Comparing the efficacy of initial percutaneous transhepatic biliary drainage and endoscopic retrograde cholangiopancreatography with stenting for relief of biliary obstruction in unresectable cholangiocarcinoma.

BACKGROUND: In patients with cholangiocarcinoma (CC), management of biliary obstruction commonly involves either up-front percutaneous transhepatic biliary drainage (PTBD) or initial endoscopic retrograde cholangiopancreatography (ERCP) with stent placement. The objective of the study was to compare the efficacy and of initial ERCP with stent placement with efficacy of initial PTBD in management of biliary obstruction in CC. METHODS: A single-center database of patients with unresectable CC treated between 2006 and 2017 was queried for patients with biliary obstruction who underwent either PTBD or ERCP. Groups were compared with respect to patient, tumor, procedure, and outcome variables. RESULTS: Of 87 patients with unresectable CC and biliary obstruction, 69 (79%) underwent initial ERCP while 18 (21%) underwent initial PTBD. Groups did not differ significantly with respect to age, gender, or tumor location. Initial procedure success did not differ between the groups (94% ERCP vs 89% PTBD, p = 0.339). Total number of procedures did not differ significantly between the two groups (ERCP median = 2 vs. PTC median = 2.5, p = 0.83). 21% of patients required ERCP after PTBD compared to 25% of patients requiring PTBD after ERCP (p = 1.00). Procedure success rate (97% ERCP vs. 93% PTBD, p = 0.27) and rates of cholangitis (22% ERCP vs. 17% PTBD, p = 0.58) were similar between the groups. Number of hospitalizations since initial intervention did not differ significantly between the two groups (ERCP median = 1 vs. PTC median = 3.5, p = 0.052). CONCLUSIONS: In patients with CC and biliary obstruction, initial ERCP with stent placement and initial PTBD both represent safe and effective methods of biliary decompression. Initial ERCP and stenting should be considered for relief of biliary obstruction in such patients in centers with advanced endoscopic capabilities.

Evaluating the early impact of Medicaid expansion on trends in diagnosis and treatment of benign gallbladder disease in Kentucky.

BACKGROUND: In January 2014, Kentucky expanded Medicaid coverage in an effort to improve access to healthcare. This study evaluated the early impact of Medicaid expansion on diagnosis and treatment of benign gallbladder disease in Kentucky. METHODS: Administrative claims data were queried for patients undergoing cholecystectomy for benign gallbladder disease between 2011 and 2015. Demographic, procedure, and outcome variables from 2011 to 2013 (PRE) and 2014-2015 (POST) were compared. RESULTS: After Medicaid expansion, patients were more likely to have their operation performed as an outpatient (80.0% vs. 78.2%, p < 0.001). A significant trend was noted toward a shorter hospital stay (p < 0.001) among inpatients. For both inpatients and outpatients, a significant shift was noted toward increased hospital charges (p < 0.001). CONCLUSIONS: The expansion of Kentucky Medicaid in 2014 has been associated with an increase in outpatient cholecystectomy, shorter hospital stays for inpatients, and increased hospital charges for both inpatients and outpatients. Increased charges for all procedures may represent a mechanism for hospitals to offset the cost of providing global care for more patients.

Efficacy of preoperative immunonutrition in locally advanced pancreatic cancer undergoing irreversible electroporation (IRE).

BACKGROUND: Improved preoperative immunonutrition has been shown to decrease the length of stay (LOS) and complications among patients undergoing elective gastrointestinal cancer surgeries. The purpose of this study was to determine whether preoperative immunonutrition supplementation decreases postoperative LOS, infectious complications, and morbidity in patients undergoing irreversible electroporation (IRE) surgery for locally advanced pancreatic cancer (LAPC). METHODS: At a regional hepatopancreatobiliary referral center within an academic medical center 71 patients receiving IRE treatment of LAPC were included in the study. The participants were divided into those receiving preoperative immunonutrition (n = 44) and those receiving no supplemental preoperative immunonutrition (n = 27). Main outcomes and measures were LOS, postoperative complications, nutritional risk index (NRI), and albumin levels. RESULTS: Patients in both groups were similar for preoperative nutrition parameters and operative therapy. Patients in the immunonutrition group experienced a statistically significant decrease in postoperative complications (p = 0.05) and LOS (10.7 vs. 17.4, p = 0.01), and less of a decrease in nutritional risk index (-12.6 vs. -16.2, p = 0.03) and albumin levels (-1.1 vs. -1.5, p < 0.01). CONCLUSION: Preoperative immunonutrition was clinically significant in decreasing postoperative complications, LOS, and improving post-surgery NRI and albumin levels in patients receiving elective IRE treatment of non-resectable pancreatic cancer. These results indicate that preoperative immunonutrition is effective and feasible in this subset of cancer patients.

Safety and advantages of combined resection and microwave ablation in patients with bilobar hepatic malignancies.

BACKGROUND: The multimodality approach has significantly improved outcomes for hepatic malignancies. Microwave ablation is often used in isolation or succession, and seldom in combination with resection. Potential benefits and pitfalls from combined resection and ablation therapy in patients with complex and extensive bilobar hepatic disease have not been well defined. METHODS: A review of the University of Louisville prospective Hepato-Pancreatico-Biliary Patients database was performed with multi-focal bilobar disease that underwent microwave ablation with resection or microwave only included. RESULTS: One hundred and eight were treated with microwave only (MWA, n = 108) or combined resection and ablation (CRA, n = 84) and were compared with similar disease-burden patients undergoing resection only (n = 84). The groups were comparable except that the MWA group was older (p = .02) and with higher co-morbidities (diabetes, hepatitis). The resection group had larger tumours (4 vs. 3.2 and 3 cm) but the CRA group had more numerous lesions (4 vs. 3 and 2, p = .002). Short-term outcomes including morbidity (47.6% vs. 43%, p = .0715) were similar between the CRA and resection only groups. Longer operative time (164 vs. 126 min, p = .003) and need for blood transfusion (p = .001) were independent predictors of complications. Survival analyses for colorectal metastasis patients (n = 158) demonstrated better overall survival (OS) (43.9 vs. 37.6 and 30.5 months, p = .035), disease-free survival (DFS) (38 vs. 26.6 and 16.9 months, p = .028) and local recurrence-free survival (LRFS) (55.4 vs. 17 and 22.9 months, p < .001) with resection only. CONCLUSION: The use of microwave ablation in addition to surgical resection did not significantly increase the morbidities or short-term outcomes. In combination with systemic and other local forms of therapy, combined resection and ablation is a safe and effective procedure.

A cost analysis of somatostatin use in the prevention of pancreatic fistula after pancreatectomy.

BACKGROUND: Studies have shown that somatostatin reduces the occurrence of postoperative pancreatic fistula. However, no study to date has analyzed the cost effectiveness of this treatment. The purpose of this study was to analyze the cost effectiveness of prophylactic somatostatin use with respect to pancreatectomy. METHODS: Review of prospectively collected 2002 patient hepato-pancreatico-biliary database from January 2007 to May 2012. Patients received somatostatin prophylactically at the discretion of their surgeon. Data were analyzed using univariate analysis to determine if somatostatin had an effect on imaging costs, lab costs, "other" costs, PT/OT costs, surgery costs, room and board costs, and total hospital costs. RESULTS: A total of 179 patients underwent pancreatectomy at a single teaching institution. Median total hospital costs were 90,673.50 (59,979-743,667) for patients who developed a postoperative pancreatic fistula versus 86,563 (39,190-463,601) for those who did not (p = 0.004). Median total hospital costs were 89,369 (39,190-743,667) for patients who were administered somatostatin versus 85,291 (40,092-463,601) for patients who did not (p = 0.821). CONCLUSIONS: Pancreatic fistulas significantly increase hospital costs, and somatostatin has been shown to decrease the rate of pancreatic fistula formation. Somatostatin has no significant effect on hospital costs.

Evaluation of quality of life following placement of self-expanding plastic stents as a bridge to surgery in patients receiving neoadjuvant therapy for esophageal cancer.

PURPOSE: To determine whether self-expanding plastic stent (SEPS) placement significantly improves quality of life and maintains optimal nutrition while allowing full-dose neoadjuvant therapy (NAT) in patients with esophageal cancer. PATIENTS AND METHODS: A prospective, dual-institution, single-arm, phase II (http://ClinicalTrials.gov: NCT00727376) evaluation of esophageal cancer patients undergoing NAT prior to resection. All patients had a self-expanding polymer stent placed prior to NAT. The European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25, Functional Assessment of Cancer Therapy-Anorexia, and Functional Assessment of Cancer Therapy-General surveys were administered prior to stenting, within 1 week post-stent placement, and at the completion of neoadjuvant therapy. RESULTS: Fifty-two patients were enrolled; 3 (5.8%) had stent migrations requiring replacement. There were no instances of esophageal erosion or perforation. All patients received some form of neoadjuvant therapy. Thirty-six (69%) received chemoradiation; 34 (93%) of these patients received the planned dose of chemotherapy, and 27 (75%) received the full planned dose of radiotherapy. There were 16 (31%) patients receiving chemotherapy alone; 12 (74%) of patients in the chemotherapy-alone group completed the planned dose of therapy. CONCLUSION: Placement of SEPS appears to provide significant improvement in quality of life related to dysphagia and eating restriction in patients with esophageal cancer undergoing neoadjuvant therapy. Consideration of SEPS instead of percutaneous feeding tube should be initiated as a first line in dysphagia palliation and NAT nutritional support.

Impact of hepatectomy margin on survival following resection of colorectal metastasis: the role of adjuvant therapy and its effects.

INTRODUCTION: The optimal width of microscopic margin and the use of adjuvant therapy after a positive margin for hepatic resection for colorectal liver metastasis (CRCLM) has not been conclusively determined. The aim of the current study is to evaluate the influence of width of surgical margin and adjunctive therapy upon disease free and overall survival. METHODS: All patients undergoing hepatectomy for CRCLM from 1997 to 2012 were identified from a prospectively maintained, IRB approved database. Patients were divided into four subgroups based on the parenchymal margin: positive, <0.1 cm, 0.1 cm-1 cm, and >1 cm. RESULTS: A total of 373 patients were included for analysis with a median follow up of 26 months (range 9-103 months) and a median overall survival of 53 months. The resection margin was positive (26 patients median OS 24 months), <0.1 cm (48 patients median OS 36 mon), 0.1 cm-1 cm (82 patients median OS 44 months), and >1 cm (217 patients median OS 64 months). The most common adjunctive therapy was chemotherapy, hepatic arterial therapy, or local. Patients with positive margins also had the shortest disease free survival (DFS), 16 months. The DFS was similar amongst the other margin groups (<0.1 cm: 21 months, 0.1-1 cm: 22 months, >1 cm 25 months). Hepatectomy margin independently influenced survival (p = 0.017) and disease free survival (p = 0.034). Patients with negative margins has similar overall recurrence rates (p = 0.36) and survival rates (p = 0.89). CONCLUSIONS: A positive surgical margin indicates a worse overall biology of disease for patients undergoing hepatectomy for CRCLM, and appropriate multi-disciplinary therapy should be considered in this high risk patient population. Marginal width if a complete resection has been achieved does not adversely effect overall surgical in patients with CRCLM.

Hepatic arterial therapy as a bridge to ablation or transplant in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a challenging malignancy as a result of the advanced course at presentation. Recent interventional advances have improved treatment of lesions unamenable to resection using drug-eluting microbeads delivered into the hepatic circulation. We hypothesize that the use of hepatic arterial therapy (HAT) will safely identify appropriate patients who can proceed to ablation and/or transplantation. We evaluated our open-label, multicenter, multinational, single-arm study including 240 patients with intermediate-staged HCC who received drug-eluting beads and were not initial candidates for transplantation or resection. We reviewed the resulting clinical data to determine factors leading to possible ablation or transplant. Of 240 patients undergoing HAT, 14 (5.8%) received ablation or transplant. We compared those receiving ablation or transplant with those receiving only HAT. Groups were similar regarding sex, age, median number of tumors (one; range, 1 to 25), Child's score, tobacco and alcohol abuse, and treatment type. Patients who were downstaged were more likely to have: hepatitis-related tumors (76 to 66%, P = 0.02), distinct lesions on imaging (92 to 76%, P = 0.004), and less than 25 per cent parenchymal involvement (84 to 59%, P = 0.0001). These patients typically had one tumor frequently in the left lobe (58.8 vs 30.9%, P = 0.0001), accessible through segmental arteries (47 vs 17%, P = 0.001), with increased segmental branch occlusion (57 vs 39%, P = 0.02). HAT should be considered a potential bridging therapy to eventual ablation or transplant in the multimodal treatment of HCC.

Intraoperative magnetic resonance imaging for ablation of hepatic tumors.

BACKGROUND: The most significant rise in the use of hepatic ablation has come from image-guided techniques with both computed tomography (CT) and ultrasound (US). The recent development of open-configuration magnetic resonance scanners has opened up an entire new area of image-guided surgical and interventional procedures. Thus the aim of this study was to evaluate the use of intraoperative MRI (iMRI) ablation of hepatic tumors performed by surgeons. METHOD: Percutaneous iMRI hepatic ablation was performed from January 2003 to February 2005 for control of either primary or secondary hepatic disease. RESULTS: Eighteen hepatic ablations were performed on 11 patients with a median age of 71 (range: 51-81) years for metastatic colorectal cancer (n = 6), hepatocellular cancer (n = 2), cholangiocarcinoma (n = 2), and metastatic neuroendocrine (n = 1). Median hospital stay was 1 day, with complications occurring in 2 patients. After a median follow up of 18 months, there have been no local ablation recurrences, 5 patients are free of disease, 4 are alive with disease, 1 has died of disease, and 1 has died of other causes. CONCLUSIONS: Image-guided hepatic ablations represent a useful technique in managing hepatic tumors. Intraoperative MRI represents a new technique with initial success that has been limited to European centers. Further evaluation in U.S. centers has demonstrated iMRI to be useful for certain hepatic tumors that cannot be adequately visualized by US or CT.

Supra-elevated CA 19-9 in a benign hepatic cyst adenoma.

BACKGROUND: Elevated CA 19-9 may be found in both cystadenomas and cystadenocarcinomas of the liver. CASE OUTLINE: A 59-year-old woman presented with right upper quadrant abdominal pain, malaise and weight loss. Physical examination and laboratory evaluation revealed a mass in the right upper quadrant and a CA 19-9 level of 68 661 U/ml. CT scan demonstrated a cystic liver mass. She underwent a right hepatectomy, and her CA 19-9 returned to normal. Pathologic analysis revealed no malignancy. DISCUSSION: In hepatic cystic neoplasms, an elevated CA 19-9 should not be used to establish the diagnosis of malignancy nor should it preclude resection.

Developmental aspects of early pancreatic cancer.

The specific cell of origin responsible for generating pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma remains unknown. During development, epithelial stem cells within embryonic pancreatic epithelium give riseto mature acinar, ductal, and islet elements. Emerging evidence suggests that cells with precursor potential also exist within adult pancreas, resulting in significant developmental plasticity among both endocrine and exocrine cell types. In this review, the contribution of developmental plasticity in initiating pancreatic metaplasia and neoplasia is considered, and evidence supporting a role for epithelial stem cells in pancreatic cancer is discussed.

p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas.

The mechanisms linking acinar cell apoptosis and ductal epithelial proliferation remain unknown. To determine the relationship between these events, pancreatic duct ligation (PDL) was performed on p53(+/+) and p53(-/-) mice. In mice bearing a wild-type p53 allele, PDL resulted in upregulation of p53 protein in both acinar cells and proliferating duct-like epithelium. In contrast, upregulation of Bcl-2 occurred only in duct-like epithelium. Both p21(WAF1/CIP1) and Bax were also upregulated in duct-ligated lobes. After PDL in p53(+/+) mice, acinar cells underwent widespread apoptosis, while duct-like epithelium underwent proliferative expansion. In the absence of p53, upregulation of p53 target genes and acinar cell apoptosis did not occur. The absence of acinar cell apoptosis in p53(-/-) mice also eliminated the proliferative response to duct ligation. These data demonstrate that PDL-induced acinar cell apoptosis is a p53-dependent event and suggest a direct link between acinar cell apoptosis and proliferation of duct-like epithelium in duct-ligated pancreas.

Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha.

BACKGROUND & AIMS: The progenitor cells responsible for transforming growth factor (TGF)-alpha-induced pancreatic ductal metaplasia and neoplasia remain uncharacterized. During pancreatic development, differentiated cell types arise from ductal progenitor cells expressing the Pdx1 homeodomain transcription factor. The aims of this study were, first, to evaluate the role of Pdx1-expressing stem cells in MT-TGFalpha transgenic mice, and second, to further characterize cell proliferation and differentiation in this model. METHODS: To assess Pdx1 gene expression in normal and metaplastic epithelium, we performed in vivo reporter gene analysis using heterozygous Pdx1(lacZ/+) and bigenic Pdx1(lacZ/+)/MT-TGFalpha mice. RESULTS: Pdx1(lacZ/+)/MT-TGFalpha bigenics showed up-regulated Pdx1 expression in premalignant metaplastic ductal epithelium. In addition to Pdx1 gene activation, TGF-alpha-induced metaplastic epithelium demonstrated a pluripotent differentiation capacity, as evidenced by focal expression of Pax6 and initiation of islet cell neogenesis. The majority of Pdx1-positive epithelial cells showed no expression of insulin, similar to the pattern observed during embryonic development. CONCLUSIONS: Overexpression of TGF-alpha induces expansion of a Pdx1-expressing epithelium characterized by focal expression of Pax6 and initiation of islet neogenesis. These findings suggest that premalignant events induced by TGF-alpha in mouse pancreas may recapitulate a developmental program active during embryogenesis.

Nonoperative management of primary colorectal cancer in patients with stage IV disease.

BACKGROUND: Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease. METHODS: A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease. RESULTS: Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group). CONCLUSIONS: Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer.

Occult breast carcinoma presenting as an axillary mass.

Breast carcinoma presents rarely (<5% of cases) as an axillary mass without an obvious primary tumor. The value of mammography in detecting an occult breast carcinoma is low, with a sensitivity of 29 per cent and specificity of 73 per cent. MRI and positron emission tomography (PET) are potentially more sensitive in this setting. We present a case recently seen at the Vanderbilt University Hospital, a 63-year-old woman with a 2-cm painless mass in the right axilla. Mammography was negative, and fine needle aspiration revealed atypical cells suspicious for malignancy. An excisional biopsy of the right axillary lymph node revealed metastatic adenocarcinoma, most likely breast primary. A PET showed increased uptake of 18-fluorodeoxyglucose and 99m Technetium in the right axilla and the right lateral breast. The patient underwent right modified radical mastectomy. The final pathological report revealed a 0.9-cm primary tumor in the upper inner quadrant of the breast and 1 of 41 nodes positive for tumor. This case confirms that mammography has low sensitivity in identifying the primary tumor in occult breast carcinoma and illustrates the usefulness of PET in identifying the primary tumor. We advocate an aggressive approach to evaluation of the breast in women presenting with metastatic adenocarcinoma in the axillary nodes. This evaluation should include clinical examination and mammography in all cases, and PET and MRI in selected cases. PET and MRI may be particularly useful when considering a breast-conserving surgical procedure.

Perforated cecal adenocarcinoma presenting as a thigh abscess.

Complicated colorectal carcinoma has several symptoms, the most common being bleeding and obstruction. Occasionally it will cause perforation, which carries a worse prognosis. We report a case of perforated adenocarcinoma of the cecum that presented as an abscess of the thigh. We also present a review of the literature on this subject.