Redo Pelvic Surgery and Combined Metastectomy for Locally Recurrent Rectal Cancer with Known Oligometastatic Disease: A Multicentre Review.

INTRODUCTION: Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. METHODS: A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. RESULTS: Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/- 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/- 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5-17.5 months) and 25.9 months (IQR 6.2-39.7 months), respectively. CONCLUSIONS: Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.

Development of a pelvic exenteration service at a tertiary referral centre.

BACKGROUND: Over one-third of primary rectal cancers are locally advanced at diagnosis, and local recurrence of rectal cancer occurs at a rate of 3-10% following primary curative resection. Extended resectional surgery, including pelvic exenteration, is the only proven therapy with curative potential in the treatment of these cancers along with many other pelvic malignancies. A microscopically clear resection margin (R0 resection) is the predominant prognostic factor affecting overall and disease-free survival. The extent and complexity of surgery required to achieve an R0 resection is associated with significant risk of morbidity and mortality. The aim of this paper is to show that pelvic exenterations can be performed with acceptable oncological and safe perioperative results in an appropriately resourced specialist centre. METHODS: Data was collected retrospectively for 61 consecutive patients treated between June 2012 and February 2017. This included patient demographics, tumour characteristics, operative, clinical and histological data, length of hospital stay, morbidity and mortality data. RESULTS: A total of 61 patients underwent surgery. Median age was 57 years (range 27-78 years). Median length of stay was 41 days (range 6-288 days). Median operative time was 624 min (range 239-1035 min); 30-day mortality was 3.3% (n = 2). Resection rates were 91.5% - R0, 6.8% - R1 and 1.7% - R2 resections. Histologically, 86.9% - adenocarcinomas, 3.3% - squamous cell carcinomas and 9.8% - represented by leiomyosarcoma, melanoma, myxoid chondrosarcoma, non-neoplastic processes and undifferentiated carcinoma. CONCLUSION: Our experience confirms that radical resectional pelvic surgery can be safely performed with acceptable results during the establishment phase of a dedicated tertiary service.

The Outcomes and Patterns of Treatment Failure After Surgery for Locally Recurrent Rectal Cancer.

OBJECTIVE: To assess the outcomes and patterns of treatment failure of patients who underwent pelvic exenteration surgery for recurrent rectal cancer. BACKGROUND: Despite advances in the management of rectal cancer, local recurrence still occurs. For appropriately selected patients, pelvic exenteration surgery can achieve long-term disease control. METHODS: Prospectively maintained databases of 5 high volume institutions for pelvic exenteration surgery were reviewed and data combined. We assessed the combined endpoints of overall 5-year survival, cancer-specific 5-year mortality, local recurrence, and the development of metastatic disease. RESULTS: Five hundred thirty-three patients who had undergone surgery for locally recurrent rectal cancer were identified. Five-year cancer-specific survival for patients with a complete (R0) resection is 44%, which was achieved in 59% of patients. For those with R1 and R2 resections, the 5-year survival was 26% and 10%, respectively. Radical resection required sacrectomy in 170 patients (32%), and total cystectomy in 105 patients (20%). Treatment failure included local recurrence alone in 75 patients (14%) and systemic metastases with or without local recurrence in 226 patients (42%). Chemoradiotherapy before exenteration was associated with a significant (P < 0.05) improvement in overall 5-year cancer-specific survival for those patients with an R0 resection. Postoperative chemotherapy did not alter outcomes. CONCLUSIONS: R0 resection of the pelvic recurrence is the most significant factor affecting overall and disease-free survival. The surgery is complex and often highly morbid, and where possible patients should be given perioperative chemoradiotherapy. Further investigations are required to determine the role of adjuvant chemotherapy.

Cystoprostatectomy versus prostatectomy alone for locally advanced or recurrent pelvic cancer.

BACKGROUND: There is minimal published data evaluating the oncological outcome of rectal resection with prostatectomy alone versus rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer. This study aims to evaluate the oncological and functional outcomes of performing rectal resection with prostatectomy alone compared with rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration. METHODS: Consecutive patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer between 1998 and 2012 were identified from a prospectively maintained database. Patients undergoing rectal resection with prostatectomy alone were compared with a control group who underwent rectal resection with cystoprostatectomy and urostomy formation. The primary outcome was overall survival. Secondary outcomes analysed in the prostatectomy group included completeness of resection, continence and erectile function. RESULTS: Eleven rectal resections with prostatectomy were compared with 20 rectal resections with cystoprostatectomy. R0 resection was achieved in 73 and 65% respectively. There was no difference in overall survival (P = 0.40). Urinary continence was achieved in 36% of prostatectomy alone patients, while 27% experienced mild incontinence. Erectile function was poor, with only one patient able to maintain normal erections. CONCLUSION: In appropriately selected patients with invasive pelvic tumours, rectal resection with prostatectomy alone provides adequate oncological outcomes. The ability to achieve an R0 resection was not compromised and overall survival is comparable with cystoprostatectomy. Urinary function is reasonable in most patients, although sexual function is compromised in almost all.

Antigen-specific CD8 T cells can eliminate antigen-bearing keratinocytes with clonogenic potential via an IFN-gamma-dependent mechanism.

The immune system surveys the skin for keratinocytes (KCs) infected by viruses or with acquired genetic damage. The mechanism by which T cells mediate KC elimination is however undefined. In this study we show that antigen-specific CD8 T cells can eliminate antigen-bearing KCs in vivo and inhibit their clonogenic potential in vitro, independently of the effector molecules perforin and Fas-ligand (Fas-L). In contrast, IFN-gamma receptor expression on KCs and T cells producing IFN-gamma are each necessary and sufficient for in vitro inhibition of KC clonogenic potential. Thus, antigen-specific cytotoxic T lymphocytes (CTLs) may mediate destruction of epithelium expressing non-self antigen by eliminating KCs with potential for self-renewal through an IFN-gamma-dependent mechanism.

Metal artifact reduction in musculoskeletal magnetic resonance imaging.

Many strategies can be employed to reduce the size and scale of metal susceptibility artifacts in the vicinity of orthopedic hardware; factors include selection of metal hardware material, patient positioning, and MRI sequence adjustments and techniques. The adjustments to sequence parameters include high spatial resolution fast spin echo sequences with minimal interecho spacing and increased receiver bandwidth. Frequency and phase encoding gradients can be orientated so misregistration artifacts arising from the metal are directed away from areas of anticipated clinical diagnostic interest. Complications arising in the vicinity of metallic hardware, including loosening, can be assessed after implication of these metal artifact reduction techniques.