Fighting Global Disparities in Cancer Care: A Surgical Oncology View.

Cancer is the second leading cause of death globally after cardiovascular disease. Long-term cancer survival has improved in the Western world due to early detection and the use of effective combined treatment modalities, as well as the development of effective immunotherapy and drug-targeted therapy. Surgery is still the mainstay for most solid tumors; however, low- and middle-income countries are facing an increasing lack of primary surgical care for easily treatable conditions, including breast, colon, and head and neck cancers. In this paper, a surgical oncology view is presented to elaborate how the Western surgical oncologist can take part in the 'surgical fight' against global disparities in cancer care, and a plea is made to strive for structural solutions, such as a partnership in surgical oncology training. The pros and cons of the use of eHealth and mHealth technologies and education programs for schools and the community are discussed as these create an opportunity to reach a large portion of the population in these countries, at low cost and with high impact.

Physician assistants in medical ward care: a descriptive study of the situation in the Netherlands.

RATIONALE, AIMS AND OBJECTIVES: Medical ward care has been increasingly reallocated from medical doctors (MDs) to physician assistants (PAs). Insight into their roles and tasks is limited. This study aims to provide insight into different organizational models of medical ward care, focusing on the position, tasks and responsibilities of the involved PAs and MDs. METHODS: In this cross-sectional descriptive study 34 hospital wards were included. Characteristics of the organizational models were collected from the heads of departments. We documented provider continuity by examination of work schedules. MDs and PAs in charge for medical ward care (n = 179) were asked to complete a questionnaire to measure workload, supervision and tasks performed. RESULTS: We distinguished four different organizational models for ward care: medical specialists in charge of admitted patients (100% MS), medical residents in charge (100% MR), PAs in charge (100% PA), both MRs and PAs in charge (mixed PA/MR). The wards with PAs had the highest provider continuity. PAs spend relatively more time on direct patient care; MDs spend relatively more time on indirect patient care. PAs spend more hours on quality projects (P = 0.000), while MDs spend more time on scientific research (P = 0.030). CONCLUSION: Across different organizational models for medical ward care, we found variations in time per task, time per bed and provider continuity. Further research should focus on the impact of these differences on outcomes and efficiency of medical ward care.

Immunohistochemical analysis of steroid hormone receptors in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory follicular skin disease. In women and men, the condition starts after puberty, has a peak in the third decade, and is rare after the menopause in women. This age distribution suggests a hormonal influence in the pathogenesis of the disease. We therefore hypothesized that apocrine glands in HS patients have a different expression of androgen receptor (AR) and estrogen receptor (ER) compared with healthy skin. METHODS: Axillary, inguinal, and perianal skin biopsies from female and male patients with HS were immunohistochemically stained for AR and ER activities. Expression of both receptors in apocrine glands of HS patients was compared with expression in apocrine glands in normal axillary or inguinal skin of a control group of women. RESULTS: Twenty-two patients with HS were included (16 women), with 10 women in the control group. In the HS group, apocrine glands were present in 11 out of 22 skin biopsies and in the control group in 4 out of 10 biopsies. Expression of ER in the apocrine gland was weak and observed in 2 out of 4 patients in the control group and in none of the HS patients. Expression of the AR was strong and observed in all apocrine glands in both groups. CONCLUSIONS: We could not demonstrate a significant difference in the expression of ER and AR in apocrine glands in skin biopsies of patients with HS, compared with healthy skin biopsies. The exact relation between sex hormones and occurrence of HS therefore remains unclear.

Implementation of the physician assistant in Dutch health care organizations: primary motives and outcomes.

Physician assistants (PAs) are trained to perform medical procedures that were traditionally performed by medical physicians. Physician assistants seem to be deployed not only to increase efficiency but also to ensure the quality of care. What is not known is the primary motive for employing PAs within Dutch health care and whether the employment of the PAs fulfills the perceived need for them. Supervising medical specialists who used PAs in their practices were interviewed about their primary motives and outcomes. The interviews were semistructured. Two scientists coded the findings with respect to motives and outcomes. In total, 55 specialists were interviewed about their motives for employing a PA, and 15 were interviewed about the outcomes of employing a PA. With respect to the primary motives for employing a PA, the most frequent motive was to increase continuity and quality of care, followed by relieving the specialist's workload, increasing efficiency of care, and substituting for medical residents. The outcomes were found to be consistent with the motives. In conclusion, the primary motive for employing a PA in Dutch health care is to increase continuity and quality of care.

Polymorphisms in alcohol-metabolizing enzymes and esophageal carcinoma susceptibility: a Dutch Caucasian case-control study.

Esophageal cancer (EC), mainly consisting of squamous cell carcinoma (ESCC) in the Eastern world and adenocarcinoma (EAC) in the Western world, is strongly associated with dietary factors such as alcohol use. We aimed to clarify the modifying role in EC etiology in Caucasians of functional genotypes in alcohol-metabolizing enzymes. In all, 351 Caucasian patients with EC and 430 matched controls were included and polymorphisms in CYP2E1, ADH and near ALDH2 genes were determined. In contrast to the results on ESCC in mainly Asian studies, we found that functional genotypes of alcohol-metabolizing enzymes were not significantly associated with EAC or ESCC in an European population.

No role for glutathione S-transferase genotypes in Caucasian esophageal squamous cell or adenocarcinoma etiology: an European case-control study.

BACKGROUND: Identifying and monitoring high-risk patients can aid the prevention of esophageal cancer (EC). The interaction of environmental risk factor exposure and genetic susceptibility may contribute to the etiology of EC. Biotransformation enzymes such as Glutathione S-Transferases (GSTs ) detoxify mutagenic and genotoxic compounds and therefore control the rate of detoxification of carcinogens. Functional polymorphisms in the genes coding for GSTs alter their enzyme activity in vitro, and were reported to modify EC risk in Asians. We hypothesized that altered enzyme activity GST genotypes influence the susceptibility for esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) in Caucasians. METHODS: We performed a case-control study including 440 Caucasian patients with EC and 592 healthy Caucasian controls matched for age and sex. Functional polymorphisms were selected and genotypes were determined in GST classes Alpha, Mu, Theta and Pi by means of polymerase chain reaction. Genotypes were classified into predicted high, intermediate and low enzyme activity categories based on in vitro activity data. The distribution of the activity genotypes were compared between patients with EAC or ESCC, and controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analyses. Gene-gene interactions were tested and for comparison purposes, the predicted low and intermediate activity genotypes were combined. Genotypes with similar risks for EAC or ESCC were combined and analyzed for multiplicative effects. RESULTS: Our analyses includes 327 patients with EAC and 106 patients with ESCC. Low or intermediate activity enzyme genotypes for GSTM1, GSTA1, GSTP1 I105V and A114V as well as for GSTT1, did not significantly modify the risk for ESCC or EAC in our Dutch population. CONCLUSION: Functional genotypes in GST genes are not involved in EAC or ESCC susceptibility in Caucasians, in contrast to results on ESCC from Asia or Africa.

Barrett associated MHC and FOXF1 variants also increase esophageal carcinoma risk.

Barrett's esophagus, with gastroesophageal reflux disease and obesity as risk factors, predisposes to esophageal adenocarcinoma (EAC). Recently a British genome wide association study identified two Barrett's esophagus susceptibility loci mapping within the major histocompatibility complex (MHC; rs9257809) and closely to the Forkhead-F1 (FOXF1; rs9936833) coding gene. An interesting issue is whether polymorphisms associated with Barrett's esophagus, are also implicated in esophageal carcinoma (EC), and more specifically EAC genesis. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from surveillance programs. Our hypothesis: Barrett associated MHC and FOXF1 variants modify EC risk in Caucasians. In a Dutch case-control study, 431 patients with EC and 605 healthy controls were included. Polymorphisms at chromosomes 6p21 (MHC) and 16q24 (FOXF1) were determined by means of real-time polymerase chain reaction (RT-PCR). Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals. The FOXF1 rs9936833 variant C allele was associated with an increased EAC susceptibility; OR, [95% CI]; 1.21, [0.99-1.47]. A sex-stratified analysis revealed a similar association in males; 1.24 [1.00-1.55]. The variant MHC rs9257809 G allele as well as the MHC heterozygous AG genotype significantly increased ESCC risk; 1.76 [1.16-2.66] and 1.74 [1.08-2.80], respectively. Sex-stratification showed that the variant G allele was especially present in female patients; 2.32 [1.04-5.20]. In conclusion, this study provides evidence that MHC rs9257809 and FOXF1 rs9936833 variants, associated with Barrett's esophagus, also increase ESCC and EAC susceptibility in Caucasians. FOX proteins are transcription factors involved in organogenesis of the GI tract, while MHC haplotypes are strongly associated with smoking behavior, a crucial risk factor for ESCC. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from (Barrett) surveillance programs.

GWAS-uncovered SNPs in PLCE1 and RFT2 genes are not implicated in Dutch esophageal adenocarcinoma and squamous cell carcinoma etiology.

Susceptibility to esophageal carcinoma (EC) is influenced by the interaction between genetic and environmental factors. To clarify the etiology of EC, several genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in PCLE1 and RFT2 genes as esophageal squamous cell carcinoma (ESCC) susceptibility loci in Asian populations. This study aimed to determine whether these SNPs also modify the risk of esophageal adenocarcinoma (EAC) and ESCC in western populations of Caucasian ethnicity. A European case-control study including 349 EC patients and 580 controls matched for age, sex, geographical location, and race was carried out. The SNPs rs2274223 in the PCLE1 gene at chromosome 10q23 and rs13042395 in the RFT2 gene at chromosome 20p13 were determined using PCR. Genotype distributions were compared between patients and controls, and odds ratios with 95% confidence intervals were calculated. The total EC group included 86 patients with ESCC and 258 patients with EAC. The distribution of PLCE1 and RFT2 genotypes did not differ between patients with EAC or ESSC, and the controls. In contrast to the modulation of the risk of ESCC in Asians, it is unlikely that the PLCE1 rs2274223 and RFT2 13042395 SNPs play a role in EAC or ESCC susceptibility in Dutch Caucasians.

EPHX1 polymorphisms do not modify esophageal carcinoma susceptibility in Dutch Caucasians.

Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Crucial risk factors are exposure to toxins or carcinogens. Microsomal epoxide hydrolase (mEH) is a biotransformation enzyme essential for the detoxification of xenobiotics. Polymorphisms in exon 3 and exon 4 of the microsomal epoxide hydrolase gene (EPHX1) modify catalytic activity of this enzyme and subsequently may play a role in EC etiology. This case-control study investigated whether these polymorphisms in the EPHX1 gene influence esophageal cancer susceptibility in a Dutch Caucasian population. A case-control study including 349 Caucasian EC patients and 581 Caucasian healthy controls was conducted and the polymorphisms Tyr113His (exon 3) and His139Arg (exon 4) in the EPHX1 gene were determined, using polymerase chain reaction. The distribution of exon 3 and exon 4 genotypes were compared between cases and controls. Analyses included a stratification according to tumor histology; esophageal adenocarcinoma (EAC) or squamous cell carcinoma (ESCC). Furthermore, on the basis of allelic in vitro enzyme activity assays, exon 3 and 4 genotypes were combined and categorized according to their predicted high, medium or low enzyme activity. Homozygosity and heterozygosity for both exon 3 and 4 polymorphisms were correlated with a decreased esophageal squamous cell carcinoma risk. Heterozygosity and homozygosity for both polymorphisms correlated with an increased and a decreased esophageal adenocarcinoma risk, respectively. Predicted intermediate and high activity genotypes were risk and protective factors for esophageal squamous cell carcinoma and esophageal adenocarcinoma, respectively. However, none of these associations were statistically significant. In conclusion, the polymorphisms in exon 3 and exon 4 of the EPHX1 gene do not seem to be modifiers of esophageal squamous cell carcinoma or esophageal adenocarcinoma risk in Dutch Caucasians.

High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk.

Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Environmental and dietary factors have crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a superfamily of enzymes essential for the detoxification of carcinogens, may alter enzyme activity and subsequently may play a role in EC etiology. Rather than solely establishing differences in genotype distribution, we investigated whether functional polymorphisms in UGT genes that can predict enzyme activity in vivo, may influence EC risk. A case-control study including 351 Caucasian EC patients and 592 Caucasian controls was conducted and polymorphisms in seven UGT genes were determined, using the polymerase chain reaction. On the basis of allelic in vitro enzyme activity measurements, genotypes were categorized according to their predicted in vivo enzyme activity into high, medium and low categories. Predicted enzyme activity groups were combined and compared between patients and controls. The UGT1A1 and UGT1A8 predicted high enzyme activity genotypes were significantly more (OR=1.62; 95% CI, 1.02-2.56) and less frequent (OR=0.36; 95% CI, 0.15-0.84) among patients with esophageal squamous cell carcinoma (ESCC), respectively. High (OR=0.42; 95% CI, 0.22-0.84) and medium (OR=0.25; 95% CI, 0.12-0.52) activity UGT2B4 genotypes were significantly less often present in ESCC patients. No association was detected between UGT genotypes and esophageal adenocarcinoma (EAC) risk. Polymorphisms in UGT genes, resulting in altered enzyme activity genotypes, do not seem modifiers of EAC risk. However, the predicted high activity UGT1A1 genotype, associated with low serum levels of the antioxidant bilirubin, was associated with an increased ESCC risk. The UGT1A8 and UGT2B4 genotypes associated with decreased predicted enzyme activities, were significantly associated with an increased risk of ESCC, probably by a decreased detoxification of carcinogens.

Spontaneous regression of a cystic retroperitoneal tumour in young women postpartum. Report of two cases.

Retroperitoneal cystic tumours are rarely found, and of these, the most common lesion is a cystic lymphangioma. We present two postpartum patients with a cystic retroperitoneal tumour which showed spontaneous regression and a review of the literature.

Metalloproteinases and their regulators in colorectal cancer.

Metalloproteinases (MPs) such as the matrix metalloproteinases (MMPs) and adamalysins (ADAMs and ADAMTS) are expressed in various stages of colorectal cancer (CRC), and some correlate with survival and prognosis. The MPs are regulated by various factors including EMMPRIN, TIMPs, and RECK. In addition, micro-RNAs are found to be relevant for both MP expression levels and CRC prognostication. Both MPs and their regulators could be potential targets for intervention and therapy in CRC.

[Second operation more frequent following breast-conserving treatment for invasive lobular than for invasive non-lobular carcinoma]. / Vaker tweede operatie na borstsparende behandeling wegens invasief lobulair dan wegens invasief niet-lobulair carcinoom.

OBJECTIVE: To establish the frequency of re-excision or mastectomy in women who had breast-conserving treatment for invasive lobular mammary carcinoma. DESIGN: Retrospective. METHOD: Data on the number of patients with invasive carcinoma from 1998-2006 were obtained from the national pathology database (PALGA) and the Dutch Comprehensive Cancer Centre East. The following data on patients who had undergone breast-conserving treatment for invasive lobular carcinoma were collected from the electronic patient records: age, localization procedure with wire-localisation and tumour size. RESULTS: The frequency of re-excision or mastectomy following initial breast-conserving surgery in 123 patients with invasive lobular carcinoma was 46.3 % versus 31.5 % in 877 patients with other types of invasive carcinoma. The number of re-excisions was higher in the group with invasive non-lobular carcinoma (4.9% versus 9.2%), and the number of conversions to mastectomy was higher in the group with invasive lobular carcinoma (41.5% versus 20.1%). The age of the patient, the localisation procedure and tumour size were not significant predictors of a tumour-free surgical margin or for the necessity of re-excision. CONCLUSION: The frequency of re-excision in patients with invasive lobular carcinoma was higher than in patients with other types of breast cancer. There was no statistically significant predictor for obtaining a tumour-free surgical margin.

Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography and computed tomography in patients with melanoma with palpable lymph node metastases: diagnostic accuracy and impact on treatment.

PURPOSE: Patients with melanoma with potentially resectable lymph node metastases require accurate staging to prevent unnecessary surgery. [(18)F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is attractive for this because melanoma typically is FDG avid. The aim of this prospective multicenter study was to perform a head-to-head comparison of FDG-PET and computed tomography (CT) in staging of patients with melanoma with palpable lymph node metastases in terms of diagnostic accuracy and impact on treatment. PATIENTS AND METHODS: All consecutive patients with palpable, proven lymph node metastases of melanoma between mid 2003 and 2007 were prospectively included. The number/site of distant metastases detected with FDG-PET and CT were recorded. Histology/cytology or 6 months follow-up were the reference standard. Intended and performed treatment was recorded. RESULTS: Distant metastases were suspected by FDG-PET in 32% of the 251 patients and by CT in 29% (P = .26). Upstaging was correct in 27% by FDG-PET and in 24% by CT (P = .18). FDG-PET detected more metastatic sites (133 v 112, P = .03), detecting significantly more bone and subcutaneous metastases. Treatment changed in 19% of patients; in 79% as a result of both scans, in 17% exclusively by FDG-PET, and in 4% exclusively by CT. In 34 patients (14%), FDG-PET had an additional value over spiral CT, and in 23 patients (9%), CT had additional value over FDG-PET. CONCLUSION: As a result of FDG-PET and CT, 27% of patients were upstaged, and treatment changed in one of five patients. FDG-PET and CT are equivalent in upstaging; however, FDG-PET detected more metastatic sites, especially bone and subcutaneous. FDG-PET and/or CT are indicated in the staging of patients with melanoma with palpable lymph node metastases.

More tumor-affected lymph nodes because of the sentinel lymph node procedure but no stage migration, because the 2002 TNM classifies small tumor deposits as pathologic N0 breast cancer.

BACKGROUND: Intensified examination of the sentinel lymph node (SN) may result in increased detection of tumor-affected lymph nodes. The authors of this report hypothesized that the introduction of the SN procedure has led to stage migration because of the intensified workup of SNs by pathologists. METHODS: After the introduction of the SN procedure, 360 patients with operable breast cancer were included prospectively from 2 large hospitals (Hospital A and Hospital B). The prospectively included patients (the "SN era" group) were compared with 88 historic controls from the year 1994 who were diagnosed with primary breast cancer before introduction of the SN procedure. RESULTS: After correcting for classic clinical and pathologic prognostic factors in a multiple logistic regression analysis, the detection frequency of lymph node involvement was significantly higher in the SN era group compared with historic controls (P = .04). However, when using the 2002 TNM classification, in which isolated tumor cells (

Magnetic resonance imaging in size assessment of invasive breast carcinoma with an extensive intraductal component.

BACKGROUND: Breast-conserving treatment of invasive breast carcinoma with an extensive intraductal component (EIC) is associated with DCIS-involved surgical margins and therefore it has an increased recurrence rate. EIC is a non-palpable lesion of which the size is frequently underestimated on mammography. This study was undertaken to evaluate the accuracy of MRI in size assessment of breast cancer with EIC. METHODS: 23 patients were identified and the mammographic (n = 21) and MR (n = 23) images were re-reviewed by a senior radiologist. Size on MR images was compared with histopathological tumour extent. RESULTS: The correlation of radiological size with histopathological size was r = 0.20 in mammography (p = 0.39) compared to r = 0.65 in MRI (p < 0.01). Mammography underestimated histopathological tumour size in 62%. MR images over- or underestimated tumour size in 22% and 30% of the cases, respectively. In poorly differentiated EIC, MRI adequately estimated the extent more often compared to moderately differentiated EIC (60% versus 25%, respectively). CONCLUSION: Size assessment of MRI imaging was more accurate compared to mammography. This was predominantly true for poorly differentiated EIC.

Magnetic resonance imaging of ductal carcinoma in situ: what is its clinical application? A review.

BACKGROUND: After breast-conserving surgery of ductal carcinoma in situ (DCIS) of the breast or invasive breast carcinoma with an extensive intraductal component, tumor-positive surgical margins are frequently found. Therefore, the extent of the intraductal disease needs to be accurately determined preoperatively. METHODS: Data for this review were identified by search of PubMed. Reference lists of selected articles were cross-searched for additional literature. RESULTS: DCIS is accurately detected with magnetic resonance imaging (MRI), but the typical malignant features are inconsistently seen and most often in high-grade DCIS or in DCIS with a small invasive component. The histopathologic extent of DCIS is more accurately demonstrated with MRI. However, overestimation due to benign proliferative lesions does frequently occur. An improved depiction of DCIS could lead to improved preoperative staging. Conversely, the identification of more extensive disease on MRI could give rise to unnecessary interventions. Therefore, MRI should be used carefully and preferable in specialized and experienced centers. CONCLUSION: [corrected] To date, there is no evidence that the use of MRI improves outcomes (ie, decreases recurrence rates) in patients with DCIS.

Management of Thyroid Gland Hemorrhage After Blunt Trauma: A Case Report and Review of the Literature.

BACKGROUND: Thyroid hemorrhage is a rare injury in patients suffering from blunt trauma to the neck. The case of a 60-year-oldwoman is describedwho developed increasing swelling in the neck with a mild inspiratory stridor after a fall from her bed. The fall had resulted in hemorrhage within a previously existing goiter. Further analysis by means of a CT scan revealed severe tracheal compression and active bleeding, which prompted immediate operative intervention. The patient recovered without complications. The decision-making process in this case is outlined, and other reports describing patients with thyroid hemorrhage after blunt cervical trauma are reviewed. CONCLUSION: Although blunt thyroid injury is an uncommon condition, failure to consider the diagnosis or failure to anticipate complications of thyroid hemorrhage may result in progressive bleeding and airway compromise. Decision making is based on the patient's vital signs and, if possible, the findings on a contrastenhanced CT scan of the neck.

Dysphagia caused by a fibrovascular polyp: a case report.

A 73-year old man presented with dysphagia for liquid and solid food. Barium contrast study of the esophagus and esophagoscopy demonstrated a fibrovascular polyp. This, almost 10 cm benign esophageal tumor, was removed surgically by a cervical esophagotomy. A fibrovascular polyp is a rare benign tumor of the esophagus, which, however, may give serious complications as asphyxia resulting from laryngeal obstruction leading to sudden death.

Metastatic dormancy imposed by the primary tumor: does it exist in humans?

BACKGROUND: In cancer patients, occult micrometastases may become apparent shortly after removal of the primary tumor. Animal experiments have shown that metastatic dormancy is maintained by apoptosis, and that primary tumor removal induces a flare-up of angiogenesis, leading to metastatic outgrowth. This phenomenon has led to the hypothesis that the primary tumor generates certain factors that inhibit angiogenesis at distant sites. It is still unknown whether such a phenomenon is operative in human cancer as well. Should it occur, it might have important therapeutic consequences. MATERIALS AND METHODS: Evidence for such a mechanism may be obtained from studies that analyze a series of tissue samples of metastases, taken before or after surgical removal of the primary lesion. RESULTS: Data from our laboratory on colorectal cancer have shown that, in the absence of the primary tumor, vascular density in the metastases is increased as well as their metabolic activity, as measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Mitotic activity is increased mildly, while levels of apoptosis are collapsed. CONCLUSION: These data indicate that a mechanism of primary-tumor-induced inhibition of angiogenesis exists, maintaining metastatic dormancy. We now suggest that this mechanism may be exploited to avoid the use of exogenous, potentially harmful angiogenesis inhibitors such as bevacizumab in a neoadjuvant setting. Treatment of patients with the primary tumor still in situ could thus be restricted to chemotherapy, since the synergistic effect of an angiogenesis inhibitor would be generated by the primary tumor itself. In the present paper the clinical relevance and possible consequences of our findings and suggestions are discussed.