Vivian E. Strong

Outcomes of Adrenalectomy for Isolated Synchronous Versus Metachronous Adrenal Metastases in Non–Small-Cell Lung Cancer: A Systematic Review and Pooled Analysis

PURPOSE Several small studies have reported that an adrenalectomy for isolated adrenal metastasis in non-small-cell lung cancer (NSCLC), along with a surgical resection for the primary lung cancer, can be curative. However, some suggest that the survival outcome among patients with a synchronous metastasis is poor. It remains unclear whether this treatment approach is warranted among those with synchronous metastasis. METHODS A search for publications on adrenalectomy for NSCLC was performed via the MEDLINE database. Studies reporting on survival outcomes and containing at least four analyzable patients who had surgery for primary lung cancer were included. Those not allowing separation of outcomes between synchronous and metachronous metastases were excluded. Synchronous metastasis was defined as a disease-free interval (DFI) of 6 months or less. RESULTS There were 10 publications contributing 114 patients; 42% of patients had synchronous metastases and 58% had metachronous metastases. The median DFIs were 0 and 12 months, respectively. Patients in the synchronous group were younger than those in the metachronous group (median age 54 v 68 years). Complications from adrenalectomy were infrequent. Median overall survival was shorter for patients with synchronous metastasis than those with metachronous metastasis (12 months v 31 months, generalized Wilcoxon P value = .02). However, the 5-year survival estimates were equivalent at 26% and 25%, respectively. CONCLUSION For an isolated adrenal metastasis from NSCLC, patients with a synchronous metastasis who underwent adrenalectomy had a shorter median overall survival than those with a metachronous metastasis. However, a durable long-term survival is achieved in approximately 25% in both groups.

Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis

BACKGROUND Pheochromocytomas are malignant in approximately 10% of patients. The histologic differentiation between benign and malignant tumors is difficult, the latter diagnosed by the presence of metastatic disease or recurrence. AIM To determine if postoperative histologic evaluation using the previously proposed Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and cell cycle/apoptosis markers can predict patients at risk for recurrence. METHODS Using the Memorial Sloan-Kettering Cancer Center adrenal database, we identified 48 patients with 51 resected pheochromocytomas (1987-2006). A senior endocrine pathologist, blinded to clinical outcome, reviewed the histopathologic characteristics of all cases using the PASS system. This pheochromocytoma scoring system is based on the presence of 12 different histologic parameters, including tumor necrosis, mitotic rate, tumor cell spindling, and the presence of large cell nests. In addition, we constructed a tissue microarray of all 5 malignant tumors and 41 of the benign tumors. By immunostaining of the tissue microarray, we assessed the expression of 7 different cell cycle/apoptosis-related genes (p53, Ki-67, Bcl-2, mdm-2, cyclin D1, p21, and p27). RESULTS Forty-three patients had a benign clinical course while 5 patients harbored a clinically malignant pheochromocytoma. Tumor necrosis (focal or confluent) was a particularly powerful indicator of malignancy present in 4 of 5 patients (80%) with malignant tumors, but only in 3 of 42 cases (7%) with benign neoplasms (P = .0009). The presence of a high mitotic rate (>3/10 high power fields) and tumor cell spindling significantly correlated with malignancy (P = .026 and .041, respectively). High cellularity was more often present in the malignant lesions (P = .050). There was a highly significant difference in PASS scores between benign and malignant cases (P = .0003). All malignant pheochromocytomas had a PASS score >/=6, well above the previously proposed >/=4 cutoff value. Two of the 4 patients testing positive for Ki-67 (>2% nuclear staining) had a clinically malignant course while only 3 (7%) of the 41 cases with lower Ki-67 positivity rate behaved in a malignant fashion (P = .055). Ki-67-positive tumor had a significantly higher chance of harboring tumor necrosis than Ki-67-negative neoplasms (P < .01). There was no difference in staining between benign and malignant pheochromocytomas using p53, Bcl-2, mdm-2, cyclin D1, p21, and p27. CONCLUSIONS (1) A PASS score of <4 predicted benign pheochromocytomas. (2) All malignant pheochromocytomas had a PASS score >/=6, which was significantly higher compared with the benign lesions. Patients with a PASS score >/=4 should be followed closely for recurrence. (3) p53, Bcl-2, mdm-2, cyclin D1, p21, and p27 appear to have no role in predicting the behavior of pheochromocytomas. Ki-67 may help identify those neoplasms at risk for recurrence by prompting the pathologist to look aggressively for adverse histologic features.

Comparisons of Gastric Cancer Treatments: East vs. West

There has been a large amount of speculation concerning the differences in the outcomes in patients who have gastric cancer in the Eastern and Western worlds. The differences in biology, surgical and adjuvant treatment have been used to explain such differences. There are clear differences observed in the histology (diffuse vs. intestinal), tumor location (proximal vs. distal), environmental exposures, dietary factors and Helicobacter pylori status. A higher incidence of gastric cancer in the East has led to screening programs, and leading to an earlier stage at presentation. Surgical treatment differs in that the extended lymph node dissection is routinely practiced in the Asian countries. Additionally, different adjuvant therapeutic regimens are used in both regions. The purpose of this review is to describe the differences in both presentation and treatment between the East and the West.

A prospective evaluation of the utility of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer†

The aim of this study was to examine prospectively the utility of adding preoperative [18F]fluorodeoxyglucose positron emission tomography (FDG‐PET)/computed tomography (CT) to routine CT, endoscopic ultrasound (EUS), and laparoscopic staging of localized gastric cancer.

Staging Laparoscopy in the Management of Gastric Cancer: A Population-Based Analysis

BACKGROUND Staging laparoscopy can detect radiographically occult peritoneal metastases and prevent futile laparotomy in patients with gastric adenocarcinoma. We sought to assess the use of staging laparoscopy for gastric adenocarcinoma in a cohort of older patients and to compare outcomes after laparoscopy alone with nontherapeutic laparotomy. STUDY DESIGN Using Surveillance, Epidemiology and End Results (SEER) population-based cancer registry data linked with Medicare claims, we identified patients aged 65 or older diagnosed with gastric adenocarcinoma between 1998 and 2005. We defined staging laparoscopy as a laparoscopic procedure from 1 month before the date of diagnosis until death and futile laparotomy as a laparotomy in the absence of a therapeutic intervention. We examined trends in the use of staging laparoscopy and compared outcomes between patients who underwent staging laparoscopy alone and those who had a futile laparotomy. RESULTS Of 11,759 patients with gastric adenocarcinoma, 6,388 (54.3%) had at least 1 surgical procedure. Staging laparoscopy was performed in 506 (7.9%) patients who had any surgery, and 151 (29.8%) of these patients did not have a subsequent therapeutic intervention. Patients who underwent staging laparoscopy alone had a significantly lower rate of in-hospital mortality (5.3% vs 13.1%, p < 0.001) and shorter length of hospitalization (2 vs 10 days, p < 0.001) than patients who had futile laparotomy. CONCLUSIONS Our findings in this large, population-based cohort suggest that staging laparoscopy is used infrequently in the management of older patients with gastric adenocarcinoma. Increased use of staging laparoscopy could reduce the substantial morbidity and mortality associated with nontherapeutic laparotomy.

A novel method to localize antibody-targeted cancer deposits intraoperatively using handheld PET beta and gamma probes.

BackgroundAssessing cancer margins, lymph nodes, and small cancer deposits intraoperatively can be challenging. A new device has become available that allows the detection of positron emission tomography (PET) radiotracers through both high-energy gamma and short-range beta emissions. These PET probes are handheld, allowing for real-time evaluation of cancer using a tool that provides surgeons with better intraoperative assessment of tumor sites.MethodsWithin the context of two institutional review board (IRB)-approved protocols investigating new applications of antibody-labeled PET scanning, 124I-labeled humanized monoclonal antibodies specific for colorectal cancer (huA33) and renal tumors (cG250) were constructed. Patients underwent preoperative PET scans, approximately seven days post-tracer infusion, when tumor-to-nontumor ratios were high. Suspected tumor deposits were evaluated intraoperatively with handheld beta and gamma PET probes.ResultsHandheld PET probes detected emissions from all tumors. Count rates from the gamma probe on tumor ranged from 48 to 306 cps, and for the beta probe ranged from 18 to 190 cps. Gamma and beta emissions exhibited a strong positive correlation. The ratio of gamma and beta counts was at least twice that of the background counts for all tumors evaluated.ConclusionsThis study is the first to demonstrate the utility of beta probes for the intraoperative detection of radiolabeled antibodies targeting cancer. Importantly, the recorded beta count rates from the beta probe correlate with the count rates from the high-energy gamma probe. Furthermore, the beta probe may offer superior specificity for real-time localization of small tumor deposits, compared to gamma probes. The intraoperative portable PET probe may prove a valuable bridge to combining tumor biology and PET technology to guide surgical therapy.

Pretreatment Neutrophil to Lymphocyte Ratio Independently Predicts Disease-specific Survival in Resectable Gastroesophageal Junction and Gastric Adenocarcinoma.

Objective:Preoperative methods to estimate disease-specific survival (DSS) for resectable gastroesophageal (GE) junction and gastric adenocarcinoma are limited. We evaluated the relationship between DSS and pretreatment neutrophil to lymphocyte ratio (NLR). Background:The patients inflammatory state is thought to be associated with oncologic outcomes, and NLR has been used as a simple and convenient marker for the systemic inflammatory response. Previous studies have suggested that NLR is associated with cancer-specific outcomes. Methods:A retrospective review of a prospectively maintained institutional database was undertaken to identify patients who underwent potentially curative resection for GE junction and gastric adenocarcinoma from 1998 to 2013. Clinicopathologic findings, pretreatment leukocyte values, and follow-up status were recorded. The Kaplan-Meier method was used to estimate DSS, and Cox proportional hazards models were used to evaluate the association between variables and DSS. Results:We identified 1498 patients who fulfilled our eligibility criteria. Univariate analysis showed that male sex, Caucasian race, increased T and N stage, GE junction location, moderate/poor differentiation, nonintestinal Lauren histology, and vascular and perineural invasion were associated with worse DSS. Elevated NLR was also associated with worse DSS [hazard ratio (HR) = 1.11; 95% CI: 1.08–1.14; P < 0.01]. On multivariate analysis, pretreatment NLR as a continuous variable was a highly significant independent predictor of DSS. For every unit increase in NLR, the risk of cancer-associated death increases by approximately 10% (HR = 1.10; 95% CI: 1.05–1.13; P < 0.0001). Conclusions:In patients with resectable GE junction and gastric adenocarcinoma, pretreatment NLR independently predicts DSS. This and other clinical variables can be used in conjunction with cross-sectional imaging and endoscopic ultrasound as part of the preoperative risk stratification process.

The role of laparoscopy for gastric surgery in the West

The only potentially curative treatment available for gastric adenocarcinoma is surgical resection. However, many controversies exist regarding treatment strategy, including whether the laparoscopic approach is appropriate. Many reports of laparoscopic techniques for cancer resection have shown oncologic equivalency to the open technique, with the known benefits of the minimally invasive approach, such as decreased pain, length of hospital stay, blood loss, and complications. The Eastern experience with laparoscopic gastrectomy has been extensive, associated with the increased incidence of early gastric cancers. However, in the West, laparoscopic approaches for gastric cancer have been more slowly accepted, largely due to the lower incidence of gastric cancer in this part of the world. Therefore, we aimed to review the technical feasibility and oncologic efficacy of the laparoscopic versus open approach to resection for gastric adenocarcinoma in the West. Review of the literature demonstrates that laparoscopic gastrectomy is a safe technique with short-term oncologic results that are equivalent in terms of margin status and lymph node retrieval and are associated with additional benefits of the minimally invasive approach, although long-term follow up is necessary. Laparoscopic gastrectomy for adenocarcinoma, similar to findings in the East, resulted in a decreased length of hospital stay, decreased narcotic use, fewer complications, and equivalent short-term oncologic outcomes. It appears that the minimally invasive approach for gastric resection of adenocarcinoma is safe and satisfies oncologic requirements, and is justified for use in selected patients.

Differences in Gastric Cancer Survival Between the U.S. and China

Previous comparisons of gastric cancer between the West and the East have focused predominantly on Japan and Korea, where early gastric cancer is prevalent, and have not included the Chinese experience, which accounts for approximately half the worlds gastric cancer.

Comparison of disease‐specific survival in the United States and Korea after resection for early‐stage node‐negative gastric carcinoma

Disease‐specific survival (DSS) for GC patients differs in Eastern and Western countries. The aim is to compare outcomes of US and Korean patients following resection of early‐stage, node‐negative gastric carcinoma (GC).