Association between thyroid gland diseases and breast cancer: a case-control study.

BACKGROUND: At the present time, there is no consensus on the association between benign thyroid diseases and breast cancer (BC). Therefore, the aim of this study is to help shed some light on the association between hyperthyroidism, hypothyroidism, and thyroiditis and breast cancer risk. METHODS: Use of the Disease Analyzer database (IQVIA) enabled us to perform a retrospective case-control study of 7408 women aged between 18 and 80, who were treated for an initial breast cancer diagnosis in a general practice in the United Kingdom between 2006 and 2015 (index date). Patients with a previous cancer diagnosis and an observation time of less than 12 months prior to the index date were excluded. The control group consisted of 7408 healthy women, who were matched to cases 1:1 by age, body mass index, hormone replacement therapy, and physician. The main outcome parameters of this study were the presence of thyroid disease (hypothyroidism, hyperthyroidism, struma, and thyroiditis) and the TSH values in the two groups. A univariate logistic regression model was used to investigate the association between benign thyroid diseases, TSH values, and BC. RESULTS: The mean age was 58.4 years in both groups. We found a significant association between thyroiditis and BC (OR: 1.91, p = 0.01) and were able to refute the association between hyperthyroidism/hypothyroidism and BC. We also found that thyroid-stimulating hormone (TSH) had no significant effect on breast cancer risk. CONCLUSION: Many experimental studies suggest a link between hyperthyroidism/hypothyroidism and BC. We were able to demonstrate an epidemiological association between thyroiditis and an increased BC risk. This shows the need for close monitoring for BC in women with thyroiditis.

Fecal and urinary incontinence are major problems associated with rectal cancer.

BACKGROUND: The goal of this retrospective cohort study was to analyze the incidence of urinary incontinence (UI) and fecal incontinence (FI) within 5 years of diagnosis in patients with rectal carcinoma (RC) and within 5 years of a randomly selected visit date in non-cancer controls followed in general practices in Germany. METHODS: Patients who had received an initial RC diagnosis at one of 1262 general practices in Germany between January 2008 and December 2017 were included in this study (index date). Patients without cancer were matched (1:1) to RC patients by sex, age, index year, and practice. The main outcome of the study was the incidence of UI and FI within 5 years of RC diagnosis. RESULTS: The study included 3249 individuals with RC and 3249 individuals without cancer (mean age 66.5 years, 57.3% males). Within 5 years of the index date, 8.6% of RC patients and 1.3% of patients without cancer received a FI diagnosis, and 16.7% of RC patients and 5.3% of patients without cancer received a UI diagnosis. Overall, RC was positively associated with both FI (hazard ratio (HR) 8.39, 95% CI 5.50-12.81) and UI (HR 3.59, 95% CI 2.91-4.44). These findings were corroborated in the different age subgroups. CONCLUSION: In accordance with the literature, we confirmed that RC is significantly associated with fecal and urinary incontinence. However, it appears that the awareness of this fact needs to be improved among general practitioners since our data show lower percentages of fecal and urinary incontinence diagnoses compared with the percentages for specialized centers reported in the literature.

Comparison Between Endoscopic Vacuum Therapy and Conventional Treatment for Leakage After Rectal Resection.

BACKGROUND: Anastomotic leakage after rectal resection represents a severe complication for the patient and requires an early and appropriate management. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in several institutions in Germany, and commercially available systems are currently distributed in approximately 30 countries worldwide. However, there is no evidence that EVT is superior to any other treatment for anastomotic leakage after rectal resection. METHODS: Twenty-one patients treated with EVT for anastomotic leakage after rectal resection were retrospectively compared to a historical cohort of 41 patients that received conventional treatment. Primary endpoints were death, treatment success and long-term preservation of intestinal continuity. Secondary endpoints were length of hospital stay and duration of treatment. RESULTS: There was no difference in mortality (p = 0.624). The intention-to-treat analysis showed a significantly higher success rate of EVT compared to conventional treatment (95.2% vs. 65.9%, p = 0.011). EVT was associated with preservation of intestinal continuity in a significant higher percentage of patients than patients undergoing conventional treatment (86.7% vs. 37.5%, p = 0.001). Conventional treatment tended to a shorter length of hospital stay (31.1 vs. 42.2 days, p = 0.066) but with no difference in overall duration of treatment. Time until closing of a diverting stoma did not differ between groups (10.2 months in the EVT group vs. 9.4 months in the conventional treatment group, p = 0.721). CONCLUSION: According to this retrospective study, conventional therapy and EVT are both options for the treatment of anastomotic leakage after rectal resection. EVT might be more effective in terms of definite healing and preservation of intestinal continuity.

Endoscopic vacuum therapy for various defects of the upper gastrointestinal tract.

BACKGROUND: Postoperative, iatrogenic or spontaneous upper gastrointestinal defects result in significant morbidity and mortality of the patients. In the last few years, endoscopic vacuum therapy (EVT) has been recognized as a new promising method for repairing upper gastrointestinal defects of different etiology. However, probably due to insufficient data and no commercially available system for EVT of the upper gastrointestinal tract, until the end of 2014, covering of esophageal defects with self-expanding metal stents (SEMS) were still the mainstay of endoscopic therapy. The aim of this article is to review the data available about EVT for various upper gastrointestinal defects. METHODS: A selective literature search was conducted in Medline and PubMed (2007-2016), taking into account all the published case series and case reports reporting on the use of EVT in the management of upper gastrointestinal defects. RESULTS: EVT works through intracorporal application of negative pressure at the defect zone with an electronic controlled vacuum device along a polyurethane sponge drainage. This results in closure of the esophageal defect and internal drainage of the septic focus, simultaneously. Compared to stenting, EVT enables regular viewing of wound conditions with control of the septic focus and adjustment of therapy. Moreover, endoscopical negative pressure is applicable in all esophageal regions (cricopharygeal, tubular, gastroesophageal junction) and in anastomotic anatomic variants. EVT can be used solely as a definite treatment or as a complimentary therapy combined with operative revision. In total, there are published data of more than 200 patients with upper gastrointestinal defects treated with EVT, showing succes rates from 70-100%. CONCLUSION: The available data indicate that EVT is feasible, safe and effective with good short-term and long-term clinical outcomes in the damage control of upper GI-tract leaks. Still, a prospective multi-center study has to be conducted to proof the definite benefit of EVT for patients with esophageal defects.

Tumor regression in rectal cancer after intensified neoadjuvant chemoradiation: a morphometric and clinicopathological study.

BACKGROUND: High interobserver variation is a well known drawback of conventional tumor regression grading, and reaching consensus among pathologists may require a considerable effort. Therefore, in this study, morphometry was tried to assess tumor regression, and its prognostic role was explored. METHODS: Tumor regression was quantified by a point counting method to yield tumor area fraction (TAF) as an index of remaining vital tumor. RESULTS: In a series of 104 patients with clinically advanced rectal cancer treated with neoadjuvant radiochemotherapy, TAFs were distributed continuously towards complete regression which was observed in 8.7% of the cases. Plotting TAFs grouped by a conventional regression grading (Dworak's) revealed considerable overlap between groups. In a control series of untreated cancers, only TAFs of cancers with an expansive invasive border were setoff clearly from TAFs obtained for the study cases, but TAFs of control cases with an infiltrative invasive border and mucinous carcinomas extended well into the range of TAFs recorded for regressing tumors. Locoregional recurrence (N = 10) was significantly associated with perineural tumor infiltration and capsule transgressing lymph node metastasis/tumor deposits but not with the degree of tumor regression. Overall survival was better for patients with major regressions (≤20th percentile by morphometry, or Dworak regression grade (DRG) 4/5), although statistical significance was not reached. CONCLUSIONS: Morphometry of tumor regression is feasible and explains why conventional regression grading is so difficult to perform. Assessment of tumor regression, by subjective grading or morphometry, does not appear to convey major prognostic information, at least not substantially beyond histopathological tumor staging. This observation discourages expending too much effort on developing this aspect of the pathomorphological workup of the resection specimens.

Prognosis of rectal cancer patients improves with downstaging by intensified neoadjuvant radiochemotherapy - a matched pair analysis.

BACKGROUND: Neoadjuvant radiochemotherapy has been proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases in standard protocols of neoadjuvant radiochemotherapy. The present study aimed at addressing the effects of an intensified neoadjuvant radiochemotherapy on long term cancer related and disease free survival. METHODS: A total of 387 patients underwent oncologic resection for rectal cancer in our institution between January 2000 and December 2009. There were 106 patients (27.4%) who received an intensified radiochemotherapy protocol completely and without excluding criteria (study group). A matched pair analysis was performed by comparing the study group with patients undergoing primary surgery and postoperative radiochemotherapy, if necessary and possible (control group). Matching was carried out in descending order for UICC stage, R-status, tumor height, T-, N-, V-, L-, M- and G-category of the TNM-system according to the histopathological staging. Follow-up data included local recurrence rate, cancer related and disease free survival. RESULTS: In the study group histopathological work-up of the specimen revealed a treatment response in terms of tumor regression in 92.5% (98/106) of these patients. Undergoing intensified neoadjuvant RCT the actuarial cancer related and disease free survival was 67.9% and 70.4%, local recurrence was 5.7% after an observation period of 4.3 ± 2.55 years. In the control group cancer related and disease free survival was 71.7% and 82.7%, local recurrence was 4.7% after an observation period of 3.8 ± 3.05 years revealing no statistical significant difference between the two groups. Moreover, estimated 5-year results of cancer related survival (66.7% vs 67.9% (controls)), the disease free survival (66.7% vs 79.9% (controls)) as well as subgroup analysis of UICC 0-III and UICC IV patients showed no difference between the study and control group as well. CONCLUSION: In our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor regression. The resulting inferior histopathological tumor stage shows the same long term local control and systemic tumor control as the control group with a primary more favorable tumor stage.

Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer?

BACKGROUND: Decision making for adjuvant chemotherapy in stage III colon cancer is based on the TNM system. It is well known that prognosis worsens with higher pN classification, and several recent studies propose superiority of the lymph node ratio (ln ratio) to the TNM system. Therefore, we compared the prognosis of ln ratio to TNM system in our stage III colon cancer patients. METHODS: A total of 939 patients underwent radical surgery for colorectal cancer between January 2000 and December 2009. From this pool of patients, 142 colon cancer stage III patients were identified and taken for this analysis. Using martingale residuals, this cohort could be separated into a group with a low ln ratio and one with a high ln ratio. These groups were compared to pN1 and pN2 of the TNM system. RESULTS: For ln ratio, the cutoff was calculated at 0.2. There was a good prognosis of disease-free and cancer-related survival for the N-category of the TNM system as well as for the lymph node ratio. There was no statistical difference between using the N-category of the TNM system and the ln ratio. CONCLUSIONS: There might not be a benefit in using the lymph node ratio rather than the N category of the TNM system as long as the number of subgroups is not increased. In our consideration, there is no need to change the N categorization of the TNM system to the ln ratio.

Intensified neoadjuvant radiochemotherapy for rectal cancer enhances surgical complications.

BACKGROUND: Neoadjuvant radiochemotherapy has proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases. The present study aimed at addressing the effects of an intensified protocol of neoadjuvant treatment on the development of postoperative complications. METHODS: A total of 387 patients underwent oncological resection for rectal cancer in our institution between January 2000 and December 2009. 106 patients received an intensified radiochemotherapy. Perioperative morbidity and mortality were analyzed retrospectively with special attention on complication rates after intensified radio-chemotherapy. Therefore, for each patient subjected to neoadjuvant treatment a patient without neoadjuvant treatment was matched in the following order for tumor height, discontinuous resection/exstirpation, T-category of the TNM-system, dividing stoma and UICC stage. RESULTS: Of all patients operated for rectal cancer, 27.4% received an intensified neoadjuvant treatment. Tumor location in the matched patients were in the lower third (55.2%), middle third (41.0%) and upper third (3.8%) of the rectum. Postoperatively, surgical morbidity was higher after intensified neoadjuvant treatment. In the subgroup with low anterior resection (LAR) the anastomosis leakage rate was higher (26.6% vs. 9.7%) and in the subgroup of patients with rectal exstirpations the perineal wound infection rate was increased (42.2% vs. 18.8%) after intensified radiochemotherapy. CONCLUSIONS: In rectal cancer the decision for an intensified neoadjuvant treatment comes along with an increase of anastomotic leakage and perineal wound infection. Quality of life is often reduced considerably and has to be balanced against the potential benefit of intensifying neoadjuvant radiochemotherapy.

A novel sialyl Le(X) expression score as a potential prognostic tool in colorectal cancer.

BACKGROUND: Treatment decisions in colorectal cancer subsequent to surgery are based mainly on the TNM system. There is a need to establish novel prognostic markers based on the molecular characterization of tumor cells. Evidence exists that sialyl Le(X) expression is correlated with an unfavorable outcome in colorectal cancer. The aim of this study was to establish a simple sialyl Le(X) staining score and to determine a potential correlation with the prognosis in a series of advanced colorectal carcinoma patients. METHODS: In order to implement routine use of sialyl Le(X) immunohistology, we established a new, easily reproducible score and defined a cutoff which discriminated groups with better or worse outcome, respectively. We then correlated sialyl Le(X) expression of 215 UICC stage III and IV patients with disease-free and cancer-related survival. RESULTS: A five-stage score could be established based on automated immunohistochemical stainings. Using a statistical model, we calculated a cutoff to discriminate between weak and strong staining positivity of sialyl Le(X). Patients with strong positive specimens had a worse cancer-related survival (P = 0.004) but no difference was observed for disease-free survival (P = 0.352). CONCLUSIONS: These results demonstrate a strong correlation between high sialyl Le(X)-expression in colorectal carcinomas and cancer-related survival. Our highly standardized and easy-to-use staining score is suitable for routine use and hence it could be recommended to evaluate sialyl Le(X)-expression as part of the standard histopathological analysis of colorectal carcinomas and to validate the score prospectively based on a larger population.

Endoscopic vacuum therapy (EVT) for acute esophageal perforation: Could it replace surgery?

Background and study aims Acute esophageal perforation is a potentially life-threating condition that demands a multidisciplinary approach. Based on recently published data indicating that EVT may be effective in managing esophageal perforation, we report our institution's experience with EVT in this clinical setting. Patients and methods We retrospectively analyzed all 10 patients with acute esophageal perforation from May 2018 to January 2021, using descriptive statistics. The primary outcome was successful closure of the perforation. Secondary outcomes included the length of treatment, number of endoscopic procedures required, and complication rate. Results All patients (site of perforation: 4 upper, 2 middle, 4 lower esophagus; etiology: 8 iatrogenic, 2 foreign body ingestion) were treated with EVT successfully. In eight cases, EVT was started immediately after the perforation, in the other two cases 1 and 2 days later. The median (interquartile range) number of endoscopic procedures was 2.5 (range, 2-3) and the median duration of treatment was 7.5 days (range, 7-11.5). The sponge was placed in eight cases intraluminally, in the other two cases initially intracavitary. No complication occurred. Conclusions EVT is highly effective for managing acute esophageal perforation within 1 to 3 weeks. Immediate start of EVT to prevent abscess formation and induce defect closure is crucial.

SEVTAR-A multicenter randomized controlled trial to investigate the impact of prophylactic endoluminal placed vacuum sponge for prevention of anastomotic leakage after low rectal resections.

Background: Low anterior resection for rectal cancer is commonly associated with a diverting stoma. In general, the stoma is closed 3 months after the initial operation. The diverting stoma reduces the rate of anastomotic leakage as well as the severeness of a potential leakage itself. Nevertheless, anastomotic leakage is still a life-threatening complication and might reduce the quality of life in the short and long term. In case of leakage, the construction can be converted into a Hartmann situation or it could be treated by endoscopic vacuum therapy or by leaving the drains. In recent years, endoscopic vacuum therapy has become the treatment of choice in many institutions. In this study, the hypothesis is to be evaluated, if a prophylactic endoscopic vacuum therapy reduces the rate of anastomotic leakage after rectal resections. Methods: A multicenter parallel group randomized controlled trial is planned in as many as possible centers in Europe. The study aims to recruit 362 analyzable patients with a resection of the rectum combined with a diverting ileostoma. The anastomosis has to be between 2 and 8 cm off the anal verge. Half of these patients receive a sponge for 5 days, and the control group is treated as usual in the participating hospitals. There will be a check for anastomotic leakage after 30 days. Primary end point is the rate of anastomotic leakages. The study will have 60% power to detect a difference of 10%, at a one-sided alpha significance level of 5%, assuming an anastomosis leakage rate of 10%-15%. Discussion: If the hypothesis proves to be true, anastomosis leakage could be reduced significantly by placing a vacuum sponge over the anastomosis for 5 days. Trial registration: The trial is registered at DRKS: DRKS00023436. It has been accredited by Onkocert of the German Society of Cancer: ST-D483. The leading Ethics Committee is the Ethics Committee of Rostock University with the registration ID A 2019-0203.

Aggressive colorectal carcinoma phenotypes of invasion can be assessed reproducibly and effectively predict poor survival: interobserver study and multivariate survival analysis of a prospectively collected series of 299 patients after potentially curative resections with long-term follow-up.

AIMS: To test whether assessment of colorectal carcinoma phenotypes of invasion can be taught successfully to pathologists not familiar with these features and to confirm their prognostic impact. METHODS AND RESULTS: A junior member of staff was supplied with written information and a generous set of images on how to type the invasive margin of colorectal carcinomas (expansive versus infiltrative) and how to assess tumour budding (counting on pan-cytokeratin immunostains; cut-off at the 66th percentile). An interobserver study yielded kappa values of 0.578 and 0.438 for typing the invasive margin and assessment of tumour budding, respectively. Margin typing improved significantly to κ=0.939 after a training session. However, using a cut-off, assessment of tumour budding improved only moderately to κ=0.629 although, numerically, divergences were within ±10%. On univariate analysis, a high-degree of tumour budding and the infiltrative type of invasive margin were strong negative prognostic factors. The Cox model included nodal status, tumour budding, serosal penetration and venous angioinvasion. Importantly, using the tumour budding counts as a numerical variable for the Cox model also yielded significant odds, allowing the constraints of a cut-off to be relinquished. CONCLUSIONS: Assessment of colorectal carcinoma phenotypes of invasion can be learnt and performed with confidence, and their prognostic impact is confirmed in this independent series.

Association between various thyroid gland diseases, TSH values and thyroid cancer: a case-control study.

BACKGROUND: The goal of this retrospective cohort study was to analyze the association between benign thyroid alteration and thyroid cancer in patients followed in general practices in Germany. METHODS: Patients aged 18-80 who had received an initial diagnosis of thyroid cancer in one of 1261 general practices in Germany between January 2009 and December 2018 were included in this study (index date). These patients were matched (1:1) to non-cancer patients by age, sex, physician and index year. The main outcome of the study was the association between various benign thyroid alterations and thyroid cancer. RESULTS: The study included 2787 patients with thyroid cancer and 2787 individuals without cancer (mean age: 52.8 years, 73.5% women). The main finding was that all benign changes in the thyroid with the exception of thyroiditis were associated with thyroid cancer. The strongest association was observed by the nontoxic goiter. Half of the patients with thyroid cancer had nontoxic goiter compared to just one-sixth of the control group. Thyrotoxicosis was found in 12.9% of the cancer group and in 3.9% of the controls. By analyzing TSH in groups, we found an association between suppressed TSH and elevated TSH levels and thyroid cancer. CONCLUSION: In accordance with the literature, we confirmed that any kind of benign thyroid alteration was associated with an elevated risk of thyroid cancer. The odds ratio was greatest for nontoxic goiter, followed by benign neoplasms of the thyroid, other disorders of the thyroid such as Hashimoto and thyrotoxicosis. We also found an elevated risk of cancer in patients with either a suppressed or elevated TSH.

The Water-Holding Procedure for Ensuring Postoperative Continence Prior Restoring Intestinal Continuity.

BACKGROUND: A defunctioning stoma can become necessary in a relevant number of patients undergoing gastrointestinal surgery. As a matter of course, patients seek an early closure of the stoma. However, preoperative management of these patients varies and the prediction of continence after stoma removal can become challenging. Patients might be fully continent despite low manometric pressures and vice versa. An easy and reliable way to predict continence after stoma reversal would improve patients' management and outcome. Although frequently performed in various surgical centers in Germany, there is no published data on the water-holding test. Hence, this is the first study evaluating the role of the test in clinical practice. METHOD: We performed a prospective pilot study to evaluate the role of anorectal manometry and the water-holding procedure as a predictor of postoperative continence prior to stoma reversal. Inclusion criteria were a successfully passed water-holding test, any type of fecal diversion and the possibility of restoring intestinal continuity. Preoperative low manometric pressure levels were not an exclusion criteria for stoma reversal. Fifty-two patients with ostomy were consecutively enrolled in this study between October 2013 and February 2016. Anorectal manometry was performed in all patients prior to stoma reversal. After stoma removal, patients were followed-up for 6 months. Postoperative incontinence was determined using the Wexner incontinence score. RESULTS: A total of 52 patients (38 males, 14 females) were included at an average age of 59 (range 33-83) years. Most frequent indications for intestinal diversion were rectal cancer surgery, IBD-related surgery, or surgery for diverticular disease. Low anterior rectal resection was performed in 17 patients (32.7%), followed by a proctocolectomy in 9 (17.3%), colectomy in 9 (17.3%), and recto-sigmoid resection in 7 patients (13.5%). Median time from stoma creation to reversal was 206 days (range 48-871 days). All patients had successfully passed the standardized water-holding test. At the same time, the majority of patients had low preoperative manometric pressure values and would normally not have been reversed at that point. The median postoperative Wexner incontinence score was at 1.5 (range 0-20), 0.5 (range 0-14), and 0 (range 0-11) at 14, 60, and 180 days after stoma reversal. Low preoperative manometric squeeze and/or resting pressure levels were not associated with a higher postoperative incontinence score at 14, 60, or 180 days after stoma reversal. CONCLUSION: A standardized water-holding test can function as an easy and reliable method before stoma reversal to predict sufficient postoperative fecal continence. In case of a sufficient water-holding test despite low manometric pressure levels, the risk for postoperative anal incontinence seems to be low. Preoperative manometric pressure levels do not appear to predict postoperative continence.

Neoadjuvant radio-chemotherapy prolongs healing of anastomotic leakage after rectal resection treated with endoscopic vacuum therapy.

BACKGROUND: Neoadjuvant radiochemotherapy (nRCT) is an important component in the treatment of advanced rectal cancer. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in many institutions in Germany. Published case series report on average success and stoma reversal rates of more than 80%. However, so far, there is no distinct report on the potential influence of nRCT on EVT. METHODS: A total of 11 patients treated with EVT for anastomotic leakage after nRCT and rectal resection were retrospectively compared with a cohort of eight patients with rectal anastomotic leakage without neoadjuvant treatment. Primary endpoints were death, treatment success, and long-term preservation of intestinal continuity. Secondary endpoint was the duration of treatment. Statistical analysis was performed using Statistical Package for Social Science (SPSS) version 23.0. RESULTS: There was no difference in mortality (0%), success rate (90.9% versus 100%, p = 0.381), or long-term preservation of continuity (63.6% versus 62.5%, p = 0.960). After nRCT, patients showed a significant longer duration of EVT (31.1 days versus 15.9 days, p = 0.040) which was associated with a significantly higher number of sponge applications (9.6 versus 5.0, p = 0.042). CONCLUSIONS: In our analysis, EVT showed success in over 90% of patients with anastomotic leakage after rectal resection for colorectal cancer, regardless of neoadjuvant treatment. However, in case of anastomotic leakage, nRCT seems to be associated with the need for a significant longer duration of EVT.

Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma?

Since 5-fluorouracil (5-FU)-based chemotherapy has become standard adjuvant treatment for patients with node-positive colonic adenocarcinoma, there has arisen the need for predictive factors. Thymidylate synthase (TS) is a major target of 5-FU's action, and high TS expression in carcinoma cells could reduce its cytostatic effect. Both, a 28-base pair repeat polymorphism and a cytosine vs. guanine single nucleotide polymorphism in the promoter region of the TS gene are known to modulate its expression. All patients with a single, non-metachronous node-positive colonic adenocarcinoma who underwent a potentially curative resection at this institution in the years 1994-2002, and who received adjuvant 5-FU (n=95) were included in this study. Ninety-four of the 95 patients were successfully genotyped: 70 patients were classified as TS gene low-expressors (2R-2R, 2R-3C and 3C-3C), and 24 patients were classified as high-expressors (2R-3G, 3C-3G and 3G-3G). Contrary to the hypothesis, Kaplan-Meier survival analysis did not reveal any differences between the groups (power of 0.8 to detect an absolute survival difference >30%). In a Cox model, venous angioinvasion and the infiltrative pattern of tumour invasion were strong adverse factors. These results argue against a practical role for the TS gene repeat polymorphism or the C/G single nucleotide polymorphism as a predictive factor. However, by careful histopathological examination a high-risk group of node-positive patients can be defined that could be candidates for studies of alternative (more aggressive) adjuvant treatment.

Tumour regression and mesorectal lymph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum.

Neoadjuvant radiation or chemoradiation is currently the treatment of choice for patients with locally advanced carcinoma of the rectum. To assess the effects of chemoradiation on tumour regression and on uninvolved mesorectal lymph nodes, a consecutive series of 76 patients receiving neoadjuvant chemoradiation and a stage-adapted control series of 57 patients without pretreatment were studied. Densities of cells positive for CD4 (T-helper cells), CD8 (cytotoxic T-cells), CD83 (mature dendritic cells), and CD57 (natural killer cells) were determined on immunostains. Tumour regression was graded, and presence or absence of extramural tumour was recorded. The densities of CD4+ T-lymphocytes and CD83+ dendritic cells in the paracortex of mesorectal lymph nodes were observed to be significantly reduced, as were the densities of CD57+ cells in the follicles; densities of CD8+ T-lymphocytes did not differ. Strong, moderate and poor tumour regression was observed in 29, 25, and 22 cases, respectively. For 12 patients, absence of extramural vital or regressing tumour was recorded, indicating pretherapeutic overstaging. The results bring to mind that neoadjuvant chemoradiation as a side effect may have a negative impact on anti-tumour immunity. Together with the drawback of overstaging the results argue for a careful selection of patients.

PEG closure in the second attempt.

BACKGROUND AND STUDY AIMS: This case report demonstrates successful endoscopic treatment of a persistent gastrocutaneous fistula after removal of a percutaneous endoscopic gastrostomy (PEG) in a 21-year-old patient with mucoviscidosis after lung transplantation. Because the initial OTSC clip (gastric) did not close the fistula sufficiently, we had to remove it and replace it with a larger OTSC clip (colon) in a second intervention. That clip finally sufficiently closed the fistula.