Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated. METHODS: In total, 257 patients with non-appendiceal PM-CRC were included from the Norwegian National Unit for CRS-HIPEC. RESULTS: In total, 180 patients received CRS-HIPEC with Mitomycin C, 77 patients received palliative surgery only. In the CRS-HIPEC group, mutBRAF was found in 24.7%, mutKRAS 33.9% and double wild-type 41.4% without differences in survival. MSI was found in 29.3% of mutBRAF cases. Patients with mutBRAF/MSI had superior 5-year survival compared to mutBRAF with MSS (58.3% vs 25.2%, P = 0.022), and better 3-year disease-free survival (DFS) compared to mutKRAS (48.6% vs 17.2%, P = 0.049). Peritoneal Cancer Index and the number of lymph node metastasis were prognostic for OS, and the same two, location and gender prognostic for DFS in multivariate analysis. CONCLUSIONS: PM-CRC with CRS-HIPEC patients has a surprisingly high proportion of mutBRAF (24.7%). Survival was similar comparing mutBRAF, mutKRAS and double wild-type cases, whereas a small subgroup with mutBRAF and MSI had better survival. Patients with mutBRAF tumours and limited PM should be considered for CRS-HIPEC.

Transanal total mesorectal excision for rectal cancer has been suspended in Norway.

BACKGROUND: Transanal total mesorectal excision (TaTME) for rectal cancer has emerged as an alternative to the traditional abdominal approach. However, concerns have been raised about local recurrence. The aim of this study was to evaluate local recurrence after TaTME. Secondary aims included postoperative mortality, anastomotic leak and stoma rates. METHODS: Data on all patients who underwent TaTME were recorded and compared with those from national cohorts in the Norwegian Colorectal Cancer Registry (NCCR) and the Norwegian Registry for Gastrointestinal Surgery (NoRGast). Kaplan-Meier estimates were used to compare local recurrence. RESULTS: In Norway, 157 patients underwent TaTME for rectal cancer between October 2014 and October 2018. Three of seven hospitals abandoned TaTME after a total of five procedures. The local recurrence rate was 12 of 157 (7·6 per cent); eight local recurrences were multifocal or extensive. The estimated local recurrence rate at 2·4 years was 11·6 (95 per cent c.i. 6·6 to 19·9) per cent after TaTME compared with 2·4 (1·4 to 4·3) per cent in the NCCR (P < 0·001). The adjusted hazard ratio was 6·71 (95 per cent c.i. 2·94 to 15·32). Anastomotic leaks resulting in reoperation occurred in 8·4 per cent of patients in the TaTME cohort compared with 4·5 per cent in NoRGast (P = 0·047). Fifty-six patients (35·7 per cent) had a stoma at latest follow-up; 39 (24·8 per cent) were permanent. CONCLUSION: Anastomotic leak rates after TaTME were higher than national rates; local recurrence rates and growth patterns were unfavourable.

ANTECEDENTES: La resección total del mesorrecto transanal (transanal total mesorectal excision, TaTME) para el cáncer de recto se ha propuesto como una alternativa al abordaje abdominal tradicional. Sin embargo, la recidiva local (local recurrence, LR) después de este procedimiento es motivo de preocupación. El objetivo de este estudio fue evaluar la LR en pacientes operados mediante TaTME. Los objetivos secundarios incluyeron la mortalidad postoperatoria, las fugas anastomóticas y el porcentaje de estomas. MÉTODOS: Se registraron los datos de todos los pacientes operados mediante TaTME y se compararon con las cohortes nacionales del Registro Noruego de Cáncer Colorrectal (Norwegian Colorectal Cancer Registry, NCCR) y del Registro Noruego de Cirugía Gastrointestinal (Norwegian Registry for Gastrointestinal Surgery, NoRGast) utilizando estimaciones de Kaplan-Meier y la prueba de log-rank para comparar curvas de LR. RESULTADOS: En Noruega, 157 pacientes se sometieron a TaTME por cáncer de recto entre octubre de 2014 y octubre de 2018. Tres de siete hospitales abandonaron el TaTME después de un total de cinco procedimientos. La LR observada fue 12/157 (7,6%), siendo ocho de ellas multifocales o extensas. La tasa estimada de LR a 2,4 años fue de 11,6 % (i.c. del 95% 6,6 a 19,9) versus 2,4 % (1,4 a 4,3) en el NCCR (log rank P < 0,001). El cociente de riesgos instantáneos (hazard ratio, HR) ajustado fue 6,7 (i.c. del 95% 2,9 a 15,3). Las fugas anastomóticas que precisaron una reintervención después de TaTME ocurrieron en un 8,4% versus 4,5% en el registro NoRGast (P = 0,047). Cincuenta y seis pacientes (35,7%) tenían un estoma en el último seguimiento; 39 (24,8%) eran permanentes. CONCLUSIÓN: Las tasas de fuga anastomótica tras una TaTME fueron más altas que los datos nacionales con tasas de LR y patrones de crecimiento desfavorables.

Beyond total mesorectal excision in locally advanced rectal cancer with organ or pelvic side-wall involvement.

BACKGROUND: In locally advanced rectal cancer (LARC), beyond total mesorectal excision (bTME) is often necessary to obtain complete resection (R0). The aim of this study was to identify prognostic determinants and compare morbidity and survival in LARC cases requiring bTME or TME surgery. METHOD: Single centre cohort study of LARC cases where all patients received neoadjuvant radiotherapy (n = 332). Data was registered prospectively in an institutional database linked to the National Registry. RESULTS: bTME surgery was performed in 224 patients, 171 with resections of adjacent organs (bTME-o group) and 53 with pelvic side-wall resections (bTME-pw group). TME surgery was performed in 108 patients. Six deaths occurred within 100 days and severe morbidity was registered in 23.8% of the whole cohort and in 25.4% of the bTME groups. The R0 rates were 93.5%, 84.2%, and 75.5% in the TME, bTME-o, and bTME-pw groups, respectively. Five-year disease free survival (DFS) was 67.3% (TME group), 54.5% (bTME-o group) and 48.7% (bTME-pw group), and five-year overall survival (OS) 78.7%, 69.0% and 60.4% respectively. Patients with involved resection margins (R1), high pT-stage, pN-positivity or poor response to neoadjuvant therapy were associated with inferior DFS and OS. CONCLUSION: In organ-threatening or infiltrating LARC, bTME surgery can be performed with low mortality and acceptable morbidity to obtain a good long-term outcome. Patients with pelvic side-wall infiltration were identified as a subgroup with increased risk of R1 resection and inferior long-term outcome.

Growth rates of pulmonary metastases after liver transplantation for unresectable colorectal liver metastases.

BACKGROUND: The previously reported SECA study demonstrated a dramatic 5-year survival improvement in patients with unresectable colorectal liver metastases (CLM) treated with liver transplantation (LT) compared with chemotherapy. The objective of this study was to assess whether immunosuppressive therapy accelerates the growth of pulmonary metastases in patients transplanted for unresectable CLM. METHODS: Chest CT scans from 11 patients in the SECA study resected for 18 pulmonary metastases were reviewed retrospectively. Tumour diameter, volume and CT characteristics were registered and tumour volume doubling time was calculated. Findings in the SECA group were compared with those of a control group consisting of 12 patients with non-transplanted rectal cancer resected for 26 pulmonary metastases. Disease-free survival (DFS) and overall survival (OS) after first pulmonary resection were determined. RESULTS: Median doubling time based on tumour diameter and volume in the SECA and control groups were 125 and 130 days (P = 0·658) and 110 and 129 days (P = 0·632) respectively. The metastases in both groups were distributed to all lung lobes and were mostly peripheral. Median DFS after LT in the SECA group and after primary pelvic surgery in the control group was 17 (range 6-42) and 18 (2-57) months respectively (P = 0·532). In the SECA group, estimated 5-year DFS and OS rates after first pulmonary resection were 39 and 51 per cent respectively. CONCLUSION: Patients treated by LT for unresectable CLM have a good prognosis following resection of pulmonary metastases. Doubling time did not appear to be worse with the immunosuppression used after LT.

Deep Pelvic Surgical Site Infection After Radiotherapy and Surgery for Locally Advanced Rectal Cancer.

BACKGROUND: High morbidity, increased mortality, and impaired long-term oncologic outcome have been reported after deep surgical site infection (SSI) in rectal cancer surgery. The rate, risk factors and consequences of deep SSI after (chemo)radiotherapy [(C)RT], and surgery for locally advanced rectal cancer (LARC) in a tertiary university hospital single centre cohort of 540 patients are presented. METHODS: Patients with LARC, operated between January 1, 2007 and December 31, 2015, were identified in the institutional prospective database. All patients had tumours threatening the mesorectal fascia or invading adjacent organs, with a high rate of T4 tumours (60 %), and all received (C)RT. Risk factors for deep SSI were calculated by multivariable logistic regression analysis. Morbidity data were assessed. Overall survival (OS) and disease-free survival (DFS) between patients with or without deep SSI were estimated. RESULTS: Of 540 patients, 104 (19 %) experienced a deep SSI, with the highest rate in the abdominoperineal resection (APR) group with 25 %. APR, good response to (C)RT (low tumour regression grade), age, and operative blood loss were identified as significant (P < 0.05) risk factors for deep SSI in multivariable analysis. No difference was found in OS (P = 0.995) or DFS (P = 0.568). Hospital stay increased with 5 days (P < 0.001), and complete wound healing at the 3-month follow-up decreased from 86 to 45 % (P < 0.001) after deep SSI. CONCLUSIONS: Deep SSI is a frequent and major complication after rectal surgery for LARC, with high morbidity, increased hospital stay and protracted wound healing. Interestingly, deep SSI did not influence long-term oncologic outcome.

Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome.

AIMS: This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. MATERIALS AND METHODS: Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. RESULTS: Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. CONCLUSIONS: In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.

Prophylactic mesh at end-colostomy construction reduces parastomal hernia rate: a randomized trial.

AIM: Parastomal hernia (PSH) is the most common complication of an end-colostomy and about one-quarter of patients need operative repair, which is often unsuccessful. A randomized trial was carried out to compare the results of using mesh or no mesh at the time of formation of a colostomy with the clinical identification of PSH as the primary outcome. METHOD: In this two-centre randomized trial (Oslo University Hospital and Sykehuset Innlandet Hospital Trust, Norway), patients with rectal cancer undergoing open pelvic surgery were randomized to receive a retromuscular synthetic mesh (study group, n = 32) or no mesh (control group, n = 26) at the time of end-colostomy formation. Postoperative follow up was not blinded and included clinical examination and routine CT. RESULTS: The median period of follow up was 40 (range: 84) months. There were no differences in demographic variables or complications between the study and control groups. PSH developed in two patients of the study group and in 12 of the control group [OR = 0.04 (95% CI: 0.01-0.30) and hazard ratio 0.134 (95% CI: 0.030-0.603); P < 0.001]. The number needed to treat to avoid one PSH was 2.5 patients. CT demonstrated an increase over time in the size of the fascial orifice in patients with PSH without mesh prophylaxis, in contrast to a stable size in patients with mesh and in the control patients who did not develop PSH. CONCLUSION: The retromuscular insertion of synthetic mesh at the time of formation of an end-colostomy reduced the risk of PSH.

Evaluation of complete cytoreductive surgery and two intraperitoneal chemotherapy techniques in Pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a low-grade malignancy characterized by mucinous tumor on the peritoneal surface. Treatment involves cytoreductive surgery (CRS) to remove all macroscopic tumor and perioperative intraperitoneal chemotherapy (PIC) to eliminate remaining microscopic disease. PATIENTS AND METHODS: Between 1994 and 2009, 93 patients were treated at the Norwegian Radium Hospital with complete CRS and PIC. PIC was administered as early postoperative intraperitoneal chemotherapy (EPIC) using mitomycin C (MMC) and 5-fluoruracil (n = 48) and as hyperthermic intraperitoneal chemotherapy (HIPEC) using MMC (n = 45). Patients were classified into three histopathological subgroups: Disseminated peritoneal adenomucinosis (n = 57), peritoneal mucinous carcinomatosis (n = 21) and an intermediate group (n = 15). Tumor distribution by peritoneal cancer index (PCI) was PCI ≤ 10 (n = 31), PCI 11-20 (n = 29), PCI ≥ 21 (n = 33). RESULTS: Recurrence was diagnosed in 38 patients and 25 patients died during follow-up. Estimated 10-year overall survival (OS) was 69% and 10-year disease-free survival (DFS) was 47%. Mean OS was 154 months (95% CI 131-171) and median OS was not reached (follow-up median 85 months (3-207)). Low-grade malignant histology (p = 0.001) and female gender (p = 0.045) were associated with improved OS. Almost equal OS and DFS were observed between patients treated with EPIC and HIPEC. CONCLUSIONS: Patients treated for PMP with complete CRS and PIC achieved satisfactory long-term outcome. The most important prognostic factor was histopathological differentiation, but acceptable survival was observed even in patients with aggressive histology and extensive intraperitoneal tumor growth. Administration of EPIC and HIPEC was equally efficacious with respect to long-term outcome.

Salvage surgery for locally recurrent rectal cancer: total mesorectal excision during the primary operation does not influence the outcome.

AIM: This study investigated whether total mesorectal excision (TME), when carried out at the original operation for rectal cancer, influenced the effectiveness of subsequent salvage treatment for pelvic recurrence. METHOD: Between September 1990 and January 2006, 124 patients underwent radiotherapy and salvage surgery at the Norwegian Radium Hospital for locally recurrent rectal cancer without known distant metastases. Most of the primary operations had been performed at other hospitals: 62 patients had undergone a non-TME procedure (most operations in this group of patients were carried out before 1994); and 62 patients had undergone a TME procedure (all operations in this group of patients were carried out after 1992). In the TME group, 17 patients also received radiosensitizing chemotherapy. RESULTS: A lower proportion of primary abdominoperineal resection and more sensitizing chemotherapy seemed to be to the advantage of the TME group, while a higher frequency of intra-operative radiotherapy might be beneficial in the non-TME group. The 5-year survival and R0 stage achievement were 30/24% and 44/40% for non-TME/TME groups. The local re-recurrence rates were nearly identical, at around 50%, for both groups. There was no change in R stage over time. CONCLUSION: A primary operation which includes TME does not reduce the effectiveness of subsequent salvage treatment for locally recurrent rectal cancer.

Adenocarcinomas on the rise--does it influence survival from oesophageal cancer?

BACKGROUND AND AIMS: A significant change in the occurrence of oesophageal squamous cell carcinomas (SCCs) in relation to adenocarcinomas (ACs) has been observed in the Norwegian population during the last 20 years (1988-2007). The AC incidence has increased from 5-10% to more than 50% nowadays, while the incidence of SCCs has decreased. Our goal was to evaluate if the change from SCC to AC and the increased effort to control reflux could be reflected in tumour stage, patient demographics and treatment results. MATERIAL AND METHODS: We analysed clinical and pathological data from 347 patients with oesophageal AC (n = 189) and SCC (n = 158) treated at The Norwegian Radium Hospital during said period for patient- and tumour characteristics, treatment modalities and survival. RESULTS: An oesophageal resection was performed in 169 of 347 patients. The median survival rate for all patients was 15 months, with a 5-year survival rate of 10%. The median survival time for operated and non-operated patients was 25 and 12 months respectively, with the corresponding 5-year survival rate of 13% and 2%. Patients with N0M0 disease operated with free resection margins presented a 5-year survival rate of 28%. CONCLUSIONS: The change from SCC to AC and the ensuing considerable efforts made in surveillance and treatment of AC did not lead to improved long time survival for our patients.

Extended total mesorectal excision in locally advanced rectal cancer (T4a) and the clinical role of MRI-evaluated neo-adjuvant downstaging.

OBJECTIVE: To compare the clinical ability of MRl taken before and after neo-adjuvant treatment in locally advanced rectal cancer (LARC) to predict the necessary extension of TME (ETME) and the possibility to achieve a R0 resection. METHOD: Prospective registration of 92 MRI evaluated T4a cancers undergoing elective surgery between 2002 and 2007 in a tertiary referral centre for multimodal treatment of rectal cancer. RESULTS: MRI identified patients in need of neo-adjuvant treatment and predicted T-downstaging in 10% and N-downstaging in 59%. Seventy-nine percent R0 resections, 18% R1 and 3% R2 were obtained after ETME in 95% of the patients and TME in the rest. Higher tumour regression grade (TRG) was achieved in higher ypT-stage (P < 0.01). Preoperative chemo radiotherapy resulted in that more patients obtained TRG1-3 compared to those receiving radiotherapy (79% vs. 57%, P = 0.02). The pelvic wall was the area of failure in 70% of the R1 resections. Tumour cells outside the mesorectal fascia scattered within fibrosis was found in 18 TRG2-3 among 33 ypT4 tumours (55%). CONCLUSION: MRl cannot discriminate tumour within fibrosis. Therefore, if a R0 resection is the goal, we advocate optimal surgery in accordance with the pre-treatment MRI. Post treatment MRI is a poor predictor of final histology and should not be relied upon to guide the extent of surgical resection. The study has initiated a new approach to histopathological classification of the removed specimen where we introduce a MRI assisted technique for investigating the areas at risk outside the mesorectal fascia in the specimen.

Preoperative irradiation and surgery for local recurrence of rectal and rectosigmoid cancer. Prognostic factors with regard to survival and further local recurrence.

OBJECTIVE: Local recurrence after rectal cancer surgery is an important clinical problem. METHOD: 150 patients with local recurrence after rectal/rectosigmoid cancer, stage M0, underwent surgery after preoperative irradiation (46-50 Gy). RESULTS: The overall 5-year survival was 27% (44% R0, 38% R1 and 17% R2-stage). Corresponding survival/local recurrence rates were 52%/27% for R0- and 14%/63% for R1-stage. No R2-resected survived 4 years. A normal pretreatment CEA level was significantly associated with increased survival but normalization following preoperative therapy was not associated with an improvement in prognosis. Survival and local recurrence were also significantly influenced by the type of primary operation. Several factors were significant for the prediction of an R0-resection in univariate analysis, but only CEA and symptoms at the time of recurrence predicted an R0-resection in multivariate analysis. A long latency time to recurrence did not significantly influence prognosis. CONCLUSION: Preoperative irradiation and surgery can result in an R0-resection and a long survival in patients with recurrence after initial treatment for rectal or rectosigmoid cancer. Also patients with an R1-resection can benefit from surgery since a substantial number will die without further local recurrence. An R0-resection is the main prognostic factor followed by CEA level, sex and type of primary operation. Normalization of CEA after preoperative treatment is not of prognostic significance. The value of the Norwegian follow-up regimen is questioned.

Prognostic factors after preoperative irradiation and surgery for locally advanced rectal cancer.

AIMS: The experience of preoperative irradiation in clinically locally advanced rectal cancer for the period 1991-2003 is reported. Prognostic factors for survival and recurrence, and parameters for obtaining a free circumferential margin were evaluated. METHODS: A prospective cohort study of 204 M0 patients given >45 Gy preoperatively (median age 66 years; 29% women; tumour level <16 cm from the anal verge). RESULTS: Multivisceral and/or pelvic wall resections were performed in 61% of the patients. R0, R1 and R2 resections were achieved in 74%, 21% and 5%. Five-year survival was 52% for all patients, 60% for R0 resections, 31% for R1 and 0% for R2. The calculated 5-year recurrence rates were 13% for R0 resections and 24% for R1 resections (p<0.035). R-stage, N-stage, age, type of rectal resection and pelvic wall resection remained significant in Cox multivariate analysis for survival. Regarding local recurrence, the following parameters were independent: N-stage, carcinoembryonic antigen (CEA) response and pelvic wall resection. Medium high tumour level and reduced histopathological differentiation are important individual factors that seem to predict increased risk for not obtaining a R0 resection. CONCLUSIONS: After preoperative irradiation and surgery, about 50% of the patients with locally advanced rectal cancer without overt metastases (M0) can be cured.

Surgery and pre-operative irradiation for locally advanced or recurrent rectal cancer in patients over 75 years of age.

OBJECTIVE: Reports of multimodal treatment regimens especially focusing on locally advanced or recurrent rectal cancer in the elderly, aged>75 years, are unavailable. We have tried to identify and evaluate pre- and peri-operative risk factors for morbidity and mortality and outcome after irradiation/surgery regimens in such patients. PATIENTS AND METHODS: Prospective registration of 86 consecutive patients aged>75 years undergoing elective surgery after irradiation 46-50 Gy for either primary locally advanced rectal cancer (n=51) or recurrent rectal cancer (n=35) from January 1991 to August 2003, 51 men and 35 women, median age 78 years (range 75-85 years) in a national cancer hospital. RESULTS: Multivisceral resections were needed in 63% of patients and 70% R0 resections were obtained in locally advanced cases and 46% in recurrent ones. Both in-hospital- and 30-day-mortality was 3.5%. Sixty-two postoperative complications occurred in 38 patients, three of them fatal. Both operation times over 5 h and transfusion of more than 3 SAG were prognostic factors regarding infections. Estimated five-year survival in R0 patients was 46%. Estimated five-year survival for patients with nonmetastatic tumours with locally advanced primary cancer was 29% and for locally recurrent rectal cancer 32%. Old males had a higher mortality rate the first year after surgery than females with only 65% relative survival compared to a matched normal population. The estimated five-year local recurrence rates were 24% for R0 resections and 54% for R1 resections (P=0.434 ns) and 24% and 45% for locally advanced and recurrent rectal cancer (P=0.248 ns), respectively. CONCLUSION: Thorough pre-operative evaluation and preparation and judicious surgery are important for achieving potentially curative treatment with acceptable morbidity in locally advanced and recurrent rectal cancer in patients over 75 years of age. We suggest that these patients should be evaluated and considered for treatment by multidisciplinary teams as younger patients.

Radical prostatectomy for locally advanced primary or recurrent rectal cancer.

AIM: Three papers including five patients have described en bloc radical prostatectomy for locally advanced rectal cancer. METHODS: Six patients (median age 63 years) underwent en bloc radical prostatectomy for locally advanced (3) or recurrent (3) rectal cancer involving the prostate. Quality of life questionnaires were answered postoperatively and the data prospectively entered in a database. RESULTS: One primary case had low anterior resection (LAR), the others abdominoperineal resections (APR) of R0 stage. Two recurrent cases had APRs and one tumour resection-all R1 stage. Anastomotic leakage led to construction of an ileal conduit in one patient and in two healed on conservative treatment. Follow up was 10-50 months. One patient died from distant metastases at 29 months postoperatively, one was operated for a single lung metastasis and one has disseminated lung metastases. None has developed local recurrence. Four of the five with anastomoses had good quality of life and none wanted an ileal conduit. CONCLUSION: In spite of a relatively high urinary leak rate the total complication rate seems to be lower than after pelvic exenteration. En bloc radical prostatectomy seems an option in selected patients otherwise needing pelvic exenteration for locally advanced or recurrent rectal cancer.