Purpose: After preoperative (radio)chemotherapy, histologic determinants for prognostification have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival. Experimental Design: A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival. Results: Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively). Conclusions: Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapyinduced regression.

Background Although early results of bariatric surgery are beneficial for most patients, some patients regain weight later. Cognitive behavioral therapy (CBT) has been suggested as a way to improve patients’ psychological health and maintaining weight loss in the longer term. The added value of preoperative CBT to bariatric surgery was examined. Pre- and posttreatment and 1-year follow-up data are presented. Methods In a multi-center randomized controlled trial, CBT was compared to a treatment-as-usual (TAU) control group. Measurements were conducted pre- and posttreatment/pre-surgery (T0 and T1) and at 1-year post-surgery (T2). Patients in the intervention group received 10 individual, weekly sessions of preoperative CBT focused on modifying thoughts and behaviors regarding eating behavior, physical exercise, and postoperative life style. Outcome measures included weight change, eating behavior, eating disorders, depression, quality of life, and overall psychological health. Results Though no significant differences between conditions were found per time point, in the CBT, condition scores on external eating, emotional eating, depressive symptoms, and psychological distress decreased significantly more over time between pre- (T0) and posttreatment (T1) pre-surgery compared to TAU. No significant time x condition differences were found at 1-year post-surgery (T2). Conclusions Compared to TAU, preoperative CBT showed beneficial effects on eating behavior and psychological symptoms only from pretreatment to posttreatment/pre-surgery, but not from pre-surgery to 1-year post-surgery. Preoperative CBT does not seem to contribute to better long-term outcomes post-surgery. Recent studies suggest that the optimal time to initiate psychological treatment may be early in the postoperative period, before significant weight regain has occurred. Trial Registration https://www.trialregister.nl Identifier: Trial NL3960.

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Background Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. Methods WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4 + and CD8 + T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. Results Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8 + T-cell differentiation. Patients with MetS had significant lower CD4 + RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4 + T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. Conclusions In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer.