CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

Ergonomic port placement in robotic colorectal surgery.

AIM: The aim of the study was to determine how spacing between ports and alignment of ports (oblique or vertical) influences manipulation angles in robotic colorectal surgery. METHOD: Abdominal CT scans of 10 consecutive robotic right hemicolectomy and 10 consecutive robotic high anterior resection patients were analysed. The manipulation angles were calculated using fixed points on the preoperative abdominal coronal CT scan. Port placements were marked on the CT scan. The fixed points used to measure the manipulation angles were from the most lateral part of the caecum, hepatic flexure, splenic flexure, the descending colon/sigmoid colon junction and the sigmoid colon/rectum junction. RESULTS: For right hemicolectomy and high anterior resection surgery, a port spacing of 8 cm compared with 6 cm resulted in greater manipulation angles. With 6-cm port spacing, wider manipulation angles were not achieved with vertical port alignment compared with oblique alignment except for dissection at the splenic flexure. CONCLUSIONS: The greatest manipulation angles were achieved with the oblique 8-cm port spacing, which should be used in most cases.

Significance of Phosphorylated Epidermal Growth Factor Receptor and Its Signal Transducers in Human Soft Tissue Sarcoma.

Abstract: Previous studies have shown that total epidermal growth factor receptor (EGFR) protein is highly expressed in soft tissue sarcoma (STS). We aimed to investigate the significance of phosphorylated-EGFR (pEGFR) and its activated-downstream signal transducers in STS tissue samples. A tissue microarray comprising 87 STS samples was assessed for total EGFR, pEGFR and its phosphorylated signal transducers and expression was correlated with clinicopathlogical parameters including patient outcome. Although the expression of total EGFR was significantly associated with adverse STS histologic grade (p = 0.004) and clinical stage (p = 0.012) similar to pEGFR, phosphorylated protein kinase B (pAkt) and phosphorylated extracellular signal regulated kinase (pERK), it is not a prognostic factor for survival. By contrast, the expression of pEGFR is an independent factor for cancer specific survival, while pERK is an independent prognostic factor for both overall and cancer specific survival in STS (p < 0.05, Cox proportional hazard model and log-rank test) in addition to the recognised factors of tumour grade and clinical stage. pERK and pEGFR are new independent prognostic factors for overall and/or cancer specific survival in STS. The expression of EGFR/pEGFR, and their associated downstream signal transducers, was associated with STS progression, suggesting that EGFR downstream signalling pathways may jointly support STS cell survival.

A Microscopic and Biomarker Evaluation of Embolic Filter Debris Collected During Carotid Artery Stenting.

PURPOSE: To evaluate and characterize debris retrieved from the cerebral embolic protection devices (EPDs) used during carotid artery stenting (CAS) and compare debris size, volume, tissue types, cellular composition, and protein biomarker expression in symptomatic and asymptomatic patients. METHODS: Distal protection filters were retrieved from 22 consecutive patients (mean age 71.6 years, range 52-85; 16 men) undergoing elective CAS between July 2012 and February 2014 for >70% internal carotid artery stenosis (mean 85.4% ± 10.3%). Six patients were symptomatic. The debris within each EPD was visually characterized using stereomicroscopy and then processed for histology and immunohistochemistry. Biomarkers were immunohistochemically measured to evaluate plaque stability [matrix metalloproteinase-9 (MMP-9)], inflammation [glycoprotein CD68 and interleukin-6 (IL-6)], or phenotype [smooth muscle (SM)-actin and type IV collagen]. The immunohistochemical results were measured using semiquantitative grading criteria based on both staining intensity and distribution in the samples. RESULTS: Macroscopic debris was visible in 5/22 EPDs; 3 of the 5 filters came from symptomatic patients. Microscopic debris was detected in all filters and ranged in size from 0.01 to 8.57 mm(2). Debris consisted of calcified, fibrous, and necrotic tissue, as well as fibrin and foam cells with no significant difference between the symptomatic and asymptomatic groups. There was no association between the degree or type of embolic material and stenosis severity, carotid tortuosity, calcium grade, soft plaque, or arch type. Symptomatic patients had a larger volume of debris (8.24 vs 0.58 mm(3), p<0.01), mean particle size (1.30 vs 0.32 mm(2), p<0.001), and expression of biomarkers IL-6 (2.17 vs 0.81, p<0.05), CD68 (2.00 vs 0.38, p<0.01), SM-actin (1.00 vs 0.25, p=0.055), type IV collagen (1.17 vs 0.25,p=0.082), and MMP-9 (1.00 vs 0.06, p<0.05). CONCLUSION: Histological analysis revealed particulate embolization in all EPDs used during CAS. Symptomatic patients had a larger volume of embolic debris, mean particle size, and the biomarkers associated with inflammation, necrotic core, and diminished fibrous cap.

Cognitive ergonomics and robotic surgery.

Cognitive ergonomics refer to mental resources and is associated with memory, sensory motor response, and perception. Cognitive workload (CWL) involves use of working memory (mental strain and effort) to complete a task. The three types of cognitive loads have been divided into intrinsic (dependent on complexity and expertise), extraneous (the presentation of tasks) and germane (the learning process) components. The effect of robotic surgery on CWL is complex because the postural, visualisation, and manipulation ergonomic benefits for the surgeon may be offset by the disadvantages associated with team separation and reduced situation awareness. Physical fatigue and workflow disruptions have a negative impact on CWL. Intraoperative CWL can be measured subjectively post hoc with the use of self-reported instruments or objectively with real-time physiological response metrics. Cognitive training can play a crucial role in the process of skill acquisition during the three stages of motor learning: from cognitive to integrative and then to autonomous. Mentorship, technical practice and watching videos are the most common traditional cognitive training methods in surgery. Cognitive training can also occur with computer-based cognitive simulation, mental rehearsal, and cognitive task analysis. Assessment of cognitive skills may offer a more effective way to differentiate robotic expertise level than automated performance (tool-based) metrics.

Ergonomic interventions to reduce upper limb musculoskeletal pain during robotic surgery: a narrative review.

There is a high prevalence of upper limb musculoskeletal pain among robotic surgeons. Poor upper limb ergonomic positioning during robotic surgery occurs when the shoulders are abducted, and the elbows are lifted off the console armrest. The validated rapid upper limb assessment can quantify ergonomic efficacy. Surface electromyography and hand dynamometer assessment of strength are the most common methods to assess muscle fatigue. A literature review was performed to find evidence of ergonomic interventions which reduce upper limb musculoskeletal pain during robotic surgery. There is a paucity of studies which have reported on this topic. In other occupations, there is strong evidence for the use of resistance training to prevent upper extremity pain. Use of forearm compression sleeves, stretching, and massage may help reduce forearm fatigue. Microbreaks with targeted stretching, active ergonomic training, improved use of armrest, and optimal hand controller design have been shown to reduce upper limb musculoskeletal pain. Future studies should assess which interventions are beneficial in reducing surgeon upper limb pain during robotic surgery.

Ergonomic hand positioning overcomes visual perception mismatch in nonsimulated robotic colorectal surgery.

The aim of the study was to compare the internal instrument and external surgeon hand positions to determine whether visual perception mismatch (VPM) is a factor during robotic colorectal surgery. Continuous video footage of 24 consecutive robotic colorectal surgery cases were analysed concurrently with sagittal video recordings of surgeon hand positions. Separated sagittal hand positions would indicate nonergonomic positioning without clutching of the robotic controls, either matching the on-screen up/down instrument tip positions (no VPM) or in the opposite direction (true VPM). Variables (30-min surgery time blocks, anatomic target, and task performed), which resulted in hand separation or VPM, were analysed. Operating with the presence of VPM for more than one duration occurred 51 times and nonergonomic sagittal hand positioning occurred 22 times. For an experienced robotic surgeon, ergonomic positioning of the hands is favoured over adjustment for VPM despite the potential higher mental workload.

Visualisation ergonomics and robotic surgery.

Stereopsis may be an advantage of robotic surgery. Perceived robotic ergonomic advantages in visualisation include better exposure, three-dimensional vision, surgeon camera control, and line of sight screen location. Other ergonomic factors relating to visualisation include stereo-acuity, vergence-accommodation mismatch, visual-perception mismatch, visual-vestibular mismatch, visuospatial ability, visual fatigue, and visual feedback to compensate for lack of haptic feedback. Visual fatigue symptoms may be related to dry eye or accommodative/binocular vision stress. Digital eye strain can be measured by questionnaires and objective tests. Management options include treatment of dry eye, correction of refractive error, and management of accommodation and vergence anomalies. Experienced robotic surgeons can use visual cues like tissue deformation and surgical tool information as surrogates for haptic feedback.

Workflow disruptions in robot-assisted surgery.

Surgical flow disruptions are unexpected deviations from the natural progression which can potentially compromise the safety of the operation. Separation of the surgeon from the patient and team members is the main contributor for flow disruptions (FDs) in robot-assisted surgery (RAS). FDs have been categorised as communication, coordination, surgeon task considerations, training, equipment/ technology, external factors, instrument changes, and environmental factors. There may be an association between FDs and task error rate. Intervention to counter FDs include training, operating room adjustments, checklists, teamwork, communication improvement, ergonomics, technology, guidelines, workflow optimisation, and team briefing. Future studies should focus on identifying the significant disruptive FDs and the impact of interventions on surgical flow during RAS.

Automated performance metrics, learning curve and robotic colorectal surgery.

BACKGROUND: The aim of this study was to evaluate the usefulness of Automated Performance Metrics (APMs) in assessing the learning curve. METHODS: A retrospective review of 85 consecutive patients who underwent total robotic colorectal surgery at a single institution between August 2020 and October 2022 was performed. Patient demographics, operation type, and APMs were collected and analysed. Cumulative summation technique (CUSUM) was used to construct learning curves of surgeon console time (SCT), use of the fourth arm, clutch activation, instrument off screen (number and duration), and cut electrocautery activation. RESULTS: Two phases with 50 and 35 cases were identified from the CUSUM graph for SCT. The SCT was significantly different between the two phases (176 and 251 min, p < 0.002). After adjustment for SCT, the APMs were not significantly different between the two phases. CONCLUSIONS: Most APMs do not offer additional learning curve information when compared with SCT analysis alone.

Improving ergonomics for the bedside assistant in robotic colorectal surgery.

The aim of the study was to document when significant bedside assistant (BA) and robotic arm collisions occurred during robotic colorectal surgery (RCS). An observational study of 10 consecutive RCS cases, from May 2022 to September 2022, was performed. Situations when there was significant collision between BA arm and robotic arm (to cause inadvertent movement of the assistant instrument) were documented. The assistant port was randomly placed to the right or the left side of the camera port. Situations which led to detrimental BA ergonomics include dissection at the most peripheral working field, proximity of the target (mesenteric vessels), small bowel retraction, placement of the assistant port in the medial position (on the left side of the camera port), during intra-corporeal suturing and robotic stapler use. The robotic console surgeon can predictably identify and avoid situations when injury to the BA may occur.

The impact of additional pathology analysis on the diagnosis and management of soft tissue tumours: a 10-year retrospective study.

In order to characterise soft tissue tumours, pathologists often utilise specialised additional tests, or may seek opinions from subspecialist pathologists due to rarity or complex morphology. Additionally, further review may be sought by subspecialist sarcoma pathologists, such as those at our tertiary referral centre in Sydney, Australia. The aim of this study was to examine the impact on diagnosis and management of this external review, following diagnosis at a specialised sarcoma unit. We collated the results of all additional external ancillary tests and specialist reviews over a 10-year period and characterised the impact on the preliminary diagnosis as 'confirmed', 'new' or 'no clear diagnosis'. We subsequently noted whether the additional findings resulted in a clinically significant change in management. Of the 136 cases sent away, 103 patients had their initial diagnosis confirmed, 29 patients received a new diagnosis and, for four patients, the diagnosis remained uncertain. Nine of the 29 patients receiving a new diagnosis had their management altered. This study demonstrated that within our specialised sarcoma unit, the majority of diagnoses provided by our specialist pathologists are confirmed on additional external testing and review, but external review does provide additional assurance and benefit to the patient.

Factors affecting upper limb ergonomics in robotic colorectal surgery.

The aim of the study was to examine the factors which may influence suboptimal ergonomic surgeon hand positioning during robotic colorectal surgery (RCS). An observational study of 11 consecutive RCS cases from June 2022 to August 2022 was performed. Continuous video footage of RCS cases was analysed concurrently with video recordings of surgeon's hand positions at the console. The outcome studied was the frequency with which either hand remained in a suboptimal ergonomic position outside the predetermined double box outlines, as marked on the surgeon's video, for >1 min. Situations which resulted in poor upper limb ergonomics were dissection in the peripheral operating field location, left-hand use, use of the stapler, dissection of the main mesenteric blood vessels, and multi-quadrant surgery. Being aware of situations when suboptimal ergonomic positions occur can allow surgeons to consciously compensate by using the clutch or pausing to take a rest break. What does this paper add to the literature?: The study is important because it is the first to look at factors which may influence poor upper limb ergonomics during non-simulated RCS. By recognizing these factors and compensating for them, it may improve surgeon ergonomics with resultant better performance.

Mesenchymal chondrosarcoma: An Australian multi-centre cohort study.

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. METHODS: We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9  (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis. CONCLUSIONS: This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.

Adjunctive ultrasonography to minimize iodinated contrast administration during carotid artery stenting: a randomized trial.

PURPOSE: To report a single-center, prospective randomized controlled trial that compared contrast use during ultrasound-assisted carotid artery stenting (CAS) to CAS procedures without ultrasound. METHODS: Between August 2010 and November 2011, 22 patients (18 men; mean age 72.8 years, range 62-84) with 25 severe symptomatic (n=3) or asymptomatic (n=22) carotid stenoses undergoing an endovascular intervention were randomly allocated (~1.1) to ultrasonography-assisted (n=13) or stand-alone (n=12) CAS. The primary endpoints were contrast use and number of selective cerebral injections. Secondary endpoints were procedure time, fluoroscopy time, any stroke, renal function assessment, major adverse cardiac events (MACE), and death. RESULTS: In the study period, 23 of 25 scheduled CAS procedures (12 ultrasound-assisted, 11 control) were completed in 20 patients; 2 procedures were aborted owing to friable plaque and difficult guidewire access, respectively. There were no deaths, stroke, MACE, or precipitation of dialysis-dependent renal failure in either group. Iodinated contrast usage was reduced by 61% (45.4±24.4 vs. 17.8±11.9 mL, p=0.002) and number of selective cerebral contrast injections by 49% (8.3 vs. 4.2, p=0.002). Neither time taken to complete the procedure (32.5 vs. 35.4 minutes, p=0.38) nor fluoroscopy time (14.5 vs. 13.9 minutes, p=0.54) differed significantly between the groups. Creatinine levels remained stable after CAS and did not differ between groups. CONCLUSION: Ultrasonography-assisted CAS is feasible and safe. Its use can significantly lower the usage of iodinated contrast and the number of selective cerebral circulation injections while not prolonging the length of the procedure or the fluoroscopy time.

Factors affecting the learning curve in robotic colorectal surgery.

Learning related to robotic colorectal surgery can be measured by surgical process (such as time or adequacy of resection) or patient outcome (such as morbidity or quality of life). Time based metrics are the most commonly used variables to assess the learning curve because of ease of analysis. With analysis of the learning curve, there are factors which need to be considered because they may have a direct impact on operative times or may be surrogate markers of clinical effectiveness (unrelated to times). Variables which may impact on operation time include surgery case mix, hybrid technique, laparoscopic and open colorectal surgery experience, robotic surgical simulator training, technology, operating room team, and case complexity. Multidimensional analysis can address multiple indicators of surgical performance and include variables such as conversion rate, complications, oncological outcome and functional outcome. Analysis of patient outcome and/or global assessment of robotic skills may be the most reliable methods to assess the learning curve.

The learning curve to attain surgical competency in robotic colorectal surgery.

INTRODUCTION: The aim of the study was to assess the robotic colorectal surgery (RCS) learning curve of an experienced surgeon. METHODS: A retrospective review of 117 consecutive patients who underwent total RCS at a single institution between October 2018 and July 2021 was performed. Patient demographics, surgery indications, operation type, intraoperative data, histopathology, morbidity and mortality, and length of stay were analysed. Cumulative summation technique (CUSUM) was used to construct a learning curve of surgeon console and total operation times (SCT and TOT). RESULTS: There was no open conversion, positive resection margin and mortality in the study population. There were four Clavien-DIndo grade III complications and one local recurrence. The range for SCT was 18-855 min (mean 214, median 211) and TOT was 68-937 min (mean 302, median 291). The SCT CUSUM graph identified change in slope at cases 44 and 88, which divided the learning curve into three distinct phases. Patient demographics were similar through the three phases. There was proportionally more cancer cases performed in the first phase (P = 0.001). The mean SCT was significantly higher in Phase 2 when compared with Phases 1 and 3 (P = 0.03). The failure rate was similar through the three phases. There was a non-significant steady decline in LOS over the three phases, from 6.9 to 6.1 days. CONCLUSION: Experienced colorectal surgeons can perform robotic surgery safely, even on patients with high complexity early in the learning curve. Audit of patient outcome should be an important component of learning curve assessment.

Robotic colorectal surgery and ergonomics.

Improved ergonomics for the operating surgeon may be an advantage of robotic colorectal surgery. Perceived robotic ergonomic advantages in visualisation include better exposure, three-dimensional vision, surgeon camera control, and line of sight screen location. Postural advantages include seated position and freedom from the constraints of the sterile operating field. Manipulation benefits include articulated instruments with seven degrees of freedom movement, elimination of fulcrum effect, tremor filtration, and scaling of movement. Potential ergonomic detriments of robotic surgery include lack of haptic feedback, visual, and mental strain from increased operating time and interruptions to workflow from crowding.

Managing patients with advanced soft tissue sarcoma: Evolving landscape from an Australian perspective.

AIM: Despite lack of advances in the first-line systemic therapy, the overall survival (OS) has continued to improve in patients with advanced soft tissue sarcoma (STS) with the recent estimation of median OS at 20 months. Several systemic therapy options are available now for the second-line and beyond, with more treatment tailored to histology and molecular subtype. The aim of this retrospective study was to characterize current patterns of care in managing patients with advanced STS (aSTS) in Australia. METHODS: Sarcoma databases from 7 Australian sarcoma services were accessed to identify patients diagnosed with locally advanced inoperable and/or metastatic STS between January 1, 2010 and December 31, 2015. Baseline clinicopathological factors and initial treatment patterns were descriptively analyzed. For the Victorian cohort where treatment of aSTS and follow-up details were available, further exploratory analysis was conducted to determine the impact of patient and tumor characteristics and the use of palliative-intent treatment OS. RESULTS: Of 2261 cases of STS, 671 were deemed as aSTS. Two thirds were relapsed disease with a mean 1.9 years from initial diagnosis. Median age at diagnosis of aSTS was 59 years (18-95 years) and 56.3% was male. Histology classification revealed four main subtypes: undifferentiated pleomorphic sarcoma (UPS) (23.1%), leiomyosarcoma (18.2%), liposarcoma (12.8%), synovial sarcoma (8.2%), and other comprising 14 STS subtypes. For the Victorian cohort (N = 361), approximately 80% of patients accessed palliative-intent treatment of various modalities. Nearly 40% of patients underwent tumor-debulking surgery or metastasectomy, of which lung wedge resection was the most common (N = 83, 47.7%). A total of 438 palliative-intent radiotherapy treatments were delivered to 259 patients (71.7%), with the majority in the form of external beam radiotherapy. Palliative-intent systemic therapy was delivered to 51.5% of patients (N = 186), mostly (73%). Anthracycline-based therapy was the most commonly delivered therapy (N = 135, 72.6%). Approximately half of the patients in each line of therapy failed to proceed to the subsequent line of systemic therapy with 29.4% receiving three or more lines of therapy (N = 55). A total of 18.3% of patient (N = 34) participated in clinical trials or accessed off-label drugs. The median OS for the Victoria cohort was 15.4 months (95% confidence interval: 12.1, 18.2). The UPS histology subtype was associated with poorer OS, whereas receiving any modality of palliative-intent treatment conferred survival benefit. CONCLUSION: In Australia, aSTS is managed with diverse treatment approaches comprising various therapy modalities. Further work is planned in describing healthcare resource utilization and estimating costs by this patient cohort.

Trends in surgical oncology research in Australia during the period 1998-2009--a bibliometric review.

OBJECTIVE: To evaluate the distribution and scope of surgical research in Australia relating to malignant diseases in the field of surgery. METHOD: Surgical publications relating to adult malignant diseases originating from Australia were identified from a systematic literature examination using PubMed during a 12-year period between 1998 and 2009. The origin of the article, journal impact factor (IF), type of research and its subspecialty discipline were recorded. RESULTS: Over a 12-year period, 1,132 papers were published in various journals at a median annual rate of 98 papers. Four hundred eighty-five (43%) papers arose from institutions in New South Wales, 225 (20%) papers from Victoria, 150 (13%) papers from South Australia, 106 (9%) papers from Western Australia, and 77 (7%) papers from Queensland. The mean IF was 3.22 (SD = 2.5). Papers were most commonly published in journals including the ANZ Journal of Surgery (n = 237, 21%), Annals of Surgical Oncology (n = 50, 4%), British Journal of Surgery (n = 38, 3%), and Diseases of the Colon and Rectum (n = 36, 3%). The mean IF of papers published per year ranged from 2.55 to 3.87. The most number of papers were published in the fields of urological oncology (n = 103, 9%), hepatopancreaticobiliary oncology (n = 144, 13%), breast oncology (n = 174, 15%), and colorectal oncology (n = 222, 20%). CONCLUSION: Bibliometric findings of this review suggest that there is a growth in high scientific research publications in the field of surgical oncology in Australia, indicating an interest in this discipline. This research trend may impact on the national research strategy for clinical cancer control.