Western Validation of a Novel Gastric Cancer Prognosis Prediction Model in US Gastric Cancer Patients.

BACKGROUND: A novel prediction model for accurate determination of 5-year overall survival of gastric cancer patients was developed by an international collaborative group (G6+). This prediction model was created using a single institution's database of 11,851 Korean patients and included readily available and clinically relevant factors. Already validated using external East Asian cohorts, its applicability in the American population was yet to be determined. STUDY DESIGN: Using the Surveillance, Epidemiology, and End Results (SEER) dataset, 2014 release, all patients diagnosed with gastric adenocarcinoma who underwent surgical resection between 2002 and 2012, were selected. Characteristics for analysis included: age, sex, depth of tumor invasion, number of positive lymph nodes, total lymph nodes retrieved, presence of distant metastasis, extent of resection, and histology. Concordance index (C-statistic) was assessed using the novel prediction model and compared with the prognostic index, the seventh edition of the TNM staging system. RESULTS: Of the 26,019 gastric cancer patients identified from the SEER database, 15,483 had complete datasets. Validation of the novel prediction tool revealed a C-statistic of 0.762 (95% CI 0.754 to 0.769) compared with the seventh TNM staging model, C-statistic 0.683 (95% CI 0.677 to 0.689), (p < 0.001). CONCLUSIONS: Our study validates a novel prediction model for gastric cancer in the American patient population. Its superior prediction of the 5-year survival of gastric cancer patients in a large Western cohort strongly supports its global applicability. Importantly, this model allows for accurate prognosis for an increasing number of gastric cancer patients worldwide, including those who received inadequate lymphadenectomy or underwent a noncurative resection.

A single visit multidisciplinary model for managing patients with mutations in moderate and high-risk genes in a community practice setting.

The introduction of screening for multiple high and moderate risk mutations in genes has resulted in a complex approach to patient care involving multiple disciplines. We sought to describe the feasibility of a single visit multidisciplinary approach to the management of patients with an identified high/moderate risk gene mutation. Patients who presented to our community hospital over a 1-year period who were found to have a high/moderate risk genetic mutation on a screening panel were referred to the High Risk Genetic Clinic. Thirty-five patients were included. The majority were female [34 (97.1%)], Hispanic [22 (62.9%)], with a family history of cancer [21 (60%)]. Mean age was 40.3 years. Most of the participants had a BRCA1 gene mutation [10 (28.6%)]. Patients were seen at the High Risk Genetic Clinic within a mean of 41.9 days from the day of genetic mutation diagnosis. Four patients did not show and were significantly younger (19.3 vs. 39.6 years, p = 0.014). In this community setting, we provided coordinated care within multiple disciplines related to a genetic mutation in a single clinic visit. Increased efforts at coordinating early care should be directed towards patients diagnosed at a younger age.

Lymphadenectomy with Optimum of 29 Lymph Nodes Retrieved Associated with Improved Survival in Advanced Gastric Cancer: A 25,000-Patient International Database Study.

BACKGROUND: Gastric adenocarcinoma is an aggressive disease with frequent lymph node (LN) metastases for which lymphadenectomy results in a survival benefit. In the US, the National Comprehensive Cancer Network guidelines recommend D2 lymphadenectomy or a minimum of 15 LNs retrieved. However, retrieval of only 15 LNs is considered by most international guidelines as inadequate. We sought to evaluate the survival benefits associated with a more complete lymphadenectomy. STUDY DESIGN: An international database was constructed by combining gastric cancer cases from the Surveillance, Epidemiology, and End Results program database (n = 13,932) and the Yonsei University Gastric Cancer database (n = 11,358) (total n = 25,289). Kaplan-Meier survival analysis was performed along with Joinpoint analysis to obtain the optimal number of LNs to retrieve based on survival. Prognostic significance of number of nodes retrieved was then confirmed with univariate and multivariate analyses. RESULTS: Analysis for both mean and median survival yielded 29 LNs removed as the Joinpoint. This was confirmed with multivariate analysis, where 15 retrieved LNs cutoff fell out of the model and 29 retrieved LNs remained intact, with a hazard ratio of 0.799 (95% CI 0.759 to 0.842; p < 0.001). Stage-stratified Kaplan-Meier analysis for a cutoff point of 29 LNs also demonstrated a statistically significant improvement in survival. CONCLUSIONS: Joinpoint analysis has allowed for the creation of a model demonstrating the point at which additional dissection would not provide additional benefit. This large international dataset analysis demonstrates that the maximal survival advantage is seen by performing a lymphadenectomy with a minimum of 29 LNs retrieved.

Beyond the whipple operation: radical resections for cancers of the head of the pancreas.

Pancreatic adenocarcinoma is the most common pancreatic malignancy, and it occurs most commonly in the pancreatic head. It has a relatively low incidence; however it is a deadly disease and is the fourth most common cause of cancer deaths for males and females in the United States. Surgical resection in the form of pancreaticoduodenectomy is the mainstay of treatment and can lead to improved overall survival as well as the possibility of a cure, although only 10 % of patients are resectable at presentation. In an attempt to improve outcomes and survival, surgeons over the decades have employed various aggressive resectional strategies to combat this disease. In this paper we review the development of pancreaticoduodenectomy and touch on the role played by the American surgeon Allan Whipple in this development. We review modern data regarding radical pancreaticoduodenectomy and extended lymphadenectomy for pancreatic head cancers, as well as data and controversies regarding arterial and venous resection performed during the course of pancreaticoduodenectomy. The role of extended and vascular resections in the treatment of pancreatic neuroendocrine tumors in contrast to adenocarcinomas is also examined. We summarize the current state of data regarding radical pancreaticoduodenectomy and discuss pushing the boundaries of surgical resection to help improve outcomes for select groups of patients.

Colorectal liver metastases: making the unresectable resectable using irreversible electroporation for microscopic positive margins - a case report.

BACKGROUND: Irreversible electroporation (IRE) is a non-thermal injury tissue ablation technique that uses electrical pulses to cause cell death. IRE damages the endothelial cells of blood vessels; however these cells re-grow, and thus IRE does not result in permanent damage to blood vessels. We report the novel use of IRE for ablation of microscopically positive margins after resection of colorectal liver metastases (CRLM) impinging on hepatic veins. CASE PRESENTATION: A 68-year-old female was found to have colon cancer and synchronous bilateral unresectable liver metastases. Chemotherapy with FOLFOX and cetuximab was initiated, with subsequent conversion to resectability of the CRLM. The patient underwent colectomy followed by right liver posterior sectionectomy with wedge resection of segment 5. Resection of tumor impinging on the left and middle hepatic veins would have required left hepatectomy, with insufficient remnant liver volume. The CRLM were meticulously dissected off the hepatic veins leaving a microscopically positive margin, and IRE was then used for margin ablation, leaving intact hepatic veins and venous blood flow. The patient is alive and without recurrent disease now 30 months after resection. Herein we review the IRE technology and its use in ablation of liver metastases. CONCLUSIONS: Use of IRE margin ablation for microscopically-positive CRLM resection may lead to long-term patient survival; further prospective randomized trials are needed to confirm this finding.

Duodenal adenocarcinoma: why the extreme rarity of duodenal bulb primary tumors?

Adenocarcinoma of the small bowel accounts for only one per cent of all gastrointestinal malignancies. Duodenal adenocarcinoma accounts for half of all small bowel adenocarcinomas. The duodenum is divided into four segments: D1 (proximal horizontal 5 cm beginning with the 3-cm duodenal bulb), D2 (descending), D3 (distal horizontal), and D4 (ascending). The most common location of duodenal adenocarcinomas is the ampullary region of D2. Based on observational experience, our hypothesis was that primary adenocarcinomas arising from the mucosa of the duodenal bulb are extremely rare or possibly nonexistent. Our institutional cancer registry provided a list of patients for the years 1990 through 2012 who had small bowel cancers. Only those patients with primary adenocarcinomas of the duodenal mucosa were reviewed. Ampullary cancers arising from bile duct mucosa were specifically excluded. Medical records were abstracted to obtain patient age, sex, race, anatomic location of the tumor, disease stage (as per American Joint Committee on Cancer 7th edition staging guidelines), operation performed, and current vital status. A total of 30 patients with primary duodenal adenocarcinomas were identified. The mean age was 58 years and 17 (57%) patients were male. The tumor locations were: D2 in 26 (87%), D3 in two (7%), and D4 in two (7%). No tumors arose from D1. The patients presented with the following stages of disease: Stage 0is in three (10%), Stage I in three (10%), Stage II in five (17%), Stage III in 15 (50%), and Stage IV in four (13%). These findings combined with a diligent review of 724 reported cases in the English language literature yielded only five clearly defined cases of adenocarcinoma arising from the mucosa of the duodenal bulb. Although a 1991 published multicenter tumor registry series of 128 localized duodenal adenocarcinomas reported 29 D1 tumors, no anatomic distinction was made between duodenal bulb and more distal D1 tumors. Earlier reports used nonanatomic divisions of the duodenum or a simple breakdown into supra-ampullary, periampullary, and infra-ampullary portions. These data beg the question as to why primary duodenal bulb adenocarcinomas are so exceedingly rare. The obvious implication is that the duodenal bulb mucosa may be physiologically, immunologically, or otherwise uniquely privileged to virtually escape oncogenic transformation. The scientific challenge and opportunity is to explore and understand the important phenomena responsible for this finding.

Incidence of inflammatory breast cancer in women, 1992-2009, United States.

BACKGROUND: The annual incidence of inflammatory breast cancer (IBC) in the United States reportedly increased during the last quarter of the twentieth century. We investigated whether that increase has continued into the twenty-first century. METHODS: We queried the Surveillance Epidemiology and End Results database for all cases of IBC in women age 20 and older between 1992 and 2009. Cases were breast tumors with at least one of the following codes: extent of disease size 998, extension 70, or ICD-3-O morphology 8530 or 8533. Age-adjusted incidence was also examined. RESULTS: During 1992-2009, the annual incidence of IBC did not increase over time in any age group, nor did it vary significantly from year to year, except between 2003 and 2004, when there was a jump from 1.6 (95 % confidence interval 1.4-1.8) to 3.1 (2.8-3.4) cases per 100,000 women. Similar changes occurred in all age and racial groups before gradually returning to prejump levels. Overall, the incidence of IBC rose steeply with age until reaching a plateau at age 65. The incidence was greatest among black women (3.0; 2.8-3.2), intermediate among white women (2.1; 2.1-2.2), and lowest among Asian women (1.4; 1.3-1.6). CONCLUSIONS: The incidence of IBC has remained essentially stable for nearly two decades. A transient jump in 2003-2004 occurred in all age and racial groups, suggesting adjustment to coding changes at that time. Often described as a disease of younger women, IBC in fact disproportionately affects older women. Racial/ethnic variation in the incidence of IBC suggests that dietary, lifestyle, or genetic factors contribute to its pathogenesis.

The unequal distribution of parathyroid neoplasms in male patients.

There is a known lesser incidence of primary hyperparathyroidism and parathyroid neoplasms in male patients. Any difference in the anatomic distribution between males and females has not been documented. Review of our institutional experience with 125 pathologically confirmed parathyroid adenomas (119) or carcinomas (six) from 2000 through 2012 was conducted. The anatomic location was identified from operative records and the distributions between males and females were compared. Ninety-two females with parathyroid neoplasms had equal anatomic distributions between left and right sides and no significant difference between superior and inferior locations (P = 0.381). In marked contrast, tumors in 33 male patients had a significant predilection for the right side (67%, P = 0.016) and inferior position (85%, P = 0.033) and most notably the right inferior position (64%, P = 0.026). For the group as a whole, inferior adenomas were significantly more common (70%, P = 0.044). All patients had postoperative normalization of serum calcium levels. Late biochemical recurrence was noted in two patients. This is the first operatively confirmed delineation of the anatomic distributions of parathyroid neoplasms in separate sexes. Based on the unexpected findings of this study, we recommend the right inferior cervical region be explored first in males with suspected parathyroid tumors of indeterminate location.

Trends in radiotherapy after breast-conserving surgery in elderly patients with early-stage breast cancer.

BACKGROUND: The benefit of adjuvant radiotherapy (RT) in elderly breast cancer patients is debatable. The purpose of this study was to evaluate trends in RT rates after breast-conserving surgery. METHODS: Breast cancer patients ≥70 years treated from 2000 to 2009 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were estrogen receptor positive with negative or unknown lymph node status. Trends in RT recommendation over years were evaluated with the Jonckheere-Terpstra test. Multiple logistic regression and Cox proportional hazard tests were used to determine factors associated with radiation recommendation and survival. RESULTS: Of 46,581 patients, 31,989 (68.7 %) were recommended RT and 14,592 (31.3 %) were not. The recommendation for RT decreased from 70.3 % in 2000 to 67.4 % in 2009 (p < 0.0001). Seven of 18 registries exhibited decreased radiation recommendation rates, and 4 of 18 exhibited an increase. Recommendation of RT was associated with earlier year of diagnosis, younger age, Asian/Pacific Islander race, and negative lymph nodes. Predictors of worse survival were no radiation [hazard ratio (HR) 1.68, 95 % confidence interval (CI) 1.61-1.75], no nodes examined (HR 1.83, 95 % CI 1.75-1.91), large (>2-5 cm) tumor size (HR 2.02, 95 % CI 1.86-2.19), older age (80+, HR 2.38, 95 % CI 2.25-2.53), and black race (HR 1.13, 95 % CI1.03-1.23). CONCLUSIONS: Rates of radiation recommendation in the elderly have been steadily decreasing without appreciable acceleration in this decline. This trend was not consistent across all registries. Continued research is necessary to assess differences in clinical practice and its impact on patient outcomes.