Jeremiah L. Deneve

Local Recurrence of Extremity Soft Tissue Sarcoma

The management of recurrent soft tissue sarcoma is a challenging problem for clinicians and has a significant physical, mental, emotional, and oncologic impact for the patient. Despite excellent limb-preservation therapies, approximately one-quarter of patients may eventually develop recurrence of disease. How to most appropriately manage these patients is a matter of debate. Several treatment options exist, including surgical resection, irradiation, systemic chemotherapy, amputation, and regional therapies. This article highlights the management of recurrent extremity soft tissue sarcoma.

Resection and Abdominal Wall Reconstruction of a Desmoid Tumor with Endometrioma Features

Desmoid tumors are rare, musculoaponeurotic mesenchymal origin tumors arising from the proliferation of well-differentiated fibroblasts. Desmoid tumors may arise from any location with the abdominal cavity, abdominal wall and extremity locations being most frequent. We present the case of a 35-year-old female with a history of endometriosis who presented palpable abdominal mass and cyclic abdominal pain. Resection was performed for a presumed desmoid soft tissue tumor. Final pathology demonstrated desmoid histology admixed with abdominal wall endometriosis (endometrioma). This unique pathologic finding has only been rarely reported and is discussed with a brief review of the literature.

Locally Advanced, Unresectable Squamous Cell Carcinoma of the Gallbladder

Primary squamous cell carcinoma (SCC) of the gallbladder is a rare malignancy of the gallbladder, accounting for less than 5% of gallbladder pathology. Initial presentation is often similar to adenocarcinoma of the gallbladder. SCC tends to be more locally aggressive, however, and possesses a worse prognosis than adenocarcinoma. We report a case of locally advanced SCC of the gallbladder.

Management of a ruptured mucinous mesenteric cyst with hyperthermic intraperitoneal chemotherapy

Mesenteric cysts are rare intra-abdominal cysts that are generally regarded as benign, and the incidence of malignancy is often cited to be 3%. The typical recommendation for treatment is complete excision to minimize recurrence. Excision can be performed laparoscopically, but this can lead to intra-abdominal dissemination of the cyst contents. There has been one case report describing the development of pseudomyxoma peritonei following rupture of a mesenteric cyst. We describe the treatment and outcome of a patient who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of an incompletely resected mucinous cystadenocarcinoma originating from the colonic mesentery.

IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma

The precise role of tumor associated macrophages remains unclear in pancreatic ductal adenocarcinoma (PDAC) while TGF-ß has an unclear role in metastases formation. In order to understand the role of IL23, an interleukin associated with macrophage polarization, we investigated IL23 in the context of TGF-ß expression in PDAC. We hypothesized that IL23 expression is associated with metastatic development and survival in PDAC. We investigated IL23 and TGF-ß protein expression on resected PDAC patient tumor sections who were divided into short-term (<12 months) survivors and long-term (>30 months) survivors. Panc-1 cells treated with IL23, TGF-ß, macrophages, or combinations thereof, were orthotopically implanted into NSG mice. Patients in the long-term survivor group had higher IL23 protein expression (P = 0.01). IL23 expression was linearly correlated with TGF-ß expression in patients in the short-term survivor group (P = 0.038). Macrophages induce a higher rate of PDAC metastasis in the mouse model (P = 0.02), which is abrogated by IL23 and TGF-ß treatment (P < 0.001). Macrophages serve a critical role in PDAC tumor growth and metastasis. TGF-ß contributes to a less tumorigenic TME through regulation of macrophages. Macrophages increases PDAC primary tumor growth and metastases formation while combined IL23 and TGF-ß pre-treatment diminishes these processes.

Ampullary adenocarcinoma: Defining predictors of survival and the impact of adjuvant therapy following surgical resection for stage I disease

Outcomes and recommendations regarding adjuvant therapy (AT) for stage I ampullary adenocarcinoma (AAC) are inadequately described. We sought to determine factors associated with survival and better define the impact of AT.

Desmoplastic small round cell tumor: A nationwide study of a rare sarcoma

Desmoplastic small round cell tumor (DSRCT) is a rare peritoneal surface malignancy. Current research is limited by the scarcity of this disease.

Molecular Alterations Associated with DNA Repair in Pancreatic Adenocarcinoma Are Associated with Sites of Recurrence

BackgroundPancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies with a rising incidence. Mutational analysis of PDAC has provided valuable information but has not yet dramatically changed the therapeutic landscape due to the number of variations detected in any one individual. The pattern of molecular alterations—gene mutations, variations in copy number, and changes in gene expression—has been described in the literature. The purpose of this study is to further investigate the molecular alterations in recurrent or metastatic PDAC based on the site of disease.MethodsMolecular alterations in patients with recurrent or metastatic PDAC from 2007 to 2015 were analyzed. The most common molecular alterations found in PDAC tumors from the pancreas were compared to metastatic PDAC specimens from the liver, lung, peritoneum, and other locations. Means were compared with a two-tailed Student’s t test or ANOVA as appropriate. Rates of molecular alterations among the different groups were compared with Pearson’s χ2.ResultsTwo thousand five hundred fifty-two patients with PDAC were identified in a retrospective database, and the 15 most common molecular alterations were utilized for analysis. The most common alterations among all patients were mutations in KRAS and PTEN (59 and 62%, respectively), with differences in prevalence by site of metastasis (p = 0.042 and p = 0.037, respectively). KRAS mutations were more commonly found in metastasis in the lung (72%) than in other sites (59%, p = 0.042). Low expression of ERCC1 was found in 49% of lung metastases from PDAC but only 15% in PDAC in the pancreas (p < 0.001). Five of the 8 molecular alterations significantly associated with site of metastatic disease were involved in DNA maintenance, repair, replication, or transcription (each p < 0.001).ConclusionsAberrant expression or mutation in genes involved in DNA maintenance is found in association with specific sites of metastatic PDAC. Personalizing therapy for metastatic PDAC based on site of disease and their associated molecular alterations warrants further investigation.

Management and outcomes following pancreaticoduodenectomy for ampullary adenocarcinoma

INTRODUCTION The purpose of this study was to evaluate outcomes following pancreaticoduodenectomy(PD) for ampullary adenocarcinoma(AAC). METHODS We evaluated patients having undergone PD for AAC and the impact of clinical/histopathologic factors and adjuvant therapy(AT) on survival. RESULTS 52 patients underwent potentially curative PD. Perineural and lymphovascular invasion were associated with decreased survival. There was no difference in survival between patients treated with PD vs. PD+AT, however, AT was more often administered to patients with N1 vs. N0 and stage II/III vs. I disease. Among patients receiving AT, we observed a trend towards improved survival when radiation was included. Recurrence occurred in 7/18(39%) stage I patients, only 2(7%) of which received AT. CONCLUSION AT did not improve survival, however was more commonly administered in advanced disease. Stage I patients had high recurrence rates but rarely received AT. Prospective evaluation of appropriate AT regimens and use in early stage patients should be considered.

Controversies in the Surgical Management of Melanoma

The surgical management of melanoma has evolved over the last several decades based on the published results and long-term follow up of several randomized clinical trials. While management of primary, localized melanoma is generally established, the management of clinically-positive metastasis, recurrent disease or distant melanoma is less clear. Controversies regarding the current surgical management of melanoma remain including the utility of sentinel lymph node biopsy for thin/thick melanoma, the role of completion lymphadenectomy for micrometastatic disease, and the indication for metastectomy for distant disease in the era of targeted therapy, as well as many others. Some of these concerns are being addressed in clinical trials while others remain unanswered. This review addresses these concepts and several others which represent current surgical controversies in the management of melanoma.