaining attention for evaluation against leishmaniasis. This study aimed to synthesize the compound's Schiff bases of Vanillin to investigate and evaluate their anti-leishmanial potentials against intracellular protozoan parasites Leishmania tropica. In the current study, the phenomena of synergism by designing Schiff bases with Vanillin enhances their desired importance. A total of five compounds Schiff bases of Vanillin were synthesized using different aromatic amines and Vanillin. The structural analysis of all the compounds was done through FT-IR (Fourier Transformer-Infrared), thin layer chromatography, and spectroscopic techniques such as 13C-NMR, mass spectrometry, and 1H-NMR. The antimicrobial properties of all the compounds ZI-1, ZI-2, BS-1, KH-1, and FA-2 against promastigotes and amastigotes forms of L. tropica were analyzed at three different concentrations 25, 50, and 100 µg/ml. The in-vitro MTT assay was performed to calculate the percent inhibition, IC50 values, and their cytotoxicity. The highest percent inhibition values against promastigote form of L. tropica were BS-1 53.78% at 25 µg/ml, ZI-2 66.95% at 50 µg/ml, and again ZI-2 76.92% at 100 µg/ml. Similarly, the highest percent inhibition values against intracellular amastigote stage were BS-1 55.77% at 25 µg/ml, ZI-2 67.78% at 50 µg/ml and again ZI-2 84.93% 100 µg/ml. The highest potency was recorded for BS-1 in both stages, with IC50 values of 9.83 and 4.27 µg/ml against promastigotes and intracellular amastigotes, respectively. The percent hemolysis as toxicity; the lowest percent hemolysis was recorded for ZI-1 at three different concentrations of 25, 50, 100 µg/ml of 2.60, 3.50, and 6.31, respectively. These results suggested that all the compounds exhibited anti-leishmanial activity, with BS-1 as the most potent. Further studies are suggested to increase the activity of compounds with structural modifications by the addition of some other synergistic, novel, and analogue compounds.

Death in the home: domestic violence against women in Khyber Pakhtunkhwa.

BACKGROUND: Domestic or Interpersonal Violence (IPV) remains a major global problem often resulting in morbidity and mortality. The present study was conducted to determine the scope of deaths related to domestic violence in the Khyber Pakhunkhwa province, Pakistan. METHODS: Data were collected on all reported female fatalities due to domestic violence for the years 2009-2011 from the records of the department of Forensic Medicine, Khyber Medical College Peshawar for analysis. RESULTS: A total of 305 deaths were reported, showing an increasing trend of 115 deaths for 2009-10 and 190 deaths for 2010-2014. The majority, 182 (59.7%) belonged to the rural areas and 123 (40.3%) to urban areas of the province. Victims were generally of the younger age groups (17% below age 16 and 42.3% between 17-32 years). Homicide was the manner of death in 293 (96.1%) while the most common causative agent was firearm injury (235, 77.1%). Head and neck injuries were most common (52.6%) followed by the chest and abdomen (31.6%) while multiple sites and extremities accounted for 15.8% of injuries. CONCLUSION: Young and adult females of KPK province of Pakistan are susceptible to homicidal deaths due to domestic violence, perpetrated through firearm injuries to the head and neck regions.

Bis(O-n-butyl dithio-carbonato-κS,S')bis-(pyridine-κN)manganese(II).

The structure of the title manganese complex, [Mn(C(5)H(9)OS(2))(2)(C(5)H(5)N)(2)] or [Mn(S(2)CO-n-Bu)(2)(C(5)H(5)N)(2)], consists of discrete monomeric entities with Mn(2+) ions located on centres of inversion. The metal atom is coordinated by a six-coordinate trans-N(2)S(4) donor set with the pyridyl N atoms located in the apical positions. The observed slight deviations from octa-hedral geometry are caused by the bite angle of the bidentate κ(2)-S(2)CO-n-Bu ligands [69.48 (1)°]. The O(CH(2))(3)(CH(3)) chains of the O-n-butyl dithio-carbonate units are disordered over two sets of sites with an occupancy ratio of 0.589 (2):0.411 (2).

catena-Poly[[diaqua-bis-(3-methyl-pyridine-κN)cobalt(II)]-µ-sulfato-κO:O'].

The environment of the Co(II) ion in the title compound, [Co(SO(4))(C(6)H(7)N)(2)(H(2)O)(2)](n), exhibits an octa-hedral configuration with the two 3-methyl-pyridine ligands lying in cis positions with respect to each other and trans to the two coordinated water mol-ecules. The axial positions are occupied by O atoms of the sulfate ions. Co and S atoms occupy special positions (twofold axis, Wyckoff position 4c). Neighboring Co(II) ions are covalently connected with each other through the sulfate ions, thus creating infinite polymeric chains that run along the c axis. The water mol-ecules are connected with neighboring sulfate ions through strong O-H⋯O hydrogen bonds. Intra-molecular hydrogen bonds parallel to the propagation direction of the chains stabilize the polymeric chains, and inter-molecular hydrogen bonds between chains connect neighboring chains with each other, thus leading to polymeric double chains.

catena-Poly[[[tetra-kis-(4-methyl-pyridine-κN)copper(II)]-µ-sulfato-κO:O'] 4.393-hydrate].

The structure of the title compound, {[Cu(SO(4))(C(6)H(7)N)(4)]·4.393H(2)O}(n), consists of Cu(2+) ions surrounded in a square-planar fashion by 4-methyl-pyridine ligands, forming two crystallographically independent Cu{H(3)C(C(5)H(4)N)}(4) units that are both located on crystallographic inversion centers. The Cu(4-methyl-pyridine)(4) units are, in turn, connected with each other via bridging sulfate anions, leading to the formation of infinite [Cu{H(3)C(C(5)H(4)N)}(4)SO(4)](n) zigzag chains along [001]. The completed coordination spheres of the Cu(2+) ions are slightly distorted octa-hedral. The axial Cu-O bonds are elongated [average length = 2.42 (4) Å] compared to the equatorial Cu-N bonds [average length = 2.043 (2) Å]. The inter-stitial space between the chains is filled with uncoordinated water mol-ecules that consolidate the structure through O-H⋯O hydrogen bonding. One of the five crystallographically independent solvent water mol-ecules is partially occupied with an occupancy factor of 0.396 (4). Due to hydrogen bonding between symmetry-equivalent water mol-ecules across inversion centers, several of the water H atoms are disordered in 1:1 ratios over mutually exclusive positions. The crystal under investigation was found to be non-merohedrally twinned in a 0.789 (1):0.211 (1) ratio by a 180° rotation around the reciprocal b axis.

Pulmonary carcinoid tumours: A multi-centre analysis of survival and predictors of outcome following sublobar, lobar, and extended pulmonary resections.

BACKGROUND: Pulmonary carcinoids are rare neoplasms, accounting for approximately 1%-2% of all lung malignancies. A retrospective analysis was undertaken of all patients who underwent surgical resection of pulmonary carcinoid tumours across multiple institutions in Melbourne, Australia. METHODS: From May 2000 through April 2020, 241 patients who underwent surgical resection of pulmonary carcinoid tumours were retrospectively reviewed. Patient demographics, pathologic data, and long-term outcomes were recorded. RESULTS: Median age was 57.7 years and the majority of patients were female (58.9% vs. 41.1%). Typical carcinoid was present in 77.1%. Histological subtype was associated with several factors. Atypical carcinoid was more likely to have larger tumour size and nodal involvement. Overall survival for typical carcinoid at 5, 10, and 15 years was 98%, 95%, and 84%, and for atypical carcinoid was 88%, 82%, and 62%, respectively. Histological subtype and age were found to be independent predictors of overall survival, with worse outcomes for atypical and those above 60 years of age. Disease-free survival was related to sublobar resection (p < 0.001, sub-hazard ratio (SHR): 6.89), lymph node involvement (p = 0.022, SHR: 3.18), and atypical histology (p < 0.001, SHR: 9.89). CONCLUSION: Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoids. Atypical histology and lymph node involvement are significant prognostic factors, and sublobar resection should not be considered in patients with either of the above features. Typical carcinoid tumour without nodal involvement may be appropriate for sublobar resection. Typical and atypical carcinoid tumours should be considered distinct disease entities, and as such treated accordingly.

Novel technique for parietal pleural dissection using a laparoscopic hernia balloon.

We describe a novel technique for the creation of a pleural tent and pleurectomy via the use of a laparoscopic hernia balloon. In this method a Spacemaker™ Structural Balloon Trocar (Covidien, USA) is tunnelled under the pleura at the site of thoracotomy or video assisted thoracoscopic surgery port and incrementally inflated under vision. This method is less traumatic than traditional methods, is more likely to provide an intact pleural tent, and allows the surgeon to operate in a near bloodless operative field.

Foliar epidermal anatomy of some selected wild edible fruits of Pakistan using light microscopy and scanning electron microscopy.

The present study is focused on the detailed foliar epidermal anatomy of some selected wild edible fruits (WEFs) from Pakistan using light microscopy (LM) and scanning electron microscopy (SEM). The studied species are Ficus racemosa L., Solanum nigrum L., Capparis spinosa L., Physalis divaricata D.Don, Rosa moschata Herrm. and Ribes orientale Desf. collected from various localities of Pakistan. The objective of the present study is to investigate qualitative and quantitative anatomical characters for the identification and differentiation of collected wild edible fruits. The characters studied are shape and size of epidermal cells, anticlinal wall pattern, trichome type and shape, average number of stomata, length and width of stomata and pore. The detailed microscopic investigation and variations in the characters recorded have a key role in the determination and authentication of wild edible fruits. This study possesses great potential for plant taxonomists to further evaluate the species at molecular and genetic levels.

The Past, Present and Future of Pulmonary Metastasectomy: A Review Article.

Pulmonary metastases are a sign of advanced malignancy and an omen of poor prognosis. Once primary tumors metastasize, they become notoriously difficult to treat and interdisciplinary management often involves a combination of chemotherapy, radiotherapy, and surgery. Over the last 25 years, the emerging body of evidence has recognized the curative potential of pulmonary metastasectomy. Surgical resection of pulmonary metastases is now commonly considered for patients with controlled primary disease, absence of widely disseminated extrapulmonary disease, completely resectable lung metastases, sufficient cardiopulmonary reserve, and lack of a better alternative systemic therapy. Since the development of these selection criteria, other prognostic factors have been proposed to better predict survival and optimize the selection of surgical candidates. Disease-free interval (DFI), completeness of resection, surgical approach, number and laterality of lung metastases, and lymph node metastases all play a dynamic role in determining patient outcomes. There is a definite need to continue reviewing these prognosticators to identify patients who will benefit most from pulmonary metastasectomy and those who should avoid unnecessary loss of lung parenchyma. This literature review aims to explore and synthesize the last 25 years of evidence on the long-term survival, prognostic factors, and patient selection process for pulmonary metastasectomy.

Pulmonary metastasectomy: analysis of survival and prognostic factors in 243 patients.

BACKGROUND: Pulmonary metastases are a sign of advanced malignant disease. Interdisciplinary management of metastatic cancer mandates the consideration of all treatment options, and in selected patients pulmonary metastasectomy can be performed with curative intent. This study aims to analyze the prognostic factors associated with survival and optimize the selection of surgical candidates. The sarcoma subset analysis aims to examine the role of multiple repeat resections for pulmonary metastatic recurrence. METHODS: A total of 243 patients were analyzed in this retrospective cohort study. Overall survival was estimated using Kaplan-Meier analysis. Univariate analyses with log-rank tests and multivariate analysis with Cox proportional hazards model were undertaken to determine the independent prognostic factors for survival. RESULTS: Multivariate analyses identified germ cell cancer (P = 0.01) and a disease-free interval of >36 months (P = 0.006) as significant independent prognostic factors for improved survival, whilst synchronous metastases (P = 0.04), multiple metastases (P = 0.005) and incomplete resection (P < 0.001) were identified as significantly poor prognostic factors. Subset analyses identified that ≥2 repeat resections within the sarcoma cohort was associated with an increased median survival of 63.5 months (P = 0.04). CONCLUSION: In selected patients, pulmonary metastasectomy can be performed with curative intent and have associated long-term survival benefits. Patients presenting with recurrent sarcoma pulmonary metastases should be considered for repeat metastasectomy.

Outcomes following resection of non-small cell lung cancer in octogenarians.

BACKGROUND: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia. METHODS: We retrospectively reviewed data from all patients aged ≥80 years who underwent curative-intent resection for NSCLC over 12 years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival. RESULTS: Two hundred patients aged ≥80 years underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those ≥83 years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients ≥83 years requiring lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83 years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02). CONCLUSION: In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.

Video-assisted thoracic surgery (VATS) lobectomy: the evidence base.

BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy provides a minimally invasive alternative for management of early stage non-small cell lung cancer, but is still only performed in a few specialized centers around the world. Questions about the safety of the surgery and its adequacy as a cancer operation remain hurdles for many surgeons. METHODS: We performed a systematic review of the literature on VATS lobectomy to assess these questions. The MEDLINE database was queried and the papers analyzed. RESULTS: Four randomized control trials, 11 case-control series, and 10 case series were reviewed. A variety of VATS techniques are used, making generalization of results difficult. The weight of this evidence suggests that VATS lobectomy can be safely performed and is an adequate cancer operation for early stage non-small cell lung cancer. There is also evidence that patients experience less pain with VATS, but that length of hospital stay is similar. CONCLUSION: In expert hands, VATS lobectomy appears to be a safe procedure. However, the published evidence is thin and ongoing study is required, preferably with standardization of VATS techniques.

Impact of sex on prognostic host factors in surgical patients with lung cancer.

BACKGROUND: Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. METHODS: Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. RESULTS: The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). CONCLUSIONS: Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men.

Correlation between molecular analysis, diagnosis according to the 2015 WHO classification of unresected lung tumours and TTF1 expression in small biopsies and cytology specimens from 344 non-small cell lung carcinoma patients.

We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected. More EGFR-mutant (78%) and ALK-rearranged (75%) tumours had morphologic adenocarcinoma than KRAS-mutant (56%) tumours. Despite no significant difference in the overall rate of any molecular abnormality between morphologic adenocarcinoma (52%) and NSCLC, favour adenocarcinoma (47%) (p = 0.18), KRAS mutations were detected more frequently in the latter group. No significant difference in the overall rate of any molecular abnormality between TTF1 positive (49%) and TTF1 negative tumours (44%) (p = 0.92) was detected, but more EGFR-mutant (97%) and ALK-rearranged tumours (92%) were TTF1 positive than KRAS-mutant tumours (68%). Rates of EGFR, KRAS and BRAF mutations and ALK rearrangements in this Australian NSCLC patient population are consistent with the published international literature. Our findings suggest that 2015 WHO classification of unresected tumours may assist in identifying molecular subsets of advanced NSCLC.

Adjuvant chemotherapy for completely resected non-small cell lung cancer: a systematic review.

PURPOSE: To conduct a systematic review and to evaluate the impact of postoperative adjuvant chemotherapy on the survival of patients with completely resected non-small cell lung cancer. METHODS: Relevant randomized trials and meta-analyses, published as articles or abstracts, were identified through electronic and hand searches by two reviewers. RESULTS: Seven meta-analyses and 26 randomized trials comparing surgery with or without chemotherapy met the pre-defined eligibility criteria for the review. The meta-analyses all showed a survival advantage for platinum- or UFT-based postoperative chemotherapy, although the results did not always achieve statistical significance. The results of individual trials were inconsistent, although recent trials have detected a large survival advantage with postoperative platinum-based chemotherapy. Differences in trial design, patient characteristics, disease stage, use of radiotherapy and chemotherapy regimen may explain the variation in results. CONCLUSIONS: Postoperative adjuvant platinum-based chemotherapy improves survival compared with surgery alone in completely resected non-small cell lung cancer. In patients fit for chemotherapy, the survival benefits strongly outweigh the adverse effects of the treatment.