Surveillance Colonoscopy in Older Stage I Colon Cancer Patients and the Association With Colon Cancer-Specific Mortality.

OBJECTIVES: Guideline-issuing groups differ regarding the recommendation that patients with stage I colon cancer receive surveillance colonoscopy after cancer-directed surgery. This observational comparative effectiveness study was conducted to evaluate the association between surveillance colonoscopy and colon cancer-specific mortality in early stage patients. METHODS: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Surveillance colonoscopy was assessed as a time-varying exposure up to 5 years after cancer-directed surgery with the following groups: no colonoscopy, one colonoscopy, and ≥ 2 colonoscopies. Inverse probability of treatment weighting was used to balance covariates. The time-dependent Cox regression model was used to obtain inverse probability of treatment weighting-adjusted hazard ratios (HRs), with 95% confidence intervals (CIs) for 5- and 10-year colon cancer, other cancer, and noncancer causes of death. RESULTS: There were 8,783 colon cancer cases available for analysis. Overall, compared with patients who received one colonoscopy, the no colonoscopy group experienced an increased rate of 10-year colon cancer-specific mortality (HR = 1.63; 95% CI 1.31-2.04) and noncancer death (HR = 1.36; 95% CI 1.25-1.49). Receipt of ≥ 2 colonoscopies was associated with a decreased rate of 10-year colon cancer-specific death (HR = 0.60; 95% CI 0.45-0.79), other cancer death (HR = 0.68; 95% CI 0.53-0.88), and noncancer death (HR = 0.69; 95% CI 0.62-0.76). Five-year cause-specific HRs were similar to 10-year estimates. DISCUSSION: These results support efforts to ensure that stage I patients undergo surveillance colonoscopy after cancer-directed surgery to facilitate early detection of new and recurrent neoplastic lesions.

The association between post-treatment surveillance testing and survival in stage II and III colon cancer patients: An observational comparative effectiveness study.

BACKGROUND: The best strategy for surveillance testing in stage II and III colon cancer patients following curative treatment is unknown. Previous randomized controlled trials have suffered from design limitations and yielded conflicting evidence. This observational comparative effectiveness research study was conducted to provide new evidence on the relationship between post-treatment surveillance testing and survival by overcoming the limitations of previous clinical trials. METHODS: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims (SEER-Medicare). Stage II and III colon cancer patients diagnosed from 2002 to 2009 and between 66 to 84 years of age were eligible. Adherence to surveillance testing guidelines-including carcinoembryonic antigen, computed tomography, and colonoscopy-was assessed for each year of follow-up and overall for up to three years post-treatment. Patients were categorized as More Adherent and Less Adherent according to testing guidelines. Patients who received no surveillance testing were excluded. The primary outcome was 5-year cancer-specific survival; 5-year overall survival was the secondary outcome. Inverse probability of treatment weighting (IPTW) using generalized boosted models was employed to balance covariates between the two surveillance groups. IPTW-adjusted survival curves comparing the two groups were performed by the Kaplan-Meier method. Weighted Cox regression was used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for the relative risk of death for the Less Adherent group versus the More Adherent group. RESULTS: There were 17,860 stage II and III colon cancer cases available for analysis. Compared to More Adherent patients, Less Adherent patients experienced slightly better 5-year cancer-specific survival (HR = 0.83, 95% CI 0.76-0.90) and worse 5-year noncancer-specific survival (HR = 1.61, 95% CI 1.43-1.82) for years 2 to 5 of follow-up. There was no difference between the groups in overall survival (HR = 1.04, 95% CI 0.98-1.10). CONCLUSIONS: More surveillance testing did not improve 5-year cancer-specific survival compared to less testing and there was no difference between the groups in overall survival. The results of this study support a risk-stratified, shared decision-making surveillance strategy to optimize clinical and patient-centered outcomes for colon cancer patients in the survivorship phase of care.

Clinical Network Systems Biology: Traversing the Cancer Multiverse.

In recent decades, cancer biology and medicine have ushered in a new age of precision medicine through high-throughput approaches that led to the development of novel targeted therapies and immunotherapies for different cancers. The availability of multifaceted high-throughput omics data has revealed that cancer, beyond its genomic heterogeneity, is a complex system of microenvironments, sub-clonal tumor populations, and a variety of other cell types that impinge on the genetic and non-genetic mechanisms underlying the disease. Thus, a systems approach to cancer biology has become instrumental in identifying the key components of tumor initiation, progression, and the eventual emergence of drug resistance. Through the union of clinical medicine and basic sciences, there has been a revolution in the development and approval of cancer therapeutic drug options including tyrosine kinase inhibitors, antibody-drug conjugates, and immunotherapy. This 'Team Medicine' approach within the cancer systems biology framework can be further improved upon through the development of high-throughput clinical trial models that utilize machine learning models, rapid sample processing to grow patient tumor cell cultures, test multiple therapeutic options and assign appropriate therapy to individual patients quickly and efficiently. The integration of systems biology into the clinical network would allow for rapid advances in personalized medicine that are often hindered by a lack of drug development and drug testing.

Adenoid Cystic Carcinoma Metastasized to Colon.

Adenoid cystic carcinoma (ACC) is an infrequent cause of malignancy that accounts for 1% of all tumors of the oral and maxillofacial region. We present a 59-year-old woman with a past medical history of adenoid cystic carcinoma of the left salivary gland treated with radiation and thoracotomy due to lung metastasis. Years after the onset of diagnosis, she presented with nonspecific gastrointestinal symptoms. For this reason, an abdominal computed tomography (CT) scan was done, revealing a liver mass in the right lobe, involving segments eight and five, concerning for malignancy. A colonoscopy was indicated for screening purposes, showing a large polyp that was biopsied. A histopathologic examination of the colon polyp and a liver biopsy was compatible with ACC metastatic carcinoma. We report this case to highlight an unusual location of metastatic ACC. Furthermore, there is no case report in the literature where colon metastasis has been described.

Where is My Spleen? - A Case of Splenosis Diagnosed Years Later after Splenectomy.

Hepatic splenosis was first described in 1939 and is a rare condition that results from splenic trauma or splenectomy. A 43-year-old man with a past medical history significant for a prior splenectomy was admitted to the hospital due to right upper quadrant pain for two days. Magnetic resonance imaging (MRI) of the abdomen suggested features of hepatic adenoma, however, a percutaneous biopsy showed the mass within the liver to be a discrete collection of splenic tissue, apparently the result of a traumatic splenic rupture years ago. Hepatic splenosis is a rare entity, and due to the asymptomatic nature of this condition, most cases are found incidentally after different imaging modalities are done. The management of this entity is based on conservative measures. We report this case to emphasize that in the appropriate clinical setting, hepatic splenosis should be considered in the differential diagnosis of a patient with a homogenous well-circumscribed liver mass.

Primary Gastric Squamous Cell Carcinoma.

Primary gastric squamous cell carcinoma (PGSCC) is an extremely rare cause of gastric malignancy. We present a 66-year-old man with a past medical history of stage I left palpebral marginal zone lymphoma status post radiation. The patient was complaining of a two-year history of bloating and early satiety. An upper endoscopy was performed, showing a 2.5 cm polypoid lesion at proximal corpus; however, the cardia and esophagus were normal. Biopsies were positive for gastric squamous cell carcinoma. He underwent partial gastrectomy and was referred to oncology for treatment. In 2011, the Japanese Gastric Cancer Association proposed diagnostic criteria for the diagnosis of PGSCC. The clinical presentation of this malignancy does not differentiate from that of other types of gastric tumors. We report this case to highlight squamous cell carcinoma as a cause of primary gastric cancer. Gastroenterologists should be aware of this entity to facilitate prompt referral to specialized centers, where surgical resection can be done.

Pulmonary Vein Thrombosis: A Recent Systematic Review.

The pulmonary veins (PVs) are the most proximal source of arterial thromboembolism. Pulmonary vein thrombosis (PVT) is a rare but potentially lethal disease; its incidence is unclear, as most of the literature includes case reports. It most commonly occurs as a complica-tion of malignancy, post lung surgery, or atrial fibrillation and can be idiopathic in some cases. Most patients with PVT are commonly asymptomatic or have nonspecific symptoms such as cough, hemoptysis, and dyspnea from pulmonary edema or infarction. The thrombi are typically detected using a variety of imaging modalities including transesophageal echocardiogram (TEE), computed tomography (CT) scanning, magnetic resonance imaging (MRI), or pulmonary angiog-raphy. Treatment should be determined by the obstructing pathological finding and can include antibiotic therapy, anticoagulation, thrombectomy, and/or pulmonary resection. The delay in diagnosing this medical entity can lead to complications including pulmonary infarction, pulmonary edema, right ventricular failure, allograft failure, and peripheral embolism resulting in limb ischemia, stroke, and renal infarction (RI).

Targeting chaperonin containing TCP1 (CCT) as a molecular therapeutic for small cell lung cancer.

Identifying new druggable targets is desired to meet the needs for effective cancer treatments. To this end, we previously reported the efficacy of a therapeutic peptide called CT20p that displays selective cytotoxicity through inhibition of a multi-subunit, protein-folding complex called Chaperonin-Containing TCP-1 (CCT). To investigate the role of CCT in cancer progression, we examined protein levels of CCT subunits in liver, prostate, and lung cancer using human tissue microarrays. We found that these cancers expressed higher levels of CCT2 as compared to normal tissues. Small cell lung cancer (SCLC) stood out as having statistically significant difference in CCT2. Higher levels of CCT2 in tumors from lung cancer patients were also associated with decreased survival. Using SCLC cell lines, we observed detectable amounts of CCT subunits and cells were susceptible to killing by CT20p. Treatment with CT20p, delivered to cells using polymeric nanoparticles, was cytotoxic to all SCLC cell lines, decreasing the levels of CCT client proteins like STAT3. In contrast, treatment with a STAT3 inhibitor was effective in one of the SCLC cell lines. While we found that CCT levels could vary in cell lines, normal tissues had low levels of CCT and minimal toxicity to liver or kidney function was observed in mice treated with CT20p. These results indicate that in SCLC, changes in CCT levels could be used as a biomarker for diagnosis and that targeting CCT for inhibition with CT20p is a promising treatment approach for those cancers such as SCLC that currently lack targeted therapeutics.

An Atypical Angiomyomatous Hamartoma With Unexplained Hepatosplenomegaly.

When a patient presented with ipsilateral lymphedema of the limb, an excisional biopsy of the left inguinal lymph node showed extensive smooth muscle and vascular proliferation replacing most of the lymph node.

Chaperonin Containing TCP-1 Protein Level in Breast Cancer Cells Predicts Therapeutic Application of a Cytotoxic Peptide.

PURPOSE: Metastatic disease is a leading cause of death for patients with breast cancer, driving the need for new therapies. CT20p is a peptide previously discovered by our group that displays cancer-specific cytotoxicity. To design the optimal therapeutic use of the peptide, we identified the intracellular target of CT20p in breast cancer cells, correlating expression patterns of the target with susceptibility to CT20p. EXPERIMENTAL DESIGN: Using polymeric nanoparticles to deliver CT20p, we assessed cytoskeletal changes, cell migration, adhesion, and viability in cells treated with the peptide. Protein pull-down experiments, coupled to mass spectrometry, enabled identification of the peptide's intracellular target. Biochemical and histologic techniques validated target identity in human cell lines and breast cancer tissue microarrays and revealed susceptibility patterns to CT20p. RESULTS: Chaperonin containing TCP-1 (CCT) was identified as the intracellular target of CT20p. Cancer cells susceptible to CT20p had increased CCT, and overexpression of CCTß, a subunit of the CCT complex, enhanced susceptibility to CT20p. Susceptible cells displayed reduced tubulin, a substrate of CCT, and inhibition of migration upon CT20p treatment. CCTß levels were higher in invasive ductal carcinomas than in cancer adjacent tissues and increased with breast cancer stage. Decreased breast cancer patient survival correlated with genomic alternations in CCTß and higher levels of the chaperone. CONCLUSIONS: Increased CCT protein in breast cancer cells underlies the cytotoxicity of CT20p. CCT is thus a potential target for therapeutic intervention and serves as a companion diagnostic to personalize the therapeutic use of CT20p for breast cancer treatment. Clin Cancer Res; 22(17); 4366-79. ©2016 AACR.

A phase II study of docetaxel, doxorubicin, and infusional 5-fluorouracil in the treatment of patients with locally advanced breast cancer.

OBJECTIVE: The primary aim of this study was to estimate the rate of clinical and pathologic response to preoperative docetaxel, doxorubicin, and infusional 5-fluorouracil in patients with locally advanced breast cancer. Secondary objective included the determination of toxicity profile. PATIENTS AND METHODS: Thirty-nine patients (median age 49 years) with histologically confirmed locally advanced breast cancer (stage IIIA or IIIB) were studied. Patients received 4 courses of chemotherapy with docetaxel (75 mg/m2 iv over 1 hour), doxorubicin (50 mg/m2 iv bolus), and 5-fluorouracil (300 mg/m2/d as continuous iv infusion on days 1-5). Treatment cycles were repeated every 21 days. Prophylactic filgastrim 5 microg/kg s/c QD was administered to all patients. Definitive surgery was performed after the completion of 4 cycles of therapy. Pathologic complete response was defined as the absence of invasive cancer in both the breast and ipsilateral axillary lymph nodes. RESULTS: The clinical objective response rate (partial plus complete) was 87% (95% confidence interval [CI]: 76-98%). Three patients (8%) had complete pathologic response. Two patients progressed preoperatively. Thirteen patients (33%) developed neutropenic fever. Fifty-three percent of the patients were hospitalized for treatment related complications. No cardiotoxicity or treatment related deaths were observed. CONCLUSIONS: Triple cytotoxic therapy based on concurrent doxorubicin and docetaxel with infusional 5-flourouracil (5-FU) does not appear to significantly improve the pathologic response in patients with locally advanced breast cancer.