Chemopreventive Potential of Phyllanthus emblica Fruit Extract against Colon and Liver Cancer Using a Dual-Organ Rat Carcinogenesis Model.

Humans are frequently exposed to various carcinogens capable of inducing cancer in multiple organs. Phyllanthus emblica (P. emblica) is known for its strong antioxidant properties and potential in cancer prevention. However, its effectiveness against combined carcinogens remains relatively unexplored. This study aimed to assess the chemopreventive potential of the ethanolic extract of P. emblica fruits against preneoplastic lesions in the liver and colon using a rat model. Rats were administered with diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) to induce hepato- and colon carcinogenesis, respectively. The ethanolic extract of P. emblica fruit at 100 and 500 mg/kg bw significantly reduced the number of preneoplastic lesions in the liver by 74.7% and 55.6%, respectively, and in the colon by 39.2% and 40.8%, respectively. Similarly, the extract decreased the size of preneoplastic lesions in the liver by 75.2% (100 mg/kg bw) and 70.6% (500 mg/kg bw). Furthermore, the extract significantly reduced the cell proliferation marker in the liver by 70.3% (100 mg/kg bw) and 61.54% (500 mg/kg bw), and in the colon by 62.7% (100 mg/kg bw) and 60.5% (500 mg/kg bw). The ethanolic extract also enhanced liver antioxidant enzyme activities and demonstrated free radical scavenging in DPPH, ABTS, and FRAP assays. Additionally, the dichloromethane fraction of P. emblica showed significant cancer prevention potential by reducing intracellular ROS and NO production by 61.7% and 35.4%, respectively, in RAW 264.7 macrophages. It also exhibited antimutagenic effects with a reduction of 54.0% against aflatoxin B1 and 52.3% against 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mutagenesis in Salmonella typhimurium. Finally, this study highlights the chemopreventive activity of P. emblica fruit extract against the initiation of early-stage carcinogenic lesions in the liver and colon in rats treated with dual carcinogens.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

Development and Validation of a Nomogram for Prognosis Prediction in Patients with Synchronous Primary Thyroid and Breast Cancer Based on SEER Database.

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.

Synchronous multiple primary cancers involving rectal cancer and pelvic classical hodgkin lymphoma: the first case report.

Multiple primary cancers (MPC) are characterized by the presence of synchronous and metachronous occurrence of two or more distinct histological tumor types. In this study, an exceptional clinical case was presented, demonstrating the coexistence of rectal adenocarcinoma and pelvic classical Hodgkin lymphoma (cHL). A 65-year-old male patient with a 2-year history of persistent mucous bloody stools was admitted to our hospital. Colonoscopy and subsequent biopsy confirmed the diagnosis of rectal adenocarcinoma. The patient underwent laparoscopic abdominoperineal resection of the rectum and regional lymph node dissection. Postoperative histopathological analysis not only substantiated the presence of rectal adenocarcinoma, but also unexpectedly identified pelvic lymph nodes harboring the features of cHL.

Susceptibility Genes Associated with Multiple Primary Cancers.

With advancements in treatment and screening techniques, we have been witnessing an era where more cancer survivors harbor multiple primary cancers (MPCs), affecting approximately one in six patients. Identifying MPCs is crucial for tumor staging and subsequent treatment choices. However, the current clinicopathological criteria for clinical application are limited and insufficient, making it challenging to differentiate them from recurrences or metastases. The emergence of next-generation sequencing (NGS) technology has provided a genetic perspective for defining multiple primary cancers. Researchers have found that, when considering multiple tumor pairs, it is crucial not only to examine well-known essential mutations like MLH1/MSH2, EGFR, PTEN, BRCA1/2, CHEK2, and TP53 mutations but also to explore certain pleiotropic loci. Moreover, specific deleterious mutations may serve as regulatory factors in second cancer development following treatment. This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.

Factors That Determine Multiple Primary Cancers in the Adult Population in the United States.

BACKGROUND: Cancer is a major public health problem worldwide and a leading cause of death in the United States. Multiple primary cancers mean that an individual has more than one cancer in the same or a different organ but does not include instances of metastasis of initial primary cancer. Several factors such as genetics, for example, BRCA1 gene mutations, may predict multiple primary cancers. Factors such as the age at first cancer diagnosis may determine the outcome of multiple primary cancers. This study aims to determine factors that determine multiple primary cancers among the adult population in the United States.  Methods: This study uses data from the Behavioral Risk Factor Surveillance System 2021 dataset. The study included all individuals recently diagnosed with cancer (sample size = 9806). All age groups were included in this study. Measures included the outcome variable number of cancers and a major independent variable: age at first cancer diagnosis. Covariates included race, sex, smoking status, and cancer treatment. Descriptive, bivariate, and multivariate logistic regressions were conducted using a statistical analysis system. It was hypothesized that individuals with age at first diagnosis of cancer at a younger age have higher odds of having multiple primary cancers as compared to individuals diagnosed at an older age.  Results: The age group of 50-64 years had the highest percentage of only one cancer type (35.87%) and of two or more cancers (35.46%). A majority of females had two or more cancers (53.52%) as compared to males (47.48%). The majority of participants with only one cancer type (80.59%) and two or more cancers (88.61%) were of White non-Hispanic ethnicity. At the multivariate level, the age group under 18 years had 9.4% higher odds of having two or more cancers compared to the age group of 18-29 years (adjusted OR (AOR)=1.094, 95%CI=1.026-1.166; p-value=0.0057). The age group 65 years and above had 11.6% lower odds of having multiple primary cancers as compared to the age group of 18-29 years (AOR=0.884; 95%CI=0.859-0910; p-value=<0.0001). The Black non-Hispanic group had 73.8% lower odds of having multiple primary cancers as compared to White non-Hispanic respondents (AOR= 0.262; 95%CI = 0.228-0.301; p-value = <0.0001). Hispanic respondents had 59.8% lower odds of having two or more cancers as compared to the White non-Hispanic group (AOR= 0.402; 95%CI=0.390-0.413; p-value=<0.0001). Current smokers had 9.7% higher odds of having multiple cancers as compared to individuals who never smoked (AOR = 1.097; 95%CI=1.066-1.129; p-value=<0.0001). Former smokers had 24.2% higher odds of having multiple cancers as compared to individuals who never smoked (AOR=1.242; 95%CI=1.224-1.261; p-value=<0.0001). Individuals who were currently on treatment had 2.676 higher odds of having two or more cancers as compared to individuals not on treatment (AOR=2.676; 95%CI=2.629-2.724; p-value=<0.0001).  Conclusion: Multiple primary cancers have been on the increase recently following advancements in anticancer therapy and cancer screening and diagnosis technology. It is important that studies that aim to demonstrate risk factors and predictors of multiple primary cancers such as the age at first diagnosis, smoking status, and cancer treatment are encouraged among public health specialists.

Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer.

BACKGROUND: Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung. METHODS: Exome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case-control association analyses were performed. RESULTS: Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations. CONCLUSIONS: We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.

Oral Squamous Cell Carcinoma and Concomitant Primary Tumors, What Do We Know? A Review of the Literature.

Head and neck cancer is among the top ten cancers worldwide, with most lesions in the oral cavity. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral malignancies and is a significant public health concern. Patients with OSCC are at increased risk for developing concomitant tumors, especially in the oral cavity, due to widely genetically susceptible mucosa to carcinogenic factors. Based on fulfilling specific criteria, these concomitant tumors can be called second primary tumors (SPTs), which can be further categorized into metachronous and synchronous tumors. This research reviews the literature that investigated the concurrent OSCC with second or multiple primaries to improve understanding of the definition, classification guidelines, and its effect on cancer survival. It also highlights the current investigation methods, the variation of standard treatment approaches due to such a phenomenon, and preventive measures discussed in the literature.

Chromophobe renal cell carcinoma with ipsilateral ureteral urothelial carcinoma: A case report.

It is very rare for different types of urological tumours to occur together, and it is even rarer for chromophobe renal cell carcinoma (CRCC) to be combined with ipsilateral ureteral urothelial carcinoma (UUC), and the symptoms are relatively homogeneous, mostly presenting as symptoms that can be observed in malignant tumours alone, and therefore are often easily missed. In the present study, a case of a patient who was admitted to the hospital for more than 3 months with no obvious cause of terminal carnivorous hematuria was reported, and ureteral carcinoma was considered in the preoperative diagnosis but not renal carcinoma. After completion of preoperative tests, laparoscopic right nephrectomy and right ureterectomy was performed. The postoperative pathological diagnosis was CRCC of the right side and low-grade UUC of the right side, and the patient did not show any significant abnormality at the postoperative follow-up. By discussing this case and reviewing the relevant literature, the present study provides clinicians with more insight.

Pathogenic variants among females with breast cancer and a non-breast cancer reveal opportunities for cancer interception.

PURPOSE: Herein, we report the frequency and distribution of germline pathogenic variants (PVs) among females with breast cancer (BC) and at least one other non-BC who underwent multi-gene panel testing (MGPT). Among females with PVs diagnosed first with BC or ovarian cancer (OC), we sought to enumerate the frequency of subsequent PV-associated cancers. METHODS: Females with BC and cancer of ≥ 1 other site (multiple primary cancers, MPC) who underwent MGPT through Ambry Genetics from March 2012 to December 2016 were included if they had testing of at least 21 genes of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53). Phenotypic data were abstracted from test requisition forms and clinical notes. RESULTS: Of 6,617 evaluable patients, most were White (70.8%) and median age at first cancer, second cancer, and MGPT was 49 (interquartile range [IQR]: 18), 59 (IQR: 16), and 63 (IQR: 16) years, respectively. PVs were found among 14.1% (932/6617) of the overall cohort and in 16.4% (440/2687) of females who were diagnosed first with BC. Among those, 55.2% (243/440) had an actionable PV associated with a subsequent cancer diagnosis including 150 OCs. Of the 2443 females with breast and ovarian cancer, few (n = 97, 9.5%) were diagnosed first with OC, limiting our analysis. CONCLUSIONS: Females with MPC, including BC, have a high frequency of germline PVs (14.1%). These data delineate the opportunities for intercepting subsequent cancers associated with genetic risk among females diagnosed first with BC.

One Patient With 4 Different Primary Cancers: A Case Report.

Background: The development of medicine, especially in oncology, has been helping prolong the cancer patients' survival, but also leads to increasing the possibility of getting multiple cancers. However, the possibility of getting 4 primary cancers in 4 different sites is extremely rare. Case presentation: A 63-year-old female patient was diagnosed with thyroid cancer in 2018, and then with right colon cancer in 2019. In 2020, this patient was diagnosed with left renal pelvis cancer, and most recently, in April 2022, she was hospitalized with bladder cancer diagnosis. Thanks to being closely and regularly followed-up, her malignancies had been detected early and treated suitably. Her health remains stable now and she is under following-up. Conclusion: Even though developing another primary cancer in a cancer survivor is not uncommon now and has the tendency to increase, a patient having 4 primary cancers in 4 different sites is still extremely rare and should be noticed, further followed up and investigated. Cancer patients and survivors need to be followed-up regularly, to early detect not only the progression or recurrence but also the second cancer (if it exists), to get timely and suitable treatment.

Case report: Rare presentation of double primary malignancies of the lung and thyroid: a difficult diagnosis.

This report describes a rare case of double primary cancer in a female patient aged 49 years who died 2 years after diagnosis. The patient was diagnosed with BRAFV600E-mutant metastatic papillary thyroid carcinoma (PTC) and ALK fusion-positive metastatic lung adenocarcinoma. She presented with multifocal thyroid lesions and underwent radical thyroidectomy and bilateral cervical lymphadenectomy. Thyroid ultrasound revealed the presence of five hypoechoic nodules with irregular margins and microcalcifications; an irregular inhomogeneous hypoechoic level IV cervical lymph node was also found on the right side. Histological analysis confirmed the presence of metastatic PTC, and the tumor tested positive for the BRAFV600E mutation. Ultrasound of the neck, which was performed 4 months postdischarge, revealed enlargement of the left-sided cervical lymph nodes; a biopsy from these nodes confirmed a diagnosis of metastatic PTC. Positron emission tomography-computed tomography scans revealed the presence of multiple pulmonary hypermetabolic foci scattered across bilateral lung fields. Multiple hypermetabolic foci were also observed in the lymph nodes on both sides of the neck, axillae, and mediastinum; in addition, there was evidence of bone destruction with hypermetabolic foci. Supplementary reports from the histological and immunohistochemical analyses of cervical lymph node tissue obtained during primary surgery confirmed the presence of metastatic PTC and poorly differentiated lung adenocarcinoma. In particular, one enlarged cervical lymph node located on the right side of the neck demonstrated tumor components of both PTC and lung adenocarcinoma. Pathological analysis of axillary lymph node puncture biopsy confirmed the presence of metastatic lung adenocarcinoma, and gene analysis revealed the presence of ALK fusion. The patient received targeted therapy based on a multidisciplinary discussion. However, she had a poor prognosis and died 2 years after the diagnosis. The initial thyroid ultrasound findings were reviewed retrospectively; the findings suggested that the possibility of double primary cancers should be considered in cases where the enlarged cervical lymph nodes are highly suspicious of PTC and present as inhomogeneous hypoechoic masses with irregular morphology.

Dual primary gastric and colorectal cancer: A complex challenge in surgical oncology.

The intricate interplay of colorectal cancer (CRC) and gastric cancer (GC) as dual primary malignancies presents a significant challenge in surgical oncology. CRC is the most common secondary malignancy in GC patients, and vice versa, evidence highlighted by advances in diagnostic procedures and therapy modalities that impact patient survival. A recent study titled "Features of synchronous and metachronous dual primary gastric and colorectal cancer" explores this enigmatic dual malignancy, uncovering crucial insights into the clinical characteristics and prognostic distinctions between synchronous and metachronous presentations. Notably, metachronous cases with a second primary cancer discovered more than six months after the first diagnosis have a better outcome, emphasizing the importance of early detection and treatment. This study underscores the prognostic role of GC stage in patient outcomes. It also sheds light on the complexities faced by synchronous cases, often presenting with unresectable CRC. Surgery-related procedures, like gastrectomy and colon resection, stand out as important predictors of increased survival, necessitating a reevaluation of current therapeutic approaches. A tailored and patient-centered strategy, considering the health of each patient individually and the feasibility of radical treatments, is essential. Continuous follow-up and monitoring are crucial as most second primary cancers arise within five years. In conclusion, early diagnosis, surgical intervention, and watchful surveillance are pivotal in managing dual primary gastric and colorectal cancer patients. Since the incidence of gastric and colorectal cancers continues to rise, the imperative need for further research, ideally with larger sample sizes, becomes evident in our pursuit of comprehensive insights that will refine clinical approaches for this intricate dual malignancy.

Synchronous gastric cancer complicated with chronic myeloid leukemia (multiple primary cancers): A case report.

BACKGROUND: With the advancement of medical technology and improvement in living standards, the incidence of multiple primary cancers has gradually increased. In particular, tumors of the digestive system account for a large proportion of multiple primary cancers. The diagnosis and treatment of chronic myeloid leukemia, particularly with synchronous gastric cancer, at the first consultation is relatively rare. CASE SUMMARY: Herein, we present the case of a middle-aged man who was referred to the Department of Hematology owing to an elevated white blood cell count. After the examination, he was diagnosed with chronic myeloid leukemia and was administered imatinib. Three months after the initial diagnosis, he visited our hospital again for abdominal pain, and further examination revealed gastric malignancy. After discussion with a multidisciplinary team, S-1 (Tegafur, Gimeracil, and Oteracil Potassium Capsules) combined with oxaliplatin-SOX regimen-was initiated. Later, the patient's condition rapidly progressed. He developed colonic obstruction and underwent an ostomy; however, he died less than 6 months after the initial diagnosis. CONCLUSION: Multiple primary cancers are influenced by environmental and genetic factors; a standardized multidisciplinary discussion plays a key role in treatment.

Overall Survival for Esophageal Squamous Cell Carcinoma with Multiple Primary Cancers after Curative Esophagectomy-A Retrospective Single-Institution Study.

Background: Advances in surgical techniques and treatment modalities have improved the outcomes of esophageal cancer, yet difficult decision making for physicians while encountering multiple primary cancers (MPCs) continues to exist. The aim of this study was to evaluate long-term survival for esophageal squamous cell carcinoma (SCC) associated with MPCs. Methods: Data from 544 patients with esophageal SCC who underwent surgery between 2005 and 2017 were reviewed to identify the presence of simultaneous or metachronous primary cancers. The prognostic factors for overall survival (OS) were analyzed. Results: Three hundred and ninety-seven patients after curative esophagectomy were included, with a median observation time of 44.2 months (range 2.6−178.6 months). Out of 52 patients (13.1%) with antecedent/synchronous cancers and 296 patients without MPCs (control group), 49 patients (12.3%) developed subsequent cancers after surgery. The most common site of other primary cancers was the head and neck (69/101; 68.3%), which showed no inferiority in OS. Sex and advanced clinical stage (III/IV) were independent risk factors (p = 0.031 and p < 0.001, respectively). Conclusion: Once curative esophagectomy can be achieved, surgery should be selected as a potential therapeutic approach if indicated, even with antecedent/synchronous MPCs. Subsequent primary cancers were often observed in esophageal SCC, and optimal surveillance planning was recommended.

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.

Multiple primary squamous cell carcinomas of the oral cavity: A cross-sectional study in vietnam.

Background: Multiple primary squamous cell carcinomas (MPSCs) of the oral cavity are very uncommon in clinical practice. This study describes the clinical features, imaging, and treatment characteristics of the oral cavity with MPSCs at the same time of diagnosis in our center. Besides, we review the literature and prior studies on MPSCs. Study design: A retrospective, descriptive study from January 2019 to December 2021 was conducted on seven patients with MPSCs of the oral cavity at the time of their first diagnosis. Evaluation of the patient's characteristics, the treatment plan, the response to treatment, and the overall survival (OS). Results: Seven male patients ranging in age from 43 to 70 years (Mean: 53.5). Positron Emission Tomography/Computed Tomography (PET/CT) revealed a significantly increased standardized uptake value (SUV) in the index tumor (SUVi = 15.76 ± 1.96). The index tumor is often staged T3, T4; whereas the synchronous tumor is typically staged T1, T2. All patients had concurrent chemoradiotherapy (CCRT) and achieved a partial response in all cases. Mean OS was 14.71 ± 11.85 months. Conclusions: MPSCs of the oral cavity at the time of diagnosis are uncommon and associated with a poor prognosis for patients. Comprehensive clinical examination, combined imaging diagnostics, with PET/CT being critical for detecting the second lesion, particularly in patients with an advanced index tumor.

Suicide and Cardiovascular Death Among Patients With Multiple Primary Cancers in the United States.

Background: Previous studies have demonstrated that patients with a cancer diagnosis have an elevated risk of suicide and cardiovascular death. However, the effects of the diagnosis of multiple primary cancers (MPCs) on the risk of suicide and cardiovascular death remain unclear. This study aimed to identify the risk of suicide and cardiovascular death among patients with MPCs in the United States. Methods: Patients with a single or MPC(s) between 1975 and 2016 were selected from the Surveillance, Epidemiology, and End Results database in a retrospective cohort study. Mortality rates and standardized mortality ratios (SMRs) of suicides and cardiovascular diseases among patients with MPCs were estimated. Results: Of the 645,818 patients diagnosed with MPCs included in this analysis, 760 and 36,209 deaths from suicides and cardiovascular diseases were observed, respectively. The suicide and cardiovascular-disease mortality rates were 1.89- (95% CI, 1.76-2.02) and 1.65-times (95% CI, 1.63-1.67), respectively, that of the general population. The cumulative mortality rate from both suicides and cardiovascular diseases among patients with MPCs were significantly higher than those of patients with a single primary cancer (Both p < 0.001). In patients with MPCs diagnosed asynchronously, the cumulative incidence rates of suicides and cardiovascular deaths were higher than those diagnosed synchronously. Among all MPCs, cancers of the pancreas and esophagus had the highest SMRs of suicide (5.98 and 5.67, respectively), while acute myeloid leukemia and brain cancer had the highest SMRs of cardiovascular diseases (3.87 and 3.62, respectively). The SMR of suicide was highest within 1 year after diagnosis, while that of cardiovascular diseases was highest 5 years after diagnosis. Conclusions: This study showed that the mortality rates from suicides and cardiovascular diseases among patients with MPCs were higher than those with a single primary cancer. Therefore, our results underscore the need for psychological assessment and targeted preventive interventions for suicides and cardiovascular diseases among patients with MPCs.

Mediastinal thymoma in a patient with previous rectal and breast cancers: A report of a case with multiple primary cancers and review of literature.

A 42-year-old female patient with intellectual disability was presented to us as a newly diagnosed case of thymoma. She was identified as a case of multiple primary cancers, including adenocarcinoma of the rectum, carcinoma of the breast, and mediastinal thymoma, in a 15-year period, who underwent chemotherapy, radiotherapy, and surgical resection.