Expression and prognostic value of transcription factor PROX1 in colorectal cancer.

BACKGROUND: PROX1 is a specific target of the ß-catenin/TCF pathway in the intestinal epithelium. It acts as a regulator of progression from a benign to a highly dysplastic phenotype in colorectal tumours. However, the clinical significance of PROX1 expression is not known. METHODS: We studied the prognostic value of immunohistochemical expression of PROX1 in a series of 517 patients with colorectal cancer (CRC). RESULTS: The majority of the tumour samples expressed PROX1 (91%, 471 out of 517). High PROX1 expression was associated with a poor grade of tumour differentiation (P<0.0001). In the subgroup of patients with colon cancer, high PROX1 expression was associated with unfavourable colorectal cancer-specific survival (CCSS) as compared with low PROX1 expression (CCSS 47% vs 62%; P=0.045; RR 1.47). The association between high PROX1 and poor outcome was further strengthened in female colon cancer patients (CCSS 38% vs 63%; P=0.007; RR 2.02). Nonetheless, in multivariate survival analysis PROX1 expression was not retained as an independent prognostic factor. CONCLUSION: High PROX1 expression is associated with a poor grade of tumour differentiation, and, in colon cancer patients, also with less favourable patient outcome. Our results strengthen the previous preclinical observations that PROX1 has a role in tumour progression in CRC.

Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age.

Papillary thyroid carcinoma (PTC) is a malignancy that has good prognosis especially among patients up to 45 years of age; about half of the patients are female and of childbearing age. Lymph node recurrence (LNR) occurs in 10%-14% of patients but is considered to be associated with relatively good prognosis. The purpose of this study was to estimate the association between patient age at primary operation, and the behavior of the disease after LNR. Between 1967 and 1994, 495 patients underwent surgery for primary PTC at the Department of Surgery, Helsinki University Central Hospital. There were 391 (79.0%) women and 104 (21.0%) men with a mean age of 44.5 years (range, 10.8-85.4 years). Fifty-eight patients in whom LNR was the first clinical sign of persistent disease after complete clinical response to primary treatment were included in this series. At the time of primary operation, 37 (64.3%) of the 58 patients who developed LNR were younger than 45 years of age and 21 patients were older. The mean times to LNR in these groups were 42.0 months (range, 3.0-194.5 months) and 49.0 months (range, 3.6-209.0 months) respectively. Carcinoma-specific 5-year survival after LNR was 100% (95% confidence interval [CI] 88.8%-100.0%) in patients ages up to 45 years and 61.1% (40.5%-82.8%) in older patients; 10-year survival rates were 100%, and 41.3% (p < 0.0001), respectively. Relative survival at 10 years was 98.6% for patients ages up to 45 years and 42.6% for older patients (p = 0.0014). Using the Cox model it was shown that development of LNR after primary treatment has an independent highly significant negative effect on survival (p < 0.001) in patients over 45 years of age. Prognosis of PTC even after LNR on patients ages up to 45 years at the time of the primary operation is almost parallel to the normal reference population, but in patients over 45 years of age the prognosis is relatively poor.

Ultrasonically activated shears in thyroidectomies: a randomized trial.

OBJECTIVE: To test whether the advantages of the ultrasonically activated shears (UAS) observed in thyroidectomies in a previous matched-pair study could be repeated in a randomized trial. SUMMARY BACKGROUND DATA: The UAS has been documented, mainly in nonrandomized studies, to be a safe and fast device in video-assisted and conventional surgery. METHODS: Thyroidectomies and lobectomies performed for benign or malignant thyroid disease between August 1997 and January 1999 were included in this series. Separate randomization, resulting in four sets of envelopes, was done for one consultant endocrine surgeon and for senior residents for both lobectomies and for total thyroidectomies. The operations performed with the UAS were compared with operations performed with the conventional method, using ligatures as the main hemostatic method. Main outcome measures were operating time, postoperative serum calcium level, palsy of the recurrent laryngeal nerve, and amount of intraoperative and postoperative bleeding. Possible bias that could have been caused by imbalance between treatment groups for surgeon experience was tested by two-way analysis of covariance. RESULTS: Thirty-six patients were randomized, 19 to the UAS and 17 to the conventional group. Mean operating time was 99.1 minutes in the UAS group and 134.9 minutes in the conventional group. The average savings in operating time with the UAS was thus 35.8 minutes. There was no difference in complications between the groups. The estimated savings in operating time would have been 1.66 times that observed in this study if the groups had been unbalanced with reference to surgeon experience. CONCLUSION: The UAS is a usable device in total thyroidectomies and lobectomies.

Long term prognosis of medullary thyroid carcinoma in 39 patients.

BACKGROUND AND AIMS: Thyroidectomy and radical cervical lymph node dissection have been suggested as primary and secondary operations aimed at achieving biochemical cure in cases of medullary thyroid carcinoma (MTC). The purpose of this study was to find out behaviour of MTC in long-term follow-up, and to estimate possible difference in biological virulence between sporadic MTC and MTC in MEN2A. MATERIAL AND METHODS: From 1967 through 1994, 39 patients with MTC, including 9 patients with hereditary disease, were operated on at the Second Department of Surgery, Helsinki University Central Hospital. Enlarged lymph nodes were dissected selectively. The main outcome measure was carcinoma-specific survival. RESULTS: In sporadic MTC, ten-year carcinoma-specific survival was 57.9% (95% CI 39.1%-76.7%) and ten-year survival after reoperation due to lymphatic node recurrence was 51.4% (CI 18.7%-84.2%). The presence of distant metastases at diagnosis (p = 0.0001) and extrathyroidal growth of the primary tumor (p = 0.0008) were independent predictors of carcinoma-specific survival in the Cox model. The risk ratio of sporadic MTC to MTC in MEN2A was 5.40 (CI 0.67-43.2) after adjusting the survival time for the size of the primary tumor. CONCLUSION: Distant metastases and the local extrathyroidal extent of the primary tumor have a significant effect on the prognosis of MTC, lymphatic node metastases and other clinical factors being less important. The biological virulence of sporadic MTC may be clinically significantly higher than that of MTC in MEN2A.

Ultrasonically activated shears in thyroid surgery.

BACKGROUND: Ultrasonically activated shears (UAS) have been documented to be both safe and fast devices in laparoscopic surgery. We studied whether the use of UAS would have some advantage in thyroid surgery. METHODS: Thyroidectomies, performed by one senior endocrine surgeon between December 1996 and February 1997, were retrospectively matched, with patients operated on by the same surgeon using the conventional method. RESULTS: Six pairs of total thyroidectomies and one pair of lobectomies could be matched. Mean operating time was 100 minutes for the patients operated on with the UAS and 154 minutes for the patients operated on with the conventional method. The mean operating time with the UAS was thus on average 64.6% of the operation time with the conventional method, with a 95% confidence interval from 50.1% to 83.5% (t = 4.00, 6 df, P = 0.007). CONCLUSIONS: In this material the use of UAS reduced significantly operating time in thyroidectomies.

Helicobacter pylori infection after partial gastrectomy for peptic ulcer and its role in relapsing disease.

OBJECTIVE: To elucidate the role of Helicobacter pylori in relapsing disease after partial gastrectomy for peptic ulcer. DESIGN: Retrospective study of gastroscopies between January 1985 and February 1988. SETTING: Department of Surgery, Helsinki University Central Hospital, Finland. PARTICIPANTS: One hundred and fifty-five patients, who had undergone partial gastrectomy for peptic ulcer disease. MAIN OUTCOME MEASURES: Correlation between clinical and laboratory data, macroscopic findings at gastroscopy and histopathology. RESULTS: At gastroscopy 41 patients showed an ulcer at the site of anastomosis or in the gastric stump and two patients had a history of a previous ulcer recurrence. The median time interval between operation and relapse was 4 years. There was no correlation between ulcer recurrence, sex, age, ABO blood group or other diseases. Smokers and patients using non-steroidal anti-inflammatory drugs (NSAIDs) or alcohol had more relapses, but the difference was not significant. The recurrence rate was higher after Billroth II (BII; 34%) than after Roux-en-Y (14%; P = 0.03) or Billroth I (BI) reconstruction (24%). Giemsa staining demonstrated H. pylori in the gastric stump of 37% of the patients. H. pylori expression was related to age but unrelated to sex, ABO blood group, NSAID use, smoking or alcohol consumption. H. pylori positivity was more common (52%) after BI than after BII (28%; P = 0.04) or Roux-en-Y resection (40%). Recurrent ulcer was more often found in gastric remnants with normal mucosa (36%) than in those with H. pylori-positive gastritis (18%; P = 0.03) or H. pylori-negative gastritis (26%). CONCLUSION: It seems that H. pylori infection plays a minor role in the pathogenesis of ulcer recurrence after partial gastrectomy for peptic ulcer disease. Eradication of H. pylori of the remnant stomach is therefore presumably not effective in preventing ulcer recurrence.

Differences in serum tumor markers between colon and rectal cancer. Comparison of CA 242 and carcinoembryonic antigen.

PURPOSE: We investigated whether there are differences in serum levels of CA 242 and carcinoembryonic antigen (CEA) between patients with colon and rectal cancer. METHODS: Preoperative serum levels of CA 242 and CEA were determined in 153 patients with colon cancer and in 107 patients with rectal cancer. RESULTS: At the recommended cut-off levels for CA 242 and CEA, the overall sensitivity of CA 242 was 39 percent for both colon and rectal cancer, whereas the sensitivity of CEA was 40 percent for colon and 47 percent for rectal cancer. A combination of CA 242 and CEA increased overall sensitivity to 57 percent in colon cancer and to 62 percent in rectal cancer, whereas specificity decreased by 10 percent, compared with CEA alone. In colon cancer either or both markers were elevated in 38, 46, 56, and 84 percent of patients with Dukes Stages A, B, C, and D, respectively. Corresponding figures for rectal cancer were 52, 46, 71, and 87 percent, respectively. CONCLUSIONS: CA 242 showed equal sensitivity for colon and rectal cancer. In Stages A, C, and D, sensitivity of CEA and of a combination of CEA and CA 242 was higher in rectal than in colon cancer, but the difference was not significant. Concomitant use of markers increased sensitivity sharply compared with use of a single marker both in colon and rectal cancer.

Serum CA 242 and CEA detect different patients with recurrent colorectal cancer.

The aim of this study was to investigate the clinical value of CA 242 and CEA in the follow-up of patients with colorectal cancer. Serial serum samples were available for analysis in 67 patients with subsequent recurrence, of which 36 patients had been treated for colonic and 31 patients for rectal cancer. Liver metastases were found in 32 patients, local recurrences in 18 patients, lung metastases in 11 patients and other distant metastases in 6 patients. The same serum samples were used in quantitating the serum levels of both CA 242 and CEA. At the time of clinical recurrence an elevated CA 242 level was found in 41 patients and an elevated CEA level in 49 patients. Thirty-six patients (54%) showed an elevation of both CA 242 and CEA, five patients (7%) had increased CA 242 alone and 13 patients (19%) increased CEA alone. Altogether, 54 patients (81%) showed an elevation of either or both markers at the time of clinical recurrence. Initially CA 242 alone began to rise in 14 patients (21%) and CEA alone in 16 patients (24%). The lead time was calculated from 28 patients that had four or more serum samples available during follow-up. CA 242 increased in median 5,7 months and CEA in median 3,4 months before clinical recurrence (p=0.34). CA 242 was more sensitive for lung metastases (64%) than CEA (45%), whereas CEA was superior to CA 242 in liver metastases (88% versus 72%, respectively) and in local recurrences (56% versus 39%, respectively). Both CA 242 and CEA seem to be useful in early diagnosis of a recurrence in the follow-up of patients with colorectal cancer.