Robert A. Ramirez

Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer

PURPOSE Pathologic nodal stage affects prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. PATIENTS AND METHODS We performed a case-control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. RESULTS We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. CONCLUSION Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC.

Use of a Surgical Specimen-Collection Kit to Improve Mediastinal Lymph-Node Examination of Resectable Lung Cancer

Introduction: Pathologic examination of mediastinal lymph nodes (MLNs) after resection of non–small-cell lung cancer is critical in the determination of prognosis and postoperative management. Although systematic nodal dissection is recommended, the quality of pathologic lymph-node staging often falls short of recommendations in practice. We tested the feasibility of improving pathologic lymph-node staging of resectable non–small-cell lung cancer by using a prelabeled specimen-collection kit. Methods: Case-control study with comparison of 51 resections, using a special lymph-node collection kit, with 51 controls matched for surgeon, extent of resection, pathologist, and T category. Appropriate statistical methods were used for all comparisons. Results: The median number of MLNs examined increased from one in the control group, to six in the case group (p < 0.001). The percentage of resections attaining the National Comprehensive Cancer Network-recommended quality of MLN examination, and the proportion that would have been eligible for recent landmark postresection adjuvant therapy trials increased significantly (p < 0.001). The duration of surgery and postoperative complication rates were similar between cases and controls. Eighteen percent of kit cases had positive MLN, compared with 8% of controls. Conclusions: The use of a specialized specimen-collection kit for MLN examination was feasible, markedly improved MLN staging, and showed a trend toward increased detection of patients with MLN metastasis, with only a modest increase in duration of surgery, and no increase in perioperative morbidity, mortality, or hospital length of stay.

Transition of a pancreatic neuroendocrine tumor from ghrelinoma to insulinoma: a case report

Pancreatic neuroendocrine tumors (PNETs) are rare with an incidence of 1 in 100,000 populations. PNETs can present either as a functional or non-functional tumor. In functional tumors the symptoms are a result of hormones such as insulin, gastrin, glucagon and vasoactive intestinal peptide (VIP) or others. Ghrelin is a 28 amino acid peptide discovered in 1999 and is thought to be involved in various physiologic and pathologic processes. Due to relatively recent discovery of this hormone, its functions in normal homeostasis and its association with various pathologic processes are still being uncovered. PNETs are a rare entity and the natural history of disease is not well known. We have presented a first ever case of metastatic PNET which presented as a ghrelinoma and later transformed into a symptomatic insulinoma. This case gives us a glimpse into an unusual variant of metastatic PNET. It also tells us that change in functional tumor biology can sometime be more morbid than the metastatic disease itself.

The role of checkpoint inhibition in non–small cell lung cancer

Background The development of immune checkpoint inhibitors has revolutionized the treatment of cancer. Their use in non-small cell lung cancer (NSCLC) remains in its infancy, but rapid progress has been made in treating metastatic NSCLC. Methods This article outlines the role of immune checkpoint inhibitors in the treatment of malignancy and reviews clinical trials of novel immunotherapies in the setting of metastatic NSCLC. Results Traditional chemotherapy with a platinum-based doublet has long been the backbone in the treatment of metastatic NSCLC. While the treatment of NSCLC can be targeted to specific mutations such as epidermal growth factor receptor, these subgroups are rare. The development of immunotherapy has expanded the treatment options for patients who have failed initial chemotherapy. Additionally, new studies have shown positive results for the use of immunotherapy in the first-line setting under certain conditions, allowing pembrolizumab to become the first immunotherapy to be approved in the first-line setting. Conclusion Treatment of NSCLC is constantly changing, and new immune checkpoint inhibitors have shown promising results. Clinical trials are examining their use in the adjuvant setting and in combination with other therapies, and these combination therapies have the potential to show even greater benefits and broader applications than the individual drugs themselves.

Response to editorial titled 'Intrapulmonary lymph node retrieval: unclear benefit for aggressive pathologic dissection'.

The TNM staging system is currently our best prognostic tool in lung cancer, but poor application of this tool is an increasingly recognized worldwide problem in thoracic oncology (1-3). The main deficiency appears to be suboptimal pathologic lymph node staging, an important problem because lymph node metastasis is the gravest prognostic feature in patients without distant metastasis, who are candidates for curative surgical intervention. The statistics are startling: 17% of lung cancer resections in the US have no lymph nodes examined (pNX) (4), 40-50% of all resections (67% of resections with ‘pN0/pN1’ disease) have no mediastinal lymph nodes examined (5,6), 12% of patients have no hilar/intrapulmonary (N1) lymph nodes examined (7), the median total lymph node count is only 4-5 and less than 15% of patients have more than 10 lymph nodes examined (8-10).

Quality of life for non-small cell lung cancer patients in the age of immunotherapy

Non-small cell lung cancer (NSCLC) is a very common and devastating disease that is accompanied by a range of symptoms. Patients can experience symptoms specific to their disease process (such as cough or dyspnea) or more generalized symptoms (such as fatigue and loss of appetite).

Prognostic Factors in Typical and Atypical Pulmonary Carcinoids

Background Typical and atypical carcinoids represent approximately 2% of all lung tumors. Survival of patients with typical bronchial carcinoids, unlike the survival of patients with most lung tumors, is generally long but dependent on stage. We report the findings of the Ochsner Medical Center/Louisiana State University (LSU) Health Sciences Center neuroendocrine tumor (NET) program. Methods A database with all patients seen at the Ochsner Medical Center/LSU NET program was queried for patients with bronchopulmonary NET. We included patients who had confirmed pathologic bronchopulmonary carcinoid and who had at least 1 clinic visit. Patients with large or small cell NETs or diffuse idiopathic pulmonary neuroendocrine cell hyperplasia were excluded. Results A total of 169 patients seen from January 1996 to March 2015 met the inclusion criteria. The mean age at diagnosis was 53 years. Of the tumors, 51% percent (86/169) were well-differentiated, 12% (21/169) were moderately differentiated, and 85% and 53% were positive on positron emission tomography and octreotide scanning, respectively. The 5- and 10-year survival rates were 88% and 81% for well-differentiated tumors and 80% and 42% for moderately differentiated tumors, respectively. The 10-year survival rates stratified by Ki-67 index ranges 0-2%, >2%-10%, and >10% were 90%, 72%, and 44%, respectively (P<0.05). Conclusion Overall, patients with bronchial carcinoids have long 5- and 10-year survival rates. We found significant survival differences between nodal status, differentiation status, and carcinoid phenotype. Interestingly, the difference in survival stratified by Ki-67 indices was statistically significant despite its absence in the World Health Organization grading system. As with gastroenteropancreatic NETs, Ki-67 index could become a valuable prognostic indicator for bronchial carcinoids.

Molecular Targets in Non–Small Cell Lung Cancer

Background Lung cancer is the second most common cancer in the United States among men and women, and it is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, patients with metastatic NSCLC received similar cytotoxic chemotherapy regimens. Genotyping studies have revealed genetic/molecular abnormalities in lung cancer. These driver mutations render a cancer dependent on that specific mutations biochemical pathway for its growth and survival. With the development of tyrosine kinase inhibitors and antibodies against specific driver mutations, the landscape of lung cancer treatment has changed from treatment based on histologic subtype to treatment based on molecularly defined subtypes. Methods In this article, we review the current molecular-targeted therapies in lung cancer. Results We review landmark trials that have led to approval of molecular-targeted therapies against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. We also explore less common mutations/molecular abnormalities and review data on the use of targeted therapies against them. Finally, we offer a treatment algorithm for patients with metastatic NSCLC that harbors actionable mutations. Conclusion Patients with advanced NSCLC should undergo mutational testing to evaluate for actionable mutations. If such a mutation is discovered, targeted therapy should be considered for first-line treatment.