Marisa D. Santos

Tumor regression grades: can they influence rectal cancer therapy decision tree?

Background. Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC). Materials and Methods. We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard tumor regression grades (TRG). We compared patients with good response (Mandard TRG1 or TRG2) versus patients with bad response (Mandard TRG3, TRG4, or TRG5). Outcomes evaluated were 5-year overall survival (OS), disease-free survival (DFS), local, distant and mixed recurrence. Results. Mean age was 64.2 years, and median followup was 56 months. No statistically significant survival difference was found when comparing patients with Mandard TRG1 versus Mandard TRG2 (p = .77). Mandard good responders (TRG1 + 2) have significantly better OS and DFS than Mandard bad responders (TRG3 + 4 + 5) (OS p = .013; DFS p = .007). Conclusions. Mandard good responders had a favorable prognosis. Tumor response (TRG) to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with LARC.

Predictive clinical model of tumor response after chemoradiation in rectal cancer

Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: “good responders” (Mandard TRG1-2) and “poor responders” (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 (IL10) gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in IL10 gene maintain predictive value, allowing a clinical model design. Conclusion: It seems possible to use pretreatment expression of blood and tissue biomarkers, and build a model of tumor response prediction to neoadjuvant chemoradiation in rectal cancer.

Mucinous Adenocarcinoma Arising in Chronic Perianal Fistula: Good Results with Neoadjuvant Chemoradiotherapy Followed by Surgery

Chronic perianal fistulas are a common clinical condition. However, their evolution to adenocarcinoma is rare. We report the case of a 48-year-old man with perianal chronic fistulas, who developed two perianal ulcerated lesions near the external orifices of the fistulas, which extended proximally as a pararectal tumor. No intestinal lesion was seen at endoscopic examination. Histopathological biopsy indicated mucinous adenocarcinoma. Staging was performed by pelvic magnetic resonance imaging (MRI) and thoracoabdominal CT scan. The patient underwent a laparoscopic colostomy followed by neoadjuvant chemoradiotherapy and then laparoscopic abdominoperineal resection followed by adjuvant therapy. We have seen a favorable outcome with no recurrence at 3 years of follow-up.

Primary intestinal Hodgkin's lymphoma associated with Crohn's disease

The authors present the case of a 37-years-old man with pancolic Crohn’s disease (CD) diagnosed 20 years ago, characterized by a penetrating behavior with need for surgery (segmental colon resection) for a colovesical fistula. Due to a corticodependent evolution, the patient has been in treatment with azathioprine for 8 years, with only partial clinical response, reason why he started infliximab (treatment continued for 3 years). An acute exacerbation prompted a colonoscopy that revealed severe inflammatory activity within the distal sigmoid and rectum with no changes in the remaining colonic and ileal mucosa (Fig. 1). Biopsies revealed infiltration of the mucosa by classic Hodgkin’s lymphoma (Fig. 2), with positivity for Epstein-Barr virus (Fig. 3) and severe inflammatory activity. Computed tomography (Fig. 4) and bone marrow aspirate excluded extra intestinal lymphoproliferative disease (LD). After multidisciplinary consultation, the patient underwent total colectomy plus abdominoperineal resection of rectum (Fig. 5) with permanent ileostomy, the main indication was based on the lack of response to the medical therapy for CD. Since the resected specimen had no evidence of involvement of the isolated lymph nodes, it was decided not to start any adjunctive therapy. Primary intestinal Hodgkin’s lymphoma is very rare presenting an incidence of less than 0.5 % (1). Its association with CD is even rarer, with only sporadic cases described in literature (2). There are still doubts whether the pathogenesis of the increased risk of LD in patients with CD correlates with the inflammatory disease activity or with the immunosuppressive treatment (3,4). The identification of Epstein-Barr virus infection in patients with Hodgkin’s lymphoma is often reported in the described cases, suggesting that this agent might be implicated in the pathogenesis of the LD (5). Primary intestinal Hodgkin’s lymphoma associated with Crohns disease

Colon carcinoma staging by endoscopic ultrasonography miniprobes

Background and Objectives: Due to the increasing use of endoscopic techniques for colon cancer resection, pretreatment locoregional staging may gain critical interest. The use of endoscopic ultrasonography (EUS) miniprobes in this context has been seldom reported. Our aim was to determine the accuracy of EUS miniprobes for colon cancer staging. Materials and Methods: Forty patients with colon cancer (2 in the cecum, 9 in the ascending colon, 5 in the transverse colon, 5 in the descending colon, and 19 in the sigmoid colon) were submitted to staging using 12 MHz EUS miniprobes. EUS and the anatomopathological results were compared with regard to the T and N stages. It was assessed if the location, longitudinal extension, or circumferential extension of the tumor had any influence on the accuracy in EUS staging. Results: Tumor staging was feasible in 39 (98%) patients except in one case with a stenosing tumor (out of 6). Globally, T stage was accurately determined in 88% of the cases. In the assessment of the presence or absence of lymph node metastasis, miniprobes presented an accuracy of 82% with a sensitivity of 67%. These results were neither affected by the location nor by the longitudinal or circumferential extension of the tumor. Conclusions: EUS miniprobes may play an important role in assessing T and N stages in colon cancer and may represent an incentive to the research of new therapeutic areas for this disease.

Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data

Background. Neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery in locally advanced rectal cancer (LARC) improves pelvic disease control. Survival improvement is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. Potential predictive factors for Mandard response are analyzed. Materials and Methods. 167 patients with LARC were treated with nCRT and curative surgery. Tumor biopsies and surgical specimens were reviewed and analyzed regarding mitotic count, necrosis, desmoplastic reaction, and inflammatory infiltration grade. Surgical specimens were classified according to Mandard TRG. The patients were divided as “good responders” (Mandard TRG1-2) and “bad responders” (Mandard TRG3-5). According to results from our previous data, good responders have better prognosis than bad responders. We examined predictive factors for Mandard response and performed statistical analysis. Results. In univariate analysis, distance from anal verge and ten other postoperative variables related with nCRT tumor response had predictive value for Mandard response. In multivariable analysis only mitotic count, necrosis, and differentiation grade in surgical specimen had predictive value. Conclusions. There is a lack of clinical and pathological preoperative variables able to predict Mandard response. Only postoperative pathological parameters related with nCRT response have predictive value.

Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial Treatment.

Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon. The patient underwent en bloc resection of tumor with jejunum and transverse bowel segment and received adjuvant chemotherapy with carboplatin and paclitaxel. Twenty months later, she was alive without disease recurrence.

Endoscopic ultrasound, GIST, and ovarian cancer

Dear Editor: Ovarian carcinoma is the most lethal gynecological cancer [1], and the endometrioid type accounts for 7–20 % of all cases [2]. The gastrointestinal stromal tumor (GIST) may mimic ovarian tumors, as reported previously by other authors [3, 4]. We present a case report of a GIST mimicking an ovarian carcinoma. A 67-year-old female underwent a colonoscopy for colon cancer screening. It showed a submucosal lesion, covered with normal appearance mucosa. An endoscopic ultrasonography showed between 4 and 14 cm from the anal margin, with the greatest transverse diameter of 42.5 by 32.7 mm, a heterogeneous lesion, hypoechoic, with slightly irregular borders, originated in the muscular layer; the luminal board counter presented itself closely adjacent to an ovary, where it was identified as a cystic lesion, and a loss of the cleavage plane. We identified a perilesional, oval, hypoechoic adenopathy, with a diameter of 11 by 5.2 mm. We suspected of a GIST or an extraintestinal tumor involving the rectum. An endoscopic ultrasonography (EUS) with fine needle (19G) aspiration with collection of sampling for histology and cytology revealed highgrade undifferentiated neoplasm suggestive of ovarian carcinoma, CD117 negative. She underwent a surgery that confirmed an endometrioid ovarian carcinoma, invading the rectum. Subsequently, the patient has started chemotherapy with carboplatin and paclitaxel and is still on treatment. Besides, there have been reported a case of primary epithelial ovarian carcinoma with gastric metastasis mimicking GIST, but to our best knowledge, there have not been reported an ovarian cancer mimicking a rectal GIST. We emphasize the high accuracy of EUS in the correct characterization of the lesion and its anatomical relations and the possibility of collecting a sample that confirms the diagnosis, allowing a more guided surgery.

17-Week Delay Surgery after Chemoradiation in Rectal Cancer with Complete Pathological Response.

Neoadjuvant chemoradiation (CRT) followed by curative surgery still remains the standard of care for locally advanced rectal cancer (LARC). The main purpose of this multimodal treatment is to achieve a complete pathological tumor response (ypCR), with better survival. The surgery delay after CRT completion seems to increase tumor response and ypCR rate. Usually, time intervals range from 8 to 12 weeks, but the maximum tumor regression may not be seen in rectal adenocarcinomas until several months after CRT. About this issue, we report a case of a 52-year-old man with LARC treated with neoadjuvant CRT who developed, one month after RT completion, an acute myocardial infarction. The need to increase the interval between CRT and surgery for 17 weeks allowed a curative surgery without morbidity and an unexpected complete tumor response in the resected specimen (given the parameters presented in pelvic magnetic resonance imaging (MRI) performed 11 weeks after radiotherapy completion).