AIMS:The purpose of the study was to evaluate the response to palliative radiotherapy in patients with painful spinal metastatic disease (SMD).MATERIALS AND METHODS:Three hundred and fifty-five patients admitted to the Norwegian Radium Hospital for radiotherapy for painful SMD were included in a prospective study and were followed up 2 months later. The Brief Pain Inventory was used to assess pain. Analgesic consumption was recalculated into the daily oral morphine-equivalent dose. The radiotherapy-related response rates were calculated using the criteria of the International Bone Metastases Consensus Group (IBMCG), taking into account the use of concomitant analgesics. The response to radiotherapy was assessed as complete or partial and non-response as stable pain, pain progression or 'other'.RESULTS:Brief Pain Inventory forms were obtained at follow-up from 229 of the 355 patients. Two months after radiotherapy, the median self-reported worst pain decreased significantly, but the median oral morphine-equivalent dose increased from 40 to 60 mg (P<0.001). Forty-three per cent of the patients reported pain relief, but a radiotherapy-related response was found in 37% of the patients. Overall correspondence between the patients' self-reported changes in pain experience and the IBMCG-based response categories was obtained in 63% of the patients.CONCLUSIONS:The radiotherapy-related response rates in our study were lower than those reported previously in patients with bone metastases in general, which possibly indicates the presence of more complex pathophysiological mechanisms of pain in SMD.

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.

Background: The importance of pTO 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 pTO PLA patients had also been given sensitizing chemotherapy and two pTO in the LR group had received pelvic hyperthermia as well.Results: pTO was achieved in 7% of 229 PLA and 8% of 190 LR patients. For the PLA group, actuarial 5-year survival of pTO was 90% versus 53% for the pT > 0 group. The difference was statistically significant. At five years local recurrence was zero in pTO patients versus 23% in pT > 0 (not significant). For the LR groups 5-year-survival was 62% for pTO versus 45% for the other pT-stages, local recurrence was 17 and 35% respectively (not significant). The seemingly better results for pTO cases of PLA cancers versus the LR ones did not reach statistical significance.Conclusion: pTO after preoperative irradiation is associated with improved survival for pTO cases of PLA. Our studies on pTO LR was suggestive of an improvement in this group as well.

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. (c) 2005 Excerpta Medica Inc. All rights reserved.

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 abdominciperineal resections (APR) of R0 stage. Two recurrent cases had APRs and one tumour resection-all RI 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. (C) 2003 Elsevier Science Ltd. All rights reserved.

Topical photodynamic therapy (PDT) of superficial basal cell carcinoma (BCC) with 5-aminolevulinic acid (ALA) has achieved promising clinical results. However, the efficacy of this therapy for thick BCC is dramatically decreased by a limited diffusion of hydrophilic ALA into the tumor. Lipophilic esters of ALA may enhance their penetration into the lesion. In this randomized, open clinical study, microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the penetration of methyl 5-aminolevulinate-induced porphyrin fluorescence in thick BCC lesions. Both the distribution pattern and the amount of porphyrins in 32 lesions of 16 patients were studied after topical application of 16, 80 or 160 mg/g of methyl 5-aminolevulinate for 3 or 18 h. A highly selective and homogeneous distribution of methyl 5-aminolevulinate-induced porphyrin fluorescence was seen in all lesions studied, with much less fluorescence in the adjacent normal skin tissues. In lesions of up to 2 mm thickness the application of 160 mg/g methyl 5-aminolevulinate for 3 h showed the highest ratio of porphyrin fluorescence depth to tumor depth (0.98±0.04), thus providing a biologic rationale for a clinical PDT trial with this regimen.

BACKGROUND:Remarkably little is known about the molecular alterations contributing to the establishment of a distant metastasis from a primary colorectal carcinoma. Previous studies on primary colorectal carcinomas have suggested an association between loss of chromosome 14 sequences and cancer progression.METHODS:In the present study, we analyzed 20 distant metastases and peripheral blood samples from 18 patients using 24 microsatellite markers spanning chromosome arm 14q. In addition, DNA from microdissected corresponding primary tumors (formalin-fixed and paraffin-embedded) was analyzed at selected 14q loci.RESULTS:Sixty-five percent (13/20) of the metastases, from 11/18 patients, showed loss of one or more markers at 14q, and the majority (94%) of the primary carcinomas showed identical 14q genotypes to those found in the metastasis. Two minimal common deleted regions were delineated in the metastases, one between markers D14S288-D14S52 at 14q13-21 and the other between D14S284-D14S81 at 14q24-31, pinpointing two previously unrecognized map positions for potential target genes. The genotype pattern of five tumors was consistent with monosomy or large chromosomal deletions spanning both potential suppressor regions. The reasons for monosomy in cancer remain unknown, but our data support the hypothesis that deletions of several tumor suppressor genes are more readily obtained by one chromosome loss than by several molecular events, and through this unison loss a growth advantage may be provided.CONCLUSION:Our data suggest that 14q loss is not a rate-limiting event in colorectal metastasis formation, but the high frequency of this alteration in primary tumors with metastatic ability, as well as in the metastases themselves, suggests it is part of the tumor clone with selective growth capacity.

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.

BACKGROUNDMethyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA.OBJECTIVESTo assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment.METHODSOf 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed histologically in 23 biopsies.RESULTSThe overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies.CONCLUSIONSWe conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.

Practically all of the exogenous photosensitizers used for clinical photodynamic therapy (PDT) target mainly vasculature. Although effective in tumor destruction, they also, unavoidably, induce phototoxicity of normal tissues. Porphyrins synthesized endogenously from 5-aminolevulinic acid (ALA) accumulate within cells. Tumor eradication would be more efficient if both cellular components and vascular stroma of a tumor could be targeted. Thus, PDT with a mixture of ALA and Photofrin (Pf, a vessel-targeted sensitizer) may simultaneously destroy the two elements. Using chemical extraction assays, pharmacokinetics of ALA and ALA-induced porphyrins were studied in the plasma and tumors of nude mice bearing human WiDr and KM20L2 colonic carcinomas after an i.p. injection of 250 mg/kg body weight of ALA. Subsequently, PDT efficacy of the two tumor models with ALA, Pf, or with the two drugs in combination was evaluated. The phototoxic effects on tumor cells in vitro with the combined drugs was also determined. Moreover, histological and ultrastructural alterations of the treated tumors were investigated, and tumor cell clonogenicity was assessed as a function of time after in vivo PDT using an in vitro colony formation assay. Finally, the photosensitivity of normal skin tissue treated according to various protocols was compared. The amounts of ALA peaked at 0.5 h after administration in both plasma and WiDr tumor. The rates of ALA clearance seemed to follow a one-compartment model with half-lives of approximately 18 and 58 min in the plasma and tumor, respectively. About 100 and 60 times higher concentrations of ALA were needed to induce a given concentration of porphyrins in the plasma and tumor, respectively, although the plasma porphyrins may not only be released from blood cells but also from other organs. Similar kinetics of distribution patterns of ALA- and ALA methylester-induced porphyrins were found in the plasma and tumors, and the elimination rates were consistent with a two-compartment model. ALA induced much more porphyrins than ALA methylester in both plasma and tumors. Tumors PDT-treated with ALA plus Pf at a low dose (1 mg/kg) grew significantly more slowly than those treated with either of the drugs in both WiDr and KM20L2 models. However, the enhanced antitumor effect was not found in the tumor cells under in vitro conditions. Morphological studies demonstrated that PDT with the combined regimen resulted in necrosis of neoplastic cells and severe disruption of tumor microvasculature. This was supported by the findings obtained from the studies of in vivo PDT and in vitro clonogenic assay that showed a progressive reduction in tumor cell viability with times following PDT. Such a combined PDT protocol did not induce any phototoxicity in normal skin tissue. These data indicate that targeting both neoplastic cells and stroma with ALA and Pf (a low dose) can potentiate antitumor PDT effect with no risk of prolonged skin photosensitivity.

Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of ip deletions in primary carcinomas (n=28), local recurrences (n=19) and metastases (n=33) from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04). The smallest region of 1p deletion overlap (SRO) defined separately for each group of lesions had the region between markers Di S2647 and D1 S2644, at 1 p35-36, in common. The genes PLA2G2A (1p35.1-36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18) were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%). The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.

Cancer of the prostate remains poorly characterized cytogenetically. This is due in part to methodological problems and in part to the paucity of radical prostatectomies, until now the main source of material for cytogenetic analyses. We have improved existing techniques for the culturing of prostatic neoplasms removed by radical prostatectomy or sampled by ultrasound-guided needle biopsy. Successful short-term cultures were obtained from all 10 prostatectomy samples and from all 10 ultrasound-guided needle biopsies, always with a pure epithelial morphology. Of the 19 cases yielding a sufficient number of high-quality metaphases for chromosome banding analysis, the single atypical epithelial hyperplasia had a normal karyotype, whereas both prostatic intraepithelial neoplasias and 12 of 16 (75%) invasive carcinomas were shown to have clonal abnormalities. Ten of the 12 (83%) karyotypically abnormal invasive carcinomas presented structural chromosomal rearrangements. A recurrent deletion, del(10)(p13), was seen in three tumors; in one of them the terminal nature of the deletion was confirmed by two-color FISH. A del(17)(p11) was seen in one PIN lesion, but since the analysis of exons 4-8 of the TP53 tumor suppressor gene revealed no mutations, there probably was no inactivation of the second TP53 allele. Our study thus leads to the following main conclusions. First, better culturing methods allow the detection of abnormal karyotypes in a much higher percentage of prostatic neoplasms than has hitherto been possible. Second, ultrasound-guided needle biopsies of prostatic neoplasms are a sufficient source of material for cytogenetic analysis. Third, a terminal deletion of the short arm of chromosome 10, del(10)(p13), seems to identify a subgroup of prostatic 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.

2102 women over 55 years of age from breast cancer kindreds as clinically defined were examined with annual clinical examination and mammography every second year. Initially, all family histories were obtained and all women were invited for genetic counselling. During screening, 37 infiltrating cancers (CA) and 9 carcinomas in situ (CIS) were found. Annual incidence rates for CA or CIS were calculated to be 0.82% for those aged 30 years or more. Annual incidence rate for contralateral cancer among those who had contracted one cancer was 6%. In the first round, 17 of 23 cancers (74%) were without spread, and this increased to 20 of 23 (87%) during follow-up. Two of 23 cancers (18%) were CIS at the first round, increasing to 7 of 23 (30%) at follow-up visits. CIS was diagnosed at a younger age than CA. Employing figures for mean sojourn time from sporadic cancer to calculate the annual incidence rate underlying the observation in the first round gave the same incidence as observed during actual follow-up. This indicates that inherited breast cancer progression is comparable with that of sporadic cancer.

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. (C) 1997 Wiley-Liss, Inc.

A biologically absorbable powder, the cornstarch lubricant used in the production of gloves, is treated with epichlorohydrin, a cross-linking agent forming one to three diether glycerine groups to create a glove lubricating powder. This agent, together with chemicals used in glove fabrication is able to interfere with important biological diagnostic procedures, such as polymerase chain reaction (PCR) and enzyme immunoassay as well as to induce a granulomatous reaction in traumatised surgical tissue.

A Ki-67 index was determined in 63 fine needle aspiration cytology (FNAC) specimens from patients with rectal cancer, 21 with primary cancers and 42 with local recurrences, Seventeen of the patients had received external irradiation before the examination, In primary cancers, in recurrences as well as in the post-irradiation cases, the mean percentage of Ki-67 positive cells was about 55% with a wide variation, The percentage of Ki-67 positive cells was independent of the length of the recurrence-free period. In conclusion, the Ki-67 antigen may well be studied in FNAC specimens. The presence of antigen did not correlate with development of recurrence, length of recurrence-free period or irradiation prior to the analysis.

BACKGROUND:The occurrence of glove powder granulomas in peritoneal nodules presumed to represent carcinomatosis has not gained widespread attention and remains a challenging clinical problem even for the experienced surgeon.STUDY DESIGN:During the past four years, we have registered ten cases of multiple glove powder granulomas, believed by the surgeon to represent tumor dissemination, but diagnosed by the pathologist as glove powder granules with the typical Maltese cross pattern when viewed under polarized light.RESULTS:Patients were referred with the presumptive diagnosis of intra-abdominal malignant disease and all had undergone at least one previous laparotomy during the past few years at a hospital that used powdered gloves. The unsuspected perioperative finding of multiple peritoneal nodules was presumed to represent carcinomatosis and resulted in the surgeon erroneously cancelling the operation in one case. In six other cases, the results of perioperative frozen sections caused the surgeon to change strategy and perform the planned procedure. Three patients had starch powder peritonitis postoperatively and one of them had a fatal pulmonary embolus. In two patients, the starch powder reaction was associated with the occurrence of true carcinomatosis and one patient later had recurrence of hepatic metastases. After a mean follow-up period of 17 months, six patients are alive with no signs of disseminated malignancy.CONCLUSIONS:Based on this information, we recommend routine pathologic documentation of all peritoneal nodules appearing to be tumor dissemination. If the results influence the surgical procedure, frozen sections should always be performed. To minimize the risk of powder-induced complications, the use of particle-free gloves is strongly recommended.