Metastatic Malignant Melanoma of the Small Bowel—Report of Two Cases

Case Report  

We report two cases of malignant melanoma metastasizing to the ileum and jejunum in a 48-year-old female and 62-year-old male, respectively. The female patient was a known case of vaginal melanoma who on follow-up developed pain abdomen 4 years after excision of the primary, whereas the male patient who was initially referred as pleomorphic spindle cell sarcoma of the groin presented with complaints of bleeding per rectum and melena 6 years later.     

Reflections on the 14th World Conference on Lung Cancer: A European Perspective

Observations from the 14th World Conference on Lung Cancer, held in Amsterdam July 3–7, 2011, are presented.Lung cancer remains the leading cause of cancer death worldwide. More than 7,000 delegates attended the 14th World Conference on Lung Cancer (WCLC) that was held in Amsterdam July 3–7, 2011. The focus of this meeting was on emerging research ushering in the era of more personalized lung cancer treatment. Besides advances in therapy, the conference program also addressed early detection, imaging, the new International Association for the Study of Lung Cancer (IASLC) staging system, palliative care, and patient advocacy. The increasingly multidisciplinary nature of lung cancer care was reflected in well-attended sessions addressing topics of a multidisciplinary character such as molecular pathology, treatment options for high-risk and elderly patients, epidemiology, cancer in never-smokers, and salvage therapy.As expected, advances in genetic subclassifications of advanced non-small cell lung cancer (NSCLC) were a major focus at the meeting because ∼50% of lung adenocarcinomas have been shown to have an identifiable driving oncogene [1] (Fig. 1). A key study presented was the phase III European Tarceva® (erlotinib) versus Chemotherapy (EURTAC) study of 174 western patients with NSCLC who had an epidermal growth factor receptor (EGFR) mutation [2]. First-line treatment of such patients with the drug erlotinib nearly led to a progression-free survival interval that was nearly double that observed with chemotherapy, 9.4 months versus 5.2 months, respectively. Nearly 55% of patients responded to erlotinib, in contrast to 15.5% who responded to chemotherapy. The lack of a significant difference in the overall survival times (22.9 months versus 18.8 months, respectively) was likely a result of the high crossover rates observed in such trials. Taken together with recent studies of this class of agent in Asian mutation-positive patients, this finding establishes that patients with EGFR mutation benefit from receiving initial treatment with the less toxic and more efficacious targeted agents. Emerging data on the newer generation EGFR inhibitors currently in early clinical trials raise the prospect of further therapeutic improvements in the near future.Open in a separate windowFigure 1.Overview of genetic alterations in non-small cell lung cancer, with targeted agents directed towards these driver mutations, based on a treatment approach proposed by the Spanish Lung Cancer Group.Abbreviations: ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; EML, echinoderm microtubule-associated protein-like; HER-2, human epidermal growth factor receptor 2; MEK, mitogen-activated protein kinase/extracellular signal–related kinase kinase; PIK3CA, phosphoinositide-3-kinase, catalytic, α polypeptide; TKI, tyrosine kinase inhibitor; wt, wild-type.Reproduced with permission. Reprinted in Lung Cancer, Vol. 74, No. 3, Bover et al., Fifth Educational Symposium of the Spanish Lung Cancer Group: Report on the Molecular Biology Workshop, 535–543 © 2011.However, it must be kept in mind that 1,227 patients had to be screened in order to identify the enriched population of 174 mutation-positive patients treated in the EURTAC study. Because clinical characteristics alone do not identify suitable patient subgroups, the need to obtain sufficient tissue to perform molecular analyses of tumors is evident. A more aggressive attitude on the part of both physicians and patients is required to achieve this goal, a point that was repeatedly stressed at well-attended workshops, educational sessions, and a hands-on session. A small proof-of-concept study demonstrated that in vivo detection of mutated tumors was possible using labeled erlotinib as a tracer for positron emission tomography scanning [3]. Such an approach may be promising in cases for which obtaining tissue for mutation analysis is impossible or very risky. Besides the issue of EGFR mutations, the degree of expression of EGFR by tumor cells was also reported to be an important predictor of benefit from treatment with an anti-EGFR antibody in combination with conventional chemotherapy [4]. This is especially interesting for squamous cell lung carcinoma because limited clinical progress has been achieved for this histological subtype.Another driving oncogene that has successfully been targeted in clinical trials has been the echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) mutation, which is estimated to be present in 3%–5% of all lung carcinomas. Overall survival data from 82 ALK⁺ patients who received the novel drug crizotinib versus matched historical controls revealed 1- and 2-year overall survival rates of 77% and 64%, versus corresponding survival rates of 73% and 33%, respectively, in controls [5]. In contrast to many molecular targeted therapies available for lung adenocarcinoma, none has yet been reported for squamous cell lung carcinoma until recently. Following the identification of possible therapeutic targets in up to 63% of squamous cell lung carcinomas [6], these targets will need to be validated in preclinical models, and early clinical trials using fibroblast growth factor receptor (FGFR)-1, FGFR-2, phosphoinositide-3-kinase, catalytic, α polypeptide, and discoidin domain receptor tyrosine kinase 2 inhibitors are either planned or ongoing.The topic of screening for lung cancer also received much attention at the meeting. The publication just prior to the WCLC meeting of results from the National Lung Screening Trial (NLST) in the U.S. revealed that there were 20% fewer lung cancer deaths and a 7% lower all-cause mortality rate when smokers, defined as current or former smokers with ≥30 pack-years of smoking, were regularly screened using low-dose spiral computed tomography (CT), compared with standard chest x-ray [7]. The study followed >53,000 current and former smokers aged 55–74 years and was closed prematurely as a result of the observed lower number of cancer deaths. A key remaining concern was the high rate of positive findings (24.15%) after CT screening, of which, 96.4% proved to be false. Consequently, 26,722 individuals had to be screened in order to obtain 87 fewer lung cancer deaths in healthy (former) smokers.The costs related to the entire NLST screening process, including follow-up examinations to evaluate findings suspicious for lung cancer and other illnesses, surgery for abnormal lesions, treatment initiated, etc., remain to be published. The IASLC issued a statement addressing, among other things, the need for measures to ensure the quality of screening management and participation of multidisciplinary groups of trained specialists [8]. The IASLC statement specifically referred to the need to await maturing data from European trials, the largest of which is the NEderlands Leuvens Longkanker Screenings Onderzoek (NELSON) trial of >20,000 smokers [9]. Mortality data from the NELSON trial will become available in 2015, and that trial will also provide important additional information on mortality gains, cost-effectiveness, and clinical management outcomes of lung cancer screening. Because it is unrealistic to screen the large number of current and ex-smokers worldwide, the IASLC emphasized the need for effective tobacco control programs. Because only 10%–15% of smokers die as a result of lung cancer, new approaches that may identify patient populations with a strong predisposition to developing lung cancer may in turn allow for more targeted CT screening.Some critics of screening hold the view that a complex and aggressive disease like NSCLC cannot be detected sufficiently early to affect outcomes, particularly because the potential benefits of detecting early-stage disease can be offset by the complications of therapy. Varying access to curative care has also been considered to be a factor accounting for differences in the cure rate for lung cancer among western European countries. In this context, a British study reporting a correlation between appointments of more thoracic surgeons and a 46% increase in the resection rate for early-stage lung cancer was encouraging [10]. However, the elderly represent the fastest growing group of patients with lung cancer, and the risks of surgery outside specialized centers for such patients are great. A population-based time trends analysis in The Netherlands population of 16 million Dutch identified a total of 4,605 patients aged ≥75 years who were diagnosed with stage I NSCLC in 2001–2009 [11]. In a country where many patients undergo surgery at low-volumes centers [12], the 30- and 90-day postsurgical mortality rates were 5.4% and 9.3%, respectively [11]. The Dutch population analysis revealed that, following the introduction of stereotactic radiotherapy in 2003, a 6.5% absolute increase in radiotherapy use was seen in elderly patients, as was a decline in untreated patients and an improvement in the median survival time of irradiated patients from 16.8 months in the early period to 26.1 months in the last period. These data indicate that issues surrounding centralization of surgical care as well as a need to provide more information on alternative therapies to surgical candidates at high risk for toxicity should to be addressed urgently.The advances presented at the Amsterdam meeting add to a growing conviction that only treatment by expert multidisciplinary teams can ensure optimal patient care and survival for lung cancer patients. Facilities for rapid diagnostic procedures, obtaining adequate histology specimens, expertise in molecular diagnostic protocols, access to guideline-compliant surgery and stereotactic radiotherapy, and managing complications of combined-modality therapies are all essential. This was illustrated in a study analyzing 400 patients seen for a second opinion at a tertiary academic center [13]. In a majority of cases, the second opinion process was initiated by a treating pulmonologist (65%), but this was at the sole initiative of the patient in 31% of cases. The second opinion consultation resulted in changes in diagnosis, disease stage, or therapy with possible consequences for therapy outcomes in 44% of all patients, and a change in policy of a potentially major character in 25% of patients. Referrals of this nature can be expected to increase in Europe in coming years, given the growing awareness by both specialists and patient groups of crucial expertise available from expert multidisciplinary teams. With health care budgets in Europe and elsewhere facing growing financial constraints, strategies that focus on redeploying existing health care resources within such expert centers or networks may be a more realistic approach in the short term than is the expectation for additional resources. Arguably, such developments may be more feasible within the less-fragmented health care structures existing in some European countries. Nevertheless, hurdles involved in implementing more personalized lung cancer treatment approaches in Europe should not be underestimated.     

Initial treatment patterns over time for anaplastic oligodendroglial tumors

Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach to treatment. We sought to determine patterns of treatment delivered over time and identify clinical correlates of specific strategies using an international retrospective cohort of 1013 patients diagnosed from 1981-2007. Prior to 1990, most patients received radiotherapy (RT) alone as initial postoperative treatment. After 1990, approximately 50% of patients received both RT and chemotherapy (CT) sequentially and/or concurrently. Treatment with RT alone became significantly less common (67% in 1980-1984 vs 5% in 2005-2007, P < .0001). CT alone was more frequently administered in later years (0% in 1980-1984 vs 38% in 2005-2007; P < .0001), especially in patients with 1p19q codeleted tumors (57% of codeleted vs 4% with no deletion in 2005-2007; P < .0001). Temozolomide replaced the combination of procarbazine, lomustine, and vincristine (PCV) among patients who received CT alone or with RT (87% vs 2% in 2005-2007). In the most recent time period, patients with 1p19q codeleted tumors were significantly more likely to receive CT alone (with temozolomide), whereas RT with temozolomide was a significantly more common treatment strategy than either CT or RT alone in cases with no deletion (P < .0001). In a multivariate polytomous logistic regression model, the following were significantly associated with type of treatment delivered: date (5-year interval) of diagnosis (P < .0001), 1p19q codeletion (P < .0001), pure anaplastic oligodendroglioma histology (P < .01), and frontal lobe predominance (P < .05). Limited level 1 evidence is currently available to guide treatment decisions, and ongoing phase III trials will be critical to understanding the optimal therapy.     

Evaluation of Chromosome Aberrations in Subjects Exposed to Environmental Tobacco Smoke in Tamilnadu,India

Numerous expert panels have concluded that there is sufficient evidence to classify involuntary smoking (or passive smoking) as carcinogenic to humans. The aim of this study is to establish whether passive smoking increases the frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes compared to controls in Tamil Nadu, India. In the present study, CA increased with an increase in environmental tobacco smoke (ETS) and active smoke exposure period in passive smokers quantified on the basis of serum cotinine levels. The passive subjects were compared with healthy normal controls to validate the results. In conclusion, these data are compatible with the current knowledge on the mechanisms of carcinogenesis of tobacco-related cancers, occurring not only in active smokers but with a high biological plausibility also in passive smokers.     

Nasopalpebral lipoma coloboma syndrome

Nasopalpebral lipoma-coloboma syndrome is characterized by nasopalpebral lipoma and eyelid coloboma. We report a case of a 16-year-old Indian girl who reported to us with this rare syndrome. Computed tomography scan showed a significantly hypodense lesion on the right side of nose which was confirmed to be a lipoma on histopathological examination. This condition should be included in differential diagnosis of conditions with congenital eyelid coloboma.     

Simple way to secure an occlusal wafer in patients with compromised dentition

The use of occlusal wafers in orthognathic surgery is very tricky. We propose an alternative using bite planes bonded the day prior to surgery and involving the maxillary first premolar to second molar.Bite planes offer many advantages whether one uses the direct method (when orthodontic preparation produces no posterior non-occlusion greater than 3mm), or the indirect method (in the opposite case or in cases of terminal edentulousness) requiring the use of an articulator. Manufacture and placement of the bite planes are much simpler than with wafers; they shorten the surgical procedure and offer the patient enhanced post-operative comfort and hygiene.

Rare case of fetal gastroschisis with aplasia of the foot and external genital organs

Gastroschisis is a rare anomaly and is usually not associated with any other congenital anomalies. The embryology of gastroschisis and omphalocele remains a matter of speculation. Incidences of gastroschisis are particularly high among pregnancies in very young women. The present case is reported because of its rare association with the condition of gastroschisis, disrupted omphalocele, with aplasia of the foot and external genital organs, as well as imperforate anus with distal rectal atresia.