Neoadjuvant radiotherapy (RT) and chemotherapy are applied to large, high-grade extremity soft tissue sarcomas to treat metastatic disease earlier and sterilize margins to perform R0 surgery. However, preoperative RT increases wound complication rates (rWC), delaying adjuvant chemotherapy or preventing it from being administered altogether. Hypofractionated neoadjuvant RT can be offered in this situation, concomitant to chemotherapy, allowing patients to receive chemotherapy as a preoperative treatment in less time with an acceptable rWC. The objectives of this protocol are to maintain low rates of morbidity and mortality compared to literature data, improving survival rates and avoiding poor responders from receiving unnecessary adjuvant chemotherapy. This noncontrolled, single-arm, phase 2 clinical trial recruited patients aged over 18 years with high-grade soft tissue sarcomas in the girdles or extremities. Three neoadjuvant chemotherapy (ifosfamide and doxorubicin) cycles were administered with 5 days of hypofractionated RT (25 Gy in 5 fractions) in the second cycle of doxorubicin only. Viable cell counts in the surgical specimen were measured, and patients in whom this value was less than 30% continued to receive an additional 3 full chemotherapy cycles as adjuvant treatment. Primary endpoint will be disease-specific survival measured by the evaluation of local and distant recurrence after neoadjuvant treatment. The secondary endpoints will be wound complication and amputation rates and chemotherapy toxicity. We also will record the viable cell rates after the schema and correlate this with survival. As seems with other solid tumors, hypofractionated RT has comparable efficacy and safety as conventional fractionation. This modality of treatment combined with chemotherapy could increase the pathological response rates and improve the outcomes of select patients. ClinicalTrials.gov NCT02812654; https://clinicaltrials.gov/ct2/show/NCT02812654 (Archived by WebCite at http://www.webcitation.org/6qC3puBOy).

Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERβ1 and ERβ5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002). These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

Background: Alternatives to the double-stapled (DS) technique for creating anastomoses after minimally invasive total mesorectal excision (TME) have been proposed to reduce complications and costs. Robotic intracorporeal single-stapled anastomosis (RISS) was developed as a technically intuitive approach. Standardizing such an intracorporeal robotic technique—which achieves adequate pelvic exposure, precise rectal transection, and secure anastomosis construction—may optimize outcomes, particularly anastomotic leakage (AL). Methods: A cohort study was conducted using our prospective institutional database and included patients < 80 years who underwent minimally invasive elective TME for extraperitoneal rectal cancer. Patients were allocated to the DS (abdominal stapled transection with double-stapled anastomosis) or RISS (robotic intracorporeal rectal transection with single-stapled anastomosis) groups. The exclusion criteria were nonrestorative procedures, intersphincteric resection, open surgery, and no indocyanine green perfusion assessments. The primary endpoint was 90-day clinical or radiological AL. Results: Among 380 TMEs, 167 met the inclusion criteria (71 RISS; 96 DS). The 90-day AL rate was significantly lower in the RISS group (5.6% vs. 16.7%; p  = 0.032). Reintervention (1.4% vs. 10.4%; p  = 0.025), overall morbidity (33.3% vs. 52.5%; p  = 0.014), and length of stay ( p  < 0.0001) were lower following RISS. Multivariable analysis revealed that DS technique (odds ratio [OR] 3.3; p  = 0.038) and comorbidities (OR 3.1; p  = 0.028) independently predicted AL. Each additional stapler firing increased the risk of AL (OR 1.62; p  = 0.016), and ≥3 firings predicted AL (OR 4.92; p  = 0.011). Conclusions: Compared with DS, RISS was associated with lower anastomotic leakage, morbidity, and reintervention and shorter hospitalization. This standardized robotic approach is safe, reproducible, and potentially cost effective.