Retrospective study of qualitative assessment in detecting synchronous and metachronous malignancies in adult cancer patients by 18 F-FDG PET/CT.

OBJECTIVES: The study aimed to evaluate the frequency of incidental suspicious lesions detected by flourine-18 fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) scans done for staging or restaging in adult cancer patients. We further determined the detection rate of synchronous and metachronous malignancies in these suspicious lesions after further investigations. MATERIALS AND METHODS: This retrospective analysis evaluated the consecutive patients with 18 F-FDG PET/CT scans done in Queen Elizabeth Hospital (QEH), Hong Kong between July 2021 and June 2022. The adult cancer patients who underwent staging or restaging 8 F-FDG PET/CT were included while the remaining were excluded. Patients' demographics, primary cancer type, tumor markers, and pathological analyses for the incidental suspicious lesions were reviewed to establish the detection rate of synchronous and metachronous malignancies. RESULTS: A total of 2054 patients fulfilled inclusion criteria with age ranging from 18 to 93 years old. Out of the 2054 patients, 304 (14.8%) were found to have incidental suspicious lesions. Of these, 206 patients (67.8%) underwent further investigations including pathological analyses. Subsequently, 84 of these 206 patients (40.8%) had pathologically proven synchronous or metachronous malignancies. CONCLUSION: The detection rate of incidental suspicious lesions in adult cancer patients who underwent 18 F-FDG PET/CT scans for staging or restaging was 14.8% and the rate of synchronous and metachronous malignancies in these suspicious lesions was 40.8%. The treatment plan of these patients may potentially be altered, which should be included in the cost-benefit analysis of using this imaging modality.

Small nodules (≤ 6 mm in diameter) of multiple primary lung cancers: prevalence and management.

BACKGROUND: Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth. METHODS: This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed. RESULTS: There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08-1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94-6.30) predicted small nodule interval growth. CONCLUSION: We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.

Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies.

BACKGROUND: Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. METHODS: To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers. RESULTS: We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer. CONCLUSIONS: Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.

Low Referral Rates for Genetic Assessment of Patients With Multiple Adenomas in United Kingdom Bowel Cancer Screening Programs.

BACKGROUND: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. OBJECTIVE: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas. DESIGN: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained. SETTING: Data were obtained from 3 centers in London, United Kingdom. PATIENTS: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test. MAIN OUTCOME MEASURES: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening. RESULTS: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment. LIMITATIONS: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population. CONCLUSIONS: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630. TASAS BAJAS DE DERIVACIN PARA LA EVALUACIN GENTICA DE PACIENTES CON ADENOMAS MLTIPLES EN LOS PROGRAMAS DE DETECCIN DEL CNCER DE INTESTINO DEL REINO UNIDO: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630.

FRAMe: Familial Risk Assessment of Melanoma-a risk prediction tool to guide CDKN2A germline mutation testing in Australian familial melanoma.

Germline mutations in CDKN2A greatly increase risk of developing cutaneous melanoma. We have constructed a risk prediction model, Familial Risk Assessment of Melanoma (FRAMe), for estimating the likelihood of carrying a heritable CDKN2A mutation among Australian families, where the prevalence of these mutations is low. Using logistic regression, we analysed characteristics of 299 Australian families recruited through the Sydney site of GenoMEL (international melanoma genetics consortium) with at least three cases of cutaneous melanoma (in situ and invasive) among first-degree blood relatives, for predictors of the presence of a pathogenic CDKN2A mutation. The final multivariable prediction model was externally validated in an independent cohort of 61 melanoma kindreds recruited through GenoMEL Queensland. Family variables independently associated with the presence of a CDKN2A mutation in a multivariable model were number of individuals diagnosed with melanoma under 40 years of age, number of individuals diagnosed with more than one primary melanoma, and number of individuals blood related to a melanoma case in the first degree diagnosed with any cancer excluding melanoma and non-melanoma skin cancer. The number of individuals diagnosed with pancreatic cancer was not independently associated with mutation status. The risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.851 (95% CI 0.793, 0.909) in the training dataset, and 0.745 (95%CI 0.612, 0.877) in the validation dataset. This model is the first to be developed and validated using only Australian data, which is important given the higher rate of melanoma in the population. This model will help to effectively identify families suitable for genetic counselling and testing in areas of high ambient ultraviolet radiation. A user-friendly electronic nomogram is available at www.melanomarisk.org.au .

Challenges in the Correct Assessment of a Case of Aggressive Thyroid Carcinoma with Synchronous Breast Cancer: A Case Report and Review of the Literature of Essential Role of Radiopharmaceuticals.

Thyroid carcinoma represents a complex pathology that can still be considered a medical challenge, despite having a better prognosis and life expectancy than most other neoplasms; also the scenario of multiple malignancies involving thyroid cancer is nowadays a common reality. MATERIALS AND METHODS: We reviewed the literature regarding the aggressive presentation of synchronous thyroid and breast cancer. In the current paper, we report the case of a 59 years-old woman, diagnosed with invasive ductal breast carcinoma and papillary thyroid carcinoma, presenting a natural history of both aggressive synchronous tumors. At the moment of hospitalization, the diagnosis was breast carcinoma with multiple secondary lesions, suggestive of lung and bone metastases, and nodular goiter. RESULTS: Searching the literature in PUBMED with the terms "thyroid carcinoma and synchronous breast carcinoma, we found 86 studies; introducing the term "aggressive," the result included 4 studies, among which, none showed to be relevant to the terms aggressive and synchronous. A similar search was done in SCOPUS finding 92 documents and after introducing the term aggressive, the number of papers was 8, none including the literature on synchronous aggressive metastatic thyroid and breast carcinoma. A majority of imaging diagnostic tools were used in this particular medical case in order to ensure the best potential outcome. The final diagnosis was papillary thyroid carcinoma with lung and unusual multiple bone metastases and synchronous invasive ductal breast carcinoma with subcutaneous metastases. CONCLUSION: The case illustrates the challenges in the correct assessment of oncologic patients, despite the advances in medical imaging and technologies and underlines the essential role of nuclear medicine procedures in the diagnostic and therapy protocols.

Secondary Malignancies: The Cost of Progress.

BACKGROUND: With advances in treatment of cancer, patients who survive their first malignancy are at risk of developing additional malignancies. Data on the risks of secondary malignancies after treatment of some of the more common cancers are lacking. METHODS: Our prospectively maintained database was queried from 1996 to 2016 to identify patients with breast cancer, colorectal cancer, melanoma, sarcoma, gastric, and pancreatic adenocarcinoma who developed additional malignancies. Predisposing clinical factors were included in our analysis. RESULTS: We identified 756 patients diagnosed with a solid malignancy who developed a second malignancy, of which 606 (80.1%) had one of the most common treated cancers. 59.5% of patients were women. 810 additional malignancies were identified in the 606 patients with breast and colon cancer being the most common secondary malignancies. Of these 606 patients, 460 (76%) patients had two malignancies; 145 (23.9%) had 3 or more malignancies. 15.2% of patients were diagnosed under the age of 40.63 years. 8.3% patients had a known genetic mutation, with BReast CAncer gene, and Lynch mutations being the most common. CONCLUSION: Advances in cancer treatment have led to higher cure rates. These patients should continue surveillance and undergo screening as they may be at risk of developing additional malignancies.

Incidence of Multiple vs First Cutaneous Squamous Cell Carcinoma on a Nationwide Scale and Estimation of Future Incidences of Cutaneous Squamous Cell Carcinoma.

Importance: Until now, most studies on cutaneous squamous cell carcinoma (cSCC) incidence rates concerned only the first cSCC per patient. Given the increase in incidence rates and the frequent occurrence of subsequent cSCCs per patient, population-based data on the incidence rates of both first and multiple cSCCs are needed. Objectives: To calculate annual age-standardized incidence rates for histopathologically confirmed first and multiple cSCCs per patient and to estimate future cSCC incidence rates up to 2027. Design, Setting, and Participants: A nationwide population-based epidemiologic cohort study used cancer registry data on 145 618 patients with a first histopathologically confirmed cSCC diagnosed between January 1, 1989, and December 31, 2017, from the Netherlands Cancer Registry and all patients with multiple cSCCs diagnosed in 2017. Main Outcomes and Measures: Age-standardized incidence rates for cSCC-standardized to the European Standard Population 2013 and United States Standard Population 2000-were calculated per sex, age group, body site, and disease stage. A regression model with positive slope was fitted to estimate cSCC incidence rates up to 2027. Results: A total of 145 618 patients in the Dutch population (84 572 male patients [58.1%]; mean [SD] age, 74.5 [11.5] years) received a diagnosis of a first cSCC between 1989 and 2017. Based on incident data, European Standardized Rates (ESRs) increased substantially, with the highest increase found among female patients from 2002 to 2017, at 8.2% (95% CI, 7.6%-8.8%) per year. The ESRs for first cSCC per patient in 2017 were 107.6 per 100 000 person-years (PY) for male patients, an increase from 40.0 per 100 000 PY in 1989, and 68.7 per 100 000 PY for female patients, an increase from 13.9 per 100 000 PY in 1989, which corresponds with a US Standardized Rate of 71.4 per 100 000 PY in 2017 for men and 46.4 per 100 000 PY in 2017 for women. Considering multiple cSCCs per patient, ESRs increased by 58.4% for men (from 107.6 per 100 000 PY to 170.4 per 100 000 PY) and 34.8% for women (from 68.7 per 100 000 PY to 92.6 per 100 000 PY). Estimation of ESRs for the next decade show a further increase of 23.0% for male patients (ESR up to 132.4 per 100 000 PY [95% prediction interval, 125.8-139.0 per 100 000 PY]) and 29.4% for female patients (ESR up to 88.9 per 100 000 PY [95% prediction interval, 84.3-93.5 per 100 000 PY]). Conclusions and Relevance: This nationwide epidemiologic cohort study suggests that incidence rates of cSCC keep increasing, especially among female patients, and that the occurrence of multiple cSCCs per patient significantly adds to the current and future burden on dermatologic health care. Revision of skin cancer policies are needed to halt this increasing trend.

Time-Driven Activity-Based Costing Comparison of Stereotactic Radiosurgery to Multiple Brain Lesions Using Single-Isocenter Versus Multiple-Isocenter Technique.

PURPOSE: Stereotactic radiosurgery (SRS) historically has been used to treat multiple brain lesions using a multiple-isocenter technique-frequently associated with significant complexity in treatment planning and long treatment times. Recently, given innovations in planning algorithms, patients with multiple brain lesions may now be treated with a single-isocenter technique using fewer total arcs and less time spent during image guidance (though with stricter image guided radiation therapy tolerances). This study used time-driven activity-based costing to determine the difference in cost to a provider for delivering SRS to multiple brain lesions using single-isocenter versus multiple-isocenter techniques. METHODS AND MATERIALS: Process maps, consisting of discrete steps, were created for each phase of the SRS care cycle and were based on interviews with department personnel. Actual treatment times (including image guidance) were extracted from treatment record and verify software. Additional sources of data to determine costs included salary/benefit data of personnel and average list price/maintenance costs for equipment. RESULTS: Data were collected for 22 patients who underwent single-isocenter SRS (mean lesions treated, 5.2; mean treatment time, 30.2 minutes) and 51 patients who underwent multiple-isocenter SRS (mean lesions treated, 4.4; mean treatment time, 75.2 minutes). Treatment time for multiple-isocenter SRS varied substantially with increasing number of lesions (11.8 minutes/lesion; P < .001), but to a much lesser degree in single-isocenter SRS (1.8 minutes/lesion; P = .029). The resulting cost savings from single-isocenter SRS based on number of lesions treated ranged from $296 to $3878 for 2 to 10 lesions treated. The 2-mm planning treatment volume margin used with single-isocenter SRS resulted in a mean 43% increase of total volume treated compared with a 1-mm planning treatment volume expansion. CONCLUSIONS: In a comparison of time-driven activity-based costing assessment of single-isocenter versus multiple-isocenter SRS for multiple brain lesions, single-isocenter SRS appears to save time and resources for as few as 2 lesions, with incremental benefits for additional lesions treated.

Major and ancillary features according to LI-RADS in the assessment of combined hepatocellular-cholangiocarcinoma.

Background The aim of the study was to investigate the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2018 for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) identifying the features that allow an accurate characterization. Patients and methods Sixty-two patients (median age, 63 years; range, 38-80 years), with pre-surgical biopsy diagnosis of hepatocellular carcinoma (HCC) that underwent hepatic resection, comprised our retrospective study. All patients were subject to multidetector computed tomography (MDCT); 23 patients underwent to magnetic resonance (MR) study. The radiologist reported the presence of the HCC by using LIRADS v2018 assessing major and ancillary features. Results Final histological diagnosis was HCC for 51 patients and cHCC-CCA for 11 patients. The median nodule size was 46.0 mm (range 10-190 mm). For cHCC-CCA the median size was 33.5 mm (range 20-80 mm), for true HCC the median size was 47.5 mm (range 10-190 mm). According to LIRADS categories: 54 (87.1%) nodules as defined as LR-5, 1 (1.6%) as LR-3, and 7 (11.3%) as LR-M. Thirty-nine nodules (63%) showed hyper-enhancement in arterial phase; among them 4 were cHCC-CCA (36.4% of cHCC-CCA) and 35 (68.6%) true HCC. Forty-three nodules (69.3%) showed washout appearance; 6 cHCC-CCAs (54.5% of cHCC-CCA) and 37 true HCC (72.5%) had this feature. Only two cHCC-CCA patients (18.2% of cHCC-CCA) showed capsule appearance. Five cHCC-CCA (71.4% of cHCC-CCA) showed hyperintensity on T2-W sequences while two (28.6%) showed inhomogeneous signal in T2-W. All cHCC-CCA showed restricted diffusion. Seven cHCC-CCA patients showed a progressive contrast enhancement and satellite nodules. Conclusions The presence of satellite nodules, hyperintense signal on T2-W, restricted diffusion, the absence of capsule appearance in nodule that shows peripheral and progressive contrast enhancement are suggestive features of cHCC-CCA.

Simultaneous versus staged resection for synchronous colorectal liver metastases: A population-based cost analysis in Ontario, Canada - Health economic evaluation.

BACKGROUND: Simultaneous compared to staged resection of synchronous colorectal cancer liver metastases is considered safe. We aimed to determine their cost implications. STUDY DESIGN: Population-based cohort was generated by linking administrative healthcare datasets in Ontario, Canada (2006-2014). Resection of colorectal cancer and liver metastases within six months was considered synchronous. Cost analysis was performed from the perspective of a third-party payer. Median costs with range were estimated using the log-normal distribution of cost using t-test with a one-year time horizon. RESULTS: Among patients undergoing staged resection (n = 678), the estimated median cost was $54,321 CAD (IQR 45,472 to 68,475) and $41,286 CAD (IQR 31,633 to 58,958) for those undergoing simultaneous resection (n = 390), median difference: $13,035 CAD (p < 0.001). Primary cost driver were all costs related to hospitalization for liver and colon resection, which was higher for the staged approach, median difference: $16,346 CAD (p < 0.001). This was mainly due to a longer median length of hospital stay in the staged vs. simultaneous group (11 vs. 8 days, p < 0.001 respectively), which was not attributable to differences in major postoperative complication rates (23% vs. 28%, p = 0.067 respectively). Other costs, including cost of chemotherapy within six months of surgery ($11,681 CAD vs. $8644 CAD, p = 0.074 respectively) and 90-day re-hospitalization cost ($2155 CAD vs. $2931 CAD, p = 0.454 respectively) were similar between groups. CONCLUSION: Cost of staged resection of synchronous colorectal cancer liver metastases is significantly higher compared to the simultaneous approach, mostly driven by a longer length of hospital stay despite similar postoperative complication rates.

Psychobehavioral risk factors for financial hardship and poor functional outcomes in survivors of multiple primary cancers.

OBJECTIVE: Survivors of multiple primary cancers (MPC) are at increased risk for poor health outcomes compared with survivors of single cancers. Using an adapted psychobehavioral stress-response model, the study purpose was to identify pathways and individual risk factors associated with poor health outcomes in adults with MPC. METHODS: Adult MPC survivors (N = 211) with first cancers (stages I-III) diagnosed within 1 to 10 years were recruited via tumor registry. Employing a cross-sectional design, established questionnaires were used to operationalize patient characteristics and theoretical constructs including perceived stress, psychological and behavioral responses, financial hardship, social role function, and physical health. Disease and treatment data were obtained via registry and medical records. Structural equation modeling (SEM) was performed to fit, test, and modify the hypothesized psychobehavioral model. RESULTS: Following measurement model refinement, an SEM linking self-management behaviors, distress, financial hardship, and functional health demonstrated a good fit: χ2 (200, N = 206) = 332.06, P < .01; Tucker-Lewis index (TLI) = .95, comparative fit index (CFI) = .96, standardized root mean residual (SRMR) = .06, root-mean-square error of approximation (RMSEA) = .06. Less use of self-management behaviors predicted higher distress which, in turn, predicted higher financial hardship; higher distress and financial hardship predicted poorer functional health. Several sociodemographic and personal factors predicted self-management behaviors and distress. CONCLUSIONS: The hypothesized stress-response model was partially supported. Data supported pathways among self-management behaviors, distress, financial hardship, and functional health. Self-management and distress may represent modifiable intervention targets for MPC survivors. High body mass index (BMI), less education, greater neuroticism, and lower social support were associated with less use of self-management behaviors and higher distress and should be further evaluated as potential markers of vulnerability.

Current Challenges in Diagnosis and Assessment of the Response of Locally Advanced and Metastatic Renal Cell Carcinoma.

Locally advanced and metastatic renal cell carcinoma (RCC) present a specific set of challenges to the radiologist. The detection of metastatic disease is confounded by the ability of RCC to metastasize to virtually any part of the human body long after surgical resection of the primary tumor. This includes sites not commonly included in routine surveillance, which come to light after the patient becomes symptomatic. In the assessment of treatment response, the phenomenon of tumor heterogeneity, where clone selection through systemic therapy drives the growth of potentially more aggressive phenotypes, can result in oligoprogression despite overall disease control. Finally, advances in therapy have resulted in the development of immuno-oncologic agents that may result in changes that are not adequately evaluated with conventional size-based response criteria and may even be misinterpreted as progression. This article reviews the common challenges a radiologist may encounter in the evaluation of patients with locally advanced and metastatic RCC. ©RSNA, 2019.

Clinical assessment of the GNAS mutation status in patients with intraductal papillary mucinous neoplasm of the pancreas.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by cystic dilation of the pancreatic duct, caused by mucin hypersecretion, with slow progression via the adenoma-carcinoma sequence mechanism. Mutation of GNAS at codon 201 is found exclusively in IPMNs, occurring at a rate of 41-75%. Recent advances in molecular biological techniques have demonstrated that GNAS mutation might play a role in the transformation of IPMNs after the appearance of neoplastic cells, rather than in the tumorigenesis of IPMNs. GNAS mutation is observed frequently in the intestinal subtype of IPMNs with MUC2 expression, and less frequently in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC). Research has focused on assessing GNAS mutation status in clinical practice using various samples. In this review, we discuss the clinical application of GNAS mutation assessment to differentiate invasive IPMNs from concomitant PDAC, examine the clonality of recurrent IPMNs in the remnant pancreas using resected specimens, and differentiate pancreatic cystic lesions using cystic fluid collected by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), duodenal fluid, and serum liquid biopsy samples.

Direct inpatient costs and influencing factors for patients with rectal cancer with low anterior resection: a retrospective observational study at a three-tertiary hospital in Beijing, China.

OBJECTIVES: The aim of the study was to investigate the direct inpatient cost and analyse influencing factors for patients with rectal cancer with low anterior resection in Beijing, China. DESIGN: A retrospective observational study. SETTING: The study was conducted at a three-tertiary oncology institution. PARTICIPANTS: A total of 448 patients who underwent low anterior resection and were diagnosed with rectal cancer from January 2015 to December 2016 at Peking University Cancer Hospital were retrospectively identified. Demographic, clinical and cost data were determined. RESULTS: The median inpatient cost wasï¿¥89 064, with a wide range (ï¿¥46 711-ï¿¥191 329) due to considerable differences in consumables. The material cost accounted for 52.19% and was the highest among all the cost components. Colostomy (OR 4.17; 95% CI 1.79 to 9.71), complications of hypertension (OR 5.30; 95% CI 1.94 to 14.42) and combined with other tumours (OR 2.92; 95% CI 1.12 to 7.60) were risk factors for higher cost, while clinical pathway (OR 0.10; 95% CI 0.03 to 0.35), real-time settlement (OR 0.26; 95% CI 0.10 to 0.68) and combined with cardiovascular disease (OR 0.09; 95% CI 0.02 to 0.52) were protective determinants. CONCLUSIONS: This approach is an effective way to relieve the economic burden of patients with cancer by promoting the clinical pathway, optimising the payment scheme and controlling the complication. Further research focused on the full-cost investigation in different stages of rectal cancer based on a longitudinal design is necessary.

Clonality assessment of multifocal lung adenocarcinoma by pathology evaluation and molecular analysis.

The aim of this study was to explore morphologic and molecular features distinguishing between multifocal lung adenocarcinoma (MLA) and intrapulmonary metastases (IMs). Sixteen patients with MLAs, a total of 34 tumors, were reviewed. Four approaches were used: (1) array-comparative genomic hybridization (CGH) as a standard clonality assessment; (2) EGFR and KRAS mutational profiles as a supplementary method; (3) comprehensive histologic assessment (CHA) was method I in pathology evaluation; and (4) CHA combined with lepidic component analysis was method II. The lepidic component was divided into low grade and high grade according to extent of atypia; tumors with low-grade lepidic component were defined as primary. Eight patients were found to have IMs and 8 to have multiple primaries (MPs) by array-CGH; 7 had MPs and 9 had IMs by method I; 5 had MPs and 11 had IMs by method II. Compared with array-CGH, method I had a lower coincidence rate (65%) than method II (85%). Univariate analysis revealed that patients with MP had a better clinical outcome than those with IM only if the MPs were diagnosed by array-CGH (P = .034) or method II (P = .027) but not EGFR/KRAS mutation (P = .843) or method I (P = .493). Our results suggest that a low-grade lepidic component is a sign of a primary tumor. CHA combined with a low-grade lepidic component (method II) is more accurate clinically and more cost-effective in distinguishing MLAs from IMs. Also, EGFR mutation is not an appropriate molecular marker for clonality assessment.

Outpatient diode laser treatment of intermediate-risk non-invasive bladder tumors without sedation: efficacy, safety and economic analysis.

OBJECTIVE: This study aimed to validate a new method for outpatient diode laser ablation of bladder tumors without sedation or pain control. METHODS: Twenty-one patients with stage Ta low-grade intermediate-risk bladder tumors underwent photodynamic-guided laser ablation of their bladder tumors and 1 month later follow-up cystoscopy with photodynamic and IMAGE1 S™-guided biopsies. Pain was measured using a visual analog scale (range 0-10). Symptoms and worries about the future disease course were calculated using the Quality of Life Questionnaire for Non-Muscle-Invasive Bladder Cancer (range 0-100, high scores indicating worse symptoms or worry). Costs of outpatient laser treatment versus inpatient conventional bladder tumor resection in the operating theatre were compared. RESULTS: Patients had a median of three tumors (range 1-12). The median pain score was 1.0 (range 0-7) during laser ablation. Median quality of life scores were 24 (range 0-67) for symptoms and 42 (0-100) for worry. Two patients had minor hematuria and five had dysuria after laser therapy. Five patients (24%) had new Ta low-grade recurrence within 13 months that was biopsied and laser treated. No tumors progressed. Four patients had tumors identified using photodynamic diagnosis, and two had flat low-grade dysplasia identified using IMAGE1 S SPECTRA A and B and photodynamic diagnosis, none of which was seen using white-light cystoscopy. Outpatient laser treatment could save about €140,000 per million inhabitants versus inpatient bladder tumor surgery. CONCLUSION: Fluorescence-guided diode lasers provide efficient and almost pain-free treatment of low-grade urothelial cancer in conscious patients and could reduce healthcare costs.

The Effect of Frailty Index on Early Outcomes after Combined Colorectal and Liver Resections.

BACKGROUND: Although previous studies have examined frailty as a potential predictor of adverse surgical outcomes, little is reported on its application. We sought to assess the impact of the 5-item modified frailty index (mFI) on morbidity in patients undergoing combined colorectal and liver resections. METHODS: Adult patients who underwent combined colorectal and liver resections were identified using the ACS-NSQIP database (2005-2015). The 5-item mFI consists of history of chronic obstructive pulmonary disease, congestive heart failure, hypertension, diabetes, and partial/total dependence. Patients were stratified into three groups: mFI 0, 1, or ≥ 2. The impact of the mFI on primary outcomes (30-day overall and serious morbidity) was assessed using multivariable logistic regression. Subgroup analyses by age and hepatectomy type was also performed. RESULTS: A total of 1928 patients were identified: 55.1% with mFI = 0, 33.2% with mFI = 1, and 11.7% with mFI ≥ 2. 75.9% of patients underwent wedge resection/segmentectomy (84.6% colon, 15.4% rectum), and 24.1% underwent hemihepatectomy (88.8% colon, 11.2% rectum). On unadjusted analysis, patients with mFI ≥ 2 had significantly greater rates of overall and serious morbidity, regardless of age and hepatectomy type. These findings were consistent with the multivariable analysis, where patients with mFI ≥ 2 had increased odds of overall morbidity (OR 1.41, 95% CI 1.02-1.96, p = 0.037) and were more than twice likely to experience serious morbidity (OR 2.12, 95% CI 1.47-3.04, p < 0.001). CONCLUSIONS: The 5-item mFI is significantly associated with 30-day morbidity in patients undergoing combined colorectal and liver resections. It is a tool that can guide surgeons preoperatively in assessing morbidity risk in patients undergoing concomitant resections.

Multiplicity of skin cancers in Queensland and their cost burden to government and patients.

OBJECTIVE: To determine the cost burden to government and patients for individuals with multiple skin cancers. METHODS: We used self-reported baseline data on socio-demographics, phenotype and sun exposure behaviours from participants in the QSkin Sun and Health Study with at least one histopathologically confirmed keratinocyte cancer or melanoma (n=5,673). Linkage to Australian Medicare data (2011-2014) provided resource data and government and out-of-pocket patient costs. Generalised linear models examined costs by frequency of skin cancer groups separately for melanoma and keratinocyte cancer. RESULTS: Over three years, 539 participants were diagnosed with melanoma (11% had ≥2 melanomas) and 5,134 participants were treated for keratinocyte cancers (10% had ≥6). Median Medicare costs per person were $1,325 (maximum $6,117) for ≥2 melanomas and $2,126 (maximum $54,618) for ≥6 keratinocyte cancers. Increased costs were associated with private health insurance. CONCLUSIONS: Individuals who are multiply affected by skin cancers are relatively common and the accompanying individual and government cost burden can be substantial. These findings support skin cancer being classified as a chronic disease. Implications for public health: Over time, the economic burden for skin cancer for individuals and health providers is high and investment in prevention remains important from an economic viewpoint.

Clinical Assessment of Reconstruction Involving Gastric Pull-Up Combined with Free Jejunal Graft After Total Pharyngolaryngoesophagectomy.

BACKGROUND: Total pharyngolaryngoesophagectomy (PLE) is used as a curative treatment for synchronous laryngopharyngeal and thoracic esophageal cancer or for multiple cancers in the cervical and thoracic esophagus. Gastric pull-up is commonly used after PLE, but postoperative complications are common. The present study evaluated these procedures in patients with esophageal cancer. METHODS: Fourteen patients (7 with synchronous pharyngeal and thoracic esophageal cancer, 4 with synchronous cervical and thoracic esophageal cancer, and 3 with cervicothoracic esophageal cancer) underwent reconstructive surgery after PLE involving gastric pull-up combined with free jejunal graft between 2004 and 2015. RESULTS: Esophagectomy via right thoracotomy was performed in 9 patients, and transhiatal esophagectomy was used in 5. The posterior mediastinal route was used in 13 patients, excluding one patient with early gastric cancer. Interposition of a free jejunal graft included microvascular anastomosis using two arteries and two veins in all patients. Anastomotic leakage and graft necrosis did not occur in any of the 14 patients who underwent the above surgical procedures. Tracheal ischemia close to the tracheostomy orifice occurred in 4 patients (28.6%), but none of these patients developed pneumonia. No hospital deaths were recorded. CONCLUSIONS: The results indicate that gastric pull-up combined with free jejunal graft is a feasible reconstructive surgery after PLE. This procedure is a promising treatment strategy for synchronous pharyngeal and thoracic esophageal cancer or multiple cancers in the cervical and thoracic esophagus. Larger series are needed to show the distinct advantages of this procedure in comparison with conventional methods of reconstruction after PLE.