Ovarian metastases in young women with colorectal cancer: a retrospective multicenter cohort study.

BACKGROUND AND PURPOSE: Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. METHODS: This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. RESULTS: In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19 months. CONCLUSION: This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC.

Prevalence of underlying malignancies in complex cysts of the breast.

INTRODUCTION: The management of complex cysts of the breast is an ongoing topic of discussion. The aim of this study was to determine the prevalence of underlying malignancy in radiologically diagnosed complex cysts, and to assess whether watchful waiting could be the preferred method to safely manage complex cysts of the breast. SUBJECTS AND METHODS: A single-center retrospective study was performed between May 2003 and November 2019 in the VieCuri Medical Centre. Women with a radiologically diagnosed complex cyst of the breast were included. Prevalence of underlying malignancy was calculated, as were absolute risk reduction and number needed to treat in order to diagnose malignancy. In addition, patient characteristics were compared to determine characteristics associated with malignancy. RESULTS: Of 78 radiologically diagnosed complex cysts of the breast, five (6,4%) were found to be malignant. The number needed to treat was calculated at 12,8 (absolute riks reduction 0,078). Age (P = 0,003) was associated with malignancy. CONCLUSION: Complex cysts of the breast could be managed more conservatively. Patient characteristics can be used to assess the eligibility for radiological follow-up. This, in turn, would lead to a lower NNT and possibly a decrease in disease burden and healthcare costs.

Incidence of arcuate line hernia in patients with abdominal complaints: radiological and clinical features.

INTRODUCTION: Acute abdominal complaints are a frequent cause for consultation in the emergency department, with a large differential diagnosis. One cause is arcuate line herniation, but this entity is little known and rarely considered during initial analysis. The incidence of arcuate line herniation in this population is unknown. METHODS: A retrospective cohort study was performed. All patients who presented to the emergency department for surgical consultation during an 18-month period with abdominal complaints in who no diagnosis was found after analysis, and who had computed tomography imaging of the abdomen were included. CT scans were reviewed with a focus on abdominal wall pathology and correlated with clinical features. RESULTS: Eight hundred and ten patients presented with abdominal complaints, 415 of these had CT scans available for review and were included in the study. In 47 patients (11.3%), an arcuate line anomaly was found, and in 14 patients (3.4%), a frank arcuate line herniation (grades 2 or 3) was found. Retrospective correlation with clinical complaints was found in 50% of these patients. Patients with arcuate line hernia had a significantly higher BMI, and diabetes mellitus and aortic aneurysm were more prevalent in these patients. CONCLUSION: Arcuate line herniation has a higher incidence than previously thought in patients with acute abdominal complaints and should be considered when evaluating these patients.

Laparotomy closure techniques: Do surgeons follow the latest guidelines? Results of a questionnaire.

PURPOSE: Incisional hernias after laparotomy are associated with significant morbidity and increased costs. Recent research on prevention of incisional hernia formation suggests that a laparotomy closure technique using a slowly absorbable monofilament suture with small fascial steps and bites in a continuous, single layer with a suture length to wound length (SL/WL) ratio of at least 4:1 is effective in lowering morbidity. Little is known about application of this evidence in daily practice. Therefore, a survey was performed among Dutch surgeons. METHODS: All members of the Dutch Surgical Society were invited to participate in a 24-question online survey on techniques and materials used for abdominal wall closure after midline laparotomy. Subgroup analysis was performed based on surgical subspecialty, type of hospital and experience. RESULTS: Response rate was 26% (402 respondents), representing 97% of all Dutch surgical departments. More than 90% of participants closed the abdominal wall in a single mass layer, using a slowly absorbable monofilament running suture The SL/WL ratio of >4:1 is practiced by only 35% of participants and preferred suture size was variable among participants. Risk factors for incisional hernia development were generally identified correctly but more than half of the participants were unaware of the incidence and time of occurrence of incisional hernia. Subgroup analysis found that gastrointestinal and oncologic surgeons preferred smaller diameter sutures and higher suture-length to wound-length ratios. Trauma, vascular and pediatric surgeons had lower estimates of incidence of incisional hernia than other subspecialties. Surgeons employed in academic hospitals were more likely to use small fascial steps and smaller suture sizes than their colleagues in non-academic hospitals. Correct estimates of incisional hernia incidence decreased when surgeons perform less than 10 laparotomies annually. CONCLUSION: Implementation of the latest evidence regarding closure techniques of the abdominal wall is not widespread. Only 35% of surgeons close the abdominal fascia using a suture length to wound length ratio of 4:1, which is recommended based on the latest evidence. Surgical trainees, gastrointestinal and oncological surgeons are most familiar with the recommended technique and use it in their daily practice. Efforts should be directed at improving spreading of this technique.

Radioimmunotherapy prevents local recurrence of colonic cancer in an experimental model.

BACKGROUND: Radioimmunotherapy (RIT) is suitable for the treatment of microscopic residual disease and might therefore have an adjuvant role after colonic cancer surgery. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of 2 x 10(6) CC531 tumour cells. The biodistribution of (111)In-labelled MG1 monoclonal antibody was assessed after intraperitoneal administration. The therapeutic efficacy of (177)Lu-labelled MG1 (74 MBq per rat), administered on the day of surgery (D0, n = 13) or 5 days later (D5, n = 13), was compared with that of carrier only (n = 13). The primary endpoint was perianastomotic tumour growth 28 days after surgery. RESULTS: (111)In-labelled MG1 preferentially accumulated in perianastomotic CC531 tumours. RIT resulted in a transient reduction in bodyweight in both treatment groups compared with controls, but there were no other signs of clinical discomfort. No macroscopic or microscopic perianastomotic tumour growth was found in eight of 11 animals in the D0 group and 11 of 13 in the D5 group, whereas 11 of 13 controls had macroscopic tumour (P = 0.011 and P = 0.001 respectively). CONCLUSION: This study suggests that RIT may be an effective adjuvant treatment for preventing local recurrence after resection of colonic cancer.

The effects of adjuvant experimental radioimmunotherapy and hyperthermic intraperitoneal chemotherapy on intestinal and abdominal healing after cytoreductive surgery for peritoneal carcinomatosis in the rat.

BACKGROUND: Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. RESULTS: At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. CONCLUSION: As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.

A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats.

BACKGROUND: Cytoreductive surgery (CS) followed by heated intraperitoneal chemotherapy (HIPEC) is considered the standard of care for the treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC). These surgical procedures result in a median survival of 2 years at the cost of considerable morbidity and mortality. In preclinical studies, radioimmunotherapy (RIT) improved survival after CS in a model of induced PC of colonic origin. In the present studies we aimed to compare the efficacy and toxicity of CS followed by adjuvant RIT in experimental PC to the standard of care, HIPEC. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in three groups of Wag/Rij rats. Treatment comprised CS only, CS + RIT or CS + HIPEC, immediately after surgery. RIT consisted of intraperitoneal administration of 74 MBq Lutetium-177 labeled MG1. HIPEC was performed by a closed abdomen perfusion technique using mitomycin C (16 mg/L during 60 minutes). The primary endpoint was survival. RESULTS: CS only or combined with RIT was well tolerated. Rats receiving CS + HIPEC were lethargic, suffered from diarrhea, and lost significantly more weight in the first postoperative week. Median survival of rats treated with CS + RIT was significantly longer than after CS alone (97 and 57 days, respectively, P < .004), whereas survival after CS + HIPEC or CS alone were not significantly different (76 and 57 days, respectively, P = .17). CONCLUSION: Survival after CS was significantly improved by RIT with Lutetium-177-MG1 in rats with PC of colorectal origin. Adjuvant HIPEC did not improve survival and was more toxic than adjuvant RIT.

Subintimal angioplasty of supra- and infrageniculate arteries.

We retrospectively reviewed our experience with subintimal angioplasty for chronic limb ischemia. Hospital records and films of all subintimal angioplasty procedures performed between October 2002 and December 2004 were reviewed and analyzed for demographic data, clinical data, and comorbid condition status. Thirty-nine subintimal angioplasties were performed in 37 patients (65% male, 35% female), with a median age of 73 years. Median follow-up was 9 months. The 30-day mortality rate was 8%. All-cause mortality was 33% after 24 months. In 23 cases (59%), a subintimal angioplasty of the superficial femoral artery (SFA) alone was performed. Both the SFA and popliteal/crural vessels were used in nine limbs (23%), the popliteal artery alone in three limbs (8%), and the crural arteries alone in four limbs (10%). Initial technical and clinical success rates were 67% and 49%, respectively. The complication rate was 28%. Twenty-four additional surgical interventions were performed after the initial angioplasty procedure, of which 12 were major amputations. Amputation-free survival (limb-salvage rate) was 69% at 12 months [95% confidence interval (CI) 52-85%], and overall survival was 69% (95% CI 52-85%) at 12 months. In patients with critical limb ischemia, subintimal angioplasty is feasible and in most cases technically successful. In these high-risk patients, often with combined cardiac, pulmonary, and diabetic risk and considered unfit for bypass surgery, subintimal angioplasty offers a safe and effective alternative.

Endovascular aneurysm repair versus open aneurysm repair: comparison of treatment outcome and procedure-related reintervention rate.

We conducted a retrospective study to compare treatment outcome and procedure-related reintervention rates of endovascular aneurysm repair (EVAR) with those of open repair. Clinical and radiological data of patients treated at the Rijnstate Hospital (Arnhem, The Netherlands) for nonsymptomatic aortic abdominal aneurysm during October 1998-January 2004 were reviewed and analyzed for demographic data, aneurysm specifics, comorbid condition status, and perioperative outcome. There were 99 patients treated with EVAR and 116 patients treated with open repair. Significant differences in age were seen between treatment groups, patients under the age of 80 being more likely to have open repair (p < 0.004). The EVAR group consisted of significantly fewer women (p < 0.029). Of seven comorbid conditions, four reached significant differences between treatment groups; patients with ischemic heart disease (p < 0.044), heart failure (p < 0.006), renal failure (p < 0.033), or peripheral arterial disease (p < 0.006) were more likely to have EVAR. Comparison of aneurysm anatomy showed no difference in size between EVAR (mean 57.7 mm, 95% CI 55.9-59.5 mm) and open repair (mean 60.1 mm, 95% CI 57.9-62.3 mm). Significant differences were seen in aneurysm neck length and diameter. Operative outcome showed differences in length of hospital stay (median, EVAR 7 vs. open repair 11 days), 30-day mortality (p < 0.048), postoperative hematoma (p < 0.001), and postoperative pulmonary infections (p < 0.001), all in favor of EVAR. Follow-up of the EVAR group showed a decrease (mean 10 mm, 95% CI 7-14 mm) of aneurysm diameter in 15% of cases during follow-up (mean 18 months, range 1-66). Despite higher age and more comorbidity of patients undergoing EVAR, 30-day mortality, postoperative pulmonary infection rate, and length of hospital stay were lower than for those undergoing open repair. Both EVAR and open repair can be performed on a subset of patients with low mortality, complication, and reintervention rates.

Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children.

BACKGROUND: Studies have suggested that early contact with pets may prevent the development of allergy and asthma. OBJECTIVE: To study the association between early, current and past pet ownership and sensitization, bronchial responsiveness and allergic symptoms in school children. METHODS: A population of almost 3000 primary school children was investigated using protocols of the International Study on Asthma and Allergies in Childhood (ISAAC). Allergic symptoms were measured using the parent-completed ISAAC questionnaire. Sensitization to common allergens was measured using skin prick tests (SPT)s and/or serum immunoglobulin (Ig)E determinations. Bronchial responsiveness was tested using a hypertonic saline challenge. Pet ownership was investigated by questionnaire. Current, past and early exposure to pets was documented separately for cats, dogs, rodents and birds. The data on current, past and early pet exposure were then related to allergic symptoms, sensitization and bronchial responsiveness. RESULTS: Among children currently exposed to pets, there was significantly less sensitization to cat (odds ratio (OR) = 0.69) and dog (OR = 0.63) allergens, indoor allergens in general (OR = 0.64), and outdoor allergens (OR = 0.60) compared to children who never had pets in the home. There was also less hayfever (OR = 0.66) and rhinitis (OR = 0.76). In contrast, wheeze, asthma and bronchial responsiveness were not associated with current pet ownership. Odds ratios associated with past pet ownership were generally above unity, and significant for asthma in the adjusted analysis (OR = 1.85), suggesting selective avoidance in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only showed an inverse association with sensitization to pollen: OR = 0.71 for having had furry or feathery pets in general in the first two years of life, and OR = 0.73 for having had cats and/or dogs in the first two years of life, compared to not having had pets in the first two years of life. CONCLUSION: These results suggest that the inverse association between current pet ownership and sensitization and hayfever symptoms was partly due to the removal of pets in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only seemed to offer some protection against sensitization to pollen.

A lower prevalence of atopy symptoms in children with type 1 diabetes mellitus.

BACKGROUND: The Th1/Th 2 concept is a model to understand the pathophysiology of certain diseases. Atopic diseases (asthma, eczema and hayfever) are characterized by a chronic inflammatory reaction that is dominated by Th 2 cells, and type 1 diabetes mellitus (DM) is Th1 cell dominated. Because it is known that Th1 and Th 2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th 2-mediated disease is lower in patients with Th1-mediated disease. OBJECTIVE: To compare the prevalence of atopic diseases between children with DM and age-matched controls. METHODS: Parents of children with DM were requested by Dutch paediatricians to complete the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire on the prevalence of atopic diseases. A control group was derived from a Dutch cross-sectional survey (the ISAAC2 study). RESULTS: We received 555 completed questionnaires, which is estimated to be 25% of the total number of Dutch children with DM. The control group consisted of 777 children. After age-matching, the questionnaires of 188 DM patients were used. Symptoms of asthma, hayfever and eczema were reported less in the group of children with DM compared with the control group (wheeze last year, OR 0.796, 95% CI 0.408-1.554; hayfever symptoms last year, OR 0.642, 95% CI 0.369-1.118; eczema symptoms last year, OR 0.693, 95% CI 0.430-1.115). CONCLUSION: The lower prevalence of astma, hayfever and eczema symptoms in DM patients compared with age-matched controls, although not statistically significant, is consistent with the Th1/Th 2 concept.

Effect of three low-dose fish oil supplements, administered during pregnancy, on neonatal long-chain polyunsaturated fatty acid status at birth.

Adequate long-chain polyunsaturated fatty acid (LCP) status during pregnancy is important. We studied the effect of three low-dose fish oil supplements, administered during uncomplicated pregnancy, on neonatal LCP status at term delivery. Supplements were administered from the second trimester to delivery, either as fish oil capsules ("fish-1": 336 mg LCPomega3, n=15; and "fish-3": 1,008 mg LCPomega3, n=20) or milk-based supplement ("Mum": 528 mg LCPomega3, n=24). Fifty-seven untreated women served as controls. Fatty acids of umbilical veins (UV) and arteries (UA) were measured. The fish-1 group showed no differences, compared to controls. The Mum group had higher 20:5omega3, 22:5omega3, 22:6omega3, LCPomega3 and 22:6omega3/22:5omega6 in UV and UA. The fish-3 group had higher 22:5omega3 and 22:6omega3 (UA), LCPomega3 and 22:6omega3/22:5omega6 (UV and UA) and 20:3omega6 (UV). A 500-1000 mg daily LCPomega3 supplement, taken either as a milk-based supplement or fish oil capsules, effectively increases fetal LCPomega3 status, without affecting LCPomega6 status.

Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia.

OBJECTIVE: To compare serum levels of angiogenic growth factors vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and angiogenin in pre-eclamptic women and matched controls. DESIGN: Retrospective analysis of -70 degrees C stored serum of women who developed pre-eclampsia and matched controls. SETTING: Department of Gynaecology and Obstetrics, St Elisabeth Hospital, Curaçao, Netherlands Antilles. SAMPLE: Thirty women with pre-eclampsia and 30 normotensive controls matched for age and gestation. RESULTS: VEGF and PIGF serum levels were significantly lower in pre-eclamptic pregnancies, compared with controls (VEGF 0.31 +/- 1.20 vs 18.30 +/- 24.97 pg/mL, P = 0.0004; PlGF 54.19 +/- 32.05 vs 497.95 +/- 340.51 pg/mL, P < 0.0001). Matched couple analysis showed VEGF serum concentrations to be lower in the majority of pre-eclamptic women and PlGF concentrations to be lower in all pre-eclamptic women. Angiogenin serum levels showed no statistical significant difference between pre-eclamptic pregnancies and controls (523.68 +/- 367.55 vs 670.41 +/- 251.54 ng/mL, P = 0.058), with matched couple analysis showing no clear pattern. CONCLUSIONS: Decreased serum levels of VEGF and PIGF characterise, and therefore seem to be of importance during (the development of), pre-eclampsia. This selective deficit of angiogenic growth factors might in part explain the shallow placentation found in this pregnancy complication.

Umbilical vessels of preeclamptic women have low contents of both n-3 and n-6 long-chain polyunsaturated fatty acids.

BACKGROUND: Preeclampsia is characterized by enhanced platelet aggregation and vasoconstriction and is related to an elevated ratio of thromboxane A2 to prostacyclin I2. OBJECTIVE: We investigated whether altered eicosanoid production in preeclamptic women could be explained by the fatty acid composition of umbilical vessel walls and platelets. DESIGN: The fatty acid composition of maternal and umbilical platelets and of umbilical arteries and veins in 27 preeclamptic women and 24 normotensive women was determined. Between-group differences were analyzed with linear discriminant analysis, the Kruskal-Wallis test, or analysis of covariance with gestational age as the covariate. RESULTS: Platelets of preeclamptic women contained lower amounts of 20:5n-3 and a higher ratio of 20:4n-6 to 20:5n-3 than did platelets of normotensive women. Additionally, linear discriminant analysis revealed higher amounts of 20:4n-6 in platelets of preeclamptic women. Umbilical arteries and veins in preeclamptic women contained lower amounts of long-chain polyunsaturated fatty acids (PUFAs) of the n-3 series, n-6 long-chain PUFAs, and 20:3n-6 than did umbilical arteries and veins of normotensive women. Umbilical arteries also had lower amounts of 20:4n-6, higher amounts of 20:3n-9, and a higher ratio of 20:3n-9 to 20:4n-6. CONCLUSIONS: Low amounts of long-chain n-3 and n-6 PUFAs in umbilical vessels of preeclamptic women with adequate n-6 status may indicate insufficient transplacental transfer of long-chain PUFAs. The low amounts of 20:4n-6, high amounts of 20:3n-9, and high ratio of 20:3n-9 to 20:4n-6 in umbilical arteries may unfavorably affect local prostacyclin production. Low amounts of 20:3n-6 in umbilical arteries and veins and low amounts of 20:5n-3 in maternal platelets may contribute to the dominance of eicosanoids derived from 20:4n-6.

Is there seasonality in human ovulation?

To study seasonality in human ovulation in a direct way, we measured the occurrence of ovulation in infertile patients with spontaneous menstrual cycles (< 6 weeks) who visited the fertility clinic at the University Hospital Nijmegen in the Netherlands for the first time in 1991 or 1992 (n = 407). Ovulation was detected using serial transvaginal ultrasound and midluteal progesterone measurement and was performed during one screening cycle. The frequency of ovulatory cycles per month varied from 73% to 93% (not statistically significant). No seasonal pattern in ovulation was found in subfecund Dutch women with spontaneous menstrual cycles. This finding was not confounded by the effects of age of the women, body mass index, or disorders that could influence ovulation.