Primary Cancers Of Other Organs Research Articles

Effect of chemoradiation on the development of second primary cancers after endoscopic resection of T1 esophageal squamous cell carcinoma.

Patients with early esophageal squamous cell carcinoma (ESCC) may develop multiple second primary ESCC and cancers in other organs even after curative endoscopic resection (ER). We investigated whether administration of chemoradiotherapy (CRT) after ER decreases the incidence of second primary cancers. We conducted a post hoc analysis of the prospective study. Among the registered 170 patients with clinical submucosal ESCC, 74 underwent ER alone, and 96 underwent ER followed by CRT (ER + CRT) because of pathological results of submucosal or lympho-vascular invasion. We compared the incidence of second primary cancers in esophagus and in other organs between two treatment groups. A univariate analysis was performed to investigate the related risk factors. All patients were followed up with esophagogastroduodenoscopy and CT every 4months for the first 3years and every 6months thereafter. Sixty-one ESCC were detected in 32 patients, and the 3-year cumulative incidence of multiple ESCCs was not different between ER + CRT and ER alone (10.4% vs. 13.5%). Sixty-three second primary cancers in other organs were detected in 45 patients, and there was no difference in the cumulative incidence between two groups. The risk factors for multiple ESCCs were high alcohol consumption and grade C multiple Lugol-voiding lesions. Heavy drinker or patients with grade C multiple Lugol-voiding lesion rather than CRT were at risk for second primary ESCC. CRT after ER did not decrease the cumulative incidence of second primary ESCC nor cancers in other organs comparing with ER alone.

Postoperative Management of Multiple Primary Cancers Associated with Non-small Cell Lung Cancer.

Modern treatment for primary cancers has improved survival. Therefore, increased numbers of patients with multiple primary cancers (MPC) associated with lung cancer may be expected. The aim of the present study was to report MPC associated with lung cancer and discuss patients' characteristics and postoperative management. Overall, 973 consecutive patients who underwent surgery for non-small cell lung cancer (NSCLC) were retrospectively studied. NSCLC with MPC was observed in 148 patients (15.2%). MPC comprised 24 synchronous (2.5%) and 124 metachronous (12.7%) diseases. Of the 124 metachronous patients, NSCLC was detected before cancers were detected in other organs (lung cancer first (LCF)) in 25 (20.2%) patients and subsequently in other organs after treatment (other organs, primary cancer-first (OCF)) in 99 (79.8%) patients. MPC was significantly associated with advanced age (p<0.0001) and chronic obstructive pulmonary disease (COPD) (p=0.0040). The leading sites of MPC in patients with synchronous tumors and those with OCF were the digestive organs. In contrast, the leading site of MPC in patients with LCF was the lung. In the latter, at least two primary lung cancers were detected within 5 years as well as 5 years after surgery for the treatment of the first detected lung cancer, while primary cancers of other organs were detected within 5 years. Advanced age and COPD may represent a high-risk of MPCs. Therefore, we recommend careful follow-up to detect MPC in the lung as well as the digestive organs beyond 5 years after treatment of the first cancer.

Usefulness of esophagogastroduodenoscopy and 18F-fluorodeoxyglucose positron-emission tomography in detecting synchronous multiple primary cancers with oral cancer.

The purpose of this study is to compare the value of screening for synchronous multiple primary cancers in other organs by esophagogastroduodenoscopy (EGD) or 18F-fluorodeoxyglucose positron-emission tomography (PET-CT) in patients newly diagnosed with oral cancer. We retrospectively examined consecutive Japanese patients who were diagnosed with oral squamous cell carcinoma (OSCC) and were screened for synchronous multiple primary cancers in other organs by EGD and/or PET-CT between January 2010 and December 2015 at our institution. The study included 190 patients (106 males and 84 females) from 36 to 93years of age (median age 68.8years). The patients were screened by EGD, PET-CT, or both before beginning treatment for OSCC. Of 190 Japanese patients with OSCC, 15 had multiple primary cancers: 13 patients had double cancer and two had triple cancers. The sites of the 17 multiple primary cancers were gastric (6), esophageal (4), and lung (3), and ovarian, colon, liver, and thyroid (1 each). All of the gastric and esophageal cancers were found by EGD and were not detected by PET-CT. For three patients, the detection of multiple cancers affected the treatment modality or order of treatment selected for the OSCC. In two cases, the oral cancer and multiple primary cancer(s) in another organ were resected simultaneously by joint surgical teams. PET-CT for oral cancer patients is an effective supporting diagnostic tool. However, the ability of PET-CT has some limitations. Especially for early detection of the upper gastrointestinal cancers, it is necessary to be supplemented by EGD.

Membrane-to-Nucleus Signals and Epigenetic Mechanisms for Myofibroblastic Activation and Desmoplastic Stroma: Potential Therapeutic Targets for Liver Metastasis?

Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment (TME), are a key source of the extracellular matrix (ECM) that constitutes the desmoplastic stroma. Through remodeling of the reactive tumor stroma and paracrine actions, CAFs regulate cancer initiation, progression, and metastasis, as well as tumor resistance to therapies. The CAFs found in stroma-rich primary hepatocellular carcinomas (HCC) and liver metastases of primary cancers of other organs predominantly originate from hepatic stellate cells (HSTC), which are pericytes associated with hepatic sinusoids. During tumor invasion, HSTCs transdifferentiate into myofibroblasts in response to paracrine signals emanating from either tumor cells or a heterogeneous cell population within the hepatic tumor microenvironment. Mechanistically, HSTC-to-myofibroblast transdifferentiation, also known as, HSTC activation, requires cell surface receptor activation, intracellular signal transduction, gene transcription, and epigenetic signals, which combined ultimately modulate distinct gene expression profiles that give rise to and maintain a new phenotype. The current review defines a paradigm that explains how HSTCs are activated into CAFs to promote liver metastasis. Furthermore, a focus on the most relevant intracellular signaling networks and epigenetic mechanisms that control HSTC activation is provided. Finally, we discuss the feasibility of targeting CAF/activated HSTCs, in isolation or in conjunction with targeting cancer cells, which constitutes a promising and viable therapeutic approach for the treatment of primary stroma-rich liver cancers and liver metastasis.

3-year safety follow-up of radium-223 dichloride (Ra-223) in patients (Pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (Mets) from ALSYMPCA.

195 Background: In ALSYMPCA, the first-in-class α-emitter Ra-223 had a highly favorable safety profile and was well tolerated. Safety monitoring of Ra-223 is essential for a complete safety profile. Here are final safety data including long-term follow-up safety 3 years after last pt’s first injection (inj). Methods: Pts received 6 inj and entered designated follow-up from 4 wks after their last inj to 3 years after first inj. Pts were to be evaluated during tx period and 9 follow-up visits. All adverse events (AEs) were collected until 12 wks after last inj; thereafter, only AEs deemed tx-related were collected. Additional long-term safety data were assessed by specific diseases including acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and new primary cancer in bone or other organs. Results: Safety population (pts receiving ≥ 1 inj) included 901 pts (Ra-223, n = 600; placebo [pbo], n = 301); 572 pts (Ra-223, n = 405; pbo, n = 167) entered follow-up. 60 pts (Ra-223, n = 49; pbo, n = 11) completed all follow-up visits. Overall, 564 (94%) Ra-223 and 292 (97%) pbo pts had ≥ 1 tx-emergent AE (Table). During long-term follow-up, there were no reports of AML, MDS, or new primary bone cancer. New primary cancers in other organs were reported: 2 Ra-223 (1 bladder, 1 lymph node mets), 3 pbo (2 skin, 1 adenocarcinoma rectum and sigmoideum), and 2 pbo cross-over pts (1 skin, 1 meningioma). Aplastic anemia was reported in 1 Ra-223 pt. Conclusions: Ra-223 remained safe and well tolerated 3 years after the last pt’s first inj. No major safety issues were identified during the ALSYMPCA 3-year long-term follow-up. Clinical trial information: NCT00699751. [Table: see text]

The outcomes of surgery in lung cancer patients with schizophrenia

There are very few reports regarding the outcome of lung cancer surgery in patients with schizophrenia, and the clinical features of such patients are still unclear. From 2004 to 2012, 11 lung cancer patients (six male, five female; mean age, 62.7 years) with schizophrenia underwent lung resections at our institutions. All patients had been institutionalized because they were unable to live independently at home. We retrospectively evaluated their postoperative clinical outcomes and long-term results. Ten of the 11 patients had comorbidities, such as diabetes mellitus and chronic obstructive pulmonary disease. Preoperatively, two patients had a history of treatment for other primary cancers in other organs, and one was on hemodialysis. A lobectomy was performed in nine patients, a segmentectomy in one, and a partial resection in one. There were no hospital deaths. The postoperative morbidity included two cases of pneumonia, one of atelectasis, and one of prolonged air leakage lasting more than 7 days. Wandering was postoperatively observed in two patients; one of these fell and fractured the left femur. At the time of our investigation, two patients were deceased, and the overall 5-year survival rate was 74.1 %. The postoperative morbidity and long-term results of schizophrenic patients with lung cancer were acceptable. Therefore, even in patients with schizophrenia, surgical treatment for lung cancer should be recommended when deemed to be necessary.

Frequency of multiple primary cancers in the lung and other organs in hemodialysis patients

We examined whether cancers frequently occur in hemodialysis patients, and therefore, investigated the features and outcomes of hemodialysis patients who had undergone surgery for non-small cell lung cancer. Between 1995 and 2011, 14 hemodialysis patients with lung cancer (8 males and 6 females) with a mean age of 67.0years successfully underwent pulmonary resection at our institution. We investigated the 5-year survival rate and causes of death. The occurrence of multiple primary cancers in our patients and other lung-cancer patients reported in the articles were statistically compared by Chi-square test. A p value <0.05 was considered to be statistically significant. The 5-year survival rate was 47.3%, and six patients had died before our investigation. Four of the six had died of non-cancerous diseases related to hemodialysis. Five of 14 patients had a history of other primary cancers in other organs, and this incidence rate of multiple primary cancers was significantly higher than in other lung-cancer patients (p=0.0071). The frequency of cancer in hemodialysis patients can be underestimated because of their early deaths by non-cancerous diseases. However, the incidence rate of multiple primary cancers may represent a unique characteristic of such patients.

Clinical course and outcome after esophagectomy with three-field lymphadenectomy in esophageal cancer

Esophagectomy with three-field lymphadenectomy has been performed for esophageal cancer. Detailed analysis of cause of death and mode of recurrence is required to determine the need for further adjuvant therapy and follow-up. A total of 208 patients who underwent esophagectomy through right thoracotomy with three-field lymphadenectomy were enrolled into the present study. Mode of first recurrence was divided into four groups: lymph node, hematogenous, mixed, and local recurrence. Excluding 16 hospital deaths, the number of deaths and 5-year survival rates were 104 patients and 7.8% for cancer recurrence, 12 patients and 53.8% for second primary cancers in other organs, and 34 patients and 31.0% for causes of death unrelated to carcinoma. In the 104 patients with relapse, 5-year survival rate of patients was 14.3% with lymph node recurrence (n = 29), 9.1% with hematogenous recurrence (n = 32), 3.1% with mixed recurrence (n = 35), and 12.5% with local recurrence (n = 8). To improve outcomes for esophagectomy with three-field lymphadenectomy, early detection of recurrent disease and regular examination of the entire body for secondary cancer is necessary.

Clinical Characteristics of Patients with Sporadic Colorectal Cancer and Primary Cancers of Other Organs

Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%), either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2%) and six breast cancers (35.2%) were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer patients with hematochezia or gastrointestinal symptoms/signs should be evaluated for the possibility of second primary CRC during their regular follow-up.

Possible association between immunocompetence and enhanced risk of multicentric carcinogenesis in both the stomach and other organs in patients with gastric cancer

In a retrospective study, we analyzed the association between the immunocompetence and multicentric carcinogenesis in both the stomach and organs other than the stomach in patients with single gastric cancer (SGC) and those with multiple gastric cancers (MGC). The incidence of primary cancers in other organs in patients with MGC (4/17, 23.5%) was significantly higher than that with SGC (15/202, 7.4%). Our analysis of the immunocompetence revealed a trend towards decreased activity of NK cells and of mitogen-induced blastogenesis in patients with MGC as compared to those with SGC. In patients with SGC, patients with primary cancers in other organs had significantly lower levels of both PHA-induced blastogenesis and CD4/CDs, and revealed a greater trend towards decreased activity of both NK cells and Con A-induced blastogenesis than patients without other primary cancers. These findings may suggest that immunocompetence plays a role in the enhanced multicentric carcinogenesis not only in the stomach but also in cancers of other organs.

REVIEW OF PRIMARY MULTIPLE CANCERS COMBINED IN THE ESOPHAGUS AND OTHER ORGAN

Among 74 patients with esophageal cancer experienced at the department from 1980 to August 1992, 18 patients (24.3%) also had primary cancers of other organs. Clinicopathological features were investigated in these 18 patients. Multiple cancers that were found within one year were regarded as synchronous, and those that were found at an interval longer than one year as heterochronous. There were 11 cases of synchronous and 7 cases of heterochronous multiple cancers, which included one cases of triple or quartet cancer. Of 11 cases of synchronous multiple cancers, 6 cases were found to have an esophageal cancer during preoperative exploration for other organ cancer, which were pharyngolaryngeal cancer for 4 cases, and rectal and lung cancer for each one case. In the meantime, during examination for esophageal cancer one case was found having gastric cancer; and during operation for esophageal cancer each one case was detected to have lung and thyroid cancer, respectively. And, cancers of the colon, liver, tongue, and gingiva were found within one year after the operation. In all heterochronous multiple cancer cases esophageal cancer was preceded by other organ cancer. These were each 2 cases of gastric and larynx cancer, and each one case of lung, colonic, and bile duct cancer, respectively; the last one was detected at 20 months following the esophageal lesion as a triple cancer case. Excision of the esophageal lesion was carried out in 10 synchronous and 4 heterochronous cases. There were 11 mortal patients, and 9 of them died of esophageal cancer, and each one, of lung and bile duct cancer. Four patients have been free of cancer. It can be said that postoperative patients should be followed up by entertaining not only a possibility recurrence but also possible occurrence of malignancy of other organs.

Patients with multiple primary gastric cancers tend to develop second primaries in organs other than the stomach

The multiple occurrence of a single cancer tends to result in the increased vulnerability of some other organs to another malignancy. In the present study, we examined a total of 1,606 patients with gastric cancer to ascertain whether the frequency of second primaries in organs other than the stomach is higher in patients with multiple gastric cancers than in those with a single gastric cancer. Primary cancers of other organs were present in 87 (5.9%) of 1,474 patients with single gastric cancer and in 16 (12.1%) of 132 patients with multiple gastric cancers. The difference was statistically significant. The most frequent site of the occurrence of a second primary was the colo-rectum, followed by the urogenital organs, uterus, breast, and lung in descending order of frequency. We therefore assume that the occurrence of multiple cancers in the stomach is not merely a chance phenomenon but is related to both genetic predisposition and environmental factors.

Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM)

To the Editor.— Rahbari and Mehregan ( Arch Dermatol 1981;117:328-331) cited Reimer et al 1 and Clark et al 2 as reporting in 1978 the first example of the FAMMM syndrome. The first report of this syndrome, however, was made in 1968 by Lynch and Krush, 3 who described two remarkable cases that had together all three of the essential elements of the FAMMM syndrome: (1) multiple moles of varying sizes and shapes that were clinically suspected of being malignant and that histologically showed very active junctional activity; (2) multiple cutaneous malignant melanomas and inordinately long survival in one patient; and (3) pedigrees disclosing a possible association with primary cancers in other organs (pancreas, respiratory tract, breast, sarcoma, and cervix). These cases were again evaluated during the 1970s, as part of our ongoing study of cancer patients at our institute for Familial Cancer Management and Control, Omaha. In 1977, Frichot and

Incidence of Multiple Primary Cancers. IV. Cancers of the Female Breast and Genital Organs

The incidence of multiple primary cancers of other organs or tissues was studied in patients with carcinomas of the breast (9,792), ovary (921), endometrium (843), and cervix uteri, vagina, or vulva (2,529). The index patients were treated during 1949–62 at the Memorial Sloan-Kettering Cancer Center, and their observed frequency of new primary cancers was compared with the age- and site-specific incidence rates reported by the population-based central registry maintained for New York State (excluding New York City). The incidence of metachronous primary carcinomas in the opposite breast was 6.1/year/1,000 patients, or 4.5 times expectation; in the patients with carcinoma of the breast, the incidence of multiple primary carcinomas of the ovary was 0.6/year/1,000 patients, or twice the normal risk, but one-tenth the risk for incurring a primary carcinoma in the opposite breast. The risk for incurring a metachronous primary carcinoma of the breast by a patient with a previous ovarian carcinoma was 3–4 times the normal risk. In patients with endometrial carcinoma, the risk of a subsequent breast carcinoma was 1.25–2.0 times the normal risk. The demonstration of a positive association of multiple primary carcinomas of the breast, ovary, and endometrium suggests demographic characteristics and etiologic factors common to these diseases. At least 3 of the 5 observed multiple, primary, soft-tissue sarcomas developed as sequelae of previous breast cancers—1 arising in irradiated tissue and 2 in a lymphedematous upper extremity. We could not conclude whether the mutual increases in the incidence of carcinomas of the breast and thyroid were biologically related or were indicative of common etiologic factors.

Incidence of Multiple Primary Cancers. II. Index Cancers Arising in the Stomach and Lower Digestive System

A cohort study of multiple primary cancers was conducted on patients treated during 1949–62, at the Memorial Sloan-Kettering Cancer Center, for cancers arising in the stomach and lower digestive system. Comparison with the New York State incidence rates revealed no increase in the number of associated or subsequent cancers of other organs or tissues among the index patients with cancer of the stomach or of the digestive organs proximal to the colon and rectum. Among the 4,771 patients with cancer of the colon and rectum, the proportion with previously (1.9%) and synchronously (3.6%) associated multiple primary cancers of the large intestine was 5.5%. The incidence of metachronous multiple primary cancers of the large intestine was 3.5 per year per 1,000 patients at risk, which represented an overall threefold excess in the observed number of primary cancers of the colon and rectum. In the patients with their index cancer in the cecum, the highest ratios were recorded of observed-to-expected cancers in both the large intestine (6.3) and other organs or tissues (2.4). In patients with index carcinomas of the colon and rectum, there were 142 clinically apparent, multiple primary cancers in other organs or tissues, or 1.4 times the expected number. After combining the experiences of patients with colon and rectal cancer, the incidence of breast cancer was significantly increased. In the patients with carcinoma of the rectum and rectosigmoid junction, the incidence of carcinoma of the urinary bladder was significantly, but inexplicably, increased. In those patients with carcinoma of the colon, the observed-to-expected ratio for carcinoma of the female genital organs was 2.1—primarily attributable to carcinoma of the endometrium. When the experience of 843 patients with endometrial carcinoma as their index cancer was considered, the increases in the observed number of associated and subsequent multiple primary cancers were similar for the large intestine, ovary, and breast. Similarly, in 921 index patients with primary ovarian carcinoma, there were 2 observed second primary cancers of the large intestine; this twofold excess was confined to the colon. These estimates of increased risk, which relate to multiple primary cancers of the large intestine, bladder, breast, and reproductive organs, have relevance both to the periodic examination of high-risk patients and to the epidemiologic pursuit of common etiologic factors.