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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related deaths in the world with an estimated number of 1.8 million new cases and about 881,000 deaths worldwide in 2018. The epidemiology of CRC varies significantly between different regions in the world as well as between different age, gender and racial groups. Multiple factors are involved in this variation, including risk factor exposure, demographic variations in addition to genetic susceptibility and genetic mutations and their effect on the prognosis and treatment response. In this mini-review, we discuss the recent epidemiological trend including the incidence and mortality of colorectal cancer worldwide and the factors affecting these trends.

Summary Introduction Pancreatic Ductal Adenocarcinoma (PDAC) is an uncommon yet fatal malignancy with numerous recent reports detailing a significant increase in the overall incidence lately. However, there is limited literature on recent incidence rates of the disease in young individuals. In this study we evaluate PDAC incidence in the US among young patients. Methods Data from 2000 to 2017 was obtained from the Surveillance Epidemiology and End Results ‘SEER’ database and analyzed using the SEER*stat software. The overall incidence, incidence trends, and survival were calculated. Results We selected 667 PDAC patients who met our inclusion criteria. We found the incidence of PDAC among young individuals to be 1.016 (95% CI, 0.940–1.096) per 1,000,000 person-years. Incidence rates were stable over the study period. Higher incidence was found among males [1.240 (95% CI, 1.122-1.366)] and blacks [1.226 (95% CI, 0.999–1.490)]. The 5-year relative survival of young patients with PDAC was 6.8%. Conclusions Among young adults, pancreatic cancer incidence has been stable over the study duration. However, disparities between subpopulations exist and further studies are warranted to better understand those observed differences.

Background We aimed to investigate the risk and survival of chronic myeloid leukemia (CML) after breast cancer (BC) diagnosis. Methods We used the Surveillance, Epidemiology, and End Results ‘SEER’ database. Females, diagnosed with BC between 1992 and 2014, were selected and followed for the development of CML after a 6-month latency period from BC diagnosis. We used the Multiple Primary Standardized Incidence Ratios session of the SEER*Stat software (version 8.3.4) to calculate the Observed/Expected (O/E) ratios with 95% confidence intervals (CI). To calculate the overall survival, we performed an unadjusted Kaplan-Meier analysis using the SPSS software. Results We included 474,866 females with BC, of which 178 were later diagnosed with CML. We found the risk of CML to increase significantly after BC diagnosis (O/E = 1.26, 95% CI: 1.08-1.45) and the risk was specifically higher within the first 5 years of diagnosis (O/E = 1.45, 95% CI: 1.16-1.8). When the risk was stratified by cancer stage, localized BC was associated with a significant increase in CML risk within 5 years of diagnosis (O/E = 1.4, 95% CI: 1.06-1.82), while regional BC was associated with a significant increase in CML risk after more than 5 years of diagnosis (O/E = 1.59, 95% CI: 1.09-2.25). Moreover, radiotherapy, chemotherapy, and presence of hormonal receptors were associated with a significant increase in CML risk in BC patients. The median overall survival of CML after BC was 28 months. Conclusion Breast cancer patients have an increased risk of developing CML and further investigation is required to establish the causes of this finding.

Importance Owing to improved survival among US patients with prostate cancer (PC), patients tend to live long enough after a PC diagnosis for non–cancer-related comorbidities to be associated with their overall survival. Although studies have investigated causes of death among patients with localized PC, data are lacking regarding causes of death among patients with metastatic PC. Objective To assess causes of death among US patients with metastatic PC from 2000 to 2016. Design, Setting, and Participants This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results Program database to analyze a sample of 26 168 US men who received a diagnosis of metastatic PC from January 1, 2000, to December 31, 2016. Data were analyzed from February 2 to July 28, 2020. Exposure Diagnosis of metastatic PC. Main Outcomes and Measures Standardized mortality ratios (SMRs) for different causes of death were calculated by dividing the observed number of deaths from each cause of death by the expected number of deaths in the age-matched US male population for the same period, adjusting for age and race/ethnicity. Results Of 26 168 patients with metastatic PC included in the analysis, 48.9% were aged 50 to 70 years (mean age at diagnosis, 70.83 years); 74.5% were White individuals, and 72.7% received a diagnosis of stage M1b metastatic PC. A total of 16 732 patients (63.9%) died during the follow-up period. The mean age at death was 74.13 years. Most deaths (59.0%) occurred within the latency period of 2 years after diagnosis of metastatic PC, whereas 31.6% occurred 2 to 5 years after diagnosis and 9.4% occurred more than 5 years after diagnosis. Of the total deaths, 13 011 (77.8%) were from PC, 924 (5.5%) were from other cancers, and 2797 (16.7%) were from noncancer causes. During all latency periods, the most common noncancer causes of death were cardiovascular diseases (SMR, 1.34; 95% CI, 1.26-1.42), chronic obstructive pulmonary disease (SMR, 1.19; 95% CI, 1.03-1.36), and cerebrovascular diseases (SMR, 1.31; 95% CI, 1.13-1.50). Conclusions and Relevance In this cohort study, deaths from noncancer causes, including cardiovascular disease, constituted a substantial number of deaths among men with metastatic PC. Therapy and follow-up should be tailored to the needs of each patient with metastatic PC, and counseling regarding future health risks should be provided.

Introduction Because of the improved colorectal cancer (CRC) survival in the U.S., patients may live long enough after CRC diagnosis to the point where non–cancer-related comorbidities may considerably impact their overall survival. In this study, we perform a long-term analysis of causes of death (CODs) following nonmetastatic CRC with respect to different demographic and tumor-related criteria. Materials and Methods We gained access to the Surveillance, Epidemiology, and End Results data to review patients diagnosed with nonmetastatic CRC during 2000–2015. We calculated standardized mortality ratios (SMRs) for each COD following CRC. SMRs represented the change of risk of a specific COD following CRC diagnoses when compared with the risk in the general U.S. population. Results We reviewed 302,345 patients, of whom 112,008 died during the study period. More deaths (68.3%) occurred within 5 years following nonmetastatic CRC diagnosis, with 76,486 deaths. CRC was the most common COD (51.4%) within 5 years of diagnosis followed by heart disease (15.2%) and other cancers (8.4%). As time passed after diagnosis, the number of CRC deaths decreased, and other noncancer causes increased to the point that after 10 years only 10.4% of deaths were attributed to CRC, 15.3% were attributed to other cancers, and 34.2% were secondary to heart disease. Conclusion Following nonmetastatic CRC diagnosis, most deaths remain secondary to CRC. Other causes, including other cancers and cardiovascular disease, represent a significant number of deaths, especially in the 5 years following initial CRC diagnosis. Our findings help guide counseling patients with CRC regarding future health risks. Implications for Practice Most common causes of death following nonmetastatic colorectal cancer (CRC) are heart diseases, other cancers, chronic obstructive pulmonary disease, and cerebrovascular diseases. Physicians should counsel patients regarding survivorship with cancer screening and focus on prevention of noncancer deaths. These findings should be considered by physicians who give care for survivors of nonmetastatic CRC.

Interferon-alpha (IFN-α)-based therapy is associated with several hematological adverse events in hepatitis C virus (HCV)-infected patients with advanced fibrosis. We performed this study to evaluate the association between Fibrosis-4 (Fib-4) index and hematological adverse events in patients with chronic HCV infection, undergoing IFN-α-based triple therapy. We included 120 HCV-infected patients, receiving triple therapy: weekly PegIFN-α, daily ribavirin (1,000-1,200 mg), and daily sofosbuvir (400 mg) for 12 weeks. We compared Fib-4 scores for patients who developed hematological adverse events at weeks 4 (w4) and w12 of treatment and w12 post-treatment versus those who did not. Treatment with the aforementioned triple regimen was associated with a sustained virological response (SVR)-12 rate of 93.9%. We found no significant associations (P 0.05) between SVR12 rate and the degree of fibrosis or the risk of hematological adverse events. The Fib-4 score could predict patients who developed hematological adverse events (anemia, leukopenia, and neutropenia) in the first month of treatment, but not in later stages. A Fib-4 cutoff value of 3.59 had high specificity for anemia, leukopenia, and neutropenia (85.1%, 87.2%, and 88.2%, respectively), but had low sensitivity for detecting the 3 events. In conclusion, the Fib-4 score may predict early hematological adverse effects in HCV-infected patients on IFN-based triple therapy.

This cohort study examines outcomes of patients with brain cancer to provide demographic details on the increase in suicide rate after brain cancer diagnosis.

Chronic pain is one of the most common clinical presentations in the primary care settings. In the US, Fibromyalgia (FM) affects about 1-3% of adults and commonly occurs in adults between the ages of 40-50 years. FM causes widespread muscular pain and tenderness with hyperalgesia and allodynia and may be associated with other somatic complaints. Hyperbaric oxygen therapy (HBOT) has been utilized and has recently shown promising effects in the management of FM and other chronic pain disorders. In HBOT, the intermittent breathing of 100% oxygen in a pressurized chamber where the pressure is higher than 1 atmosphere absolute (ATA) has been utilized. HBOT exhibits a significant anti-inflammatory effect through reducing production of glial cells and inflammatory mediators which results in pain alleviation in different chronic pain conditions. HBOT can also influence neuroplasticity and affects the mitochondrial mechanisms resulting in functional brain changes. In addition to that, HBOT stimulates nitric oxide (NO) synthesis which helps in alleviating hyperalgesia and NO-dependent release of endogenous opioids which seemed to be the primary HBOT mechanism of antinociception. Moreover, aerobic exercise and meditative movement therapies (MMT) have gained attention for their role in pain alleviation through different anti-inflammatory and antioxidant mechanisms. In this review, we aim to elucidate the different mechanisms of HBOT and aerobic exercise in attenuating pain as adjuvant therapy in the multidisciplinary treatment strategy of chronic pain, and more particularly fibromyalgia.

Previous studies of ethnic disparities in colorectal cancer (CRC) have focused mainly on patients of Caucasian and African-American descent. We aimed to evaluate outcomes for a range of races, representing a broader demographic of the US population. The Surveillance, Epidemiology, and End Results database was queried to identify patients with CRC diagnosed between 1994 and 2014. We performed unadjusted Kaplan-Meier test and multivariable covariate-adjusted Cox models to calculate the overall and CRC-specific survival of patients according to their race. We identified 401,723 patients diagnosed with CRC between 1994 and 2014. Overall survival (OS) and CRC-specific survival were compared across different races stratified by age, sex, marital status, disease stage and grade, and undergoing surgery as a treatment. Overall, Asian/Pacific Islanders and Hispanics had improved CRC-specific survival compared to Whites (HR = 0.873, 95%CI 0.853–0.893, P

Cholangiocarcinoma is an aggressive malignancy with few available studies assessing incidence and mortality. In this study, we aim to investigate trends of incidence and mortality in a large nation-wide epidemiologic study.We used SEER 18 database to study cholangiocarcinoma cases in the US during 2000-2015. Incidence and mortality rates of cholangiocarcinoma were calculated by race and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software.We reviewed 16,189 patients with cholangiocarcinoma, of which 64.4% were intrahepatic. Most patients were whites (78.4%), males (51.3%), and older than 65 years (63%). A total of 13,121 patients died of cholangiocarcinoma during the study period. Cholangiocarcinoma incidence and mortality were 11.977 and 10.295 and were both higher among Asians, males, and individuals older than 65 years. Incidence rates have significantly increased over the study period (APC=5.063%, P.001), while mortality increased significantly over the study period (APC=5.964%, P.001), but decreased after 2013 (APC=-25.029, P.001).The incidence and mortality of cholangiocarcinoma were increasing in the study period with significant observed disparities based on race and gender.

Background Most clinical trials on colorectal cancer (CRC) exclude cases who have history of a prior malignancy. However, no prior research studied this history’s actual impact on the survival of CRC. In the paper, we study the effects of having a malignancy preceding CRC diagnosis on its survival outcomes. Methods CRC patients diagnosed during 1973–2008 were reviewed using the SEER 18 database. We calculated overall survival and cancer-specific survival of subsequent CRC, and more specifically stage IV CRC, using Kaplan-Meier test and adjusted Cox models. Results A total 550,325 CRC patients were reviewed, of whom 31,663 had history of a prior malignancy. The most commonly reported sites of a prior malignancy were: prostate, breast, urinary bladder, lung, and endometrium. Patients with history of a prior non-leukemic malignancy or history of a prior leukemia were found to have worse overall survival (HR = 1.165 95%CI = 1.148–1.183, P

We aimed at finding the impact of prior malignancies on the survival of patients with endometrial adenocarcinoma using SEER database (from 1973 to 2014). We identified 127,988 patients who were diagnosed with endometrial adenocarcinoma (6485 had a prior malignancy), and we compared the overall and cancer-specific survival based on the presence or absence of a prior malignancy and the latency period between the two diagnoses using Kaplan-Meier test and Cox models. Adjusted cox models showed that a history of a prior malignancy neither affected the overall survival nor the cancer-specific survival of stage IV cases in all latency groups except the one diagnosed within 1 year of the first cancer. Therefore, there is no rational explanation for excluding stage IV endometrial adenocarcinoma patients with a prior malignancy from clinical trials except for the group that was diagnosed with endometrial adenocarcinoma within 1 year from the first cancer.Impact statement

Introduction: Melanoma is a highly malignant tumor that has been repeatedly reported in chronic lymphocytic leukemia (CLL) patients. We aim to assess the epidemiologic characteristics of this association and emphasize the importance of carefully approaching such cases. Methods: Patients who were diagnosed with CLL between 2000 and 2015 and registered in the Surveillance, Epidemiology and End Results (SEER) database of the US National Cancer Institute were identified using the SEER*stat software (version 8.3.5). The Multiple Primary Standardized Incidence Ratios session of the SEER*stat software (version 8.3.5) was used to calculate the observed/expected (O/E) ratios of melanoma. Results: 48,876 CLL cases were reviewed, of which 474 developed a second primary melanoma of the skin. O/E ratio was 2.07 (95% CI 1.89-2.27), and excess risk was 9.7 per 10,000. The increase in melanoma risk was higher within the first 5 years following CLL diagnosis; O/E = 2.22 (95% CI 1.56-2.14) and excess risk was 10.43 per 10,000. It was higher in males compared to females O/E was 2.10 (95% CI 1.89-2.33) and 1.98 (95% CI 1.62-2.40) in males and females, respectively, and in people aged 45-64; O/E = 2.30 (95% CI 1.95-2.70). Out of 7827 CLL patients receiving chemotherapy, 70 later developed melanoma with a significant O/E of 2.28 (95% CI 1.77-2.88) and an excess risk of 10.66 per 10,000. Conclusion: CLL increases the risk of developing melanoma, especially within 5 years of the diagnosis, and in white males aged between 45-64 years. It is crucial to keep rigorous screening, high-suspicion and close follow-up for recurrence in consideration while managing these patients.

The focus on noncancer causes of death in patients with breast cancer (BC) remains superficial. The objective of the current study was to assess and quantify causes of death after BC diagnosis.In total, 754,270 women with BC in the United States who were diagnosed during 2000 through 2015 and retrieved from the Surveillance, Epidemiology, and End Results (SEER) program were studied. Standardized mortality ratios (SMRs) for causes of death were calculated.Of the included patients, 183,002 (24.3%) died during the follow-up period. The greatest proportion of deaths (46.2%) occurred within 1 to 5 years after diagnosis. Most deaths occurred from BC itself or from other cancers, and the number of BC deaths decreased as more years passed after diagnosis. The most common noncancer causes of death within10 years after diagnosis were heart diseases followed by cerebrovascular diseases. However,10 years after diagnosis, the most common noncancer causes of death were heart diseases followed by Alzheimer disease. Patients had a statistically significant higher risk of death from chronic liver diseases within 5 to 10 years after diagnosis compared with the general population (SMR, 1.23; 95% CI, 1.09-1.38) and had statistically significant higher risks of death from Alzheimer disease (SMR, 1.21; 95% CI, 1.14-1.29) and from diseases of the heart (SMR, 1.06; 95% CI, 1.02-1.09)10 years after diagnosis.Although BC remains the most common cause of death after BC diagnosis, other non-BC causes of death (mainly heart and cerebrovascular diseases) represent a significant number of deaths among patients with BC. These findings provide important insight into how BC survivors should be counselled regarding future health risks.

Kunbaz, Ahmad/0000-0003-2209-8187; Saad, Anas/0000-0003-0101-0131; Santos, Joao Vasco/0000-0003-4696-1002; Alahdab, Fares/0000-0001-5481-696X WOS:000455459500005 PubMed ID: 30630456 BackgroundTransitional cell carcinoma (TCC) accounts for around 95% of bladder cancers and is the 4th most common cancer among men and the tenth most common in women, in the US. There is a constant need to clarify current TCC incidence and mortality rates among different population groups for better clinical practice guidelines. We aimed to describe the TCC incidence and incidence-based mortality by demographic and tumor-related characteristics over the last 40years in the US.MethodsWe obtained data from the SEER 18 registries to study TCC cases that were diagnosed between the years 1973 and 2014. We calculated incidence rates and incidence-based mortality rates in different demographic and tumor-related characteristics and expressed rates by 100,000 person-years. We then calculated the annual changes in incidence and incidence-based mortality rates and displayed them as annual percent changes (APCs).ResultsThere were 182,114 patients with TCC between 1973 and 2014 in the United States. Overall incidence rates of TCC increased 0.16% (95% CI, 0.02-0.30, p=.02) per year over the study period. However, the incidence declined significantly since 2007; (95%CI,-1.89- -0.77, p

Glioblastoma multiforme (GBM) patients with a prior malignancy are usually excluded from clinical trials on GBM based on the assumption that this history will affect their survival outcomes. This practice may affect clinical trial accrual and limit the gathering of knowledge essential to the formulation of therapeutic options for this patient population. However, not much is known about the real impact of these prior malignancies on the survival of patients with subsequent GBM. We aimed to investigate the degree of such an impact.We used the Surveillance, Epidemiology, and End Results (SEER) Program to analyze data of GBM patients diagnosed between 1973 and 2014. We calculated the overall and GBM-specific survival of these patients using the unadjusted Kaplan-Meier test and the multivariable covariate-adjusted Cox models.Of 51,158 GBM patients, 3,076 had a prior malignancy. The unadjusted Kaplan-Meier test showed worse overall and GBM-specific survivals for patients who had a prior history of cancer. However, after adjusting for age at diagnosis of GBM, sex, race, marital status, and conduction of surgery, multivariable covariate-adjusted Cox models showed that having a prior malignancy did not significantly affect neither overall survival (HR = 1.025, 95%CI = .986 - 1.066, p = .213) nor GBM-specific survival (HR = 1.005, 95%CI = .963 - 1.049, p = .810).Our findings suggest that the broad practice of excluding patients with a prior history of cancer should be reconsidered as it may adversely affect accrual, trial completion rates, and generalizability of the results.

Background Pneumoperitoneum poses an important diagnostic sign determining the urgency of management of patients in an emergency department. Chilaiditi sign is a rare radiologic finding of large intestines transposition between the diaphragm and the liver. If the patient becomes symptomatic, then the condition is called Chilaiditi syndrome. Case presentation We present a rare case of a 49-year-old Egyptian man who presented to our emergency department complaining of cough and vague abdominal discomfort who was found to have Chilaiditi syndrome diagnosed radiologically by computed tomography scan. He was conservatively managed rather than undergoing invasive non-warranted diagnostic and therapeutic testing that may have resulted in increased morbidity. Conclusions A review of the current literature on Chilaiditi syndrome is provided with a focus on increasing the familiarity of health care professionals with the conditions and stressing the importance of a physical examination in evaluating patients with what appears to be air under the diaphragm.

Background The suicide risk after a new cancer diagnosis remains a controversial issue. This study examines the suicide risk within the year after a cancer diagnosis. This is the largest study to assess recent trends in suicide risk after a cancer diagnosis. Methods Data were obtained from the Surveillance, Epidemiology, and End Results Program. All patients diagnosed with cancer between 2000 and 2014 were selected. The event was defined as death due to suicide within the first year after a cancer diagnosis, and patients who experienced the event after their diagnosis were observed. The observed/expected (O/E) ratio was assessed as well as the excess risk per 10,000 person-years to determine the suicide risk change after the diagnosis in comparison with the general population. Results A total of 4,671,989 patients with cancer were included; 1585 committed suicide within 1 year of their diagnosis. The risk of suicide increased significantly with an O/E ratio of 2.52 and with an excess risk of 2.51 per 10,000 person-years. When the risk of suicide was studied according to the cancer site, the highest increases in the O/E ratio came after diagnoses of pancreatic cancer (8.01) and lung cancer (6.05). The risk of suicide also increased significantly after a diagnosis of colorectal cancer with an O/E ratio of 2.08. However, the risk of suicidal death did not increase significantly after breast and prostate cancer diagnoses. Conclusions The risk of suicide increases significantly in the first year after a diagnosis of cancer in comparison with the general population, and this increase varies with the type and prognosis of cancer. Close observation and referral to mental health services, when indicated, are important for mitigating such risk.

Renal-cell carcinoma (RCC) is one of the common malignancies in the United States. RCC incidence and mortality have been changing for many reasons. We performed a thorough investigation of incidence and mortality trends of RCC in the United States using the cell Surveillance, Epidemiology, and End Results (SEER) database.The 13 SEER registries were accessed for RCC cases diagnosed between 1992 and 2015. Incidence and mortality were calculated by demographic and tumor characteristics. We calculated annual percentage changes of these rates. Rates were expressed as 100,000 person-years.A total of 104,584 RCC cases were reviewed, with 47,561 deaths. The overall incidence was 11.281 per 100,000 person-years. Incidence increased by 2.421% per year (95% confidence interval, 2.096, 2.747; P .001) but later became stable since 2008. However, the incidence of clear-cell subtype continued to increase (1.449%; 95% confidence interval, 0.216, 2.697; P = .024). RCC overall mortality rates have been declining since 2001. However, mortality associated with distant RCC only started to decrease in 2012, with an annual percentage change of 18.270% (95% confidence interval, -28.775, -6.215; P = .006).Despite an overall increase in the incidence of RCC, there has been a recent plateau in RCC incidence rates with a significant decrease in mortality.

Pancreatic cancer is one of the most fatal malignancies and the fourth leading cause of cancer-related mortality in the USA. Most clinical trials involving pancreatic adenocarcinoma (PAC) patients exclude subjects with a prior malignancy because of the possible effect of prior malignancies on survival. However, no data in the medical literature support this assumption. In this paper, we aim to study the impact of having a prior malignancy on the survival outcomes of stage IV PAC. We used the surveillance, epidemiology, and end results database to review patients with stage IV PAC diagnosed between 1973 and 2014. We calculated overall and pancreatic cancer-specific survival of these patients using unadjusted Kaplan-Meier test and multivariable covariate-adjusted Cox models. We reviewed 66,874 stage IV PAC patients, of which 4942 had a prior malignancy. Kaplan-Meier and Cox models showed that a history of prior malignancy did not cause significant difference in overall survival (HR = 0.938, 95%CI = 0.880–1.000, p = .052). However, a prior malignancy was associated with a better pancreatic cancer-specific survival (HR = 0.855, 95% CI = 0.796–0.918, p

Background Pancreatic cancer is the fourth-leading cause of cancer deaths in the United States. The silent nature of the disease and its poor prognosis, the need for further research, along with the need to assess the outcomes of current approaches necessitate an ongoing evaluation of the epidemiology and mortality-trends of this malignancy. Continuous monitoring of disease-patterns, on population-levels, may help scientists assess the quality of healthcare delivery, boost their understanding of diseases' characteristics and risk factors, and detect gaps whereby further research is needed. None of the previous reports shed light on pancreatic adenocarcinomas (PAC), the most common type of Pancreatic Cancer, as the primary outcome. In this study we aim to investigate PAC’s incidence and mortality trends over the last four decades in the United States. Methods We used SEER 9 database to study PAC cases during 1974-2014. Incidence and mortality rates were calculated by sex, age, race, state and stage of PAC. Annual percent change (APC) was calculated using joinpoint regression software. Results We reviewed 67,878 PAC cases; most of these cases were in the head of pancreas. Overall PAC incidence rates increased 1.03% (95% CI, 0.86-1.21, p

Usually, clinical trials on esophageal cancer exclude patients with a prior malignancy, assuming that this may influence survival outcomes. However, little is known about the impact of a prior malignancy on its prognosis.The Surveillance, Epidemiology, and End Results database (SEER) was used to review patients with stage IV squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus during 1973-2014. We calculated overall and esophageal cancer-specific survival using unadjusted Kaplan-Meier and multivariable covariate-adjusted Cox models.A total of 7,807 patients with stage IV SCC, and 11,238 patients with stage IV AC were reviewed, of which 652 and 840 patients, respectively, had a prior malignancy. Kaplan-Meier curves did not show difference in overall survival of SCC or AC in patients with prior malignancy. Stage IV AC patients with prior malignancy did not show different esophageal cancer-specific survival. However, esophageal cancer-specific survival was better among stage IV SCC patients with prior malignancy. Similar results were observed in Cox models after adjustment for: age, sex, race, marital status, grade, site in esophagus, and undergoing surgery.Prior malignancy does not adversely impact survival of stage IV esophageal cancer. These results should be taken into consideration when designing clinical trials.

Background The available literature on the incidence, management and prognosis of primary malignant cardiac tumors [PMCTs] is limited to single-center studies, prone to small sample size and referral bias. We used data from the Surveillance, Epidemiology, and End Results [SEER]-18 registry (between 2000 and 2014) to investigate the distribution, incidence trends and the survival rates of PMCTs. Methods We used SEER*Stat (version 8.3.4) and the National Cancer Institute’s Joinpoint Regression software (version 4.5.0.1) to calculate the incidence rates and annual percentage changes [APC] of PMCTs, respectively. We later used SPSS software (version 23) to perform Kaplan-Meier survival tests and covariate-adjusted Cox models. Results We identified 497 patients with PMCTs, including angiosarcomas (27.3%) and Non-Hodgkin's lymphomas [NHL] (26.9%). Unlike the incidence rate of NHL (0.108 per 106 person-years) that increased significantly (APC=3.56%, 95% CI, [1.445 to 5.725], P=.003) over the study period, we detected no significant change (APC=1.73%, 95% CI [−3.354 to 7.081], P=.483) in the incidence of cardiac angiosarcomas (0.107 per 106 person-years). Moreover, our analysis showed that the overall survival of NHL is significantly better than angiosarcomas (P Conclusion Our analysis showed a significant increase in the incidence of cardiac-NHL over the past 14 years with a significantly better survival than angiosarcomas. To further characterize these rare tumors, future studies should report data on the medical history and diagnostic and treatment modalities in these patients.

To systematically review the evidence for an association between maternal depression and the risk of diarrheal illness in infants.This study is a meta-analysis.Nine databases were searched systematically for studies that investigated the risk of diarrheal illness in infants born to mothers with depression.Our search strategy yielded 10 studies of the association between maternal depression and the risk of diarrheal illness in infants: eight studies of postnatal depression, two studies of antenatal depression, and one study of perinatal depression. Our meta-analysis showed that infants born to mothers with postnatal depression were more likely to develop diarrheal illness (odds ratio [OR] = 1.902, 95% confidence interval [95% CI] = 1.385-2.612, P 0.001, n = 18,585). A similar trend was noted for antenatal depression (OR = 2.703, 95% CI = 0.920-7.942, P = 0.071, n = 583). Only one study reported an association between perinatal depression and risk of diarrhea in infants (OR = 1.848, log OR = 0.614, standard error = 0.093, n = 107,587).Only a few studies so far have identified an association between maternal depression and risk of diarrhea in infants. The evidence available to date suggests that infants born to mothers with depression are more likely to develop diarrhea than infants whose mothers do not have depression.

Display Omitted We propose a smartphone application that diagnose Obstructive Sleep Apnea.The design takes advantage of a smatrphone's built-in sensors to screen OSA.We examine the system's ability to screen OSA as compared to the golden standard. Obstructive sleep apnea (OSA) is a serious sleep disorder which is characterized by frequent obstruction of the upper airway, often resulting in oxygen desaturation. The serious negative impact of OSA on human health makes monitoring and diagnosing it a necessity. Currently, polysomnography is considered the gold standard for diagnosing OSA, which requires an expensive attended overnight stay at a hospital with considerable wiring between the human body and the system. In this paper, we implement a reliable, comfortable, inexpensive, and easily available portable device that allows users to apply the OSA test at home without the need for attended overnight tests. The design takes advantage of a smatrphone's built-in sensors, pervasiveness, computational capabilities, and user-friendly interface to screen OSA. We use three main sensors to extract physiological signals from patients which are (1) an oximeter to measure the oxygen level, (2) a microphone to record the respiratory effort, and (3) an accelerometer to detect the body's movement. Finally, we examine our system's ability to screen the disease as compared to the gold standard by testing it on 15 samples. The results showed that 100% of patients were correctly identified as having the disease, and 85.7% of patients were correctly identified as not having the disease. These preliminary results demonstrate the effectiveness of the developed system when compared to the gold standard and emphasize the important role of smartphones in healthcare.

Background We evaluated the risk of cardiac death in patients with prior cancer diagnoses and compared risk by cancer type and ethnicity in a large US population. Method Utilizing the Surveillance, Epidemiology, and End Results database, data on patients with a cancer diagnosis between 2000 and 2014 were obtained. We calculated the standardized mortality ratio (SMR) of cardiac death after a cancer diagnosis and the excess risk per 10,000 person-years. We stratified the analysis according to the time interval between cancer and cardiac events, cancer site, cancer stage, and race. Results A total of 4,671,989 patients with a cancer diagnosis were included, of which 163,255 died due to cardiac causes within 10 years of diagnosis. We found a significantly higher rate of cardiac death for cancer patients [SMR=1.16, 95% confidence interval (CI) 1.15–1.16] compared to the general population. When observed for each cancer site, the highest SMR was after a diagnosis of hepatocellular carcinoma (SMR=2.58, 95% CI 2.45–2.72), pancreatic cancer (SMR=2.36, 95% CI 2.25–2.47), and lung cancer (SMR=2.30, 95% CI 2.27–2.34). Patients with metastatic disease had a higher rate of cardiac death (SMR=2.16, 95% CI 2.13–2.19). When stratified by ethnicity, SMR for cardiac death was 1.76, 2.28, 3.68, 2.65, and 1.84 for whites, blacks, American Indians/Alaska Natives, Asians/Pacific Islanders, and Hispanics, respectively. Conclusions Cancer patients are more vulnerable to cardiac death than the general population, especially those with nonwhite ethnicity; liver, lung, and pancreatic cancers; and history of metastasis. Healthcare providers should be aware of this risk and pay particular attention to the highest-risk groups.

Pathobiological mechanisms that contribute to pulmonary vasoconstriction, lung vascular remodeling, and the development of right heart failure include the generation of reactive oxygen and nitrogen species and the response of lung vascular and cardiac cells to these molecules. We review the information regarding oxidant stress balanced by antioxidant mechanisms and the role of oxidants and antioxidants in hypoxic pulmonary hypertension and their potential role in an animal model of severe pulmonary arterial hypertension (PAH).In human lung tissue from patients with idiopathic PAH, we find reduced superoxide dismutase activity and high expression of the oxidant stress markers nitrotyrosine and 8-OH-guanosine. In the Sugen 5416/chronic hypoxia model of PAH, lung tissue expression of nitrotyrosine and hemeoxygenase 1 (HO-1) is substantial, while HO-1 expression in the failing right ventricle is decreased. This model, based on administration of the VEGF receptor blocker Sugen 5416 and chronic hypoxia (Su/Hx), reproduces many of the characteristic features of severe angioobliterative human PAH. Treatment of Su/Hx rats with protandim, which nuclear factor erythroid-2 related factor (Nrf2)-dependently upregulates the expression of genes encoding antioxidant enzymes, protects against right heart failure without affecting angioobliterative PAH.In human severe PAH, patient survival is determined by the function of the stressed right ventricle; investigation of oxidative and nitrosative stresses and their potential contribution to right heart failure is necessary.Antioxidant therapeutic strategies may be of benefit in the setting of human severe PAH. Whether antioxidant strategies affect lung vascular remodeling and/or prevent right heart failure remains to be examined.

Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy. We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients. Treatment-naive HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared. A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4 ± 10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P = 0.03). The HCV genotype did not correlate with steatosis or SVR. Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy.

Despite multiple advances in the management of retinoblastoma, enucleation remains an essential therapeutic modality. We studied patients who underwent enucleation at the King Hussein Cancer Center in Jordan. We retrospectively reviewed medical records of children with retinoblastoma who were treated at our center from June 2002 to February 2008. Twenty-eight eyes from 27 patients were enucleated. Median age at diagnosis was 1.1 years (range, 0.3-6.3 years). Twenty-six eyes (93%) had advanced disease (RE groups IV and V). Seventeen patients (61%) had unilateral retinoblastoma, and 11 (39%) had bilateral retinoblastoma. The median time from diagnosis to enucleation was 0.45 months (range, 0-45 months; mean, 4.4 months) and was longer for patients with bilateral retinoblastoma (median, 2.2 vs. 0.2 months; P = 0.034). Twenty enucleated eyes (71%) did not show high-risk pathologic features. Seventeen eyes with advanced intraocular disease were enucleated at the time of presentation, whereas chemoreduction was attempted for the other 19 eyes with advanced intraocular disease. Enucleation was then recommended for nine (47%) of those eyes. Enucleation at the time of diagnosis was feasible for most patients with advanced disease. Attempted salvage of eyes with advanced disease is justified, particularly in patients with bilateral disease. We were able to salvage almost half of these eyes. We hope our study provides new insights for counseling patients.

Fifty-eight adolescent patients with relapsed or primary refractory Hodgkin's lymphoma underwent high-dose chemotherapy (HDC) and autologous SCT (ASCT). The median age at ASCT was 17 years (range 14-21). The disease had relapsed in 24 patients (41%) and was refractory to initial chemotherapy in 34 (59%). ESHAP salvage chemotherapy before ASCT resulted in 88% response. After ASCT, complete remission (CR; including CR-unconfirmed) was seen in 41 patients (71%) and partial remission in 7 (12%). The overall response rate was 83%. One patient did not respond and nine (15%) had progressive disease. Three more patients achieved CR after consolidative radiation post-ASCT. There was no transplant-related mortality. At a median follow-up of 43 months from ASCT, 31 patients (53%) are alive in CR, 5 (9%) are alive with disease and 22 (38%) have died (21 from disease and 1 unrelated). The actuarial probabilities of event-free and overall (OS) survival are 45 and 55% at 11 years. The only negative prognostic factor for OS was the presence of B symptom at relapse or progression (11-year OS 27 vs 60%, P=0.003).

Hashimoto encephalopathy (HE) is a controversial autoimmune disorder, probably underdiagnosed, that causes a wide variety of neurological manifestations. Symptoms differ among patients and may be very severe in some cases. However, it can be treated, with a very good prognosis. In our case, a teenaged girl with a family history of migraine, vitiligo and benign paroxysmal positional vertigo presented with severe ataxia, vomiting and hypotension. She had a history of similar, but milder, symptoms and was misdiagnosed several times. She had subclinical hypothyroidism, and high levels of antithyroid antibodies. There were abnormal MRI and visual evoked potential findings. After excluding other more common causes, we diagnosed her as having ‘Hashimoto Encephalopathy’, and started treatment with corticosteroids, on which she showed dramatic improvement. After about 2 years of presentation, the patient is able to continue her life independently.

Background: There is lack of knowledge on the epidemiological characteristics of brain tumors in Middle Eastern countries. The objective of this study was to study the epidemiological features of primary brain tumors in Jordan. Methods: We conducted a prospective cohort study incorporating data from 16 hospitals in Jordan during a 1 year period (May 1, 2011-April 30, 2012). All primary brain tumors diagnosed in Jordan during the study period were identified. The following parameters were retrieved from patients' files: age, gender, histological type, and location. The demographic data of the country was obtained from the National Department of Statistics. Results: A total of 313 primary brain tumors were identified during the study period. The incidence of primary brain tumors in Jordan among the general population was 5.01 per 100,000 person-years (5.38 in females and 4.65 in males). The incidence in pediatric, adult, and elderly patients was 2.09, 7.29, and 14.38 per 100,000 person-years, respectively. The most common histological types were meningioma (26.2%), glioblastoma (18.9%), astrocytoma (14.1%), and pituitary adenoma (9.3%). Conclusions: The incidence of primary brain tumors in the Jordanian population is relatively low, in part due to the young age of the general population.

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established.

Ectopic pancreas in the thoracic cavity is uncommon. We report 2 patients who had large cystic or cystic-solid masses containing pancreatic tissue in the thorax. Their clinical presentation, imaging, and pathologic findings are described. Both patients underwent total surgical resection of the masses, with no recurrence.

Hepatocellular carcinoma (HCC) is the second most common primary malignant hepatic tumor in children. It often develops in patients with underlying liver disease. We report the clinicopathologic features of an unusual HCC occurring in an infant who presented with features of Cushing's syndrome due to bilateral adrenal hyperplasia. The tumor is characterized by epithelial syncytial giant cells. Giant cell carcinoma of the liver has been previously reported, but the cells were osteoclast-like (ie, mesenchymal type) and not epithelial type as it is in this patient. We propose to use the term HCC, syncytial giant cell type, to denote this apparently novel lesion.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of disorders with various etiologies. Recent molecular and genetic studies have categorized the spectrum of types. Liver transplantation is a curative modality of treatment in this disease. We report our experience with 13 patients with PFIC who underwent living related liver transplantation. The follow-up periods ranged from 12 to 50 months. Two children died at 1 and 2 years posttransplantation, leading to a decrease in survival rate from 100% in the first year to 84.6%.

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients out of 113 (113 patients out of 153 had complete analysis) with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%; 92% had ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) as salvage. Post-ASCT evaluation showed response in 50 patients (76%), complete response (CR) in 37 (56%), partial response in 14 (21%), no response or stable disease in three (5%) and progressive disease in 10 (15%) patients. Six patients achieved CR after XRT (5) or surgery (1), making a total with CR of 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival 78 and 57 months, respectively. EFS and overall survival (OS) are 36 and 64%, respectively. In all 47% patients are in CR. Twenty-two (33%) patients died of the disease. Multivariate analysis showed elevated lactic dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.

Hepatic granuloma (HG) has a high reported incidence in Saudi Arabia (14.6%). We aimed to identify the incidence of HG in our centres and review its presenting features and underlying aetiology.A total of 5531 liver biopsies were screened through a computer database over 13 years. Sixty-six (1.2%) patients fulfilled our inclusion criteria. The patients were then divided into three groups according to the aetiology. Group 1, tuberculosis (n=26); Group 2, viral hepatitis B and C (n=11); and Group 3, idiopathic (n=9). The demographical data and the clinical and biochemical features of all the groups were analysed.Infections comprised of 72.2% of HG. The incidence of tuberculosis was 42.6%, viral hepatitis 16.3% and idiopathic 14.8%. Fever (47.5%), weight loss (42.6%) and fatigue (45.9%) were commonly found symptoms. Fever and weight loss were significantly more frequently presenting symptoms in Group 1 than in Groups 2 and 3 (P=0.0002, 0.04, 0.001 and 0.02 respectively). The mean bilirubin levels in Group 1 were significantly lower than in Groups 2 and 3 (P=0.04 and 0.03 respectively). The mean albumin levels were significantly lower in Group 3 compared with Group 2 (P=0.002), and Group 1 had lower levels compared with Group 2 (P=0.018).The incidence of HG is much lower than reported previously from this region. Tuberculosis and viral hepatitis are the most common causes and, contrary to previous reports, schistosomiasis is rare. Fever and weight loss distinguished tuberculous HG.

This study aimed to determine whether the production, in renal transplant recipients, of antibodies directed against donor HLA mismatches is predictive of transplant failure.The failure study group comprised 112 adult recipients of primary renal transplants who had re-entered the transplant waiting list after failure of the first graft. A control group of 123 recipients with functioning transplants was selected from transplantations performed during the same time period, in which patients had equivalent HLA matching and immunosuppression and a minimum of 5 years of follow-up. Sera taken before transplantation and at 1, 3, and 6 months and annually after transplantation were tested by enzyme-linked immunoabsorbent assay (ELISA) for the presence of HLA class I- and class II-specific antibodies. Antibody specificity was defined by a combination of cytotoxicity, ELISA, and flow cytometry techniques to determine whether the antibodies were directed against donor mismatches.All recipients were negative for donor HLA-specific antibodies before transplantation. After transplantation, 57 (50.9%) of the 112 patients in the failure group produced donor HLA-specific antibodies compared with 2 (1.6%) of the 123 controls (P0.0001; odds ratio [OR]=64.98; confidence interval [CI], 14.78-399.51). For 60% of the donor-specific antibody-positive patients, antibodies were detected before transplant failure. In 17 cases, these were class I specific; in 14 cases, class II specific; and in 3 cases, specific for both class I and II.This study has demonstrated that the production of posttransplantation antibodies directed against donor HLA-A, -B, -Cw, -DR, and -DQ mismatches are all strongly predictive of transplant failure.

To report a rare case of oesophageal Paget's disease and its rarer combination with submucosal gland carcinoma of the lower oesophagus.A 74-year-old Saudi female was admitted with the complaint of dysphagia. Endoscopic examination showed an ulcerated tumour at the gastro-oesophageal junction. Initial biopsy showed an undifferentiated carcinoma with pagetoid spread in the oesophageal stratified squamous epithelium. Oesophago-gastrectomy specimen showed a lobulated, poorly differentiated mucous gland carcinoma at the gastro-oesophageal junction. The tumour showed focal acinar differentiation and obvious cancerization of the submucosal glands, somewhat similar to the breast lobular carcinoma in situ. One of the isolated and cancerized submucosal glands also showed carcinoma in situ of its duct. Oesophageal surface epithelium showed extensive pagetoid spread, both over and away from the main tumour. The pagetoid tumour cells showed selective positivity for cytokeratin 7, cytokeratin Cam 5.2, BerEP4 and to a lesser extent for CEA.As far as we know, this is the fifth case report of oesophageal Paget's disease and the first report of its association with the underlying mucous gland carcinoma.

Juvenile hyaline fibromatosis (JHF) is a rare hereditary disease characterized by the deposition of hyaline ground substance, which is described as fibrillogranular material on electron microscopy. Approximately 65 cases have been reported to date in the English language literature. We add 3 new cases of children presenting with multiple subcutaneous nodules. We have described the light microscopic, electron microscopic, and immunohistochemical features of these nodules. The characteristic chondroid appearance on light microscopy is imparted by large peripheral vesicles in the stromal cell cytoplasm. Ultrastructurally, the fibroblasts have shown evidence of defective synthesis of collagen, which is then deposited as fibrillogranular material in the matrix. Immunohistochemical studies have shown CD68+ macrophages and multinucleated histiocytic giant cells in all five specimens from our 3 cases. As far as we know, the presence of giant cells has not been reported in the literature. The main purposes of this report are to highlight the presence of macrophages as a constant constituent of the stromal cells in JHF and to review the literature on this subject.

Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected siblings who are the product of a first degree cousin marriage. The first 2 presented with typical Reye-like syndrome with unconsciousness, hepatomegaly, hypoglycemia, hyperammonemia and very high liver enzymes. Liver biopsy showed steatosis. On screening of the complete family, the 3rd sibling was found to have hepatomegaly. The 3 siblings showed an acyl carnitine profile with very high free carnitine with almost absent long chain acyl carnitines, suggestive of carnitine palmityl transferase I deficiency. This was confirmed by enzyme analyses in fibroblast cultures. These patients were effectively treated with a diet high in carbohydrate, low in long chain fatty acids with medium chain triglycerides. In conclusion, carnitine palmityl transferase I deficiency is an important cause of Reye-like syndrome, which may be treated easily with very good results if detected early in life.

We report here, the first pediatric living-related liver transplant in Saudi Arabia and the Middle East. Our patient is a 2 year old girl with a diagnosis of progressive familial intrahepatic cholestasis, causing intractable pruritus and failure to thrive requiring liver transplantation. The child was successfully transplanted using a segment of her mother's liver for living-related liver transplantation. Two years post-transplantation the patient is doing well. With the ongoing crises in cadaveric organ availability and the high prevalence of pediatric liver disease, living related liver transplantation is an ideal solution to this difficult and challenging problem.