Ilknur Bilkay Gorken

Effects of preoperative chemoradiotherapy on anal sphincter functions and quality of life in rectal cancer patients

PurposeDeterioration of anorectal function after long-course preoperative chemoradiotherapy combined with surgery for rectal cancer is poorly defined. We conducted a prospective study to evaluate the acute and long term effects of preoperative chemoradiotherapy on anorectal function and quality of life of the patients.MethodsThere were 26 patients in surgery group and 31 patients in preoperative chemoradiotherapy group. Anorectal function and quality of life of the patients were assessed by anorectal manometry, incontinence score, quality of life questionnaire.ResultsSignificant lower resting pressures in both groups and lower maximal squeeze pressures in the preoperative chemoradiotherapy group were observed after postsurgical evaluations compared with the paired pretreatment ones. In the surgery group, both the Wexner continence score, FIQL score, and the rectoscopy score were comparable before and after surgery, whereas significant worsening in the Wexner score was observed in the preoperative chemoradiotherapy group postoperatively (P < 0.01). Significant reduction in anal canal resting pressures and squeeze pressures, Wexner score, and FIQL score were observed immediately after the completion of preoperative chemoradiotherapy. Significant lower maximal squeeze pressures and worsening of the Wexner scores were observed in the preoperative chemoradiotherapy group compared to the surgery group during the postoperative assessments (P < 0.05 and P < 0.01, respectively).ConclusionsBoth total mesorectal excision and preoperative chemoradiotherapy may adversely affect the anorectal function. Careful selection of the patients who will benefit from neoadjuvant therapy and identifying the patients with a high risk of developing functional problems may help to improve functional outcomes for the treatment of rectal cancer.

Survivin, p53, and Ki-67 as predictors of histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiotherapy

PurposeThe ability to predict response to chemoradiotherapy before the treatment may allow protecting poorly responding patients from the side effects of neoadjuvant treatment. Several molecular markers have been proposed to radio and chemosensitivity of rectal cancer. In this study, from pre-irradiation tumor biopsies, a novel and promising candidate factor survivin, and p53 and Ki-67 were assessed as predictors of response to preoperative chemoradiotherapy.Materials and methodsExpression of each marker was evaluated by immunohistochemistry on pretreatment biopsies from 37 patients having rectal cancer treated with preoperative chemoradiotherapy and curative surgery. Treatment response was assessed histopathologically in the resected surgical specimen.ResultsThere was no correlation between expression of p53, Ki-67, and survivin with response to preoperative chemoradiotherapy and prognosis.ConclusionsOur data suggest that these molecular markers are not helpful to identify patients who would have benefit from neoadjuvant treatment of rectal cancer. Further investigations are necessary to select patients for preoperative treatment based on analysis of the preoperative biopsies.

Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c‐erb‐B2 overexpression of tumors were re‐evaluated. Mann–Whitney U, chi‐squared, Kaplan–Meier, and Fishers exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high‐grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c‐erbB‐2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c‐erb‐B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log‐rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c‐erb‐B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

Diffusion-weighted MRI and MR volumetry in the evaluation of tumor response after preoperative chemoradiotherapy in patients with locally advanced rectal cancer

PURPOSE To determine the diagnostic performance of diffusion-weighted MRI and MR volumetry for the assessment of tumor response after preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIALS AND METHODS Forty-three patients with rectal cancer who underwent preoperative CRT were prospectively examined for the study. This prospective study was approved by our institutional review board. DW- and high resolution T2-weighted imaging were performed before and after therapy. Two different diffusion gradients (b = 0 and b = 600, then separately b = 0 and b = 1000) were applied. The mean tumor volume and mean ADC values were measured before and after therapy. To evaluate the responders and nonresponders to neoadjuvant CRT, two criteria, ypT stage determined in the pathologic examination after treatment and histopathologic tumor regression grade (Ryan), were used as reference standards. The patients with a lower ypT stage than T stage in the first MRI before neoadjuvant CRT were evaluated as the responder group, while the patients with a higher or the same ypT stage relative to the first MRI T stage were evaluated as the nonresponder group. According to Ryan tumor regression grade, grade 1 was evaluated as the responders, whereas grades 2 and 3 were evaluated as the nonresponder group. The percentage ADC increase and percentage tumor volume regression were compared between the responders and nonresponders using two reference standards: T downstaging and tumor regression grade (TRG). RESULTS Before CRT, the mean tumor ADC in the responder group was significantly lower than that in the nonresponder group (p < 0.001). At the end of CRT, the mean percentage of tumor ADC change in the responder group was significantly higher than that in the nonresponder group. The percentage tumor volume regression of the responders was significantly higher than that of the nonresponders (p = 0.001). The cut-off ADC value for discriminating between the responders and nonresponders after treatment was determined to be (b = 600) 1.03 × 10(-3)mm(2)/s and the sensitivity, 71%; specificity, 79%; accuracy, 74%; positive predictive value, 81%; negative predictive value, 68% respectively. The cut-off value for discriminating between the responders and the nonresponders after treatment was determined for b = 1000 as 1.20 × 10(-3)mm(2)/s and the sensitivity, 42%; specificity, 84%; accuracy, 60%; positive predictive value, 77%; negative predictive value, 53%. CONCLUSION The increase in the mean tumor ADC and percentage tumor volume regression in patients with rectal cancer treated with preoperative CRT was correlated with good response. DW MR imaging is a promising non-invasive technique that can help predict and monitor early therapeutic response in patients with rectal cancer who undergo CRT.

Paclitaxel-carboplatin induced radiation recall colitis.

Some chemotherapeutic agents can “recall” the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.

Detection of Bilateral Multifocal Breast Cancer Using Tc-99m Sestamibi Imaging: The Role of Delayed Imaging

PURPOSE Early determination that breast cancer is bilateral and multifocal can change therapy strategy and, subsequently, mortality and morbidity rates. The authors present a case with bilateral, multifocal breast cancer detected only by Tc-99m sestamibi imaging. METHODS Early and delayed Tc-99m sestamibi imaging and dynamic MRI were performed in a patient with a right-sided lesion shown on mammography. RESULTS Although early Tc-99m sestamibi imaging detected bilateral breast cancer foci, both dynamic MRI and mammography missed the lesion in the left breast. Additional lesions seen on delayed Tc-99m sestamibi images of the left breast, which were initially thought to be benign, completely disappeared after concomitant chemotherapy and radiotherapy, suggesting multifocal malignant lesions in the left breast. CONCLUSION This case suggests that Tc-99m sestamibi may be useful for detecting bilateral cancer, and delayed imaging may give additional information regarding the possible multifocal nature of the disease.

Expression of matrix metalloproteinase-2 and survivin in endometrioid and nonendometrioid endometrial cancers and clinicopathologic significance

Objective To determine matrix metalloproteinase-2 and survivin expressions in endometrial cancers, their relation to clinical and histologic parameters and to investigate any difference in the expression of these markers between endometrioid and nonendometrioid cancers. Methods Ninety-five patients with endometrial cancer, were included. Matrix metalloproteinase-2 and survivin expressions were analyzed immunohistochemically from paraffin-embedded tissues by using specific monoclonal antibodies. Results Survivin nuclear expression was higher in endometrioid cancer as compared to nonendometrioid cancer (p=0.040), but there was no difference for cytoplasmic survivin and matrix metalloproteinase-2 expressions between type I and type II carcinomas. Survivin cytoplasmic staining was significantly lower in patients with deep myometrial invasion (p=0.038). Nuclear expression of survivin is decreased in histologic grade 3 tumors compared to grade 1 and 2 tumors (p=0.013), but there is no difference between grade 1 and 2. We did not find any statistically significant difference between survivin or matrix metalloproteinase-2 expressions and survival. Conclusion Survivin and matrix metalloproteinase-2 are present in endometrioid and nonendometrioid cancers. Grade 1 and 2 tumors and carcinomas having myometrial invasion less than 50% have higher survivin expression. These results supports that, survivin may play an important role in early stage tumors and early phases of tumor development. We did not find any association between matrix metalloproteinase-2 expression and classical prognostic factors in endometrial cancer and both proteins were not associated with survival.

A pilot study for human tumor/DNA banking: returned more questions than answers

A pilot study was performed for setting up the Dokuz Eylül University Breast Tumor DNA Bank (DEUBTB) to facilitate the sharing of tumor DNA/RNA samples and related data from cases collected by collaborators specializing in the breast cancer diseases between 2004 and 2006. The pilot study aimed to provide answers for certain questions on: (1) ethical concerns (informing the volunteer for donating specimen, anonymizing the sample information, procedure on sample request), (2) obtaining and processing samples (technical issues, flowchart), (3) storing samples and their products (storing forms and conditions), (4) clinical database (which clinical data to store), (5) management organization (quality and quantity of personnel, flowchart for management relations), (6) financial issues (establishment and maintenance costs). When the bank had 64 samples, even though it is quite ready to supply samples for a research project, it revealed many questions on details that may be answered in more than one way, pointing that all biobanks need to be controlled by a higher degree of management party which develops and offers quality standards for these establishments.

The value of liver-based standardized uptake value and other quantitative 18F-FDG PET-CT parameters in neoadjuvant therapy response in patients with locally advanced rectal cancer: correlation with histopathology.

AimWe aimed to investigate the value of PET-CT in therapy response and the correlation of quantitative PET parameters with histopathologic results in patients with locally advanced rectal cancer (LARC) before and after neoadjuvant chemoradiotherapy. We also analyzed the correlation of PET-CT parameters between Ki-67 and glucose transporter 1 (GLUT1). Patients and methodsA total of 29 patients diagnosed with LARC who had undergone a biopsy between 2009 and 2012 were included in our study. Quantitative PET parameters [standardized uptake value (SUV)max−mean, lean body mass SUVmax−mean, tumor/liver SUV, retention index , and [INCREMENT]SUVmax] were measured before and after therapy using PET-CT. Tumor regression grade (TRG) was evaluated according to Wheeler’s classification. Patients in grade 1 were considered responders, whereas patients at grades 2 and 3 were considered nonresponders. Immunohistochemical staining with Ki-67 and GLUT1 was performed on biopsy and surgical specimens. The correlation between staining ratios and SUV was also investigated. ResultsSUV parameters were significantly decreased after therapy (P<0.001). Twelve (41%) patients were at TRG1, 10 (35%) were at TRG2, and seven (24%) were at TRG3. A cutoff SUVmax of 5.05 to discriminate between responders and nonresponders after treatment revealed a sensitivity of 57%, specificity of 73%, negative predictive value of 65%, positive predictive value of 67%, and accuracy of 66%. Using a cutoff of 3.55 for the SUVmean (standardized measurement of SUV with 1.2-cm-diameter region of interest) revealed a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 67, 76, 67, 76, and 72%, respectively. For a cutoff of 1.95 for the tumor SUVmean/liver SUVmean, these diagnostic values after therapy were 73, 78, 82, 67, and 76%, respectively. We found a moderate correlation between liver-based SUVmax (r=−0.35, P=0.019) and SUVmean (r=−0.31, P=0.036) with GLUT1 after therapy. Quantitative PET parameters and retention index were moderately correlated with Ki-67. ConclusionPET-CT is a useful method for assessing the response to neoadjuvant chemoradiotherapy in patients with LARC. The most significant parameter for assessing treatment response using SUV parameters is the tumor/liver ratio.

Post-mastectomy Adjuvant Radiotherapy (PMRT)

Mastectomy can remove any detectable macroscopic disease, but some tumor foci might remain in the locoregional tissue (i.e., chest wall or lymph nodes), that could lead the locoregional recurrence (LRR) of the disease. Post-mastectomy adjuvant radiotherapy (PMRT) has potential to eliminate such microscopic disease. The risk of LRR after mastectomy is 3–46 %, depending on the stage of the disease and prognostic factors. PMRT has been recommended for patients with ≥4 positive axillary lymph nodes but not given for most women with node-negative disease. Patients with one to three positive axillary lymph nodes constitute a gray zone. PMRT indications and side effects will be discussed in this chapter.