Medium Rectum Research Articles

Clinical characteristics and outcomes in patients with early-onset locally advanced rectal cancer.

70 Background: Despite a reduction in both the incidence and mortality of CRC in the elderly population, recent studies have highlighted an increase in the incidence of early-onset CRC (EO-CRC). Clinical and prognostic data in this context are limited and conflicting. The aim of our study was to evaluate the clinical differences and outcomes of patients with early onset locally advanced rectal cancer. Methods: We retrospectively collected data from 305 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was overall survival (OS) while while secondary objectives were overall response rate (ORR) and major TRG. Results: Twenty five (8,2%) pts were EO-RC and 280 (91,8%) were LO-RC. In EO-RC the locations were distributed as follows: 9 (36%) lower rectum, 13 (52%) medium rectum, and 3 (12%) upper rectum. Pathologic responses were as follows: 3 (12%) TRG-0, 6 (24%) TRG-1, 10 (40%) TRG-2, and 6 (24%) TRG-3. While the radiological responses were as follows: 2 (8%) CR, 15 (60%) PR, 7 (28%) SD, and 1 (4%) PD. In LO-RC the locations were: 78 (27,8%) lower rectum, 153 (54,6%) medium rectum, and 49 (17,6%) upper rectum. Pathologic responses were as follows: 29 (10,4%) TRG-0, 60 (21,4%) TRG-1, 159 (56,8%) TRG-2, and 32 (11,4%) TRG-3. Radiological responses were as follows: 25 (8,9%) CR, 155 (61,4%) PR, 64 (22,9%) SD, and 19 (6,8%) PD. The 10 year overall survival was significantly higher in LO-RC patients compared to EO-CRC patients: 92.54% versus 70.83% (p = 0.0005). Conclusions: Compared to LO-RCs, EO-RC patients had more frequent low rectal tumors and higher rates of major pathological responses. Despite this, 10-year OS was found to be inferior in EO-RC. Further studies and insights will be necessary to better understand the biological and clinical characteristics of early-onset tumors.

Probe-Based Confocal Endomicroscopy May Improve the Diagnosis of Clinical Complete Response After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Neoplasia

Introduction: Neoadjuvant chemoradiotherapy (nCRxt) followed by surgery represents the optimal approach for medium and distal advanced rectal tumors; however patients with clinical complete response (cCR) may be followed closely without surgery (watch and wait policy). Magnetic resonance imaging (MRI) and endoscopy have low sensitivity for the diagnosis of cCR. Probe-based confocal endomicroscopy (pCLE) represents a real time in vivo method allowing acquisition of optical biopsies with 1000 times magnification, evaluating both cellular and vascular patterns. Aim: to evaluate the contribution of pCLE in the diagnosis of cCR after nCRxt for advanced rectal cancer. Methods: We evaluated 40 patients with locally medium and distal advanced rectal neoplasia (T3 - T4, or N+) between October 2016 and February 2018 who underwent nCRxt (5-fluoroucacil, 5040 cGy), and who were submitted to pCLE. Cell irregularity, atypical glands, vascular enlargement and tortuosity were considered pCLE patterns of malignancy. pCLE was performed pre and post nCRxt, and guided tissue biopsies subsequently. Images of pCLE post nCRxt were recorded and blinded compared to the histology of the surgical specimens. Results: Twenty-one patients had tumor lesions located at medium rectum and 19 patients at distal rectum. Twenty-three (57.5%) patients were men. Mean age was: 63.15 years, varying from 36 to 82 years. Thirty-three had only partial nresponse, all of them confirmed by pCLE. Seven patients (17.5%) had good endoscopic response, and presented only a small ulcer (n=3) or residual scar (n=4). In this subgroup of patients, pCLE post nCRxt correctly diagnosed all but one (6/7 patients). Two negative pCLE patients were confirmed by surgical pathology. Three positive pCLE patients presented pathological residual disease in the surgical specimen. pCLE misdiagnosed one patient who was considered positive, however the surgical pathological result showed only mucin areas without neoplastic cells. One negative pCLE patient has been followed up for one year without any evidence of recurrence at endoscopy and MRI. pTNM stages of the subgroup were: 2 ypT0 ypN0, 1 ypT0 ypN1, 1 ypT1 ypN0, and 2 ypT2ypN0. Conclusion: 1. pCLE could be useful for improving the diagnosis of cCR, and may alter the patient management; 2. pCLE procedure might be valuable for identifying the patients with advanced rectal cancer who will benefit from watch and wait policy, avoiding surgical treatment and consequently achieving better quality of life.

Survival by lymph node ratio (IG) in colorectal cancer patients in Oncologos del Occidente from Caldas: Colombia 1997–2012.

641 Background: Colorectal cancer is the third cause of cancer death in the western world and in Colombia the fifth leading cause. The Caldas State being one of the five with the highest mortality rates. There are many prognostic factors reported in the literature but the clinical stage is the most important mainly determined by the number of involved nodes but exist other factors in their evaluation. It has been proposed Lymph Node Ratio (IG) ( Nro. (+) nodes / Nro. nodes removed x 100) for the analysis of nodal stage but there is controversy about its usefulness in various contexts. Methods: We made a descriptive study of patients with colorectal cancer attending at ONCOLOGOS DEL OCCIDENTE from Caldas - Colombia, who applied the Lymph node ratio (IG) and related to demographic, clinical and others prognostic factors in order to see its relation with overall survival at 5, 10 and 15 years. Results: 333 patients with 66% colon cancer, under 40 years 12% , women 50%, 68% without ACE data prior treatment, 41% on right colon, 49% medium rectum, 44% localized stage, 2% pathological complete response and 3% no classification data. Obstruction (29%), ulceration (25%) and 30% without prognostic factors, 33% had 12 or more lymph nodes removed, 50% N0 (TNM), 21% N2; the resected nodes, positive nodes, relapse, prior ACE and TNM as significant variables, 27% relapsed mainly liver, 50% had nodal index group 1 (0%); group 2 (1-20%) 15%, 14% group 3 (21-40%) and 21% group 4 (> 40%) . Mean follow-up: 53.7 months (SD: 43.8, Range:0 -218 months) and overall survival 64% at 5 years and 54% at 10 and 15 years. Conclusions: With an inadequate number of lymph nodes removed (33%) and multiple prognostic factors, Lymph node ratio is proposed like an independent prognostic factor in patients with colorectal cancer associated with overall survival at 5, 10 and 15 years, on which a therapeutic decision can be based.

Rectal leiomyosarcoma, three-year follow-up

Rectal leiomyosarcomas are rare tumors originated from smooth muscle cells. Differential diagnosis includes gastrointestinal stromal tumors (GIST), leiomyomas or schwannomas, and the differentiation of these tumors is usually made through immunohistochemistry. Due to its rarity, the standard treatment has not been defined. The purpose of this study was to present the follow-up of a patient with leiomyosarcoma of medium rectum submitted to exclusive operative treatment. The tumor size was 6 cm and it had a high mitotic index. The patient remains with good urinary function and good sphincter function, and free of the disease after a three-year follow-up.

B1 versus B2 Dukes stage rectal cancer: prospective evaluation of 87 patients in a single institution and quest for re-evaluation of the current protocol.

Current protocols indicate surgery as single modality of therapy for B1 stage rectal cancer and surgery with adjuvant therapy for B2 stage. The aim of our study was to analyze the five-year survival rate for patients with surgically treated B1 and B2 rectal cancer and to assess the impact of adjuvant therapy on overall survival. Our epidemiological clinical study was based on a prospective analysis of 87 cases of B1 (n=32) and B2 (n=55) rectal cancers operated between 2000 and 2003. Survival evaluation was done through a prospective cohort followup study. There were 33 female and 54 males with a median age of 60 years (IQR 39-74). Tumor location was low rectum for 23 patients (26.4%), medium rectum for 30 patients (34.5%) and high rectum at 34 patients (37.9%). We performed Miles operation in 42 cases, Dixon resection in 26 cases and Hartmann operation in 18 patients. There was no difference in the number and type of postoperative complications between groups. There were no local recurrences in the B1 stage group but 7 cases (12.7%) in the B2 stage group. Distant metastases were recorded in 8 patients (25%) in the B1 group and 2 patients (3.6%) in the B2 group. The survival rate at 5 years (S5) was better for the B2 stage S5=69.9% than B1 stage S5=53.5% (p=0.001). Patients with B1 stage rectal cancer might benefit from adjuvant/neoadjuvant therapy.

Avaliação da expressão do gene MGMT nos tecidos normal e neoplásico de doentes com câncer colorretal

To evaluate the expression of tissue repair gene MGMT by comparing normal and neoplastic colonic mucosa in patients with colorectal cancer (CRC). We studied 44 patients with colorectal cancer confirmed by histopathology. We excluded patients suspected of belonging to families with hereditary colorectal cancer (HNPCC and FAP) and patients with cancer of the lower or medium rectum treated with neoadjuvant chemoradiotherapy. The MGMT gene expression was assessed by the technique of polymerase chain reaction in real time (RT-PCR). The comparison of results for MGMT gene expression between normal and neoplastic tissues was made by paired Student's t test, adopting a significance level of 5% (p <0.05). Tissue expression of the MGMT gene in all patients was lower in tumor tissue when compared to normal tissue (p = 0.002). The repair gene MGMT is less expressed in tumor tissue compared to normal tissues in patients with sporadic CRC.

Laparoscopic total mesorectal excision for rectal cancer: experience of a single center with a series of 174 patients

Laparoscopic total mesorectal excision for low rectal cancer is not considered a gold standard treatment due to the high conversion rate and the long operation time. A retrospective review examined a surgical series of 174 laparoscopic low rectal resections involving total mesorectal excision (1995-2006), with particular reference to technical points as well as surgical and oncologic outcomes. Miles operations and partial mesorectal excisions were excluded. The cancer affected the low rectum in 110 cases and the medium rectum in 64 cases. A total of 68 patients were subjected to neoadjuvant radiochemotherapy. The anastomosis was mechanical for 83.3% of the cases and intersphinteric through the perineum for 16.6% of the cases. Protective ileostomy was performed in 112 cases. The conversion rate was 4.6%. The mesorectum remained intact in 91.6% of the cases and was partially interrupted in 15 of the cases. In no case was it totally discontinued. The postoperative morbidity rate was 16.7%, and the mortality rate was 0.57%. The incidence of anastomotic fistulas was 14.4%. The percentage was higher for males (18.6 vs 8.3%) and correlated with the low distance of the tumor from the anal verge (18.2 vs 7.8%) and the absence of a protection ileostomy (20.9 vs 10.7%). After an average follow-up period of 48.6months (range, 24-149months), six patients (3.44%) experienced a pelvic recurrence. The 5-year overall survival rate was 75.4%, and the disease-free survival rate was 61.9%. Laparoscopic total mesorectal excision for low rectal cancer is safe and effective, allowing surgical and oncologic outcomes similar to those reported for open surgery.

Posterior pelvic exenteration for primary rectal cancer

Indications for and the prognosis of posterior pelvic exenteration (PPE) in rectal cancer patients are not clearly defined. The aim of this study was to analyse the indications, complications and long-term results of PPE in patients with primary rectal cancer. A retrospective review included patient demographics, tumour and treatment variables, and morbidity, recurrence, and survival statistics. These results were compared with a group of female patients who underwent standard resection for primary rectal cancer in the same period (non PPE group). The series included 30 women with an average age of 56.7 years (range 22-78). Tumour location was recorded in three cases in the upper rectum, 13 cases in the medium rectum and 14 cases in the lower rectum. A sphincter-preserving procedure was performed in 70% of the patients. Mean operative time was 4.2 h (range 2-7.5 h). Overall major morbidity rate in this series was 50% and mean hospital stay was 19.7 days (range 9-60 days). There was no hospital mortality. Pathological reports showed direct invasion of uterus, vagina or rectovaginal septum in 19 cases, involvement of perirectal tissue in 25 cases and positive lymph nodes in 18 cases. Comparison between PPE and non PPE groups showed no differences in mean tumour diameter, histological grade and tumour stage, but patients in the first group were younger. Although low tumours were seen more frequently in the PPE group (P = 0.003), the rate of sphincter-preserving procedure was comparable in both groups. Operative time was longer (P = 0.04) and morbidity was higher (P = 0.0058) in the PPE group. Local recurrence with or without distant metastases for the whole series was 30%. Five-year survival rate for patients who underwent curative resections (TNM I-III) was 48% in the PPE group vs 62% in the non PPE group (P = 0.09). In the present series, PPE prolonged operative time, increased postoperative complications and showed a trend toward poor prognosis in recurrence and survival. However, PPE offers the only hope for cure to patients with a primary rectal cancer that is adherent or invades reproductive organs.

Preoperative radiation and daily oral uft in combination with leucovorin (LV) in locally advanced rectal (LARC) cancer

3676 Background: The aim of this multicentric study is to evaluate the toxicity and effectiveness of the addition of daily UFT - LV and preoperative pelvic radiation for uT3 N0 -N1 LARC defined by transrectal ultrasound(T.R.U.). Methods: Pretreatment staging included rigid rectoscopy with biopsy, T.R.U., pelvic CT scan. 300 mg/m2 UFT were given 5 days a week for 5 weeks + LV 75 mg/day, with pelvic radiotherapy (45Gy in 25 fractions of 1.8Gy per fraction) delivered using a 4 field technique and megavoltage photons. Pretreament detection of 5-FU catabolic deficiency was performed with plasma uracil measurement and 8 dihydropyrimidine dehydrogenase (DPD) mutations detection. Quality of life (QOL) was evaluated according to QLQ-C30. Surgery was performed 4–6 weeks later, just after uTNM evaluation. Since 07–2002 to 09–2003, 85 pts with LARC were accrued. Partial results are now available, with 29 patients fully evaluable for tolerance and efficacy. Results: Patients characteristics: 29 males/females: 19/10; median age 64) in clinical and uTNM III : N0 11, N1 18; lower rectum : 9, medium rectum : 20. Results: at least 14 patients achieved major uTNM downstaging, but 6 patients were not evaluable due to persistant inflammatory effects; 7 pts (25%) had complete pathological responses. Compliance to chemotherapy was excellent.Toxicity: all the pts but 1 completed RT as planned while 4 did not receive all the planned chemotherapy because of grade III-IV diarrhoea. 5 pts had 4 grade 3 and 1 grade 4 diarrhoea according to NCI-CTC): pretreament uracil plasma levels = 20 μg/l in 4 patients and 1 heterozygous DPYD 2A mutated patient. Conclusion: Our partial results suggest that daily UFT-LV - RT combination is safe and feasible with interesting 7/29 pathological complete responses. For patients N- at pathologic exam, no adjuvant chemotherapy and no implantable disc device had to be set, part of an improved Q.O.L. Detection of DPD deficiency appears necessary. Final results will be presented at ASCO meeting. A randomised study is planned. No significant financial relationships to disclose.

Preoperative radiation and daily oral uft in combination with leucovorin (LV) in locally advanced rectal (LARC) cancer

3676 Background: The aim of this multicentric study is to evaluate the toxicity and effectiveness of the addition of daily UFT - LV and preoperative pelvic radiation for uT3 N0 -N1 LARC defined by transrectal ultrasound(T.R.U.). Methods: Pretreatment staging included rigid rectoscopy with biopsy, T.R.U., pelvic CT scan. 300 mg/m2 UFT were given 5 days a week for 5 weeks + LV 75 mg/day, with pelvic radiotherapy (45Gy in 25 fractions of 1.8Gy per fraction) delivered using a 4 field technique and megavoltage photons. Pretreament detection of 5-FU catabolic deficiency was performed with plasma uracil measurement and 8 dihydropyrimidine dehydrogenase (DPD) mutations detection. Quality of life (QOL) was evaluated according to QLQ-C30. Surgery was performed 4–6 weeks later, just after uTNM evaluation. Since 07–2002 to 09–2003, 85 pts with LARC were accrued. Partial results are now available, with 29 patients fully evaluable for tolerance and efficacy. Results: Patients characteristics: 29 males/females: 19/10; median age 64) in clinical and uTNM III : N0 11, N1 18; lower rectum : 9, medium rectum : 20. Results: at least 14 patients achieved major uTNM downstaging, but 6 patients were not evaluable due to persistant inflammatory effects; 7 pts (25%) had complete pathological responses. Compliance to chemotherapy was excellent.Toxicity: all the pts but 1 completed RT as planned while 4 did not receive all the planned chemotherapy because of grade III-IV diarrhoea. 5 pts had 4 grade 3 and 1 grade 4 diarrhoea according to NCI-CTC): pretreament uracil plasma levels = 20 μg/l in 4 patients and 1 heterozygous DPYD 2A mutated patient. Conclusion: Our partial results suggest that daily UFT-LV - RT combination is safe and feasible with interesting 7/29 pathological complete responses. For patients N- at pathologic exam, no adjuvant chemotherapy and no implantable disc device had to be set, part of an improved Q.O.L. Detection of DPD deficiency appears necessary. Final results will be presented at ASCO meeting. A randomised study is planned. No significant financial relationships to disclose.