High Risk Of Cancer Recurrence Research Articles

Long-term Recurrence and Progression Patterns in a Contemporary Series of Patients with Carcinoma In Situ of the Bladder With or Without Associated Ta/T1 Disease Treated with Bacillus Calmette-Guérin: Implications for Risk-adapted Follow-up

BackgroundLimited data are available on patients with carcinoma in situ (CIS) of the bladder managed according to current clinical practice guidelines. ObjectiveTo assess the patterns of recurrence, progression to muscle-invasive bladder cancer (MIBC), and upper tract urothelial carcinoma (UTUC) in patients with CIS, and to compare the effectiveness of adequate versus inadequate bacillus Calmette-Guérin (BCG) immunotherapy. Design, setting, and participantsA retrospective analysis of 386 patients with CIS of the bladder with or without associated pTa/pT1 disease treated with BCG between 2008 and 2015. Outcome measurements and statistical analysisKaplan-Meier estimations and an inverse probability of treatment weighting (IPTW)-Cox regression were performed to compare recurrence-free survival (RFS) and progression-free survival (PFS) and UTUC incidence over time for patients who received adequate versus inadequate BCG treatment. Results and limitationsThe median follow-up was 70.5 mo. At 5 and 10 yr, RFS was 82% and 52%, PFS was 93.6% and 75.8%, and UTUC incidence was 1.7% and 2.9%, respectively. Most recurrence (73.6%) and progression (69.1%) events occurred in the first 3 yr of follow-up, while 38.7% of UTUC incident events were recorded after 5 yr of follow-up. IPTW-Cox regression revealed that patients who received BCG treatment had a lower risk of recurrence (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.13–0.34), progression (HR 0.46, 95% CI 0.25–0.87), and UTUC incidence (HR 0.24, 95% CI 0.09–0.64). Limitations include the retrospective design and potential selection bias. ConclusionsPatients with CIS of the bladder show a high risk of recurrence, progression, and UTUC incidence. Most of these outcomes occur during the first 3 yr of follow-up, but a significant proportion of the events occur at long-term follow-up. Although receipt of adequate BCG treatment improves outcomes, intensive and long-term surveillance may be warranted. Patient summaryWe investigated the long-term cancer control outcomes for patients with carcinoma in situ (CIS; cancerous cells that have not spread from where they first formed) of the bladder. Patients with CIS have a high risk of cancer recurrence and progression. Treatment with bacillus Calmette-Guérin (BCG) improves outcomes.

Weakly supervised deep learning for prediction of treatment effectiveness on ovarian cancer from histopathology images.

Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70 % of advanced patients are with recurrent cancer and decease. Surgical debulking of tumors following chemotherapy is the conventional treatment for advanced carcinoma, but patients with such treatment remain at great risk for recurrence and developing drug resistance, and only about 30 % of the women affected will be cured. Bevacizumab is a humanized monoclonal antibody, which blocks VEGF signaling in cancer, inhibits angiogenesis and causes tumor shrinkage, and has been recently approved by FDA as a monotherapy for advanced ovarian cancer in combination with chemotherapy. Considering the cost, potential toxicity, and finding that only a portion of patients will benefit from these drugs, the identification of new predictive method for the treatment of ovarian cancer remains an urgent unmet medical need. In this study, we develop weakly supervised deep learning approaches to accurately predict therapeutic effect for bevacizumab of ovarian cancer patients from histopathological hematoxylin and eosin stained whole slide images, without any pathologist-provided locally annotated regions. To the authors' best knowledge, this is the first model demonstrated to be effective for prediction of the therapeutic effect of patients with epithelial ovarian cancer to bevacizumab. Quantitative evaluation of a whole section dataset shows that the proposed method achieves high accuracy, 0.882±0.06; precision, 0.921±0.04, recall, 0.912±0.03; F-measure, 0.917±0.07 using 5-fold cross validation and outperforms two state-of-the art deep learning approaches Coudray et al. (2018), Campanella et al. (2019). For an independent TMA testing set, the three proposed methods obtain promising results with high recall (sensitivity) 0.946, 0.893 and 0.964, respectively. The results suggest that the proposed method could be useful for guiding treatment by assisting in filtering out patients without positive therapeutic response to suffer from further treatments while keeping patients with positive response in the treatment process. Furthermore, according to the statistical analysis of the Cox Proportional Hazards Model, patients who were predicted to be invalid by the proposed model had a very high risk of cancer recurrence (hazard ratio = 13.727) than patients predicted to be effective with statistical signifcance (p<0.05).

Intraoperative radiation therapy for locally advanced and recurrent head and neck cancer.

6058 Background: Intraoperative Radiation Therapy (IORT) allows precise delivery of radiation therapy (RT) to a limited target area at high risk of cancer recurrence while minimizing RT to nearby organs at risk. IORT may be particularly beneficial for patients with locally recurrent head and neck cancer (HNC) in a previously irradiated field and for locally advanced HNC cases, in which obtaining negative surgical margins may be difficult. This study aims to present a single institution experience with IORT for HNC patients. Methods: This study included HNC patients treated consecutively with IORT at our institution between 2014 and 2018. Charts were reviewed for patients’ and tumors’ characteristics, IORT technical details, IORT-induced adverse events, and treatment outcomes. Results: The study included 23 eligible patients. Median patient age was 66 (range 33-91). Tumor sites included parotid gland (43%), lymph nodes (43%), oral tongue (9%), and ear (4%). 52% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), while 48% received salvage IORT after local tumor recurrence. The median prescribed IORT dose was 7.5 Gy (range 5-14 Gy) in a single fraction prescribed to 5 mm depth with Flat applicators (median diameter of 5 cm). 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke, a second patient (4%) experienced protracted wound healing. At a median follow-up of 36 months (range 2-81), 42% of patients presented with no evidence of disease (NED), overall survival was 54%, 13% of patients were alive with disease, and 46% died with disease. Local-regional recurrence rate was 39% (median time to local recurrence was 18 months, range 2-60), rate of distant metastasis was 43% (median time to distant metastasis was 23 months, range 5-60), and 30% of patients had both local-regional recurrence and distant metastases. The percent of local-regional recurrence and distant metastases among patients receiving salvage IORT was 64% and 73% respectively, compared to 23%, and 15% respectively in those receiving upfront IORT with or without adjuvant EBRT. Conclusions: In this single institution chart review study, IORT to locally advanced and recurrent HN cancer patients was a safe treatment modality, with tumor control comparable to historical EBRT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HN cancer.

Potential Refinement of Recurrence Score by pSTAT3 Status.

The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (<26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population.

Assessment of dietary quality in patients on surveillance for colorectal cancer (CRC) using a computerized food frequency questionnaire (FFQ).

66 Background: Poor dietary patterns are clearly implicated in the pathogenesis of CRC and are increasingly associated with worsened CRC outcomes, including a higher risk of cancer recurrence and mortality. We evaluated the use of a novel computerized FFQ technology to assess dietary patterns in patients with CRC who were undergoing cancer surveillance. Methods: We recruited patients with stage I-III CRC who had completed curative intent therapy at least 1 year but no more than 5 years prior to enrollment. Dietary assessment was conducted using a computerized FFQ (VioScreen) either in clinic or at home. Dietary quality was defined by the Healthy Eating Index (HEI) 2015 score which was calculated automatically by the FFQ technology. Statistical significance was determined using Pearson correlation and analysis of variance (ANOVA). Results: Twenty patients (14 colon, 6 rectal; 12 male, 8 female; median age 66 [49-80]; median 3 years from diagnosis) were recruited between 10/2020-9/2021. Fourteen patients did FFQ remotely and 6 in-person. Nineteen patients were white/non-Hispanic. All received surgery, 20% radiation (all rectal) and 75% chemotherapy. Mean HEI 2015 total and sub-scores are shown in the table. There were significant differences in dietary quality by age &lt;65 vs ≥65 (HEI 58.3 vs. 72.6, p=0.025), body-mass-index (BMI) normal/overweight vs. obese (HEI 72.4 vs. 58.6, p=0.033), and marital status of married vs non-married (HEI 61.7 vs. 76.7, p=0.032). There were no differences in dietary quality by level of education, tumor site (colon vs. rectal) or gender. There was a significant negative correlation with increased time since diagnosis and lower dietary quality (r= -0.67, p&lt;0.001). Conclusions: Dietary patterns can be determined using a computerized FFQ in patients with CRC on surveillance both remotely and in-person. This population has a wide range of dietary patterns with particularly low scores in whole grain, fatty acid, sodium and saturated fat. Patients who are older, non-obese, non-married, and closer to completion of cancer therapy have higher dietary quality scores. Future studies of integrating a computerized FFQ into cancer care will determine whether personalized interventions targeting specific dietary patterns can improve diet quality.[Table: see text]

A high tumour-stroma ratio (TSR) in colon tumours and its metastatic lymph nodes predicts poor cancer-free survival and chemo resistance.

Despite known high-risk features, accurate identification of patients at high risk of cancer recurrence in colon cancer remains a challenge. As tumour stroma plays an important role in tumour invasion and metastasis, the easy, low-cost and highly reproducible tumour-stroma ratio (TSR) could be a valuable prognostic marker, which is also believed to predict chemo resistance. Two independent series of patients with colon cancer were selected. TSR was estimated by microscopic analysis of 4µm haematoxylin and eosin (H&E) stained tissue sections of the primary tumour and the corresponding metastatic lymph nodes. Patients were categorized as TSR-low (≤ 50%) or TSR-high (> 50%). Differences in overall survival and cancer-free survival were analysed by Kaplan-Meier curves and cox-regression analyses. Analyses were conducted for TNM-stage I-II, TNM-stage III and patients with an indication for chemotherapy separately. We found that high TSR was associated with poor cancer-free survival in TNM-stage I-II colon cancer in two independent series, independent of other known high-risk features. This association was also found in TNM-stage III tumours, with an additional prognostic value of TSR in lymph node metastasis to TSR in the primary tumour alone. In addition, high TSR was found to predict chemo resistance in patients receiving adjuvant chemotherapy after surgical resection of a TNM-stage II-III colon tumour. In colon cancer, the TSR of both primary tumour and lymph node metastasis adds significant prognostic value to current pathologic and clinical features used for the identification of patients at high risk of cancer recurrence, and also predicts chemo resistance.

Structure modification and biological evaluation of indole-chalcone derivatives as anti-tumor agents through dual targeting tubulin and TrxR

Microtubule target agents (MTAs) are widely-used clinical anti-cancer drugs for decades, but the acquired drug resistance severely restricted their application. Thioredoxin reductases (TrxR) was reported to be overexpressed in most tumors and closely related to high risk of cancer recurrence and drug resistance, making it a potential target for anticancer drug discovery. Multi-target-directed ligands (MTDLs) by a single molecule provide a logical and alternative approach to drug combinations. In this work, based on the structure-activity relationships obtained in our previous study, some structure modifications were performed. On one hand, the retained skeleton structure of MTAs endowed its tubulin polymerization inhibition activity, on the other hand, the selenium-containing structure and α,β-unsaturated ketone moiety endowed the TrxR inhibition activity. As results, the newly obtained compounds exhibited superior anti-proliferative activities towards various human cancer cells and drug-resistance cells, and displayed high selectivity towards various human normal cells. The mechanism study revealed that the dual effect of cell cycle arrest triggered by targeting tubulin and the abnormal accumulation of ROS caused by TrxR inhibition eventually lead to cell apoptosis. Notably, compared with the MTA agents CA-4P, and the TrxR inhibitor Ethaselen, the optimized compound 14c, which served as dual-targeting inhibitor of tubulin and TrxR, exerted greatly improved in vivo anti-tumor activity. In summary, 14c deserved further consideration for cancer therapy.

A misdiagnosed case of blastic plasmacytoid dendritic cell neoplasm experiencing multiple recurrences who\xa0underwent allogeneic stem cell transplantation: a case report

BackgroundBlastic plasmacytoid dendritic cell neoplasm represents a rare type of hematologic malignancy that often manifests itself through various skin lesions. It commonly affects the elderly male population. Lymph nodes, peripheral blood, and bone marrow involvement are the typical findings that justify its aggressive nature and dismal prognosis. On histopathological assessment, malignant cells share some similarities with blastic cells from the myeloid lineage that make immunohistochemistry staining mandatory for blastic plasmacytoid dendritic cell neoplasm diagnosis.Case presentationA 35-year-old Asian man presented with cervical lymphadenopathy followed by an erythematous lesion on his left upper back. At first, the lesion was misdiagnosed as an infectious disease and made the patient receive two ineffective courses of azithromycin and clarithromycin. Six months later, besides persistent skin manifestations, he felt a cervical mass, which was misdiagnosed as follicular center cell lymphoma. Tumor recurrence following the chemoradiation questioned the diagnosis, and further pathologic assessments confirmed blastic plasmacytoid dendritic cell neoplasm. The second recurrence occurred 3 months after chemotherapy. Eventually, he received a bone marrow transplant after complete remission. However, the patient expired 3 months after transplant owing to the third recurrence and gastrointestinal graft versus host disease complications.ConclusionsEarly clinical suspicion and true pathologic diagnosis play a crucial role in patients’ prognosis. Moreover, allogenic bone marrow transplant should be performed with more caution in aggressive forms of blastic plasmacytoid dendritic cell neoplasm because of transplant side effects and high risk of cancer recurrence.

Clinical Characteristics and Outcomes of Cancer Survivors Undergoing Heart Transplantation

<h3>Purpose</h3> Heart transplantation (HT) remains the gold standard treatment for advanced heart failure (HF). Cancer survivors (CS) are at increased risk of developing HF in general and in some cases advanced HF. New consensus statements for organ transplantation in CS support the utilization of HT amongst select CS . The aim of this study was to examine clinical characteristics and outcomes of CS undergoing HT. <h3>Methods</h3> Retrospective cohort study of patients undergoing HT at a large medical center between Jan 1, 2010 and October 2020. CS were defined as those with history of malignancy other than non-melanoma skin cancer (CA) prior to HT. Baseline demographics, CA history and survival data were obtained from electronic medical records. <h3>Results</h3> 57(10.2%) CS were identified out of total of 560 HT recipients during the study period. Median age at the time of transplantation was 60 (IQR 50-65) years, and 60% of patients were male. Common pre-transplant malignancies included 13 breast CA (22.8%), 13 leukemia/lymphoma (22.8%), 8 prostate CA (14%), and 4 testicular CA (7%). 24 CS (42.1%) had received previous anthracycline therapy, and 23 CS (40.4%) had received chest radiation. Median follow-up time post-transplantation was 3.2 years (IQR 1.6-6.9 years). At the end of the study period, 50 of 57 (87.7%) CS were alive. Causes of deaths included infection (n=4), recurrent CA (n=2), and primary graft failure (n=1). Overall 9 patients (15.8%) developed 10 malignancies post HT. 4 patients had recurrence of their prior CA (2 breast ,1 colon, 1 prostate), while 6 patients developed new primary CA (prostate, renal, thyroid, lung, melanoma, lymphoma). The Kaplan Meier 5 year CA free survival was 69.8%(CI 49.8-83.1) (Figure 1) <h3>Conclusion</h3> CS appear to be at high risk of CA recurrence after HT; however infection is the leading cause of death on short term follow up. Longer follow-up is needed to understand long-term outcomes in this heterogenous group of patients to guide listing criteria, immunosuppression and CA screening.

Analysis of oncological safety of autologous fat grafting after immediate breast reconstruction.

Fat grafting is now a common procedure for breast reconstruction. Many clinical studies have reported its aesthetic efficacy and oncological safety, but some experimental studies raise about the recurrence risk because of its regenerating property. This study aims to investigate the possibility of cancer recurrence associated with fat grafting. In this retrospective cohort study, we analyzed a total of 339 patients who had undergone immediate reconstructive surgery after nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) in our institution between February 28, 2009 and March 23, 2019. Patients who had undergone breast conserving surgery, radical mastectomy, or delayed reconstruction were excluded. We used univariate and multivariate Cox proportional hazards regression models to evaluate the association between fat grafting and cancer recurrence. Among the 339 patients during a median follow-up of 52 months, 27 patients (8.0%) were confirmed to have recurrent cancer. Of 67 patients who had undergone fat grafting, 10 patients were confirmed to have cancer recurrence. In multivariate analyses, fat grafting [hazard ratio (HR), 2.52; 95% CI, 1.005-6.317; P=0.0488] was independently associated with cancer recurrence. In population of breast cancer patient who underwent immediate reconstruction in our institution, fat grafting showed significant higher risk of cancer recurrence. Although these results are at odds with many existing studies, it suggests that more careful follow-up may be necessary for patients who had undergone fat grafting after reconstructive surgery.

MTOR INHIBITORS ENHANCE ANTITUMOR ACTIVITY OF LIVER NATURAL KILLER CELLS IN MICE

Background: Liver transplantation (LT) is the best available option for patients with end stage liver disease and HCC. However, recipients are at high risk of cancer recurrence and infection, due to immunosuppressive (IS) therapy. IS used in LT commonly consist of calcineurin inhibitor (CNI) or a mechanistic target of rapamycin (mTOR), anti-metabolite and corticosteroids. Liver is an important immunological organ with a unique microenvironment. Innate and adaptive immune responses shapes the balance between immune tolerance and activation. It is well-known that IS drugs targeting the adaptive component of immunity, while innate immune cells become the only self-defense mechanism against neoplastic cells and infectious agents. However, the effect of IS drugs on liver resident immune cells are not well known. In this study, we analyzed the effect of two main IS drugs, calcineurin inhibitors and mTOR inhibitors on adaptive and innate immune components of the liver in mice Method: C57/BL6 mice were treated by intraperitoneal injection of mTORi (rapamycin and everolimus) and CNI (cyclosporine) for 7 days. Twenty-four hours after the last injection, liver mononuclear cells (LMNCs), splenocytes were collected. The proportion of T cells, NKT cells and NK cells and various functional molecules were analyzed by flow cytometry. Result: The proportion of TCR+NK1.1- T cells, TCR+NK1.1+ NKT cells in LMNC did not differ in both CNI mTORi treated groups. TCR-NK1.1+NK fraction in LMNCs was significantly increased in mTORi group (9.5 in mTORi groups versus 7.8 in control group), CNI treatment had no effect on NK cells frequency. mTORi treatment significantly upregulated the TRAIL positive NK cells (38.5%±4.0 in mTORi group vs 21.0%±8.3 in untreated, p =0.003). CNI treatment oppositely significantly decreased the TRAIL positive NK cell population (16.4%±4.2 in CNI group vs 21.0%±8.3 in untreated, p <0.05). CD 69 and Nkp46 expression on liver NK cells were not changed significantly in both mTORi and CNI treated groups in comparison to control group. Moreover, liver NK cells from mTORi treated mice showed significantly higher cytotoxicity against TRAIL-sensitive Hepa1-6 cells (30.1% ± 13.0 vs 13.5 %± 6.0, p=0.009). Cytotoxicity against TRAIL resistant YAC-1 mouse lymphoma was not significantly enhanced after mTORi treatment (53.6 % ± 4.4 vs 39.9% ± 1.2). Conclusion: mTOR inhibitors has ability to enhance liver resident NK cell activity. This result suggests that mTOR inhibitors might be useful to maintain anti-microbe and anti-tumor immunity even under immunosuppressive condition after transplantation.

Improving health engagement and lifestyle management for breast cancer survivors with diabetes

Breast cancer survivors with type 2 diabetes are at high risk for cancer recurrence, serious health complications, more severe symptoms, psychological distress, and premature death relative to breast cancer survivors without diabetes. Maintaining glycemic control is critical for decreasing symptoms and preventing serious health problems. Many breast cancer survivors with type 2 diabetes have difficulty maintaining diabetes self-management behaviors and achieving glycemic control. Both cancer and diabetes-related symptoms (e.g., physical symptoms and psychological distress) are often barriers to engaging in diabetes self-management strategies. This study evaluates a novel diabetes coping skills training (DCST) intervention for improving breast cancer survivors' abilities to manage symptoms and adhere to recommended diabetes self-management behaviors. The telephone-based DCST protocol integrates three key theory-based strategies: coping skills training for managing symptoms, adherence skills training, and healthy lifestyle skills training. A randomized clinical trial will test the DCST intervention plus diabetes education by comparing it to diabetes education alone. Symptoms, distress, diabetes self-management behaviors, and self-efficacy will be assessed at baseline and 3, 6, and 12 months. Glycosylated hemoglobin (HbA1c) will be assessed at baseline, 6, and 12 months. This study addresses a critical gap in the care of breast cancer survivors by evaluating a novel behavioral intervention to improve the management of symptoms, adherence, and glycemic control in breast cancer survivors with type 2 diabetes. Special considerations for this medically underserved population are also provided. The findings of this study could lead to significant improvements in clinical care and beneficial outcomes for breast cancer survivors.Trials registration: ClinicalTrials.gov, NCT02970344, registered 11/22/2016.

PLSCR1 and XKR8: New markers for low-grade glioma progression and outcome

Abstract Background One of the most frequently diagnosed oncological diseases among young persons is Low-grade glioma (LGG). More than 80% of LGGs progress to higher-grade tumors always lethal to a patient. LGG is an extremely heterogeneous group of primary glial brain tumors with a quite variable rate of recurrence, survival, and response to treatment. Thus a study of new biomarkers associated with disease progression and patient outcome is useful to improve patient management. Genes involved in key cellular processes, e.g., apoptosis, are promising prognostic and predictive cancer markers. Phosphatidylserine (PS) plays an essential role in apoptosis signaling. Several studies suggested PS is dysregulated in the tumor microenvironment and offends the development of anti-cancer immune response. The scramblases PLSCR1 and XKR8 allegedly could be associated with the progression and outcome of LGG since they could be involved in the development of immunity via regulation of PS activity by its bidirectional translocation in the plasma membrane. Thus this study was aimed to evaluate associations of PLSCR1 and XKR8 with disease-free and overall survival of LGG patients. Methods Gene expression values and clinical information of 530 LGG patients were downloaded from TCGA Low-Grade Glioma study using the public resource CBioPortal. According to gene expression values (RNA Seq V2 RSEM) patients were divided into two groups: with downregulated ( mean) PLSCR1 or XKR8 gene. The Kaplan-Meier procedure and Log-Rank test were used for survival analysis. All calculations were performed in the integrated development environment - RStudio. Results It was shown the LGG patients with upregulated PLSCR1 (p = 2.54e-14) and XKR8 (p = 7.33e-15) gene had worse disease prognosis than other patients. Similar associations were seen in the study of LGG progression, where patients with upregulated PLSCR1 (p = 7.75e-07) and XKR8 (p = 5.59e-10) gene had a higher risk of cancer recurrence. Conclusions Consequently, PLSCR and XKR8 genes could be considered as new prognostic biomarkers of LGG progression and outcome. Legal entity responsible for the study Research Laboratory Biomarker. Funding The work was performed according to the Russian Government Program of Competitive Growth of KFU. Disclosure All authors have declared no conflicts of interest.

A Masquerading Mass: An Appendiceal Fecalith Posing as a Submucosal Lesion

Colonoscopy remains the gold standard for colon cancer prevention and surveillance. Colorectal cancer is one of the leading causes of cancer-related deaths in America. According to the CDC, 139,992 patients were diagnosed with colon cancer in 2014, making it the third most common cancer to affect both sexes. Routine colonoscopies oftentimes reveal unexpected findings. When this happens, it is important to keep an open mind when formulating a differential diagnosis. The following is the case of a routine surveillance colonoscopy highlighted by a finding, which ultimately unveiled an unexpected etiology. A 74-year-old Caucasian male with history of prostate cancer under surveillance, sigmoid colon adenocarcinoma (T3N0M0) s/p laparoscopic sigmoidectomy 8 years ago presented to our institution for a routine surveillance colonoscopy. His previous surveillance colonoscopies were negative. His routine labs were within normal limits. He denied any weight loss, abdominal pain, and displayed no symptoms consistent with GI bleeding. Our colonoscopy revealed 4 tubular adenomas (ranging from 5mm to 2cm in size), which were removed, and a hard, ulcerated nodular mass (2cm in diameter, seen in Figure 1) at the appendiceal orifice. The mass was biopsied extensively, however pathology was not diagnostic. Due to suspicion the mass was related to an underlying malignancy, we ordered a CEA and CT scans of the chest, abdomen, and pelvis. CEA was within normal limits, and imaging was significant for a 1.7cm soft tissue mass with central calcification (Figure 2). At that point, etiologies highest on our differential were carcinoid tumor, mucocele, and GIST. Our surgery colleagues proceeded with a laparoscopic appendectomy. Pathology of the removed tissue showed a markedly dilated appendiceal base with a luminal fecalith, and fibrous obliteration of the distal appendix. No malignancy was found and the etiology of the ulcerated submucosal lesion turned out to be an appendiceal fecalith. On our literature search, there are only a few reports of a fecalith presenting as a cecal submucosal mass. This case highlights the importance of maintaining a broad differential diagnosis when finding unexpected lesions during colonoscopy. In a patient such as this with a higher risk of cancer recurrence, malignancy is usually high on our differential. Even a colonic mass can have a unique and unexpected etiology such as an appendiceal fecalith.1662_A Figure 1. Colonoscopy images of the appendiceal mass1662_B Figure 2. CT imaging of the abdomen showing the 1.7 cm soft tissue mass with central calcification seen at the appendix

Recurrence of Renal Cell Cancer After Renal Transplantation in a Multicenter French Cohort.

Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation. We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed. Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period. Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.

Rheumatoid arthritis treatment in patients with a history of cancer.

What is the best treatment option in patients with active rheumatoid arthritis who have a history of malignant disease? Rheumatologists are increasingly faced with this question in their daily practice. As uncontrolled high disease activity is an important risk factor for further comorbidities and shortened life expectancy, the treatment has to be effective, without bearing a higher risk for cancer recurrence. What data is available today to guide treatment decisions and how robust is its evidence? As patients with prior cancer are usually not included in randomized controlled trials, all data we have to elucidate this topic stems from observational cohort studies, mainly biologics registers established in several European countries. The registries investigated the risk of recurrence of cancer mainly by comparing treatments with csDMARDs and TNF inhibitors. Few results are available so far for the treatment with rituximab. However, because of their observational design, the data can only reflect current clinical practice. Because of the lack of evidence, questions such as: are biologics soon after cancer diagnosis safe, remain. There is still insufficient data for patients with a very recent history of cancer. However, in patients with cancer being in longer remission, observational data suggest no increased risk of overall cancer recurrence when they are treated either with TNF inhibitors or rituximab.

Discriminative Spectral Pattern Analysis for Positive Margin Detection of Prostate Cancer Specimens using Light Reflectance Spectroscopy

ABSTRACTFor localized prostate cancer, one treatment is prostatectomy which surgically removes the prostate gland. However, some undetectable cancer cells may be left as positive surgical margins, leading to a high risk of cancer recurrence. It is highly desirable to develop a portable and accurate classification methodology that detects positive margins on human prostate specimens immediately after their removal during surgery. This study applied data mining techniques on the light reflectance spectroscopy (LRS) data taken from ex-vivo human specimens and developed a novel classification algorithm that could enable real-time, positive-margin identification during surgery.Specifically, the LRS measurements taken from human prostate specimens ex vivo were classified to normal or cancerous tissue with support vector machines and were also classified to normal, cancerous and transition-to-cancer class with an ensemble of trees. The data in this study were highly overlapped and imbalanced among classes. We solved the overlapping issue by defining a middle class (transition-to-cancer), and by optimizing a moving spectral window through the range of LRS. To solve the imbalanced problem, we removed irregular tissue measurements, followed by application of random undersampling from the majority class. We achieved sensitivity and specificity of 100% and 82% for binary classification.

Tobacco treatment implementation within 28 commission on cancer accredited programs in the Northeast region of the USA: A pilot study

Cancer survivors are a rapidly growing population and an important target for tobacco treatment interventions. Continued smoking after the diagnosis of cancer is associated with a higher risk of cancer recurrence and mortality. Systematic tobacco cessation programs are effective. This study surveyed American College of Surgeons Commission on Cancer (CoC) programs in the Northeast region of the USA regarding their tobacco control programs. Seventy percent of cancer survivors are treated within CoC programs. The purpose of this study was to describe the extent of implementation of tobacco treatment and determine the organizational delivery of tobacco treatment as measured by the presence of goals to address smoking, leadership support, and integration of tobacco treatment guidelines into care delivery. Data were collected by a survey. The Assessment of Chronic Illness Care questionnaire was used to collect data on implementation of tobacco treatment services. Descriptive statistics were used to analyze the data. Most programs (78.6%) had an electronic health record and of these 68% captured smoking status. Implementation of tobacco treatment was not optimal for identifying smokers, providing patients with community linkages or self-care cessation support. Implementation of decision aides for pharmacotherapy and reassessment of smoking status were the least developed areas. Moreover, the organizational delivery for tobacco treatment was less than optimal. Many cancer programs have not implemented systems to deliver optimal tobacco treatment. Efforts should be made to help cancer programs develop sustainable system-wide programs that address the urgent need to deliver tobacco treatment to all cancer survivors.

Novel characteristics of alpha-fetoprotein (AFP)-producing gastric cancer.

BackgroundAlthough serum AFP level is increased in the AFP-producing gastric cancer (GC) patient, AFP-producing GC may become recurrent without re-elevation of serum AFP level. Therefore, novel characteristics of AFP-producing GC such as other biomarkers are to be explored.Results35 AFP-GC and 48 non-AFP-GC patients were included. Our present study revealed that blood type O (15 cases, 42.8%) and A (18 cases, 37.5%) were predominantly observed among AFP-GC and non-AFP-GC patients, respectively. Intriguingly, the least consistently was blood type AB (8.5%, 14.6%). Among AFP-GC patients, pre-operative serum AFP levels were weakly and reversely associated with pre-operative percentage of lymphocytes in the peripheral blood (R2 = 0.1556). The level of alkaline phosphatase (ALP) was highly correlated with the level of lactate dehydrogenase (LDH) (R2 = 0.6682) and CEA (R2 = 0.6813). The level of CEA was moderately correlated with the level of LDH (R2 = 0.3903). By contrast, no any associations between ALP, LDH, CEA, AFP, and peripheral lymphocytes were observed among those 48 non-AFP-GC patients.Materials and MethodsRetrospective analysis was carried out for 2773 inpatients of gastric cancer from January 2012 to November 2016 in the Second Affiliated Hospital of Zhejiang University School of Medicine.ConclusionsThe aggressive biological features of AFP-producing GC are closely associated with abnormality of other tumor biomarkers and decrease of the proportion of peripheral lymphocytes, implying that post-operative increase of peripheral lymphocytes might benefit GC patients. Combined use of multiple biomarkers is of significance in comprehensive evaluation of AFP-producing GC patients and assessment for those with high risk of cancer recurrence.

Does delayed esophagectomy after endoscopic resection affect outcomes in patients with stage T1 esophageal cancer? A propensity score-based analysis.

Although endoscopic resection (ER) may be sufficient treatment for early-stage esophageal cancer, additional treatment is recommended when there is a high risk of cancer recurrence. It is unclear whether delaying esophagectomy by performing and assessing the success of ER affects outcomes as compared with immediate esophagectomy without ER. Additionally, long-term survival after sequential ER and esophagectomy required further investigation. Between 2011 and 2015, 48 patients with stage T1 esophageal cancer underwent esophagectomy after ER with curative intent at our institution. Two-to-one propensity score methods were used to identify 96 matched-control patients who were treated with esophagectomy only using baseline patient, tumor characteristics and surgical approach. Time from initial evaluation to esophagectomy, relapse-free survival, overall survival, and postoperative complications were compared between the propensity-matched groups. In the ER+esophagectomy group, the time from initial evaluation to esophagectomy was significantly longer than in the esophagectomy only group (114vs. 8days, p<0.001). The incidence of dense adhesion (p=0.347), operative time (p=0.867), postoperative surgical complications (p=0.966), and postoperative length of hospital stay (p=0.125) were not significantly different between the groups. Moreover, recurrence-free survival and overall survival were also similar between the two groups (p=0.411 and p=0.817, respectively). Treatment of stage T1 esophageal cancer with ER prior to esophagectomy did not increase the difficulty of performing esophagectomy or the incidence of postoperative complications and did not affect survival after esophagectomy. These results suggest that ER can be recommended for patients with stage T1 cancer even if esophagectomy is warranted eventually.