Primary Rectal Adenocarcinoma Research Articles

Preoperative chemoradiotherapy changes the size criterion for predicting lateral lymph node metastasis in lower rectal cancer.

The purpose of this study was to identify the size criteria of lateral lymph node metastasis in lower rectal cancer both in patients who underwent preoperative CRT and those who did not. This study enrolled 150 patients who underwent resection for primary lower rectal adenocarcinoma with lateral lymph node dissection between 2013 and 2015. Patients were divided into two groups: the CRT group, treated with preoperative chemoradiotherapy before surgery, and the non-CRT group, treated with surgery alone. The short-axis diameter of each dissected lateral lymph node was measured. Receiver-operating characteristic curves were generated to reveal the optimal cutoff values for determining lateral lymph node metastasis in both groups. In the non-CRT group (n=131), the ROC curve demonstrated that the optimal cutoff value for determining metastasis was 6.0mm, with a sensitivity of 78.5% and specificity of 82.9%, and the AUC was 0.845. In comparison, in the CRT group (n=19), the optimal cutoff value was 5.0mm, with a sensitivity of 71.4% and specificity of 85.3% and an AUC of 0.836. The cutoff size for determining lateral lymph node metastasis was smaller in the CRT group than in the non-CRT group.

Differences in plasminogen activation in primary rectal adenocarcinoma with and without liver metastasis.

e15111 Background: Plasminogen activators play a key role in the cascade fibrinolytic system as they catalyze plasmin formation from plasminogen (PG). Plasminogen activators together with plasmin are directly or indirectly involved in tumor growth. The purpose of the study was to compare the plasminogen activation system in primary adenocarcinomas (РА) of the rectum (R) with and without liver metastases (LM). Methods: Tissues of tumors (РА, st. III, G2, 38-74 years) and their perifocal zone (PZ) with LM (T2-3NхM1, n = 24) and without them (T2-3N0M0, n = 32) were studied by ELISA. Results: The studied parameters did not differ in apparently intact R tissues in the resection line (RL) with and without LM. Plasmin-α2-antiplasmin complex (PAP) was 1.4 times higher in PA with LM than without LM (p < 0.05). Prourokinase and urokinase levels (uPA-Ag and uPA-act) were 12.4 and 3.7 higher than in RL. uPA-Ag and uPA-act in PA+LM were higher than without LM by 1.4 and 1.6 times. PG levels and α2-macroglobulin (α2M) activity in PA+LM were lower by 1.5 and 2.7 times than in PA without LM and lower than in RL (p < 0.01). All studied parameters, except α2M, in PA+LM were activated more than in PA without LM. Low α2M content supposed realization of effects of uPA and plasmin in insufficient inhibitory control. Most parameters in PZ+LM were between the levels in PA and RL being significantly different from both and significantly exceeding the values in PZ of PA without LM. α2М was an exception being 1.8 times lower in PZ of PA+LM than in PZ of PA without LM. The results demonstrated higher uPA and РАР levels in PA and its PZ with LM than without them, with increased PG consumption and decreased α2M activity in these parts of the rectum. Activation of plasminogen system in tissues of PA+LM and in PA without LM was unidirectional. Conclusions: Levels of uPA and PAP, as well as low α2M content in PA and PZ with LM can be used as an indicator of tumor metastatic activity.

A single institution's long-term follow-up of patients with pathological complete response in locally advanced rectal adenocarcinoma following neoadjuvant chemoradiotherapy.

This paper aimed to study the long term follow-up of patients with primary rectal adenocarcinoma receiving neoadjuvant chemoradiotherapy who obtained a pathological complete response (pCR) and identify factors predicting complete response. Retrospective review of notes, histology, pre-operative full blood count and imaging of patients with primary rectal adenocarcinoma diagnosed in our institute from 2000 to 2012 from a prospectively maintained database were used. SPSS version 22.0 was used for statistical analysis. Three hundred eighty patients diagnosed with primary rectal adenocarcinoma were identified, 277 received neoadjuvant chemoradiotherapy followed by curative resection. Forty-six patients obtained a pCR (ypT0N0) with no local recurrence and two metastatic recurrences on follow-up. Patients with a pCR have a significantly improved overall survival and disease-free survival compared to a non-pCR (150.0 and 136.1 vs 77.5 and 84.7months, p=0.001). On univariate analysis, increased tumour height above anal verge, low lymph node yield, high pre-operative haemoglobin and a low neutrophil-lymphocyte ratio are significant factors identifying a pCR. Multivariable analysis of the above factors confirmed tumour height above anal verge as significant in obtaining a pCR. Patients with rectal adenocarcinoma who develop a pCR following neoadjuvant chemoradiotherapy have improved overall and disease-free survival. We have identified distance from anal verge, low lymph node yield, high pre-operative haemoglobin and low neutrophil-lymphocyte ratio as significant predictors of developing a pCR.

Limited accuracy of DCE-MRI in identification of pathological complete responders after chemoradiotherapy treatment for rectal cancer.

To examine whether post-chemoradiotherapy (CRT) DCE-MRI can identify rectal cancer patients with pathologic complete response (pCR). From a rectal cancer surgery database 2007-2014, 61 consecutive patients that met the following inclusion criteria were selected for analysis: (1) stage II/III primary rectal adenocarcinoma; (2) received CRT; (3) underwent surgery (4); underwent rectal DCE-MRI on a 1.5-T MRI scanner. Two experienced radiologists, in consensus, drew regions of interest (ROI) on the sagittal DCE-MRI image in the tumour bed. These were exported from ImageJ to in-house Matlab code for modelling using the Tofts model. K trans, K ep and v e values were compared to pathological response. Of the 61 initial patients, 37 had data considered adequate for fitting to obtain perfusion parameters. Among the 13 men and 24 women, median age 53years, there were 8 pCR (22%). K trans could not distinguish patients with pCR. For patients with 90% or greater response, mean K trans and K ep values were statistically significant (p = 0.032 and 0.027, respectively). Using a cutoff value of K trans = 0.25min-1, the AUC was 0.71. K trans could be used to identify patients with 90% or more response to chemoradiotherapy for rectal cancer with an AUC of 0.7. • Chemoradiotherapy for rectal cancer causes decreased blood flow and permeability in the tumour bed. • Lower values of blood flow and permeability correlate with good tumour response. • K trans of 0.25min -1 best identifies patients with ≥90% response with AUC 0.71.

Local recurrence after curative resection for rectal carcinoma: The role of surgical resection.

Local recurrence of rectal cancer is difficult to treat, may cause severe and disabling symptoms, and usually has a fatal outcome. The aim of this study was to document the clinical nature of locally recurrent rectal cancer and to determine the effect of surgical resection on long-term survival.A retrospective review was conducted of the prospectively collected medical records of 2485 patients with primary rectal adenocarcinoma who underwent radical resection between September 1994 and December 2008.In total, 147 (5.9%) patients exhibited local recurrence. The most common type of local recurrence was lateral recurrence, whereas anastomotic recurrence was the most common type in patients without preoperative concurrent chemoradiotherapy (CCRT). Tumor location with respect to the anal verge significantly affected the local recurrence rate (P < 0.001), whereas preoperative CCRT did not affect the local recurrence rate (P = 0.433). Predictive factors for surgical resection of recurrent rectal cancer included less advanced tumor stage (P = 0.017, RR = 3.840, 95% CI = 1.271-11.597), axial recurrence (P < 0.001, RR = 5.772, 95% CI = 2.281-14.609), and isolated local recurrence (P = 0.006, RR = 8.679, 95% CI = 1.846-40.815). Overall survival after diagnosis of local recurrence was negatively influenced by advanced pathologic tumor stage (P = 0.040, RR = 1.867, 95% CI = 1.028-3.389), positive CRM (P = 0.001, RR = 12.939, 95% CI = 2.906-57.604), combined distant metastases (P = 0.001, RR = 2.086, 95% CI = 1.352-3.218), and nonsurgical resection of recurrent tumor (P < 0.001, RR = 4.865, 95% CI = 2.586-9.153).In conclusion, the clinical outcomes of local recurrence after curative resection of rectal cancer are diverse. Surgical resection of locally recurrent rectal cancer should be considered as an initial treatment, especially in patients with less advanced tumors and axial recurrence.

REOX: Effectiveness evaluation of re-exposure to oxaliplatin in patients with metastatic colorectal cancer.

764 Background: Colorectal cancer has high incidence and mortality rates. Treatment of metastatic colorectal adenocarcinoma has evolved since the approval of irinotecan, oxaliplatin and monoclonal antibodies with survival surpassing 30 months in contemporary trials. Nevertheless there is paucity of effective options after failure of these protocols. Thus re-exposure to previously used drugs became a treatment strategy. We aimed to evaluate the efficacy of retreatment with oxaliplatin in mCRC and its correlation with clinicopathological features. Methods: We retrospectively analyzed 83 patients with mCRC who underwent REOX treated at a single cancer center in Brazil. REOX was defined as a second trial of an oxaliplatin containing regimen after a previous failure. Primary endpoint was time to treatment failure (TTF) after REOX. Results: Median age of our cohort was 53.5y. Female/Male: 51.8%/48.2%. Primary colon was found in 67.5% while 32.5% had primary rectal adenocarcinoma. KRAS status was wild type in 57.8% and mutated in 39.8%. Exclusive hepatic metastasis was found in 19.3%. Median follow-up after REOX was 31m. Main chemotherapy regimen was mFOLFOX6 (84.3%). Bevacizumab and Cetuximab were used in 42.2% and 6% respectively. Most patients underwent REOX in third and fourth lines, 48.2% and 25.3% respectively. Median time to treatment failure (mTTF) after REOX was 6.04m. Overall survival was 10.04m. Disease control (CR + PR + SD) was observed in 56.6%, while 42.2% had progressive disease (PD). Reasons for interruption were as follows: PD (68.7%), toxicity (19.3%) and metastasectomy (2.4%). Patients who attained disease control had better OS (14.5m) compared with patients who had PD (14.5m versus 6.24m, p &lt; 0.0001). Patients with exclusive hepatic metastasis had a trend to a better TTF compared to other metastasis sites (8.96m X 6.01m, p = 0.2). Regarding KRAS status, there was no difference in mTTF (wt 6.68m, mut 6.04m, p = 0.14). Conclusions: In the setting of pretreated mCRC patients where there are few options available, REOX remains an effective treatment, with mTTF of 6.04m in our cohort. This could be related to progression of cell clones sensitive to the drug after a time lapse since the previous exposure.

Anatomical hepatectomy for liver metastasis from rectal adenocarcinoma presenting with intrabiliary extension: a case report.

Liver metastases from colorectal carcinoma commonly form nodular lesions in the liver parenchyma. We report a case of liver metastasis from rectal adenocarcinoma that extended predominantly into the bile duct. A 62-year-old Japanese man underwent low anterior resection for rectal adenocarcinoma 9 years ago. Approximately 3 years later, he underwent radiofrequency ablation therapy for a metastatic liver tumor. Nine years after surgery, a tumor in liver segment III exhibiting intrabiliary extension was discovered; it was unclear if this was a metastatic liver tumor or intrahepatic cholangiocarcinoma. Accordingly, we performed a left hepatectomy with lymph node dissection. The tumor was negative for cytokeratins 7 and 20, and was histologically similar to the primary rectal adenocarcinoma; it was diagnosed as rectal carcinoma metastasis. The patient has survived for 3 years after the hepatic surgery, for 9 years after radiofrequency ablation therapy, and for 12 years after the primary surgery. This case shows that liver metastasis from colorectal carcinoma can present as a predominantly intrabiliary growth that mimics intrahepatic cholangiocarcinoma on imaging. Moreover, our case provides evidence for the superiority of anatomical hepatectomy over partial hepatectomy for metastatic liver tumors with intrabiliary growth arising from rectal adenocarcinomas.

Next-Generation Sequencing of Matched Primary and Metastatic Rectal Adenocarcinomas Demonstrates Minimal Mutation Gain and Concordance to Colonic Adenocarcinomas.

-Colorectal carcinoma is the third most common cause of cancer death in males and females in the United States. Rectal adenocarcinoma can have distinct therapeutic and surgical management from colonic adenocarcinoma owing to its location and anatomic considerations. -To determine the oncologic driver mutations and better understand the molecular pathogenesis of rectal adenocarcinoma in relation to colon adenocarcinoma. -Next-generation sequencing was performed on 20 cases of primary rectal adenocarcinoma with a paired lymph node or solid organ metastasis by using an amplicon-based assay of more than 2800 Catalogue of Somatic Mutations in Cancer (COSMIC)-identified somatic mutations. -Next-generation sequencing data were obtained on both the primary tumor and metastasis from 16 patients. Most rectal adenocarcinoma cases demonstrated identical mutations in the primary tumor and metastasis (13 of 16, 81%). The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7, GNAS, FGFR3, BRAF, NRAS, PIK3CA, and SMAD4. -The somatic mutations identified in our rectal adenocarcinoma cohort showed a strong correlation to those previously characterized in colonic adenocarcinoma. In addition, most rectal adenocarcinomas harbored identical somatic mutations in both the primary tumor and metastasis. These findings demonstrate evidence that rectal adenocarcinoma follows a similar molecular pathogenesis as colonic adenocarcinoma and that sampling either the primary or metastatic lesion is valid for initial evaluation of somatic mutations and selection of possible targeted therapy.

Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer

The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for 5-year OS (P = 0.106). This study confirmed that HER-2 was expressed in a part of patients with rectal cancers and might be used as a negative predictor. The results may support the trials to assess the efficacy of trastuzumab in treating HER-2 positive rectal cancer patients.

Primary Rectal Adenocarcinoma Metastasizing to Bilateral Breasts - a Rare Case Demonstrated by (18) F-FDG PET/CT.

Primary Rectal Adenocarcinoma Metastasizing to Bilateral Breasts - a Rare Case Demonstrated by (18) F-FDG PET/CT.

Primary Rectal Lymphoma Responding to Chemotherapy as Sole Treatment: A Case Report

Primary rectal lymphoma is a rare disease. Unlike other primary gastrointestinal lymphomas (stomach, small intestine, and colon) the behavior of this kind of lymphoma, as well as its management, is not fully understood. Most of the literature available, despite being limited, has recommended different modalities in treatment and has varying outcomes. Hence there is still no available consensus guidelines. We present a case of a 52-year-old woman with constipation and hematochezia. Physical examination was essentially normal except for a palpable rectal mass. There was no lymphadenopathy appreciated. The initial impression was a primary rectal adenocarcinoma but work-up done were unremarkable including CEA. Histopathology with immunostaining revealed a diagnosis of diffuse large B-cell lymphoma (DLBCL) of the rectum, Lugano stage IIE. Despite unofficial recommendations of surgical management for a resectable, low stage lesion, the patient underwent chemotherapy only (R-CHOPS) for 6 cycles resulting to both clinical and endoscopic response. Despite our present success with our patient, we cannot recommend based on a single case. Our case can be included in the very few cases of primary rectal lymphoma that can be accumulated altogether and subject to a larger scientific study that will lead to a better understanding of this rare disease.

Complications urinaires des exentérations pelviennes pour cancer du rectum avec envahissement urinaire

Pelvic exenteration for rectal cancer is indicated in locally advanced rectal tumors or pelvic recurrence invading adjacent organs. The oncologic goal being a complete R0 resection. Our aim was to study the urinary complications resulting from pelvic exenterations with urinary reconstruction in order to obtain a complete local control of the disease. Between April 2004 and June 2013, 42 patients who underwent pelvic exenteration for primary or recurrent rectal adenocarcinoma with urinary tract reconstruction were included. The urinary reconstruction was performed based on preoperative imaging and intraoperative findings. We studied early (within 30 postoperative days) and late urinary morbidity, as well as postoperative carcinologic control. Forty-two exenterations were performed for primary rectal cancer (n=15) or pelvic recurrence (n=27). R0 complete resection was achieved in 64% of patients. The resection was incomplete (R1) on the urinary tract in 9.5% of patients. The urinary reconstruction methods used were: 31 transileal ureterostomies after total exenteration (bricker procedure), 6 ureteral reimplantations on psoic bladder, 2 ureteroileoplasties, 2 partial cystectomies and one ureteral resection with simple ligation. The median follow-up was 20 months. The perioperative mortality was 2.3% (n=1) and postoperative overall morbidity was 64%. Early and late urinary morbidity was 23.8% and 21.4% respectively. Six patients developed major urinary complications (≥ Clavien IIIb). Pelvic exenteration with urinary resection resulted in our experience, in a local disease control of 64% (including a 90.5% for the urinary tract) at the price of an acceptable early specific morbidity and a low mortality that seems to justify an aggressive surgical approach.

Synchronous collision neuroendocrine tumor and rectal adenocarcinoma: a case report.

Collision tumors are thought to arise from the accidental meeting of two independent tumors. Adenocarcinoma is the most common malignant rectal tumor, while neuroendocrine tumor (NET) is relatively rare. Due to the endoscopy and reporting, the overall incidence of NETs was increasing recently but still less than 1 per 100,000. This means that a combination of an adenocarcinoma and NET is a very rare finding and an actual collision of these tumors even more so. We report here a highly unusual case of a 64-year-old woman who had collision tumors composed of a primary rectal adenocarcinoma and NET showing a "side by side" pattern. Resection margins are free of both the tumors. The postoperative course was uneventful. The patient underwent a protocol CT scan at 3months after surgery, which did not show any recurrence. Both the malignant adenocarcinoma and the NET would make a great influence in the rest lifetime and a follow up will be continued, although the CT did not show any recurrence until now. To the best of our knowledge, this is the first reported case of such an occurrence.

Dynamic magnetic resonance imaging evaluation of pelvic reconstruction with porcine dermal collagen mesh following extra-levator abdominoperineal excision for primary rectal cancer.

Extra-levator abdominoperineal excision for rectal cancer includes resection of the levator ani muscle and therefore makes pelvic reconstruction advisable. The aim of our study was to evaluate morphologic and functional long-term results of pelvic floor augmentation with porcine dermal collagen mesh by dynamic magnetic resonance imaging and clinical examination. Twenty consecutive patients underwent perineal reconstruction with porcine dermal collagen mesh following extra-levator abdominoperineal excision for primary rectal adenocarcinoma with curative intent between 2009 and 2012. Patient perioperative and postoperative data were collected prospectively. There were one cancer-related and two noncancer-related deaths in the follow-up period, and another three patients refused the dynamic magnetic resonance imaging. Fourteen patients were included in the study. The median time period from surgery to dynamic magnetic resonance imaging and clinical examination was 31 months (range 19-56). Wound infections were observed in 43% (6 of 14) of these patients in the postoperative period, but no mesh had to be removed. No focal mesh defect, no damage on the suture line, and no perineal hernia were detected on dynamic magnetic resonance imaging. Clinical examination revealed no pathological findings in any patient. The implantation of a porcine dermal collagen mesh is an effective and reliable option for pelvic floor reconstruction after extra-levator abdominoperineal excision. Despite a high incidence of primary wound infections, the healing rate was satisfactory, no mesh had to be removed, and long-term stability could be achieved.

Tumor neoangiogenesis detection by confocal laser endomicroscopy and anti-CD105 antibody: Pilot study.

To evaluate neoangiogenesis in patients with colon cancer by two fluorescently labeled antibodies on fresh biopsy samples imaged with confocal laser endomicroscopy (CLE). CLE is an imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution. An important question in validating tumor angiogenesis is what proportion of the tumor vascular network is represented by pre-existing parent tissue vessels and newly formed vessels. CD105 (endoglin) represents a proliferation-associated endothelial cell adhesion molecule. In contrast to pan-endothelial markers, such as CD31, CD105 is preferentially expressed in activated endothelial cells that participate in neovascularization. Thus, we evaluated CD105 and CD31 expression from samples of ten patients with primary rectal adenocarcinoma, using a dedicated endomicroscopy system. A imaging software was used to obtain the Z projection of the confocal serial images from each biopsy sample previously combined into stacks. Vascular density and vessel diameters were measured within two 50 μm x 475 μm rectangular regions of interest centered in the middle of each image in the horizontal and vertical direction. The results were averaged over all the patients and were expressed as the mean ± SE. The use of an anti-CD105 antibody was found to be suitable for the detection of blood vessels in colon cancer. Whereas anti-CD31 antibodies stained blood vessels in both normal and pathologic colon equally, CD105 expression was observed primarily in malignant lesions, with little or no expression in the vessels of the normal mucosa (244.21 ± 130.7 vessels/mm(3) in only four patients). The average diameter of anti-CD105 stained vessels was 10.97 ± 0.6 μm in tumor tissue, and the vessel density was 2787.40 ± 134.8 vessels/mm(3). When using the anti-CD31 antibody, the average diameter of vessels in the normal colon tissue was 7.67 ± 0.5 μm and the vessel density was 3191.60 ± 387.8 vessels/mm(3), while in the tumors we obtained an average diameter of 10.88 ± 0.8 μm and a vessel density of 4707.30 ± 448.85 vessels/mm(3). Thus, there were more vessels stained with CD31 than CD105 (P < 0.05). The average vessel diameter was similar for both CD31 and CD105 staining. A qualitative comparison between CLE vs immunohistochemistry lead to similar results. Specific imaging and quantification of tumor microvessels are feasible in human rectal cancer using CLE examination and CD105 immunostaining of fresh tissue samples.

American Joint Committee on Cancer and College of American Pathologists regression grade: a new prognostic factor in rectal cancer.

The American Joint Committee on Cancer and the College of American Pathologists provide guidelines for reporting pathologic response to neoadjuvant treatment of rectal cancer. The clinical relevance of these tumor regression grading guidelines is undefined. This study evaluates the prognostic significance of the American Joint Committee on Cancer/College of American Pathologists regression grading. This is a retrospective cohort study based on data from a prospectively maintained colorectal cancer database. The cohorts were defined by American Joint Committee on Cancer/College of American Pathologists tumor regression grade. This study was performed at a single tertiary referral center. Five hundred thirty-eight patients with primary rectal adenocarcinoma who underwent neoadjuvant therapy between 1992 and 2012 were identified. The primary outcome measures were overall and disease-free survival, cancer-specific mortality, and cumulative recurrence rate. Five hundred thirty-eight patients were included, 105 of whom (19.5%) were American Joint Committee on Cancer/College of American Pathologists grade 0, 153 patients (28.4%) were grade 1, 181 patients (33.6%) were grade 2, and 99 (18.4%) were grade 3. Kaplan-Meier analysis revealed that American Joint Committee on Cancer/College of American Pathologists grade was associated with significant differences in overall survival (p < 0.001), disease-free survival (p < 0.001), and cumulative recurrence (p < 0.001). No local recurrences were observed in American Joint Committee on Cancer/College of American Pathologists grade 0 patients. Five-year overall survival rates were 89%, 74%, 63%, and 40% (p < 0.001); 5-year disease-free survival rates were 85%, 64%, 54%, and 33% (p < 0.001); and 5-year recurrence rates were 7%, 18%, 25%, and 33% (p <0.001) for American Joint Committee on Cancer/College of American Pathologists grades 0, 1, 2, and 3. After adjusting for significant covariates, including pathologic stage, American Joint Committee on Cancer/College of American Pathologists grade remained an independent predictor of overall survival (p < 0.001), disease-free survival (p < 0.001), and cumulative recurrence (p < 0.001) in Cox regression analyses. This was a retrospective study. There was a low local recurrence rate in our population, limiting the sensitivity of recurrence analyses. This is the first study to delineate American Joint Committee on Cancer/College of American Pathologists regression grade as an independent oncologic prognostic factor. This information can be used in discussions with patients who have rectal cancer.

Sphincter preservation rates after radical resection for rectal cancer in the United States veteran population: opportunity for improvement in early disease.

Sphincter preservation (SP) is an important goal of rectal cancer surgery. We hypothesized that SP rates among veteran patients have increased and are comparable to national rates, and that a subset of patients with early disease still undergo non-SP procedures. Patients with nonmetastatic primary rectal adenocarcinoma who underwent curative-intent rectal resection were identified from the Veterans Affairs Central Cancer Registry (VACCR) database (1995-2010). SP trends over time were described and compared to the Surveillance, Epidemiology, and End-Results (SEER) population. Subset analysis was performed in patients with nonirradiated, pathologic stage 0-I rectal cancers, a population that may qualify for novel SP strategies. Of 5,145 study patients, 3,509 (68 %) underwent SP surgery. The VACCR SP rate increased from 59.9 % in 1995-1999 to 79.3 % in 2005-2010, when it exceeded that of SEER (76.9 %, p = 0.023). On multivariate analysis, recent time period was independently associated with higher likelihood of SP (odds ratio [OR] 2.64, p < 0.001). Preoperative radiotherapy (OR 0.51, p < 0.001) and higher pathologic stage (OR 0.37, stage III, p < 0.001) were negative predictors. In patients with nonirradiated pathologic stage 0-I cancers, SP rates also increased, but 25 % of these patients underwent non-SP procedures. Within this subset, patients with clinical stage 0 and I disease still had significant rates of abdominoperineal resection (7.7 and 17.0 %, respectively). SP rates among veterans have increased and surpass national rates. However, an unacceptable proportion of patients with stage 0-I rectal cancers still undergo non-SP procedures. Multimodal treatment with local excision may further improve SP rates in this subset of patients.

Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiotherapy for rectal cancer?

Numerous molecular markers have been investigated as potential predictors of tumor responses to preoperative chemoradiotherapy (preCRT) for rectal cancer. To develop a system in which biomarkers are used to predict the likelihood of a pathologic complete response (pCR) to preCRT. This is a retrospective analysis of tumor specimens collected prior to preCRT from 81 patients who underwent curative resection for primary rectal adenocarcinoma between June 2008 and February 2012. Using tissue microarrays and immunohistochemistry, expression levels of twelve candidate biomarkers (p53, p21, Bcl2, Bax, EGFR, Cox-2, MLH-1, MSH-2, Ku70, VEGF, TS, Ki-67) were evaluated in paraffin-embedded tumor samples collected before preCRT. The correlation between biomarker expression levels and the pathologic response to preCRT was assessed based on histopathological staging (pTNM) and tumor regression grade (TRG). Expression levels of 4 biomarkers (p53, VEGF, p21, Ki67) correlated with pCR. Patients showing low expression of p53 and/or high expression of VEGF, p21, and Ki67 exhibited a significantly greater pCR rate. A scoring system devised so that one point was given for each biomarker whose expression level correlated with pCR (score range: 0-4) showed that 1 of 26 patients with scores of 0 to 1 achieved pCR, whereas 26 of 55 patients with scores of 2 to 4 achieved pCR (3.8% vs. 47.3%, p < 0.001). For prediction of pCR, the scoring system showed 96.3% sensitivity, 46.3% specificity, a 47.3% positive predictive value, and a 96.2% negative predictive value. Immunohistochemistry has limitations related to reproducibility and the ability to provide quantitative information. In addition, this study lacks test and validation sets. Expression levels of 4 biomarkers correlated with pCR after preCRT for rectal cancer. A scoring system based on levels of biomarker expression showed good sensitivity and negative predictive value for pCR.

Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer

BackgroundComplete pathological response occurs in 10–20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis.Case presentationA 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence.ConclusionThe presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy alone in patients with stages II-III rectal adenocarcinoma (without metastasis).

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the primary staging of rectal cancer

BackgroundIn this study we aimed to determine the need for 18F-flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the preoperative staging of rectal carcinoma in our large patient group according to level and location of tumor.MethodTotally, 97 patients diagnosed with primary rectal adenocarcinoma between May 2009 and July 2011 were included in the study. Preoperative staging was performed by evaluating contrast-enhanced thoracic, abdominal, and pelvic computed tomographies. After staging by conventional methods, all patients underwent an 18F-FDG PET/CT. In all cases, the relationship between 18F-FDG uptake and gender, tumor height at the anal canal, localization in the rectal wall, plasma carcinoembryonic antigen levels, histopathological tumor type, and tumor stage were examined.ResultsWhile the ceCT was normal in 4 (4%) patients, it was positive for the rectum in 93 (95%), pelvic lymph nodes in 22 (22%), and distant metastases in 14 (14%) (liver (8), lung (8), bone (2), distant lymph nodes (6), and uterus (1)). Using computed tomography, disease stages were determined as stage 0, 1, 2, 3, and 4 in 4, 8, 48, 23, and 14 patients, respectively; 18F-FDG PET/CT was normal in two (2%) patients. The mean SUVmax of FDG-positive rectal tumors was calculated as 17.31 ± 9.37. Additionally, 18F-FDG uptake was seen in pelvic lymph nodes in 15 (15%) patients and in distant organs in 24 (24%) patients (liver (9), lung (12), bone (5), distant lymph nodes (11), uterus (1), and sigmoid colon (1)). According to an 18F-FDG PET/CT, 2, 7, 47, 20, and 21 patients were staged as stage 0, 1, 2, 3, and 4, respectively. In 14 patients (14.4%), the stage of the disease was either changed, and there was a need to make adjustments to the patient’s treatment strategy (n = 10), or the type of operation was changed (n = 4). In seven patients (0.7%), findings from 18F-FDG PET/CT images did not require any changes of the treatment plan.ConclusionF-FDG PET/CT provides new findings in addition to conventional techniques in the staging of primary rectal cancer. These findings could change the patients’ treatment strategies.