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.

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.

Palliative interventions and prognosis in patients with advanced esophageal cancer.

In a retrospective review, in order to describe the palliative care and prognosis of patients with advanced cancer of the esophagus, the clinical characteristics and the treatment modalities applied were explored in relation to survival and symptom relief for 261 patients treated without curative potential. The data were obtained from a study of all patients with cancer of the esophagus treated at the Norwegian Radium Hospital in the 10-year period from 1990 to 1999. Medical data of the patients were reviewed and missing clinical information was retrieved from local hospitals and general practitioners. The patients were divided into three groups based upon the overall survival from start of treatment to death. Survival ≤3 months is in this paper, defined as 'short,' while survival > 6 months is defined as 'long.' Median survival for the total group of patients was 4 months. The 1-, 2-, and 3-year survival was 8%, 3%, and 1%, respectively. Patients with short survival (n= 107) had more advanced disease, lower performance status, and more dysphagia, weight loss, and pain and used more analgesics than patients with long survival (n= 91). Tumor characteristics such as localization, tumor length, and histology were not significantly associated with survival. This result was confirmed in a logistic regression analysis (with backward stepwise elimination) including sex, age, clinical stage, tumor length, tumor localization, histology, performance status, dysphagia, weight loss, and pain, where clinical stage, performance status, weight loss, and pain were included in the final model. A large variety of first-line palliative treatments were applied within the studied time period; external radiotherapy ± brachytherapy (n= 149), brachytherapy alone (n= 44), endoluminal stent (n= 28), laser evaporization (n= 8), chemotherapy (n= 5), and best supportive care only (n= 27). There were no clear differences in the effect on dysphagia between the modalities. Fourteen percent of the patients had treatment related complications. In conclusion, symptoms, performance status, and use of analgesics seemed to better prognosticate survival than tumor characteristics other than stage of disease. Our study reveals that knowledge about prognostic factors is crucial for the choice of palliative treatment. Even though all of the different treatment modalities seemed to provide relief of dysphagia, several other factors should be considered when deciding which treatment modality to offer. The time to onset of relief, duration of response, level of complications, and time spent in hospital should be a part of the decision-making process when selecting the appropriate treatment.

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.

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.

Nationwide quality assurance of rectal cancer treatment.

OBJECTIVE: The purpose of this prospective study was to examine the influence of the efforts for nationwide quality assurance of rectal cancer treatment. The study focuses on local recurrence and overall survival. METHODS: This study includes all 3388 Norwegian patients with a rectal cancer within 15 cm from the anal verge treated with curative intent in the period November 1993-December 1999. A comprehensive educational programme was established, and training courses were arranged in different Health Regions demonstrating the TME technique. A specific Rectal Cancer Registry enabled the monitoring of outcome of rectal cancer treatment for single hospitals. Radiotherapy was given to 10% of the patients. RESULTS: The risk of local recurrence has been significantly reduced, so that in 1999 the level was 50% below that observed in 1994 (Hazard ratio (HR)1999=0.5; 95% CI 0.4-0.8, P=0.002). Similarly, during 1998, the mean national overall survival was significantly improved, compared to the rate in 1994 (HR1998=0.8; 95% CI 0.6-1.0, P=0.014). CONCLUSION: The prognosis for rectal cancer can be improved by increased organizational focus on rectal cancer treatment and by establishing a rectal cancer registry monitoring treatment standards throughout the country.

Surgical treatment of primary locally advanced rectal cancer in Norway.

AIMS: Most reports on locally advanced rectal cancer come from specialized centres, with a selected patient material. The purpose of this study was to examine the results after surgical treatment of patients with locally advanced rectal cancer at a population level. METHODS: National cohort study of 896 patients undergoing surgery for a locally advanced primary adenocarcinoma of the rectum from November 1993 to December 2001. RESULTS: Surgery with resection was undertaken in 724 patients and 172 patients underwent palliative procedures. Of 557 patients treated for cure, a R0 resection was achieved in 342 (61%). In a multivariate analysis, pre-operative radiotherapy was the only factor with a positive association with R0 status (odds ratio 3.7, 95% confidence interval (CI) 2.1-6.4). Five-year local recurrence rates were 18% (CI 14-23) for R0 resections and 40% (CI 26-52) for R1 resections. Overall 5-year survival rate was 23%; for the group of patients with a R0 resection the survival rate was 49%. CONCLUSION: The radical resection rate and survival rates in this national study were similar to those reported from specialized centres.

Quality of life and functional outcome following anterior or abdominoperineal resection for rectal cancer.

AIMS: The aims of the study were (1) to evaluate quality of life (QoL) and functional outcome in patients following anterior resection (AR) or abdominoperineal resection (APR) for rectal cancer, and (2) whether these outcomes were dependent on the level of anastomosis. METHODS: Patients who were without recurrent or metastatic disease were identified from the Norwegian Rectal Cancer Registry. QoL was assessed by the EORTC questionnaires QLQ-C30 and QLQ-CR38, and rectal function by a short questionnaire. Of 319 patients studied, 229 had undergone AR and 90 APR. The median age was 73 years, and the median time since surgery was 64 months. RESULTS: Mean QoL scores for body image and male sexual problems were better following AR than APR (P<0.01), also in patients with a low (< or = 3 cm) anastomosis. Patients who had undergone AR had higher mean scores for constipation (P<0.001) and more often used anti-diarrhoeal medication (P=0.005), than patients who had undergone APR. Patients with a low anastomosis (< or = 3 cm) had more incontinence for gas and solid stools (P<0.05), and had more incontinence (P=0.006) compared with patients with higher anastomosis, but there was no difference in QoL. Subgroup analysis showed that irradiated patients (n=34) had worse rectal function in terms of frequency, urgency, and incontinence (P<0.01). CONCLUSIONS: Although rectal function was impaired in patients with low anastomosis, patients who had undergone AR had better QoL than patients who had undergone APR.

Anastomotic leakage following routine mesorectal excision for rectal cancer in a national cohort of patients.

OBJECTIVE: Mesorectal excision is successfully implemented as the standard surgical technique for rectal cancer resections in Norway. This technique has been associated with higher rates of anastomotic leakage (AL) and the purpose of this study was to examine AL in a large national cohort of patients. METHODS: This was a prospective national cohort study of 1958 patients undergoing rectal cancer surgery with anterior resection in Norway from November 1993 to December 1999. RESULTS: The overall rate of AL was 11.6% (228 of 1958 patients). In a multivariate analysis, the risk of AL was significantly higher in males (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.2), in patients receiving pre-operative radiotherapy (OR 2.2, CI 1.0-4.7) and in low level (4-6 cm) (OR 3.5, CI 1.6-7.7) and ultra-low level (< or = 3 cm) anastomoses (OR 5.4, CI 2.3-12.9). The presence of a diverting stoma was associated with a 60% reduction in the risk of AL (OR 0.4, CI 0.3-0.7) for anastomoses 6 cm and below. 30-day mortality was significantly higher for the patients with AL (7.0%, CI 3.7-10.3) compared with no AL (2.4%, CI 1.7-3.2) AL had no significant effect on local recurrence rate (log rank P=0.608). CONCLUSION: Low anastomoses should be defunctioned to avoid AL and the associated high perioperative mortality. No effect of AL on local recurrence was found in this large cohort.

Inadvertent perforation during rectal cancer resection in Norway.

BACKGROUND: Inadvertent perforation of the bowel or tumour is a relatively common complication during resection of rectal cancer. The purpose of this study was to examine intraoperative perforation following the introduction of mesorectal excision as a standard surgical technique in Norway. METHODS: This was a prospective national cohort study of 2873 patients undergoing major resection of rectal carcinoma at 54 Norwegian hospitals from November 1993 to December 1999. RESULTS: The overall perforation rate was 8.1 per cent (234 of 2873 patients). In a multivariate analysis, the risk of perforation was significantly greater in patients undergoing abdominoperineal resection (odds ratio (OR) 5.6 (95 per cent confidence interval (c.i.) 3.5 to 8.8)) and in those aged 80 years or more (OR 2.0 (95 per cent c.i. 1.2 to 3.5)). The 5-year local recurrence rate was 28.8 per cent following perforation, compared with 9.9 per cent in patients with no perforation (P<0.001); survival rates were 41.5 and 67.1 per cent respectively (P<0.001). CONCLUSION: The risk of intraoperative perforation was significantly greater in patients with rectal cancer undergoing abdominoperineal resection and in those aged 80 years or more. The high local recurrence rates and reduced survival following perforation call for increased attention to avoid this complication.

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.

Quality of life in patients with urinary diversion after operation for locally advanced rectal cancer.

AIMS: When locally advanced or recurrent rectal cancer involves the bladder or prostate, curative treatment often requires pelvic exenteration. The aim was to assess the quality of life (QoL) in disease-free patients with urinary diversion after extensive surgery for advanced rectal cancer. METHODS: Twelve patients with urinary diversion (cases) were compared with 25 randomly selected patients given the same treatment, but without urinary diversion (controls). An age- and gender-adjusted general population was identified (reference). QoL was assessed with the EORTC questionnaires QLQ-C30, QLQ-CR38, and parts of the QLQ-BLM30. RESULTS: The cases did not report significantly worse overall QoL than the controls or the reference population. Both cases and controls had low mean scores of sexual function, and high mean scores of male sexual problems. In the nine cases that had two stomas, overall QoL was not worse than in the control or reference groups. CONCLUSIONS: Tumour-free patients did not report worse QoL scores than the controls or the general population, despite most having two stomas and low sexual function. Fear of reducing the patient's QoL should not be a major contraindication when surgery with urinary diversion is warranted to obtain curative resection.

Intra-operative irradiation (IORT) for primary advanced and recurrent rectal cancer. a need for randomised studies.

The aim of this study was to determine the impact of intra-operative irradiation (IORT) combined with pre-operative external beam irradiation (EBRT) and surgical resection in patients with locally advanced primary or recurrent rectal cancer. 64 patients with locally advanced primary cancer and 104 with recurrence had EBRT (46-50 Gy) before surgery. 80 patients received IORT (median dose 15 Gy energy 12 MeV). 80 patients had R0 resections, 47 R1 and 41 R2 resections. More R1 resections were performed in the IORT group, more R0 and R2 resections in the non-IORT group. Median follow-up was around 22 months. 146 patients were resected, 22 had exploratory laparotomy. The cumulative overall survival was similar for both the IORT and non-IORT groups. 5-year survival for primary cancers was 48% versus 28% for recurrences. No R2 resections survived 3.5 years. 5-year-survival for R0 resections was nearly 60% and around 30% for R1 resections. The survival curves of the patients given and not given IORT treatment was not statistically different when R0, R1 and R2 resections were analysed separately. IORT did not seem to influence the local recurrence rate when R0 and R1 resections were analysed separately or in a multivariate analysis. The IORT and non-IORT groups were not identical with regard to type of cancer and R-stage. Still the lack of an identifiable impact of IORT suggests that there is a need for randomised studies of the IORT effect.

Location of pelvic recurrence after 'curative' low anterior resection for rectal cancer.

AIMS: It has been emphasized that the mesorectum is the key to local recurrence after resection for rectal cancer. In view of this we studied the location of recurrences, relative to the bed of the primary tumour, the neorectum and the level of anastomoses, in patients referred for recurrences after low anterior resection (LAR) in the <>. METHODS: The relative level above the anal verge of the primary cancer, the anastomosis and the recurrence was registered by proctoscopy in 46 patients operated on for recurrent cancer after low anterior resection. The origin of the recurrence was determined from the operative specimen. RESULTS: The median level of the primary cancers was 10 cm above the anal verge, with the anastomoses 2 cm lower, the majority being within 2 cm. Most recurrences were within 1 cm of the anastomosis. No rectal cancer occurred more than 3 cm distal to the anastomosis. Seventy to 80% of recurrences started peri-rectally, most invading the anastomosis. CONCLUSIONS: The tumour bed is most often the origin of the recurrence. Recurrences were mostly due to inadequate radial, and in a few cases longitudinal, dissection of the mesorectum. Virtually all recurrences were within reach of the examining finger. At follow-up of rectal cancers most local recurrences can therefore be identified earlier by digital examination than by proctoscopy.

Mesorectal excision for rectal cancer: a view from Europe.

The local recurrence rate after rectal cancer surgery is discussed as related to conventional and total mesorectal excision (TME) techniques. Studies now show that the wide variation in results between centers and among surgeons depends, at least in part, on differences in surgical technique. We conclude that local tumor recurrence rate is lower after TME than after conventional surgery and emphasize the importance of a standardized macroscopic evaluation of the resected specimen. Population-based registration to evaluate the quality of surgery is recommended. It is also suggested that randomized studies on adjuvant treatment for rectal cancer should include a "surgery only" arm when a local tumor recurrence rate of 10% or less is being studied. Until such investigations are performed, we conclude that the role for adjuvant treatment is questionable and that TME surgery is preferred as the treatment option for Stage T1-T3 rectal cancers.

Combined modality treatment including intraoperative radiotherapy in locally advanced and recurrent rectal cancer.

BACKGROUND: Treatment of locally advanced and recurrent rectal cancer usually has a high local recurrence rate and poor survival. Promising results have been reported by combined external radiotherapy, extensive surgery and intraoperative radiotherapy (IORT). METHODS: One hundred fifteen patients with locally advanced rectal cancers fixed to the pelvic wall or locally recurrent rectal cancers underwent preoperative external radiotherapy with 46-50 Gy. Six to 8 weeks later radical pelvic surgery was attempted, and was combined with intraoperative electron beam radiotherapy (15-20 Gy) in 66 patients. The patients were followed closely to evaluate complication rate, local and distant recurrence rate and survival. RESULTS: Surgery with no macroscopic tumour remaining was obtained in 65% of the patients with no postoperative deaths. Pelvic infection was the major complication (21%). Although the observation time is short (3-60 months), the local recurrence rate seems low (22%) and survival seems promising (about 60% at 4 years) in patients with complete tumour resection, in contrast to patients with residual tumour (none living at 4 years). CONCLUSIONS: The combined modality treatment with preoperative external radiotherapy and extensive pelvic surgery with IORT is sufficiently promising to start a randomized trial on the clinical value of IORT as a boost treatment in the multidisciplinary approach to this disease.

Esophageal and gastric carcinoma in Norway 1958-1992: incidence time trend variability according to morphological subtypes and organ subsites.

The occurrence of adenocarcinoma (AC) of the esophagus and gastric cardia has shown large increases in many but not all examined populations. This trend is in contrast with a decrease in distal gastric AC and a relative stability of esophageal squamous cell carcinoma. Our study aimed to describe esophageal and gastric carcinoma time trends in the Norwegian population between 1958 and 1992 based on data from the Cancer Registry of Norway. Estimated esophageal AC rates have accelerated over the study period, reaching average annual increases of 17% in men and 14% in women between 1983 and 1992. The occurrence of esophageal squamous cell carcinoma was relatively stable in both sexes. Proximal gastric cancer rates were stable in males and decreased somewhat in females. Distal gastric tumors showed decreases in both sexes, but were more pronounced in females. The strong increase in esophageal AC incidence parallels similar increases in the United States and some other countries. Although the observed increase may be explained to some extent by a shift in the classification of esophago-cardial adenocarcinomas, the figures are compatible with a real increase. AC of the esophagus, the proximal stomach and the distal stomach exhibit different epidemiological features, both in terms of sex ratios and time trends, suggesting risk factor differences between the subsites.