3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization.

INTRODUCTION: Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. MATERIALS AND METHODS: Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2-5 (T2), and 6-12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. RESULTS: Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). CONCLUSION: NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.

Prognosis factors for recurrence in patients with locally advanced rectal cancer preoperatively treated with chemoradiotherapy and adjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by total mesorectal excision has improved the outcome of locally advanced rectal carcinoma. OBJECTIVE: The aim of this study was to identify independent prognosis factors of disease recurrence in a group of patients treated with this approach. DESIGN AND PATIENTS: This study was retrospective in design. Data from patients with locally advanced rectal cancer who had completed treatment from 2000 to 2010 were reviewed. SETTINGS: The analysis was performed in a tertiary referral center. MAIN OUTCOME MEASURES: The primary outcomes measured were the recurrence risk factors. RESULTS: The cohort consisted of 228 patients; 69.3% of them were men, and median age was 59 years. Stage III rectal cancer was found in 64.9% of patients. The most frequently administered therapy was concurrent capecitabine, oxaliplatin, and 7-field radiotherapy, followed by 3-field radiotherapy and fluoropyrimidines. After a median follow-up of 49 months, 23.7% of the patients experienced disease recurrence: 2.6% had local recurrence, 21.1% had distant metastases, and 0.5% had both. Factors significantly correlated with recurrence risk in multivariate logistic regression were y-pathological stage (III vs I/II: OR = 2.51), tumor regression grade (1/2 vs 3+/4: OR = 3.34; 3 vs 3+/4: OR = 1.20), and low rectal location (OR = 2.36). The only independent prognosis factor for liver metastases was tumor regression grade (1/2 vs 3+/4: OR = 4.67; 3 vs 3+/4: OR = 1.41), whereas tumor regression grade (1-2 vs 3+/4: OR = 5.5; 3 vs 3+/4: OR = 1.84), low rectal location (OR = 3.23), and previous liver metastasis (OR = 7.73) predicted lung recurrence. LIMITATIONS: This is a single institutional experience, neoadjuvant combined therapy is not homogeneous, and the analysis has been performed in a retrospective manner. CONCLUSIONS: Patients with low third locally advanced rectal cancer with a poor response to neoadjuvant chemoradiotherapy (high y-pathological stage or low tumor regression grade) are at high risk of recurrence. Intense surveillance and the design of alternative therapeutic approaches aimed to lower the distant failure rate seem warranted.

Surgical training on rectal cancer surgery: do supervised senior residents differ from consultants in outcomes?

INTRODUCTION: The present work is a comparative study to investigate the independent effect of tutored senior residents on rectal cancer surgery in an academic university hospital. The variable "surgeon" is held to be a major determinant of outcome following total mesorectal excision (TME) for rectal cancer. OBJECTIVE: We hypothesized that TME can be tutored to senior surgical residents without compromising surgical and oncological outcomes. METHODS: Demographics, preoperative characteristics, and surgical data from consecutive patients undergoing elective TME in an academic center over the last decade were retrospectively reviewed from a prospectively collected database. Outcomes were compared in the two cohorts by a principal surgeon (senior resident or staff) and supervised in all cases by a senior colorectal consultant. Association of outcome variables with the type of surgeon was determined by univariate and multivariate analyses and results were corrected by tumor's height. RESULTS: A total of 230 patients were treated over the study period; 136 (59 %) surgeries were performed by staff surgeons (group S) and 94 (41 %) by residents (group R). Both groups were comparable except for distance to anal verge; staff surgeons operated on lower tumors and performed a high percentage of coloanal anastomosis. There were no statistical differences between groups in terms of surgical and oncological outcomes when tumors were located over 7 cm from the anal verge. CONCLUSIONS: Rectal surgery can be performed by senior residents with equal results to staff surgeons when there is direct supervision by a senior consultant and when the tumor is located in the mid-upper rectum (>7 cm from the anal verge). For lower tumors, a careful selection must be made as the operation may require a higher level of training.

Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice.

The preferred treatment of choice in muscle-invasive bladder cancer (MIBC) is usually transurethral resection followed by cystectomy, with neoadjuvant chemotherapy being a second option. As the treatment is associated with relevant side effects, a great effort is being made to improve the selection of patients, with molecular subtyping being one of the main strategies. Our aim was to develop an immunohistochemical algorithm for subtyping MIBCs. After a literature review, we have developed a simple algorithm to subtype MIBCs based on their morphology and three common antibodies: GATA3, CK5/6, and p16. We applied it to 113 muscle-invasive carcinomas. The positivity threshold for GATA3 and CK5/6 was 20% with at least moderate intensity, while p16 was 70% with moderate to intense nuclear and cytoplasmic staining. Cases GATA3 + CK5/6 - were considered luminal, while cases GATA3 - CK5/6 + were classified as nonluminal/basal squamous. Luminal p16 + cases were labeled as genomically unstable and luminal p16 - as Uro-like. Cases GATA3 + CK5/6 + with a predominantly basal pattern were labeled luminal, while diffuse cases were labeled nonluminal/basal squamous. All GATA3-CK5/6 - cases were considered nonluminal and were divided into mesenchymal-like or neuroendocrine, depending on the morphology. We were able to classify the 113 cases as: 82 (72.57%) were luminal, being 47 Uro-like (41.59%) and 35 (30.97%) genomically unstable; 31 (27.43%) were nonluminal, being 24 basal/squamous (21.24%), two (1.76%) mesenchymal-like, and five (4.42%) neuroendocrine like. We have achieved a feasible and cost-effective algorithm to subtype MIBCs from morphological features and the use of three common antibodies. Further studies in external cohorts are necessary to validate these results.

Accuracy of endoscopic ultrasound to assess tumor response after neoadjuvant treatment in rectal cancer: can we trust the findings?

BACKGROUND: The finding that some rectal cancers respond to neoadjuvant chemoradiation is broadening new surgical options for the treatment of some of these tumors that, until now, required a total mesorectal excision. Nevertheless, a fine match between clinical and pathological response is required when planning conservative surgical approaches. OBJECTIVE: This study aims to prospectively validate the use of endoscopic ultrasound as a predictor of clinical and pathological tumor response in patients with locally advanced rectal cancer. DESIGN: : This is an observational study of a cohort of patients undergoing chemoradiation followed by surgery. SETTINGS: This study was conducted at a tertiary medical center. PATIENTS: A total of 235 consecutive patients who underwent chemoradiation followed by surgery at a single institution during a 7-year period were included. MAIN OUTCOME MEASURES: All tumors were staged and restaged at 4 to 6 weeks after neoadjuvant treatment. Downsizing and downstaging were calculated between the initial and posttreatment measures and correlated to the pathological stage. The accuracy of endoscopic ultrasound to predict response was determined. RESULTS: Findings after chemoradiation showed T-downstaging in 54 patients (23%) and N-downstaging in 110 (47%). Overstaging occurred in 88 (37%) patients and was more commonly observed than understaging (21 patients; 9%). Related to the pathological report, endoscopic ultrasound correctly matched the T stage in 54% and the N stage in 75% of tumors. Sensitivity, specificity, and positive and negative predictive values to predict nodal involvement were 39%, 91%, 67%, and 76%. Accuracy was not influenced by such factors as age, distance of the tumor from the anal verge, or time to surgery. LIMITATIONS: This study was limited by the lack of comparison with other imaging methods. CONCLUSIONS: Endoscopic ultrasound allows prediction of involved lymph nodes in 75% of the cases; however, 1 in 5 patients are missclassified as uN0 after neoadjuvant treatment. In our point of view, this percentage is too high to rely only on this diagnostic modality to support a "wait and see" approach.

The impact of major postoperative complications on long-term outcomes following curative resection of colon cancer.

PURPOSE: The objective is to analyze the impact of severe postoperative complications in patients undergoing curative surgery for colon cancer. MATERIAL AND METHODS: From a prospective database, we identified patients with stage I-III disease (AJCC) who underwent surgery between 2000 and 2014. Patients were selected with major complications (IIIb on the Clavien-Dindo classification) and with no major complications. Variables were analyzed in both groups. Local, peritoneal and distant recurrence together with overall survival and disease-free survival were analyzed. RESULTS: Of a total of 950 patients, 51 (5.3%) experienced major complications. Operative mortality was 2.6%. Age, ASA grade, urgent surgery, pre-operative hemoglobin, right-sided location, operative time, transfusion, conversion to open surgery, were all associated with major complications (all P < 0.05). With a median follow-up of 84.8 and 40 months in both groups, there was greater incidence of local recurrences in patients experiencing complications (2.4% vs 7.8%; P = 0.03 OR 3.39, 95% CI 1.12-10.24), being more marked in stage III patients (4.2% vs 21%; P = 0.005, OR 6.13 95% CI 1.74-21.56). In the stage III group, peritoneal recurrence was significantly greater in patients with complications (13.6% vs 31.6%; P = 0.04 OR 2.92 95% CI 1.04-8.18). Patients with major complications had a significantly lower overall survival (P = 0.024) than patients with no complications both at 5 years (78.9% vs 68.8%) and 10 years (74.6% vs 32.1%). The same trend was observed for disease-free survival (71.6% vs 48.3% and 69.8% vs 32.2%; P = 0.013). CONCLUSION: The development of major complications following colectomy for colon cancer has a negative impact on long-term oncologic outcomes, especially in stage III disease.