Tumors can suppress the host immune system by employing a variety of cellular immune modulators, such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). In the peripheral blood of patients with advanced stage melanoma, there is an accumulation of CD14 þ HLA-DR lo/À MDSC that suppress autologous T cells ex vivo in a STAT-3-dependent manner. However, a precise mechanistic basis underlying this effect is unclear, particularly with regard to whether the MDSC induction mechanism relies on cell-cell contact of melanoma cells with CD14 þ cells. Here, we show that early-passage human melanoma cells induce phenotypic changes in CD14 þ monocytes, leading them to resemble MDSCs characterized in patients with advanced stage melanoma. These MDSC-like cells potently suppress autologous T-cell proliferation and IFN-g production. Notably, induction of myeloid-suppressive functions requires contact or close proximity between monocytes and tumor cells. Further, this induction is largely dependent on production of cyclooxygenase-2 (COX-2) because its inhibition in these MDSC-like cells limits their ability to suppress T-cell function. We confirmed our findings with CD14 þ cells isolated from patients with advanced stage melanoma, which inhibited autologous T cells in a manner relying up prostaglandin E2 (PGE 2 ), STAT-3, and superoxide. Indeed, PGE 2 was sufficient to confer to monocytes the ability to suppress proliferation and IFN-g production by autologous T cells ex vivo. In summary, our results reveal how immune suppression by MDSC can be initiated in the tumor microenvironment of human melanoma. Cancer Res; 73(13); 3877-87. Ó2013 AACR.
The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively. Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function.
Ripstein rectopexy can be performed with low mortality and recurrence rate, but with a high early complication rate. There were also some serious late complications. Continence was improved, although increased constipation was a problem in some patients, especially among those with internal rectal intussusception.
The present study demonstrates that the risk of developing a rectal prolapse in patients with rectal intussusception is small. This risk should, therefore, not be used as an indication for surgery.
BackgroundPostmastectomy reconstruction using a deep inferior epigastric perforator (DIEP) flap is increasingly being performed in patients with breast cancer. The procedure induces extensive tissue trauma, and it has been hypothesized that the release of growth factors, angiogenic agonists and immunomodulating factors may reactivate dormant micrometastasis. The aim of the present study was to estimate the risk of breast cancer recurrence in patients undergoing DIEP flap reconstruction compared with that in patients treated with mastectomy alone.MethodsEach patient who underwent delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013, was compared with up to four controls with breast cancer who did not receive a DIEP flap. The control patients were selected using incidence density matching with respect to age, tumour and nodal status, neoadjuvant therapy and year of mastectomy. The primary endpoint was breast cancer‐specific survival. Survival analysis was carried out using Kaplan–Meier survival estimates and Cox proportional hazard regression analysis.ResultsThe analysis included 250 patients who had 254 DIEP flap reconstructions and 729 control patients. Median follow‐up was 89 and 75 months respectively (P = 0·053). Breast cancer recurrence developed in 50 patients (19·7 per cent) in the DIEP group and 174 (23·9 per cent) in the control group (P = 0·171). The 5‐year breast cancer‐specific survival rate was 92·0 per cent for patients with a DIEP flap and 87·9 per cent in controls (P = 0·032). Corresponding values for 5‐year overall survival were 91·6 and 84·7 per cent (P < 0·001). After adjustment for tumour and patient characteristics and treatment, patients without DIEP flap reconstruction had significantly lower overall but not breast cancer‐specific survival.ConclusionThe present findings do not support the hypothesis that patients with breast cancer undergoing DIEP flap reconstruction have a higher rate of breast cancer recurrence than those who have mastectomy alone.
Background: Techniques based on radio frequency (RF) energy have many applications in medicine, in particular tumour ablation. Today, mammography screening detects many breast cancers at an early stage, facilitating treatment by minimally invasive techniques such as radio frequency ablation (RFA). The breast cancer is mostly surrounded by fat, which during RFA-treatment could result in preferential heating of the tumour due to the substantial differences in electrical parameters. The object of this study was to investigate if this preferential heating existed during experimental in vitro protocols and during computer simulations.
Rectocele is a frequent finding in constipated patients. However, constipation is not always relieved by rectocele repair, which may be due to other overlooked reasons for constipation. The study was designed to investigate patients with rectocele, in order to elucidate concomitant colorectal disorders and their association with rectocele. One hundred and twelve female patients suffering from severe constipation and rectal emptying difficulties were investigated using defecography, electrophysiology, anorectal manometry and colon transit time. Fifty-six patients with rectocele demonstrated by defecography were compared with 56 patients without rectocele, but with other abnormal findings at defecography. The frequency of paradoxical anal sphincter reaction (PSR) was higher in patients with rectocele (60%) than in patients without rectocele (24%). The present study supports an association between rectocele and PSR. We suggest that constipated patients with a rectocele should be investigated thoroughly before rectocele repair is considered. Further studies on the effect of biofeedback training in patients with rectocele and PSR are indicated.
The purpose of this study was to determine the safety and efficacy of percutaneous ultrasound (US) guided preferential radiofrequency ablation (PRFA) of unifocal human invasive breast carcinoma with largest radiological diameters of up to 16 mm. Thirty-three patients were enrolled in a study to be treated prior to scheduled partial mastectomy. A needle-shaped treatment electrode, successively developed in two different sizes, was placed into the center of the lesions using ultrasound guidance. A temperature of 85 degrees C was maintained for 10 min. The analysis of the resected specimen was performed using conventional histopathological methods with the aim to determine the size of the lesion as well as the potential viability of tumor cells. Of the 33 patients enrolled 31 were treated. In 26 (84%) patients a complete ablation of the tumor was achieved. Ultrasound guided preferential radiofrequency ablation of small breast carcinoma is feasible and patient friendly. The success rate depends on accurate preoperative diagnostic imaging as well as an exact position of the needle electrode.
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