Incidence Of Primary Tumors Research Articles

Primary omental smooth muscle tumor in an adult male: a diagnostic dilemma for leiomyoma: a case report

BackgroundThe greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient.Case presentationA 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up.Discussion and conclusionWe encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research.

SURG-28. PRESENTATION OF A POSTERIOR FOSSA TUMOR AT A HOSPITAL IN WESTERN JAMAICA

Abstract The posterior cranial fossa is part of the cranial cavity, located between the foramen magnum and tentorium cerebelli that houses the cerebellum, pons and medulla oblongata. Commonly, tumors arising from this region in adults are cerebellar metastases or schwannomas of the vestibular nerve – the incidence of primary neoplasms is uncommon and more reserved for the pediatric population. A 28 year old female was in her usual state of health until last year when she started experiencing recurrent headaches with associated vomiting and intermittent loss of consciousness. A CT brain was done upon presentation to the hospital that revealed a 4th ventricle mass with obstructive hydrocephalus. A ventriculoperitoneal (VP) shunt was done thereafter to decompress the ventricular system, in anticipation for further surgical intervention for mass. Occipital craniotomy and resection of tumor was done and patient managed in a multidisciplinary manner in the intensive care unit. Post-operative course was marked by occipital pseudomeningocele with an associated CSF leak; a lumbar drain was placed in situ until complete resolution of leak. Histological analysis showed WHO Grade II Astrocytoma. Adult primary posterior fossa tumors are rare and can present with a constellation of symptoms. Although patient presented with findings in keeping with the diagnosis of an ependymoma, close clinical follow up will be required henceforth due to the refractory nature of such a low grade astrocytoma post-resection. Radiotherapy can also be considered in further management of case.

Comparison of personal and shared frameshift neoantigen vaccines in a mouse mammary cancer model

BackgroundIt is widely hoped that personal cancer vaccines will extend the number of patients benefiting from checkpoint and other immunotherapies. However, it is clear creating such vaccines will be challenging. It requires obtaining and sequencing tumor DNA/RNA, predicting potentially immunogenic neoepitopes and manufacturing a one-use vaccine. This process takes time and considerable cost. Importantly, most mutations will not produce an immunogenic peptide and many patient’s tumors do not contain enough DNA mutations to make a vaccine. We have discovered that frameshift peptides (FSP) created from errors in the production of RNA rather than from DNA mutations are potentially a rich source of neoantigens for cancer vaccines. These errors are predictable, enabling the production of a FSP microarray. Previously we found that these microarrays can identify both personal and shared neoantigens. Here, we compared the performance of personal cancer vaccines (PCVs) with that of a shared antigen vaccine, termed Frameshift Antigen Shared Therapeutic (FAST) vaccine, using the 4 T1 breast cancer model. Sera from 4 T1-tumor bearing mice were assayed on the peptide microarray containing 200 Fs neoantigens, for the PCV, the top 10 candidates were select and personal vaccines constructed and administrated to the respective mice. For the FAST, we selected the top 10 candidates with higher prevalence among all the mice challenged. Seven to 12 days challenged mice were immunized, combined or not with immune checkpoint inhibitor (ICI) (αPD-L1 and αCTLA-4). Primary and secondary tumor clearance and growth were evaluated as well as cellular and humoral immune response against the vaccine targets by IFN-γ ELISPOT and ELISA. Lastly, we analyzed the immune response of the FAST-vaccinated mice by flow cytometry in comparison to the control group.ResultsWe found that PCVs and FAST vaccines both reduced primary tumor incidence and growth as well as lung metastases when delivered as monotherapies or in combination with ICI. Additionally, the FAST vaccine induces a robust and effective T-cell response.ConclusionsThese results suggest that FSPs produced from RNA-based errors are potent neoantigens that could enable production of off-the-shelf shared antigen vaccines for solid tumors with efficacy comparable to that of PCVs.

Trends in peritoneal surface malignancies: evidence from a Czech nationwide population-based study

BackgroundThe aim of this study is to identify the incidence trends of primary and secondary peritoneal surface malignancies in a representative Czech population.MethodsData were obtained from patients registered in the Czech National Cancer Registry between 1979 and 2016. The incidence rates were analyzed between 2012 and 2016. To observe the incidence trends, we analyzed the data from two time periods, 1979–2005 and 2006–2016. The analyzed data included age, sex, and the histological types and primary origins of the malignancies. The Cochrane-Armitage test for linear trends was used for verification of the null hypothesis. The significance level established for hypothesis testing was p = 0.05.ResultsBetween 2012 and 2016, 230 patients with primary peritoneal tumors were identified and divided into the following groups according to their “International Statistical Classification of Diseases and Related Health Problems, 10th revision” codes: malignant neoplasm of specified parts of the peritoneum (C48.1); malignant neoplasm of the peritoneum, unspecified (C48.2); and malignant neoplasm of overlapping sites of the retroperitoneum and peritoneum (C48.8). Moreover, 549 primary tumors of the appendix (C18.1, encompassing all appendiceal malignancies) and 3137 secondary synchronous peritoneal carcinomatoses of other primary origins were documented. The age-adjusted incidence of primary peritoneal tumors in 2012–2016 was 4.36/year/1,000,000 inhabitants. The age-adjusted incidence of synchronous secondary peritoneal malignancies in 2014–2016 was 99.0/year/1,000,000 inhabitants. The diagnoses of primary peritoneal malignancies followed a stable trend between 1979 and 2016. However, the incidences of primary tumors of the appendix increased by 76.7%.ConclusionsThe data produced in our study ought to clarify the status of peritoneal surface malignancies in the Czech Republic, which can lead to improved planning and development of therapeutic interventions as well as physician training.

Trends in the incidence of primary brain, central nervous system and intracranial tumors in Israel, 1990–2015

BackgroundThe association between cellphone technology and brain, central nervous system (CNS) and intracranial tumors is unclear. Analysis of trends in incidence of such tumors for periods during which cellphone use increased dramatically may add relevant information. Herein we describe secular trends in the incidence of primary tumors of the brain and CNS from 1990 to 2015 in Israel, a period during which cellphone technology became extremely prevalent in Israel. MethodsAll cases of primary brain, CNS and intracranial tumors (excluding lymphomas) diagnosed in Israel from 1990 to 2015 were identified in the Israel National Cancer Registry database and categorized by behavior (malignant; benign/uncertain behavior) and histologic type. Annual age-standardized incidence rates by sex and population group (Jews; Arabs) were computed, and the annual percent changes and 95% confidence intervals per category were calculated using Joinpoint software. ResultsOver 26 years (1990–2015) no significant changes in the incidence of malignant brain, CNS and intracranial tumors were observed, except for an increase in malignant glioma incidence in Jewish women up to 2008 and Arab men up to 2001, which levelled off in both subgroups thereafter. The incidence of benign/uncertain behavior brain, CNS and intracranial tumors increased in most population groups up to the mid-2000s, a trend mostly driven by changes in the incidence of meningioma, but either significantly decreased (Jews) or stabilized (Arabs) thereafter. ConclusionsOur findings are not consistent with a discernable effect of cellphone use patterns in Israel on incidence trends of brain, CNS and intracranial tumors.

Intratibial Injection Causes Direct Pulmonary Seeding of Osteosarcoma Cells and Is Not a Spontaneous Model of Metastasis: A Mouse Osteosarcoma Model.

Although metastasis is the major cause of mortality in patients with osteosarcoma, little is known about how micrometastases progress to gross metastatic disease. Clinically relevant animal models are necessary to facilitate development of new therapies to target indolent pulmonary metastases. Intratibial injection of human and murine osteosarcoma cell lines have been described as orthotopic models that develop spontaneous pulmonary metastasis over time. However, there is variability in reported injection techniques and metastatic efficiency. We aimed to characterize a widely used murine model of metastatic osteosarcoma, determine whether it is appropriate to study spontaneous pulmonary metastasis by establishing a reliable volume for intratibial injection, determine the incidence of primary tumor and metastatic formation, determine the kinetics of pulmonary metastatic seeding and outgrowth, and the contribution of the primary tumor to subsequent development of metastasis. The metastatic mouse osteosarcoma cell line K7M2 was injected into the tibia of mice. The maximum volume that could be injected without leakage was determined using Evan's blue dye (n = 8 mice). Primary tumor formation and metastatic efficiency were determined by measuring the incidence of primary tumor and metastatic formation 4 weeks after intratibial injection (n = 30). The kinetics of metastatic development were determined by performing serial euthanasia at 1, 2, 3, and 4 weeks after injection (n = 24; five to six mice per group). Number of metastatic foci/histologic lung section and metastatic burden/lung section (average surface area of metastatic lesions divided by the total surface area of the lung) was calculated in a blinded fashion. To test the contribution of the primary tumor to subsequent metastases, amputations were performed 30 minutes, 4 hours, or 24 hours after injection (n = 21; five to six mice per group). Mice were euthanized after 4 weeks and metastatic burden calculated as described previously, comparing mice that had undergone amputation with control, nonamputated mice. Differences between groups were calculated using Kruskal-Wallis and one-way analysis of variance. The maximum volume of cell suspension that could be injected without leakage was 10 μL. Intratibial injection of tumor cells led to intramedullary tumor formation in 93% of mice by 4 weeks and resulted in detectable pulmonary metastases in 100% of these mice as early as 1 week post-injection. Metastatic burden increased over time (0.88% ± 0.58, week 1; 6.6% ± 5.3, week 2; 16.1% ± 12.5, week 3; and 40.3% ± 14.83, week 4) with a mean difference from week 1 to week 4 of -39.38 (p < 0.001; 95% confidence interval [CI], -57.39 to -21.37), showing pulmonary metastatic growth over time. In contrast, the mean number of metastatic foci did not increase from week 1 to week 4 (36.4 ± 33.6 versus 49.3 ± 26.3, p = 0.18). Amputation of the injected limb at 30 minutes, 4 hours, and 24 hours after injection did not affect pulmonary metastatic burden at 4 weeks, with amputation as early as 30 minutes post-injection resulting in a metastatic burden equivalent to tumor-bearing controls (48.9% ± 6.1% versus 40.9% ± 15.3%, mean difference 7.96, p = 0.819; 95% CI, -33.9 to 18.0). There is immediate seeding of the metastatic site after intratibial injection of the K7M2 osteosarcoma cell line, independent of a primary tumor. This is therefore not a model of spontaneous metastasis. This model should not be used to study the early components of the metastatic cascade, but rather used as an experimental model of metastasis. Improved understanding of this commonly used model will allow for proper interpretation of existing data and inform the design of future studies exploring the biology of metastasis in osteosarcoma.

Abstract 5264: Chemoprevention of rat oral carcinogenesis by black raspberry phytochemicals

Abstract It is expected that in 2016, there will be an estimated 48,330 new cases and 9,570 deaths due to oral cancer in the US, which is about one person every hour every day. Due to the epithelial field defects associated with oral carcinogenesis, tumor recurrence and second primary tumor incidence are common. Recently conducted Phase I Clinical trials demonstrate the ability of black raspberries (BRBs) to modulate inflammatory biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. From these human trials we have established a molecular signature of BRB responsive biomarkers. However, it is essential that a preclinical animal model of BRB chemoprevention which recapitulates the fundamental features of human oral carcinogenesis be developed, so that we can evaluate potential mechanisms of action and validate molecular biomarkers of BRB efficacy. We therefore established the ability of BRB to inhibit oral lesion formation in a rat model of 4-nitroquinoline 1-oxide (4NQO) induced oral carcinogenesis and examined molecular efficacy using a clinically relevant transcriptional signature. Oral cancer was induced in F344 rats using 4NQO in drinking water for 10 weeks followed by regular drinking water for 16 weeks. Rats were administered a diet containing 5 or 10 percent lyophilized BRBs. Tongue tissues were examined for lesion multiplicity, incidence and histopathological features. Clinically derived pro-inflammatory and pro-survival molecular biomarkers were also determined by real-time PCR and ELISA. Dietary administration of 5 and 10 percent BRBs reduced combined lesion incidence and multiplicity by -39.3% and -28.6% respectively. Histopathological analyses of tongue sections further demonstrate the chemopreventive ability of dietary BRB administration in the rat model. Pro-survival and pro-inflammatory biomarkers were downregulated in BRB administered 4NQO induced rats compared to untreated 4NQO induced rats. Our study shows that dietary administration of BRB inhibits oral carcinogenesis in the rat 4NQO model. The rat 4NQO model is suitable for interrogating mechanisms of action of BRB-mediated oral cancer chemoprevention. Citation Format: Steve Oghumu, Thomas Knobloch, Jennifer Ahn-Jarvis, Logan Weghorst, Kyle Horvath, Paul Geuy, Christopher Weghorst. Chemoprevention of rat oral carcinogenesis by black raspberry phytochemicals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5264. doi:10.1158/1538-7445.AM2017-5264

Salivary gland pleomorphic adenoma in the Netherlands: A nationwide observational study of primary tumor incidence, malignant transformation, recurrence, and risk factors for recurrence

IntroductionWhereas salivary gland pleomorphic adenoma (SGPA) is the most common type of salivary gland tumor, little is known about its epidemiology because national cancer registries do not register this disease. ObjectivesTo establish SGPA incidence trends, rates of secondary malignant transformation and recurrence and associated factors in the Netherlands. Materials and methodsData on incidence, epidemiology, secondary malignant transformation and recurrence were retrieved from the Dutch pathology registry (PALGA) for the years 1992, 1997, 2002, 2007, and 2012. Multivariate analysis was performed to discover the risk factors for recurrence. Results3506 cases of SGPA were recorded implying an overall European standardized rate of 4.2–4.9 per 100,000 person-years. Our figures showed a female preponderance (1:1.43) with an annual 1% rise in female incidence (95% confidence interval [CI]: 0.2–1.8) and a bimodal age distribution in women (p<0.0001). The overall 20-year recurrence rate was 6.7%, and median time to first recurrence was 7years.Positive and uncertain resection margins and younger age at diagnosis were risk factors for recurrence, with odds ratios (ORs) of 4.62 (95%CI 2.84–7.51), 4.08 (95%CI 2.24–7.43), and 0.42 (95%CI 0.29–0.63) respectively. Tumor locations in the minor salivary glands had lower odds of recurrence than tumors in the parotid (OR 0.24; 95% CI: 0.07–0.77; p<0.016). Malignant transformation occurred in 0.15% of SGPAs (3.2% of recurrences). ConclusionThis first nationwide study clearly showed sex differences in SGPA epidemiology, possibly suggesting some underlying hormonal mechanism. Long-term recurrence risks were low, and secondary malignant transformation risks were very low.

The incidence of secondary pelvic tumors after previous (chemo)radiation for rectal cancer.

491 Background: The aim of this study was to analyze the association between radiotherapy (RT) for rectal cancer and the development of second primary tumors. Methods: Data on all surgically treated, non-metastasized primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from a population-based cancer registry and retrospectively reviewed. To estimate the cumulative incidence of a second tumor, Fine and Gray’s competing risk model was used with death as a competing event. Standardized incidence ratios (SIR’s) were calculated for comparison with the incidence of primary tumors in the general population, taking in account sex, age and calendar year. Results: The cohort consisted of 29,214 patients of which 15,454 patients had undergone (chemo)RT. Median follow-up was 6.2 years (range 0-24). 3655 patients were diagnosed with at least one second primary tumor of which 808 patients had pelvic tumors. The SIR for any second tumor was 1.14 (95% confidence interval [CI] 1.10-1.17), resulting in 23.3/10,000 excess cases per year. RT reduced the cumulative incidence of second pelvic tumors compared to patients who received no RT (SHR 0.70, 95% CI 0.61-0.81). Second pelvic tumors were more common in patients who underwent post-operative RT than in patients who underwent pre-operative RT (SHR 1.37, 95% CI 1.10-1.70). Organ-specific analyses showed that second prostate tumors were less common in patients who received RT compared to patients who received no RT (SHR = 0.51, 95% CI 0.43-0.62). RT also reduced the risk for a second primary tumor in the rectum(sigmoid) compared to patients who did not receive RT (SHR 0.59 95% CI 0.37-0.94). Patients who received post-operative RT had higher chances of developing a second rectum(sigmoid) tumor then patients who received pre-operative RT (SHR 2.25, 95% CI 1.07-4.73). Patients without RT had worse overall survival than patients who received RT (hazard ratio 1.22, 95% CI 1.19-1.26). Conclusions: In this nationwide study, patients with previous rectal cancer had a slightly increased chance of developing another primary tumor compared with the general population. We found a protective effect of RT on the development of secondary pelvic tumors, predominantly for prostate cancer.

E40 - Clinical Outcome of Patients With Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment

Background: At the time of diagnosis, 25% of patients (pts) with colorectal cancer (CRC) present synchronous unresectable metastases. The best therapeutic option for this pts is not yet defined: primary tumor resection (PTR) followed by chemotherapy or upfront chemotherapy without PTR? Methods: We conducted a prospective observation trial. Main study's objective was to describe the incidence of primary tumor–related complications in pts with stage IV CRC who received up-front oxaliplatin- or irinotecan-based combination chemotherapy with or without target therapies. Secondary objectives were: overall response rate (ORR- according to RECIST criteria), toxicity (CTCAE v4), progression free survival (PFS) and clinical benefit (defined as: increase in body weight and appetite, improvement of existing symptoms such as pain, bleeding, anorexia, asthenia). Results: From July 2013 to January 2015, 38 pts with median age of 65.8 years (range 44-83), were enrolled. Primary tumors were: right colon (cecum, ascending or transverse colon) in 26.3% of pts, left colon (descending or sigmoid) in 52.6% and rectum in 21.1%. The most common sites of metastasis were: liver (65.8%), retroperitoneal nodes (48.1%), lung (52.7%), peritoneum (21.1%), bone (21.1%) and brain (13.2%). Metastases involved one site or organ in 52.6% of pts, two sites in 26.3%, three sites in 13.2% and four sites in 7.9%. Of 38 pts, 97,4% never required surgical palliation of their primary tumor. One patients (2,6%) required medical therapy for primary tumor subobstruction. No bleeding or intestinal perforation were observed in the site of primary tumor. After 6 months, 94.7% of pts was evaluable for response: ORR was 25%, no complete response (CR), was observed, disease control rate (CR + partial response + stable disease) was 75% and progression was 25%; median PFS was 9.3 months (range 3-15). Grade 3/4 toxicities were as follows: neutropenia 19.2%; diarrhea 11.3%; nausea-vomiting 1.6%. Pain improved in 80% of pts, constipation in 60% of pts with less need for medical treatment (laxatives and enemas toileting), appetite improved in 64.8% of pts and an increase in body weight was observed in 48.3% of pts. Conclusions: These data showed that upfront chemotherapy, without routine prophylactic resection, could be an appropriate therapeutic option for pts with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis.

BNip3 is a hypoxia-inducible protein that targets mitochondria for autophagosomal degradation. We report a novel tumor suppressor role for BNip3 in a clinically relevant mouse model of mammary tumorigenesis. BNip3 delays primary mammary tumor growth and progression by preventing the accumulation of dysfunctional mitochondria and resultant excess ROS production. In the absence of BNip3, mammary tumor cells are unable to reduce mitochondrial mass effectively and elevated mitochondrial ROS increases the expression of Hif-1α and Hif target genes, including those involved in glycolysis and angiogenesis—two processes that are also markedly increased in BNip3-null tumors. Glycolysis inhibition attenuates the growth of BNip3-null tumor cells, revealing an increased dependence on autophagy for survival. We also demonstrate that BNIP3 deletion can be used as a prognostic marker of tumor progression to metastasis in human triple-negative breast cancer (TNBC). These studies show that mitochondrial dysfunction—caused by defects in mitophagy—can promote the Warburg effect and tumor progression, and suggest better approaches to stratifying TNBC for treatment.

Abstract 3955: The tumor suppressor C/EBPdelta promotes hypoxia-induced EMT and expression of stem cell markers through inhibition of FBXW7: Implications for mammary tumor metastasis.

Abstract The transcription factor CCAAT/enhancer binding protein delta (C/EBPδ) exhibits tumor-suppressor like-qualities such as downregulation of cyclin D1, and promotion of growth arrest and apoptosis. However, using a mouse model of mammary tumorigenesis (MMTV-Neu), we had found that C/EBPδ has dual functions. C/EBPδ suppresses primary tumor incidence while also augmenting metastatic progression. The pro-metastatic function of C/EBPδ can be correlated with a role in hypoxia adaptation and expression of pro-inflammatory genes and macrophage activation. C/EBPδ exerts both of these functions through inhibition of FBXW7, a component of SCF E3 ubiquitin ligase complex, which targets substrates such as c-myc and Notch for degradation (Balamurugan et al, 2010; Balamurugan et al., under revision). Hypoxia is believed to promote tumor progression in part by inducing epithelial-mesenchymal transition (EMT), which contributes to the generation of stem-like cancer cells (CSCs). In the present study, we found that hypoxia-induced EMT and expression of CSCs markers were compromised in Cebpd null primary tumor cells and in human breast tumor cells when C/EBPδ expression was silenced. On the other hand, silencing of the C/EBPδ-repressed gene FBXW7 was sufficient to induce a mesenchymal-like phenotype. Loss of FBXW7 has been shown to promote acquisition of stemness. In line with this notion, we found that overexpression of FBXW7 in the breast tumor cell line MDA-MB-468 reduced expression of aldehyde dehydrogenase 1 (Aldh1), C/EBPδ and the active form of NOTCH (NICD). Together, these data suggest that C/EBPδ augments - whereas its target FBXW7 prevents - EMT and breast cancer stem cell development, which may be an additional mechanism by which C/EBPδ promotes metastatic progression. Our current investigations are aimed at understanding how the different functions of C/EBPδ are integrated depending on cellular environment and context that results in its tumor promoting function despite its tumor suppressor role. Citation Format: Balamurugan Kuppusamy, Esta Sterneck. The tumor suppressor C/EBPdelta promotes hypoxia-induced EMT and expression of stem cell markers through inhibition of FBXW7: Implications for mammary tumor metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3955. doi:10.1158/1538-7445.AM2013-3955

A VOLUMINOUS LEFT ATRIAL MYXOMA IN A 62-YEAR OLD MAN WITH ATRIAL FIBRILLATION: A CASE REPORT AND REVIEW OF THE LITERATURE

The incidence of primary tumors of the heart varies between 0.0017 and 0.19 percent in unselected patients at autopsy.Three of four tumors are benign and nearly half the benign heart tumors are myxomas. We present a case report of a 62-year-old caucasian man without known cardiovascular risk factors presented at the emergency room (ER) for palpitations. The initial EKG showed rapid atrial fibrillation around 100 bpm and the patient complained of a recent dyspnea at exertion. Cardiac ultrasound was performed to rule out valvular or ischemic disease and measure the size of the left atrium. It showed a voluminous mass of 6 cm x 5 cm in the left atrium. The surgical removal of the tumor was indicated and a CT scan of the coronary arteries was performed in this 62-year-old patient that showed mild stenosis on the LAD. The patient was sent to cardiac surgery. This case suggests that prompt surgical treatment was safe with a low operative mortality and good long term prognosis. Cardiac ultrasound was the method of choice for diagnosis and follow-up. Contrast echocardiography allowed differentiating between cardiac tumors, myxomas and thrombi in most cases due to the difference in vascularisation.

Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition.

Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

Patterns of Local Extension and Regional Spread in Early Stage Nasal NK/T-cell Lymphoma Based on Magnetic Resonance Imaging

Patterns of Local Extension and Regional Spread in Early Stage Nasal NK/T-cell Lymphoma Based on Magnetic Resonance Imaging

P3-071 - Impact of Primary Tumor Resection on Survival for Incurable and Asymptomatic Stage IV Colorectal Cancer and Incidence of Primary Tumor Related Complications in Unresected Patients: Results of a Single-Institution Retrospective Study

ABSTRACT Background Primary tumor resection is recommended to manage symptoms such as perforation, obstruction, and bleeding in patients with incurable stage IV colorectal cancer. However, management of asymptomatic patients has not been established. Methods We carried out a retrospective analysis in seventy-seven asymptomatic patients who started chemotherapy with the diagnosis of incurable stage IV colorectal cancer at our institution between March of 2006 and August of 2011. As for impact of primary tumor resection on survival, we compared overall survival between resected and unresected patients and evaluated some predictive factors in association with survival. In unresected patients, we evaluated incidence of primary tumor related complications and some predictive factors associated with the incidence of complications. Results Median follow-up period was 14.0 months. A total of 37 patients underwent resection of the primary tumor, whereas 40 patients were managed without resection. Patient characteristics were well-balanced between the two groups. Resected patients had significantly better median survival time compared with unresected patients (24.3 versus 14.0 months). Perioperative complications in resected patients were low in both frequency and severity, and the period from resection to either discharge or start of chemotherapy was not significantly extended. Univariable analysis identified three significant predictive factors of survival: location of primary tumor, number of distant metastasis, and ALP, and ALP was also a significant predictor of survival in multivariable analysis. Incidence of primary tumor related complications was 25%, and univariable analysis identified no predictive factors. Conclusions Primary tumor resection in patients with incurable and asymptomatic stage IV colorectal cancer may be associated with better overall survival, and primary tumor related complications may be unavoidable to some extent in unresected patients. We plan to present the updated results with extended follow-up period at the presentation.

Challenge of Primary Tumor Management in Patients With Stage IV Colorectal Cancer

Optimal first-line therapy of patients who present with primary intact, unresectable stage IV colorectal cancer is controversial. Despite limited data, there are strong biases for either up-front primary tumor resection or for first-line systemic chemotherapy. The argument for up-front primary tumor resection is based on the desire to avoid potential complications of the intact primary tumor (IPT) such as bleeding, obstruction, or tumor perforation. Indeed the concern regarding the risk of primary tumor–related complications during systemic therapy, particularly with bevacizumab, has led both surgical and medical oncologists to advocate primary tumor resection at the time of diagnosis. In fact, the majority of US patients presenting with stage IV disease will still undergo noncurative primary tumor resection. However, during the past decade, several highly active systemic agents, both cytotoxic and biologic, have become available for the treatment of patients with metastatic colorectal cancer. As a result, the median survival duration of patients with unresectable metastatic disease has increased from 9 to 12 months with fluorouracil alone to up to 24 months with sequential modern cytotoxic and biologic treatments. Therefore, it may be generally accepted that, in these patients, systemic chemotherapy with or without primary resection is the essential treatment modality to prolong survival. But these modern agents also have increased activity on the primary tumor and can even induce complete response. Moreover, recent retrospective studies have observed low rates of primary tumor–related complications during treatment in patients with initially asymptomatic disease. Thus the old question of how best to manage the primary tumor continues to be debated. In the article that accompanies this editorial, investigators from the National Surgical Adjuvant Breast and Bowel Project (NSABP) have reported the final results of a phase II prospective, single-arm study of primary systemic chemotherapy with fluorouracil, oxaliplatin (mFOLFOX6) and bevacizumab for patients with asymptomatic primary intact unresectable stage IV colorectal cancer (NSABP C-10). The investigators aimed to directly address the concerns for both primary tumor–related complications associated with first-line systemic therapy in patients with asymptomatic disease and the risk of tumor complications with the use of bevacizumab in this setting. A total of 86 patients from 29 different institutions were evaluated with the primary eligibility criteria being that the treating clinician identified the patient to be asymptomatic with respect to his or her primary tumor. After a median follow-up of 20.7 months, the majority of the patients could be successfully managed nonoperatively without the need for primary tumor intervention, meeting the study’s primary end point. Median overall survival was 19.9 months and the overall rate of major morbidity related to the IPT was 16.3% (95% CI, 7.6% to 25.1%) at 24 months. Thustheinvestigatorsconcludedthatfirst-linecombinationtherapy withmFOLFOX6andbevacizumabdidnotresult inanunacceptablerate of primary tumor–related complications and that noncurative resection of the asymptomatic primary tumor in these patients could be avoided. These findings confirm prior retrospective reports demonstrating low rates of intestinal complications with either fluorouracil-based or more modern systemic chemotherapies. In their prospective evaluation, however, the NSABP investigators have further demonstrated the safety of first-line chemotherapy with bevacizumab in patients with intact but asymptomatic tumors. Indeed, 73.3% of the patients still had not required primary tumor resection at the time of death or last follow-up. This timely report has moved clinical treatment decision making forward and provides prospective evidence that routine noncurative resection may be unnecessary. But this relatively small study also highlights the need to address several other unanswered questions. Establishing that the patient is asymptomatic is the key eligibility criteria for this approach. However, perhaps for pragmatic needs of achieving accrual, “asymptomatic” in this study was broadly defined as having “no evidence of bowel obstruction or perforation, and no active bleeding requiring a transfusion.” Ultimately, it was the treating physician at each one of the 29 different institutions who had to adjudicate whether or not a patient who notes no symptoms, tolerates oral intake, and has bowel movements but is obstructed to the passage of an adult colonoscope (or perhaps some other variation on this theme) is labeled as having asymptomatic disease. This key issue of understanding which patients are eligible for this approach can also influence the true incidence of primary tumor–related morbidity (ie, not all patients with asymptomatic disease are the same). Notably, despite the frequency with which patients with stage IV are identified, and despite the relatively broad eligibility criteria, it took the 29 sites more than 3 years to accrue the 86 eligible patients to the study, perhaps reflecting difficulty on the part of the clinicians for deciding that a patient’s disease was indeed asymptomatic. Another unanswered question is when and how should endoluminal surveillance be performed. No endoluminal surveillance strategy was prespecified, and given the number of investigators in the 29 JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 26 SEPTEMBER 1

Avaliação da morbidade e da mortalidade após ressecções hepáticas

To describe morbidity and mortality in patients undergoing hepatectomy. We evaluated hepatectomy according to type of surgery, perioperative blood transfusion, hospital stay, complications and postoperative mortality. For statistical analysis we used the Ficher's exact test, considering significant p values <0.05. We performed 22 (31.43%) major hepatectomies, 13 (18.57%) being right hepatectomies extended to segments IVa and IVb, nine (12.86%) left hepatectomies, among these, six included the segment I. We conducted 48 (68.57%) minor hepatectomies, 36 (51.43%) segmental resections and 12 (17.14%) non-anatomical resections. The main indication for resection was colorectal adenocarcinoma metastasis in 27 (38.57%) patients. The higher incidence of primary tumor was hepatocellular carcinoma in 14 (20%) patients, followed by cholangiocarcinoma in six (8.57%). Among the 13 (18.57%) resections for benign diseases, the predominant one was intrahepatic lithiasis (n = 6). Six patients (8.57%) received perioperative blood transfusion. Hospital stay ranged from 2 to 28 days (mean four days). Eight (11.43%) patients developed postoperative complications. Overall mortality was 8.57%, mostly in patients with hepatocellular carcinoma (5.71%). Metastatic colorectal adenocarcinoma was the main indication for surgery and minor hepatectomies were the most common procedures. Despite the low overall incidence of postoperative complications, there was high morbidity and mortality in cirrhotic patients with hepatocellular carcinoma.

Human and Mouse Colon Cancer Utilizes CD95 Signaling for Local Growth and Metastatic Spread to Liver

Analysis of clinical colon cancer specimens show alterations in the CD95 (Fas Ag/Fas L) pathway as tumors progress from local to metastatic disease, suggesting that this pathway may play a role in invasive behavior of colon cancer. However, direct causality between these alterations and clinical disease progression has not been shown. Surgically resected metastatic colon cancer samples were evaluated for Fas Ag/L and apoptosis. Alterations in the Fas-signaling pathway found in human samples were recreated through a series of staged transfection experiments in the MC38 mouse colon cancer cell line and the effects on growth tested in vitro and in vivo. Expression of FLICE-like inhibitory protein confers apoptosis resistance, increasing the incidence of primary tumors through a survival advantage by avoiding apoptosis and inducing Fas-mediated proliferation. Coexpression of Fas L enables colon cancer cells to metastasize to the liver from local tumors as well as from intravenous injection of cells. MC38-FasL/FLICE-like inhibitory protein colon cancer cells induce apoptosis in hepatocytes via activation of type II Fas Ag signaling, thus creating a niche conducive to tumor growth and fueling their own growth via Fas proliferative signaling. Alterations in the Fas Ag pathway which inhibit apoptosis and increase Fas-mediated proliferation directly increase local colon cancer growth, and enhance metastasis to the liver. Delineating points in the pathway responsible for growth and metastasis will offer targets that may be exploited for therapy.

The effect of green tea on oxidative damage and tumour formation in Lobund–Wistar rats

A number of epidemiological studies suggest that the consumption of green tea reduces the incidence of prostate cancer. As the major catechins present in green tea are potent antioxidants, we hypothesized that genetic and cellular damage induced by oxygen free radicals could be significantly reduced by potent antioxidants in green tea, thus reducing the cumulative genetic and cellular damage with age, and slowing or preventing tumour formation. Long-term administration of a decaffeinated green tea extract to Lobund-Wistar rats for periods up to 26 months almost halved the incidence of primary tumours in the genitourinary tract when compared with an age-matched cohort receiving just water. We observed no inhibition of DNA adduct formation or lipid peroxidation in animals consuming green tea compared with animals consuming deionized water. The decrease in tumour formation was associated with an increase in 8-hydroxy-2'deoxyguanosine and 4-hydroxynonenal content (markers of DNA adduct formation and lipid peroxidation, respectively) in the epithelium of the ventral prostate in aging animals. In addition, there was an increase in 8-hydroxy-2'deoxyguanosine expression, but no change in 4-hydroxynonenal expression in the seminal vesicles of older animals. An age-associated increase in expression of the antioxidant enzymes manganese superoxide dismutase and catalase in the epithelium of the ventral prostate of aging animals was observed. Furthermore, there was also an increase in manganese superoxide dismutase expression, but no change in catalase expression in the seminal vesicles of older animals. These data demonstrate that consumption of green tea decreases the incidence of genitourinary tract tumours in the Lobund-Wistar rat, but has no effect on age-associated DNA adduct formation and lipid peroxidation in the ventral prostate and seminal vesicles of the aging rat.