Hyperthermic intraperitoneal chemotherapy in colorectal cancer.

BACKGROUND: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. PATIENTS AND METHODS: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. RESULTS: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. CONCLUSIONS: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

Short-term results after robot-assisted surgery for primary rectal cancers requiring beyond total mesorectal excision in multiple compartments.

AIM: Rectal cancers requiring beyond total mesorectal excision (bTME) are traditionally operated using an open approach, but the use of minimally invasive robot-assisted procedures is increasing. Introduction of minimal invasive surgery for complex cancer cases could be associated with compromised surgical margins or increased complication rates. Therefore, reporting results both clinical and oncological in large series is important. Since bTME procedure reports are heterogeneous, comparing results is often difficult. In this study, a magnetic resonance imaging (MRI) classification system was used to describe the bTME surgery according to pelvic compartments. METHODS: Consecutive patients with primary rectal cancer operated with laparoscopic robot-assisted bTME were prospectively included for 2 years. All patients had tumors that threatened the mesorectal fascia, invaded adjacent organs, and/or involved metastatic pelvic lateral lymph nodes. Short-term clinical outcomes and oncological specimen quality were registered. Surgery was classified according to pelvic compartments resected. RESULTS: Clear resection margins (R0 resection) were achieved in 95 out of 105 patients (90.5%). About 26% had Accordion Severity Grading System of Surgical Complications grade 3-4 complications and 15% required re-operations. About 7% were converted to open surgery. The number of compartments resected ranged from one to the maximum seven, with 83% having two or three compartments resected. All 10 R1 resections occurred in the lateral and posterior compartments. CONCLUSIONS: The short-term clinical outcomes and oncological specimen quality after robot-assisted bTME surgery were comparable to previously published open bTME surgery. The description of surgical procedures using the Royal Marsden MRI compartment classification was feasible.

Navigation-Assisted Surgery for Locally Advanced Primary and Recurrent Rectal Cancer.

BACKGROUND: In some surgical disciplines, navigation-assisted surgery has become standard of care, but in rectal cancer, indications for navigation and the utility of different technologies remain undetermined. METHODS: The NAVI-LARRC prospective study (NCT04512937; IDEAL Stage 2a) evaluated feasibility of navigation in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC). Included patients had advanced tumours with high risk of incomplete (R1/R2) resection, and navigation was considered likely to improve the probability of complete resection (R0). Tumours were classified according to pelvic compartmental involvement, as suggested by the Royal Marsden group. The BrainlabTM navigation platform was used for preoperative segmentation of tumour and pelvic anatomy, and for intraoperative navigation with optical tracking. R0 resection rates, surgeons' experiences, and adherence to the preoperative resection plan were assessed. RESULTS: Seventeen patients with tumours involving the posterior/lateral compartments underwent navigation-assisted procedures. Fifteen patients required abdominosacral resection, and 3 had resection of the sciatic nerve. R0 resection was obtained in 6/8 (75%) LARC and 6/9 (69%) LRRC cases. Preoperative segmentation was time-consuming (median 3.5 h), but intraoperative navigation was accurate. Surgeons reported navigation to be feasible, and adherence to the resection plan was satisfactory. CONCLUSIONS: Navigation-assisted surgery using optical tracking was feasible. The preoperative planning was time-consuming, but intraoperative navigation was accurate and resulted in acceptable R0 resection rates. Selected patients are likely to benefit from navigation-assisted surgery.

Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study.

Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM. Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed. Findings: Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy. Interpretation: Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting. Funding: None.

Cancer therapy with isolated limb perfusion. / Kreftbehandling med isolert ekstremitetsperfusjon.

For locally advanced soft tissue sarcomas and metastases from melanoma located in the extremities, mutilating surgery or amputation may be necessary to achieve local control. Isolated limb perfusion with high-dose chemotherapy may represent an alternative to amputation for this patient group.

Metastases in locally advanced rectal cancer undergoing curatively intended treatment.

BACKGROUND: The main cause of mortality in locally advanced rectal cancer (LARC) is metastatic progression. The aim of the present study was to describe frequency, pattern and outcome of metastatic disease in a cohort of LARC patients after curative resection. METHODS: This was a single-centre cohort study of 628 LARC cases after neoadjuvant chemoradiotherapy/radiotherapy (CRT/RT) and surgery. Data, including the first site of metastasis, was registered in an institutional database linked to the National Cancer Registry. RESULTS: Metastases were diagnosed in 270 patients (43.0%) with liver and lungs as the first site in 113 and 96 cases, respectively. Involved resection margins, high tumour stage and poor response to CRT/RT were associated with metastasis development and inferior overall survival (OS). Metastasectomy was performed in 76 (67.3%) patients with liver metastases and 28 (29.2%) patients with lung metastases. Five-year OS was 89% in patients without metastases and 32% in metastatic cases. In patients selected for metastasectomy, 5-year OS was 69% and 53% for lung and liver metastases, respectively. Corresponding numbers without metastasectomy were 12% and 0%. CONCLUSION: In this large LARC cohort undergoing curatively intended treatment, liver and lung metastases occurred at similar frequencies. Liver as the first metastatic site was associated with inferior long-term outcome, while selection for metastasectomy was associated with better OS, with more than half of the resected patients being alive five years after LARC surgery. Our results show that the presence of resectable metastatic disease at diagnosis should not exclude a curative therapeutic approach in LARC.

ImmunoPeCa trial: Long-term outcome following intraperitoneal MOC31PE immunotoxin treatment in colorectal peritoneal metastasis.

BACKGROUND: The ImmunoPeCa trial investigated the use of intraperitoneal MOC31PE immunotoxin as a novel therapeutic principle for the treatment of peritoneal metastasis from colorectal cancer (PM-CRC). We here report long-term outcome from the trial. METHODS: This was a dose-finding trial aiming to evaluate safety and toxicity (primary endpoint) upon a single dose of intraperitoneal MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with mitomycin C. Overall survival (OS) and disease-free survival (DFS) were secondary endpoints. Twenty-one patients received the study drug at four dose levels on the first postoperative day, including six patients constituting an expansion cohort. RESULTS: With a 34-month follow-up, the median OS was not reached and the estimated 3-year OS was 78%. Median DFS for all patients was 21 months and the 3-year DFS was 33%, with a median follow-up of 31 months. When excluding patients with potential favorable characteristics from the analysis (n = 4), the median DFS was 13 months and the 3-year OS 72%. CONCLUSIONS: The promising long-term outcome combined with low systemic absorbance, high drug concentration and cytotoxic activity in peritoneal fluid support further investigations of clinical efficacy.

Integrative genomic analysis of peritoneal malignant mesothelioma: understanding a case with extraordinary chemotherapy response.

Peritoneal malignant mesothelioma is a rare disease with a generally poor prognosis and poor response to chemotherapy. To improve survival there is a need for increased molecular understanding of the disease, including chemotherapy sensitivity and resistance. We here present an unusual case concerning a young woman with extensive peritoneal mesothelioma who had a remarkable response to palliative chemotherapy (platinum/pemetrexed). Tumor samples collected at surgery before and after treatment were analyzed on the genomic and transcriptional levels (exome sequencing, RNA-seq, and smallRNA-seq). Integrative analysis of single nucleotide and copy-number variants, mutational signatures, and gene expression was performed to provide a comprehensive picture of the disease. LATS1/2 were identified as the main mutational drivers together with homozygous loss of BAP1 and PBRM1, which also may have contributed to the extraordinary chemotherapy response. The presence of the S3 mutational signature is consistent with homologous recombination DNA repair defects due to BAP1 loss. Up-regulation of the PI3K/AKT/mTOR pathway after treatment, supported by deactivated PTEN through miRNA regulation, is associated with cancer progression and could explain chemotherapy resistance. The molecular profile suggests potential benefit from experimental targeting of PARP, EZH2, the PI3K/AKT/mTOR pathway and possibly also from immune checkpoint inhibition. In addition to providing the molecular background for this unusual case of peritoneal mesothelioma, the results show the potential value of integrative genomic analysis in precision medicine.

Vertical Rectus Abdominis Musculocutaneous Flap Repair Improves Perineal Wound Healing after Abdominoperineal Resection for Irradiated Locally Advanced Rectal Cancer.

BACKGROUND: Radiotherapy (RT) and subsequent abdominoperineal resection (APR) for locally advanced rectal cancer (LARC) is associated with significant perineal wound morbidity. The aim of the present study was to investigate if vertical rectus abdominis musculocutaneous (VRAM) flap repair after APR in LARC patients improves perineal wound healing compared with direct perineal wound closure (non-VRAM). METHODS: LARC patients (n = 329) operated with APR between January 2006 and December 2015 after neoadjuvant RT of ≥ 25 Gy were identified, including 260 and 69 patients in the non-VRAM and VRAM groups, respectively. Perineal wound healing was assessed 3 months postoperatively, and risk factors for perineal wound complications and associations with short- and long-term outcome were analyzed. RESULTS: Delayed perineal wound healing after 3 months was more frequent in the non-VRAM group (31.5%) compared with the VRAM group (10.4%) (p < 0.01). In the non-VRAM group, 26.9% of patients developed pelvic abscess, compared with 10.1% in the VRAM group (p < 0.01). Significant risk factors for perineal wound morbidity were non-VRAM (odds ratio [OR] 3.94, 95% confidence interval [CI] 1.72-9.00; p = 0.02), positive circumferential resection margin (R1; OR 3.64, 95% CI 1.91-6.93; p < 0.01), pelvic abscess (OR 3.27, 95% CI 1.90-5.63; p < 0.01), and short-course RT (OR 3.81, 95% CI 1.75-8.30; p < 0.01). Perineal wound morbidity was not associated with impaired long-term oncologic outcome. CONCLUSIONS: VRAM flap reconstruction of the perineum is associated with an increased wound healing rate and may protect against pelvic abscess development. However, procedure-related long-term morbidity is incompletely studied and the procedure should be reserved for selected patients.

Novel Treatment with Intraperitoneal MOC31PE Immunotoxin in Colorectal Peritoneal Metastasis: Results From the ImmunoPeCa Phase 1 Trial.

BACKGROUND: MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC. METHODS: This was a dose-escalating phase I trial to evaluate the safety and toxicity (primary endpoint), pharmacokinetic profile, and neutralizing antibody response (secondary endpoints) upon intraperitoneal administration of MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with Mitomycin C. Fifteen patients received the study drug at four dose levels (3+3+3+6), administered intraperitoneally as a single dose the day after CRS-HIPEC. RESULTS: No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. There was negligible systemic absorption of the study drug. Drug concentrations in peritoneal fluid samples were in the cytotoxic range and increased in a dose-dependent manner. MOC31PE recovered from peritoneal cavity retained its cytotoxic activity in cell-based assays. All patients developed neutralizing antibodies. CONCLUSIONS: Intraperitoneal administration of MOC31PE was safe and well tolerated, and combined with low systemic uptake, MOC31PE seems ideal for local intraperitoneal treatment. The drug will be further evaluated in an ongoing phase II expansion cohort.

Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis in Norway: Prognostic factors and oncologic outcome in a national patient cohort.

BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can offer long-term survival to patients with resectable peritoneal metastasis (PM) from colorectal cancer (CRC), a condition with otherwise dismal prognosis. This study describes short- and long-term outcome in a national patient cohort and aims to identify prognostic factors. METHODS: All patients treated with CRS-HIPEC for non-appendiceal PM-CRC in Norway 2004-2013 were included (n = 119), and outcome and potential prognostic factors were examined using survival- and ROC-curve analysis. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) were 36% and 14%, respectively, with 45 months median follow-up. The only factor associated with OS in multivariable analysis was peritoneal cancer index (PCI), with HR 1.05 (1.01-1.09) for every increase in PCI-score (P = 0.015). Peritoneal relapse was associated with shorter OS than distant metastasis (P = 0.002). ROC-curves identified PCI > 12 as a marker with 100% specificity for prediction of disease relapse. Severe postoperative complications (Clavien-Dindo ≥ 3) occurred in 15% of patients and there was no 100-day mortality. CONCLUSIONS: Long-term outcome was in line with published results, morbidity was acceptable and there was no 100-day mortality. The results reemphasize CRS-HIPEC as an important treatment option in PM-CRC, with particularly good results in patients with PCI < 12. J. Surg. Oncol. 2016;114:222-227. © 2016 Wiley Periodicals, Inc.

Nationwide improvement of rectal cancer treatment outcomes in Norway, 1993-2010.

BACKGROUND: The Norwegian Rectal Cancer Project was initated in 1993 with the aims of improving surgery, decreasing local recurrence rates, improving survival, and establishing a national rectal cancer registry. Here we present results from the Norwegian Colorectal Cancer Registry (NCCR) from 1993 to 2010. MATERIAL AND METHODS: A total of 15 193 patients were diagnosed with rectal cancer in Norway 1993-2010, and were registered with clinical data regarding diagnosis, treatment, locoregional recurrences and distant metastases. Of these, 10 796 with non-metastatic disease underwent tumour resection. The results were stratified into five time periods, and the treatment outcomes were compared. Recurrence rates are presented for the 9785 patients who underwent curative major resection (R0/R1). RESULTS: Among all 15 193 patients, relative five-year survival increased from 54.1% in 1993-1997 to 63.4% in 2007-2010 (p < 0.001). Among the 10 796 patients with stage I-III disease who underwent tumour resection, from 1993-1997 to 2007-2010, relative five-year survival improved from 71.2% to 80.6% (p < 0.001). An increasing proportion of these patients underwent surgery at large-volume hospitals; and 30- and 100-day mortality rates, respectively, decreased from 3.0% to 1.4% (p < 0.001) and from 5.1% to 3.0% (p < 0.011). Use of preoperative chemoradiotherapy increased from 6.5% in 1993 to 39.0% in 2010 (p < 0.001). Estimated local recurrence rate after major resection (R0/R1) decreased from 14.5% in 1993-1997 to 5.0% in 2007-2009 (p < 0.001), and distant recurrence rate decreased from 26.0% to 20.2% (p < 0.001). CONCLUSION: Long-term outcomes from a national population-based rectal cancer registry are presented. Improvements in rectal cancer treatment have led to decreased recurrence rates of 5% and increased survival on a national level.

Molecular detection (k-ras) of exfoliated tumour cells in the pelvis is a prognostic factor after resection of rectal cancer?

BACKGROUND: After total mesorectal excision (TME) for rectal cancer around 10% of patients develops local recurrences within the pelvis. One reason for recurrence might be spillage of cancer cells during surgery. This pilot study was conducted to investigate the incidence of remnant cancer cells in pelvic lavage after resection of rectal cancer. DNA from cells obtained by lavage, were analysed by denaturing capillary electrophoresis with respect to mutations in hotspots of the k-ras gene, which are frequently mutated in colorectal cancer. RESULTS: Of the 237 rectal cancer patients analyzed, 19 had positive lavage fluid. There was a significant survival difference (p = 0.006) between patients with k-ras positive and negative lavage fluid. CONCLUSION: Patients with k-ras mutated cells in the lavage immediately after surgery have a reduced life expectation. Detection of exfoliated cells in the abdominal cavity may be a useful diagnostic tool to improve the staging and eventually characterize patients who may benefit from aggressive multimodal treatment of rectal cancer.

Pseudomyxoma peritonei--two novel orthotopic mouse models portray the PMCA-I histopathologic subtype.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease, most commonly originating from appendiceal lesions and characterized by accumulation of mucinous tumor tissue in the peritoneal cavity. Since the disease is infrequent, the task of carrying out studies of treatment efficacy and disease biology in the clinical setting is challenging, warranting the development of relevant in vitro and in vivo PMP models. METHODS: Human tumor tissue was implanted in the peritoneal cavity of nude mice to establish two orthotopic models exhibiting noninvasive intraperitoneal growth without metastasis development. RESULTS: Xenograft tissues have retained essential properties of the original human tumors, such as macro- and microscopic growth patterns, mucin production as well as expression of carcinoembryonal antigen, cytokeratins 20 and 7 and the proliferation marker pKi67. Upon microscopic examination, the human tumors were categorized as the PMCA-I (peritoneal mucinous carcinomatosis of intermediate features) subtype, which was conserved through 14 examined passages in mice, for the first time modeling this particular histopathologic category. CONCLUSION: In conclusion, two novel orthotopic models of human PMP have been established that consistently portray a distinct histopathologic subtype and reflect essential human tumor properties. Xenografts can easily and reproducibly be transferred to new generations of mice with acceptable passage periods, rendering the models as attractive tools for further studies of PMP biology and treatment.

Clinical outcome in patients with complete pathologic response (pT0) to preoperative irradiation/chemo-irradiation operated for locally advanced or locally recurrent rectal cancer.

BACKGROUND: The importance of pT0 stage after preoperative radiation/chemoradiation is unclear. METHODS: Four hundred and nineteen patients had preoperative irradiation (46-50 Gy/2 Gy fractions) for primary locally advanced (PLA) or locally recurrent (LR) rectal cancer. 141 PLA and 65 LR cases with R0 resections/M0 stage are studied. Two of the pT0 PLA patients had also been given sensitizing chemotherapy and two pT0 in the LR group had received pelvic hyperthermia as well. RESULTS: pT0 was achieved in 7% of 229 PLA and 8% of 190 LR patients. For the PLA group, actuarial 5-year survival of pT0 was 90% versus 53% for the pT > 0 group. The difference was statistically significant. At five years local recurrence was zero in pT0 patients versus 23% in pT > 0 (not significant). For the LR groups 5-year-survival was 62% for pT0 versus 45% for the other pT-stages, local recurrence was 17 and 35% respectively (not significant). The seemingly better results for pT0 cases of PLA cancers versus the LR ones did not reach statistical significance. CONCLUSION: pT0 after preoperative irradiation is associated with improved survival for pT0 cases of PLA. Our studies on pT0 LR was suggestive of an improvement in this group as well.

Hydronephrosis as a prognostic factor in pelvic recurrence from rectal and colon carcinomas.

BACKGROUND: After multimodal treatment estimated 5-year survival of locally recurrent rectal cancer is about 25%. Hydronephrosis secondary to pelvic recurrence of colorectal cancer is a condition claimed to represent a contraindication to surgery due to a dismal prognosis. METHODS: Prospective registration of 193 consecutive patients operated for pelvic recurrence in rectal or colon cancer from January 1991 until March 2002 at a tertiary referral hospital, 121 men and 72 women, median age 67 years, all given irradiation preoperatively. Twenty-three of 193 had hydronephrosis prior to preoperative irradiation for recurrent disease. RESULTS: R-0 stage resection was obtained in 22% of patients with hydronephrosis and in 41% without. The median survival times in patients without metastasis were 27 and 32 months, respectively, and 5-year survival rates were 11% and 25%. CONCLUSIONS: An aggressive surgical approach offers patients with pelvic recurrence from rectal and colon cancer the best potential for survival. The presence of hydronephrosis probably indicates a lower chance for complete surgical resection of the recurrence, but local control and improved survival may still be achieved, and about two thirds of patients may benefit from the operation.

Operative treatment of locally recurrent rectal cancer.

Few centres with varying regimens have published studies including more than 100 patients on the treatment of locally recurrent rectal cancer. The results vary considerably. Thus there seems to be a need for more studies to establish the potential benefit of a more widespread treatment of these cancers. In total, 193 patients had surgery for locally recurrent rectal cancers after preoperative irradiation 46-50 Gy in 2 Gy fractions. The patients were followed up and the data prospectively entered in a database. In 88 patients with primary low anterior resection, 3% had lower end of tumour located more than 2 cm above the anastomosis, 5% more than 2 cm below the anastomosis; 13% had exploratory laparotomy, 8% low anterior resections, the rest equally frequent abdomino-perineal resections, Hartmann's operations, and tumour resections. Nearly half had resection of part of the pelvic wall. Hysterectomy was performed in 15% and cystoprostatectomy in 9%. Three patients had en bloc prostatectomy. R0 resections were achieved in 39%, R1 in 36%, and R2 or no resection in 25%. R0 stage was twice as often achieved after a primary low anterior resection as after abdomino-perineal resections. The 30-days postoperative mortality was 1%. Postoperative morbidity was 48%, most frequently pelvic abscesses. Estimated 5-year survival was 18% for the total group. There was a statistically significant difference in survival and local re-recurrences between R0 / R1 and R2 stages. The results are discussed relative to recent studies. Patients in whom R0 resections can be achieved will benefit from the treatment, and probably patients with R1 resections would also benefit. Such operations should possibly be performed in specialised centres as joint ventures between various surgical subspecialities.