A Case of Acute Pancreatitis Associated with Early-Stage Adenocarcinoma of the Gallbladder.

BACKGROUND Gallstones are a common cause of acute pancreatitis. The proposed mechanism by which choledocholithiasis induces pancreatitis is mechanical obstruction of the ampulla leading to the reflux of bile into the pancreatic duct or edema resulting from a gallstone's passage. To our knowledge, there are no previously reported cases of gallbladder adenocarcinoma as a potential cause of acute pancreatitis. Herein, we describe a patient who presented with acute necrotizing pancreatitis, without other associated risk factors, who was found to have a fragmented friable polypoid gallbladder adenocarcinoma. CASE REPORT A 55-year old Hispanic female with prediabetes presented to the Emergency Department with severe epigastric abdominal pain radiating to her back. The patient's clinical presentation, laboratory tests and computed tomography imaging were suggestive of acute necrotizing pancreatitis and a gallbladder lesion concerning for neoplasm. After clinical resolution of her pancreatitis, the patient was brought to the operating room for a cholecystectomy. Final pathology revealed a stage T1aN0 gallbladder adenocarcinoma. CONCLUSIONS We have presented a patient with acute necrotizing pancreatitis in the absence of alcohol abuse, gallstones, biliary sludge, hypertriglyceridemia, hypercalcemia, or hereditary predisposition. Without evidence of other etiologies, we hypothesize that the friable tumor fragments of the gallbladder adenocarcinoma might be the underlying cause of pancreatitis in this patient.

Effect of Negative Pressure Wound Therapy on Wound Complications Post-Pancreatectomy.

Surgical site infection (SSI) and incisional hernia are common complications after major pancreatectomy. We investigated the effects of negative pressure wound therapy (NPWT) on short- and long-term wound outcomes in patients undergoing pancreatectomy. A randomized controlled trial comparing the effect of NPWT with standard surgical dressing (SSD) on wounds was performed in 265 patients undergoing open gastrointestinal resections from 2012 to 2016. We performed a subset analysis of 73 patients who underwent pancreatectomy. Wound complications in the first 30 days and incisional hernia rates were assessed. There were 33 (45%) female patients in the study and the average BMI was 27.6. The pancreaticoduodectomy rate was 68 per cent, whereas 27 per cent of patients underwent distal or subtotal pancreatectomy, and 4 per cent total pancreatectomy. Incisional hernia rates were 32 per cent and 14 per cent between the SSD and NPWT groups, respectively (P = 0.067). In the SSD (n = 37) and NPWT (n = 36) cohorts, the superficial SSI, deep SSI, seroma, and dehiscence rates were 16 per cent and 14 per cent (P > 0.99), 5 per cent and 8 per cent (P = 0.67), 16 per cent and 11 per cent (P = 0.74), and 5 per cent and 3 per cent (P ≥ 0.99), respectively. After adjusting for pancreatic fistula and delayed gastric emptying, no statistically significant differences in the primary outcomes were observed. These findings were true irrespective of the type of resection performed. Short- and long-term wound complications were not improved with NPWT. We observed a trend toward decreased incisional hernia rates in patients treated with NPWT. Owing to the multifactorial nature of wound complications, it is yet to be determined which cohorts of pancreatectomy patients will benefit from NPWT.

Recurrence patterns and associated factors of locoregional failure following neoadjuvant chemoradiation and surgery for esophageal cancer.

BACKGROUND: Despite neoadjuvant chemoradiation (nCRT) followed by esophagectomy for locally advanced esophageal cancer, locoregional recurrence (LRR) is common and factors associated with LRR have not been clearly identified. METHODS: Patients were identified from a single institution, prospectively maintained database (1996-2013). Patterns of recurrence were described and associated factors of LRR were analyzed using competing risks regression models. RESULTS: Of the 456 patients treated with nCRT and surgery, 167 patients developed recurrence. Locoregional and distant recurrences were observed in 69 (15.1%) and 140 (30.9%) patients, respectively. Time to recurrence (13.6 vs 10.4 months, P = 0.20) and median overall survival (29.3 vs 19.1 months, P = 0.12) were no different among the 27 patients (6%) who developed a solitary LRR compared to patients who developed distant recurrence. Univariable analysis identified lymphovascular invasion (HR 1.46, P = 0.07), lymph node ratio >0.5 (HR 2.16, P = 0.02), positive margin (HR 1.95, P = 0.05), lack of response to neoadjuvant therapy (HR 1.99, P < 0.01), clinical T stage (HR 2.62, P < 0.01) and final T3/4 stage (HR 2.06, P < 0.01) as factors significantly associated with LRR. Clinical T stage and response to neoadjuvant treatment were independently associated with LRR on multivariable analysis. CONCLUSIONS: Although aggressive tumor biology plays a significant role in LRR, optimizing neoadjuvant treatments to obtain a complete pathologic response may lead to improved locoregional control.

Patterns of recurrence and long-term outcomes in patients who underwent pancreatectomy for intraductal papillary mucinous neoplasms with high grade dysplasia: implications for surveillance and future management guidelines.

BACKGROUND: While intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions, its natural history following resection is unknown. METHODS: A retrospective review of HGD-IPMN patients (1999-2015) was performed. Recurrence patterns and clinical outcomes following pancreatectomy were analyzed and the indications for surgery were explored based on current guidelines. RESULTS: HGD was diagnosed in 100 of 314 patients (32%) following pancreatectomy for IPMN. IPMNs were classified as main duct, branch duct, or mixed in 15, 58 and 27 patients, respectively. Following resection, 25 patients had low-risk residual disease in the remnant pancreas. With a median follow-up of 35 months (range 1-129), 9 patients developed progressive or recurrent disease, 4 of whom underwent additional pancreatectomy. Three patients developed invasive adenocarcinoma. Median time to recurrence was 15 months (range 7-72). Based on the management algorithm from the international consensus guidelines, resection was indicated in 76 patients (76%). Other indications for surgery included mixed-duct IPMN(13), increased cyst size(7) and other(4). CONCLUSION: The prognosis of HGD-IPMN following resection is good; however, HGD may be a marker for developing IPMN recurrence or adenocarcinoma. Current guidelines regarding surgical indications for IPMN can miss a significant number of patients with HGD.

Phase II Randomized Trial of Negative-Pressure Wound Therapy to Decrease Surgical Site Infection in Patients Undergoing Laparotomy for Gastrointestinal, Pancreatic, and Peritoneal Surface Malignancies.

BACKGROUND: Surgical site infections (SSIs) remain a major source of morbidity and cost after resection of intra-abdominal malignancies. Negative-pressure wound therapy (NPWT) has been reported to significantly reduce SSIs when applied to the closed laparotomy incision. This article reports the results of a randomized clinical trial examining the effect of NPWT on SSI rates in surgical oncology patients with increased risk for infectious complications. STUDY DESIGN: From 2012 to 2016, two hundred and sixty-five patients who underwent open resection of intra-abdominal neoplasms were stratified into 3 groups: gastrointestinal (n = 57), pancreas (n = 73), or peritoneal surface (n = 135) malignancy. They were randomized to receive NPWT or standard surgical dressing (SSD) applied to the incision from postoperative days 1 through 4. Primary outcomes of combined incisional (superficial and deep) SSI rates were assessed up to 30 days after surgery. RESULTS: There were no significant differences in superficial SSIs (12.8% vs 12.9%; p > 0.99) or deep SSI (3.0% vs 3.0%; p > 0.99) rates between the SSD and NPWT groups, respectively. When stratified by type of surgery, there were still no differences in combined incisional SSI rates for gastrointestinal (25% vs 24%; p > 0.99), pancreas (22% vs 22%; p > 0.99), and peritoneal surface malignancy (9% vs 9%; p > 0.99) patients. When performing univariate and multivariate logistic regression analysis of demographic and operative factors for the development of combined incisional SSI, the only independent predictors were preoperative albumin (p = 0.0031) and type of operation (p = 0.018). CONCLUSIONS: Use of NPWT did not significantly reduce incisional SSI rates in patients having open resection of gastrointestinal, pancreatic, or peritoneal surface malignancies. Based on these results, at this time NPWT cannot be recommended as a therapeutic intervention to decrease infectious complications in these patient populations.

A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype.

Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype.

Tumor regression grade in gastric cancer: Predictors and impact on outcome.

BACKGROUND: The clinical value and prognostic implications of histologic response to neoadjuvant chemotherapy in gastric cancer is unknown. METHODS: Tumor regression grade (TRG) was recorded in 58 gastric cancer patients identified from two institutional surgical databases. TRG 1a/b represented histologic responders (<10% viable tumor), while TRG 2/3 represented non-responders (>10% viable tumor). RESULTS: TRG 1a/b was recorded in 10 patients (17%), while 48 patients (83%) had a TRG 2/3 response. Larger tumor size (OR 0.24; 95%CI 0.09, 0.64; P = 0.004) and clinical downstaging (OR 30.0; 95%CI 3.26, 276; P = 0.003) were the only factors predictive of histologic response. TRG 1a/b responders had 3-year survival of 70.0% and an estimated overall survival of >69.8 months compared to 38.2% and 22.8 months in non-responders; however, this trend was not statistically significant (P = 0.535). While TRG could not predict survival (OR 2.40; 95%CI 0.46, 12.57; P = 0.300), patient age (OR 1.06; 95%CI 1.00, 1.11; P = 0.035), and the number of positive lymph nodes (≥7; OR 0.05; 95%CI 0.07, 0.27; P < 0.001) were independent predictors of survival. CONCLUSIONS: Few gastric cancers demonstrate histologic response to neoadjuvant chemotherapy. While TRG may be a valid marker for treatment response, its predictive value and clinical application in gastric cancer remains unclear. J. Surg. Oncol. 2016;114:434-439. © 2016 Wiley Periodicals, Inc.

Is Linitis Plastica a Contraindication for Surgical Resection: A Multi-Institution Study of the U.S. Gastric Cancer Collaborative.

BACKGROUND: Current staging and treatment guidelines for gastric adenocarcinoma do not differentiate between linitis plastic (LP) and non-LP cancers. Significant controversy exists regarding the surgical management of LP patients. METHODS: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 gastric cancer patients who underwent resection between 2000 and 2012 were identified. Clinicopathologic and outcomes data of 58 LP patients were compared to 811 non-LP patients. RESULTS: Stage III/IV disease was more common at presentation in LP patients compared with non-LP patients (90 vs. 44 %, p < 0.01). Despite the fact that most LP patients underwent total gastrectomy (88 vs. 39 %, p < 0.01), final positive margins were more common in LP patients (33 vs. 7 %, p < 0.01). The use of frozen section allowed 15 intraoperative positive margins in 38 patients to be converted to negative final margins. Median overall survival (OS) was significantly worse in patients with LP (11.6 vs. 37.8 months, p < 0.01). There was no difference in median OS of LP patients based on stage (I/II, 17.3 mo; III, 10.6 mo; IV, 12.0 mo; p = 0.46). LP and non-LP patients who underwent optimal resection (negative margin and D2/3 lymphadenectomy) had better survival compared with those with nonoptimal resections. The median OS for optimally resected stage III LP (n = 22) and stage III non-LP (n = 185) patients was nearly identical (26.7 vs. 25.3 mo; p = 0.69). CONCLUSIONS: Future staging systems and treatment guidelines should differentiate between LP and non-LP gastric cancers. Long-term survival in select LP patients who undergo optimal resections is comparable to optimally resected non-LP patients.

The prognostic value of residual nodal disease following neoadjuvant chemoradiation for esophageal cancer in patients with complete primary tumor response.

BACKGROUND: The prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) to neoadjuvant chemoradiation (nCRT) for esophageal cancer is unknown. METHODS: ypT0N+ responders were identified from a single institution database of esophageal cancer patients undergoing esophagectomy and were compared to patients without locoregional disease (ypT0N0) and to non-complete responders (ypT+). RESULTS: Out of 487 patients, 196 ypT0N0 and 14 ypT0N+ patients were identified. Pre-treatment stage was similar between ypT0N0 and ypT0N+ patients: 66% versus 73% of patients had uT3 disease (P = 0.50) and 76% versus 55% had nodal involvement (P = 0.49), respectively. Locoregional recurrence (43%) was more common in ypT0N+ patients. Median overall survival (OS) was worse in ypT0N+ patients (14.8 months) compared to ypT0N0 patients (92.2 months) and ypT+ patients (38.0 months, P < 0.001). Median OS of ypT0N+ patients was similar to ypT+ stage II (29.6 months, P = 0.84) and stage III (27.5 months, P = 0.95) disease. No difference in median OS existed in patients with residual nodal disease (n = 163) based on local response (14.8 months in ypT0N+ and 22.5 months in ypT+N+ patients, P = 0.55). CONCLUSIONS: Residual nodal disease in esophageal cancer patients with complete response in the primary tumor following nCRT portends a poor prognosis and behaves similar to pathologic stage II/III disease.

Significance of signet ring cells in high-grade mucinous adenocarcinoma of the peritoneum from appendiceal origin.

Significance of signet ring cells in mucinous adenocarcinoma of the peritoneum from appendiceal origin has never been specifically studied. We retrospectively reviewed cases of mucinous adenocarcinoma of the peritoneum from appendiceal origin (n = 55) and collected clinical follow-up data. Signet ring cells were identified in 29 of 55 cases. No low-grade mucinous adenocarcinoma case (n = 11) had signet ring cells, whereas 29 of 44 high-grade mucinous adenocarcinoma cases did. Cases of high-grade mucinous adenocarcinoma were subdivided into 3 groups: (1) high-grade mucinous adenocarcinoma without signet ring cells (n = 15), (2) high-grade mucinous adenocarcinoma with signet ring cells only within mucin pools (n = 20), and (3) high-grade mucinous adenocarcinoma with signet ring cells invading tissue (n = 9). Overall survival (OS) and progression-free survival were subsequently evaluated. Five-year OS for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools were similar at 31.8% (SE, 14.4%) and 35.8% (SE, 13.9%), respectively. A significant survival difference was seen for cases of high-grade mucinous adenocarcinoma with signet ring cells invading tissue with a median OS of 0.5 years versus 2.9 and 2.4 years (P = .04 and P = .03), respectively, for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools. Finding signet ring cells floating in extracellular mucin pools made no prognostic difference when compared with cases of high-grade mucinous adenocarcinoma without signet ring cells. In contrast, high-grade mucinous adenocarcinoma with signet ring cells invading tissue was significant for worse survival, and thus, we propose reporting signet ring cell tissue invasion particularly when extensive.

Metastatic colorectal cancer: survival comparison of hepatic resection versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Liver resection has long been considered the standard of care for resectable colorectal hepatic metastases (HM). Patients with colorectal peritoneal surface disease (PSD) are now also being treated with aggressive therapy in the form of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective comparison of optimally-treated colorectal cancer patients with HM or PSD obtained from prospectively maintained databases (1991-2010). RESULTS: Liver resection was performed on 179 patients with HM, while 93 PSD patients received a complete cytoreduction followed by HIPEC. Patients differed in terms of age, performance status, site of primary cancer, T stage, and the use of perioperative chemotherapy. Five-year overall survival for HM patients was 36 %, with a median survival of 46 months, compared with 26 % and 34 months in patients with PSD (p = 0.024). When stratified by resection status, R0 HM (n = 170) and R0 PSD (n = 48) patients had similar median survival (49 vs. 41 months; p = 0.39). Median survival following R1 resection was also similar among HM (n = 9) and PSD (n = 45) patients (28 vs. 23 months; p = 0.68). Multivariate analysis identified distinctly different independent prognostic factors between HM and PSD patients. Major morbidity was 21 and 23 % (p = 0.88), while mortality was 3.9 versus 5.4 % (p = 0.55) in the HM and PSD patients, respectively. CONCLUSION: Colorectal HM and PSD are distinct biologic diseases with different presentations and unique prognostic factors. However, long-term survival following CS/HIPEC is comparable to liver resection when stratified by completeness of resection. Furthermore, perioperative morbidity and mortality are similar.

Molecular determinants of susceptibility to oncolytic vesicular stomatitis virus in pancreatic adenocarcinoma.

BACKGROUND: M protein mutant vesicular stomatitis virus (M51R-VSV) has oncolytic properties against many cancers. However, some cancer cells are resistant to M51R-VSV. Herein, we evaluate the molecular determinants of vesicular stomatitis virus (VSV) resistance in pancreatic adenocarcinoma cells. METHODS: Cell viability and the effect of ß-interferon (IFN) were analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Gene expression was evaluated via microarray analysis. Cell infectability was measured by flow cytometry. Xenografts were established in athymic nude mice and treated with intratumoral M51R-VSV. RESULTS: Four of five pancreatic cancer cell lines were sensitive to M51R-VSV, whereas Panc 03.27 cells remained resistant (81 ± 3% viability 72 h after single-cycle infection). Comparing sensitive MiaPaCa2 cells with resistant Panc 03.27 cells, significant differences in gene expression were found relating to IFN signaling (P = 2 × 10(-5)), viral entry (P = 3 × 10(-4)), and endocytosis (P = 7 × 10(-4)). MiaPaCa2 cells permitted high levels of VSV infection, whereas Panc 03.27 cells were capable of resisting VSV cell entry even at high multiplicities of infection. Extrinsic ß-IFN overcame apparent defects in IFN-mediated pathways in MiaPaCa2 cells conferring VSV resistance. In contrast, ß-IFN decreased cell viability in Panc 3.27 cells, suggesting intact antiviral mechanisms. VSV-treated xenografts exhibited reduced tumor growth relative to controls in both MiaPaCa2 (1423 ± 345% versus 164 ± 136%; P < 0.001) and Panc 3.27 (979 ± 153% versus 50 ± 56%; P = 0.002) tumors. Significant lymphocytic infiltration was seen in M51R-VSV-treated Panc 03.27 xenografts. CONCLUSIONS: Inhibition of VSV endocytosis and intact IFN-mediated defenses are responsible for M51R-VSV resistance in pancreatic adenocarcinoma cells. M51R-VSV treatment appears to induce antitumor cellular immunity in vivo, which may expand its clinical efficacy.

Perioperative systemic chemotherapy for appendiceal mucinous carcinoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The role of systemic chemotherapy (SC) in conjunction with cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in appendiceal mucinous carcinoma peritonei (MCP) is unknown. METHODS: A retrospective review (1999-2011) of MCP patients who had undergone CS/HIPEC with or without perioperative SC. RESULTS: Twenty-two low-grade MCP patients treated with CS/HIPEC and SC were matched to patients who received CS/HIPEC alone. Median overall survival (OS) was 107 months for patients treated with perioperative SC compared to 72 without (P = 0.46). CS/HIPEC was performed on 109 patients with high-grade MCP: 70 were treated with perioperative SC, while 39 were not. Median OS (22.1 vs. 19.6 months, P = 0.74) and progression-free survival (PFS) (10.9 vs. 7.0 months, P = 0.47) were similar in patients treated with SC compared to CS/HIPEC alone. Progression while on pre-operative SC was seen in eight patients (17%), while four (8%) had a partial response. Treatment with post-operative SC was associated with longer PFS (13.6 months) compared to pre-operative SC (6.8 months, P < 0.01) and CS/HIPEC alone (7.0 months, P = 0.03). CONCLUSIONS: Post-operative SC appears to improve PFS in patients with high-grade appendiceal MCP treated with CS/HIPEC. In contrast, there is no evidence to support the routine use of perioperative SC in low-grade disease.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from rectal cancer.

BACKGROUND: Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the treatment most likely to achieve prolonged survival in peritoneal carcinomatosis (PC). Yet the efficacy of HIPEC in rectal patients is controversial because of the retroperitoneal location of the primary tumor. Therefore, we reviewed our experience in patients with PC from a rectal primary tumor. METHODS: A retrospective analysis of a prospective database of 950 HIPEC procedures was performed. Performance status, age, albumin level, prior surgical score, resection status, morbidity, mortality, and survival were reviewed. RESULTS: A total of 13 and 204 patients with PC from rectal and colon cancer, respectively, were identified. Median follow-up was 40.1 and 88.1 months, respectively. Eastern Cooperative Oncology Group (ECOG) score was zero or one for 92 % of patients with rectal cancer and 83 % for colon, while R1 resection was achieved in 54 and 51 %. The 30-day mortality was 5 % for colon cancer. There were no deaths in the rectal group. The morbidity for the colon and rectal groups was 57 and 46 %, respectively, with a 23 % 30-day readmission rate. In univariate analysis, age, ECOG, prior surgical score, albumin level, and node and resection status were not statistically significant in predicting survival for the rectal cancer patients. Median survival for the rectal and colon groups was 14.6 versus 17.3 months, while the 3-year survival was 28.2 versus 25.1 %. CONCLUSIONS: Our data demonstrate similar 3-year survival for patients with rectal and colon cancer PC treated with CS/HIPEC. This can be attributed to patient selection bias. Selected rectal cancer PC patients should not be excluded from an attempted cytoreduction and HIPEC.

Prevention of surgical site infections in high-risk patients with laparotomy incisions using negative-pressure therapy.

BACKGROUND: This study evaluates the efficacy of negative-pressure therapy (NPT) in preventing surgical site infections (SSIs) in high-risk surgical oncology patients. METHODS: A retrospective analysis of 191 operations for colorectal, pancreatic, or peritoneal surface malignancies was performed. Incisional NPT was used in patients with multiple SSI risk factors. Rates of SSIs were compared with patients treated with a standard sterile dressing (SSD). RESULTS: NPT was used in 104 patients, whereas SSDs were used in 87 patients. Despite being at an increased risk of SSI, patients treated with NPT developed fewer superficial incisional SSIs compared with SSD patients (6.7% vs 19.5%, P = .015). In a subgroup analysis of clean-contaminated cases, NPT was associated with fewer superficial incisional SSIs (6.0% vs 27.4%, P = .001), fewer total SSIs (16.0% vs 35.5%, P = .011), and fewer wound openings for any reason (16.0% vs 35.5%, P = .011). CONCLUSIONS: Our findings suggest that NPT decreases SSIs in high-risk surgical oncology patients.

Variation in susceptibility of human malignant melanomas to oncolytic vesicular stomatitis virus.

BACKGROUND: Vesicular stomatitis virus (VSV) is a novel, anti-cancer therapy that targets cancer cells selectively with defective antiviral responses; however, not all malignant cells are sensitive to the oncolytic effects of VSV. Herein, we have explored the mechanistic determinants of mutant M protein VSV (M51R-VSV) susceptibility in malignant melanoma cells. METHODS: Cell viability after VSV infection was measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability assay in a panel of melanoma cell lines. VSV infectability, viral protein synthesis, and viral progeny production were quantified by flow cytometry, (35)S-methionine electrophoresis, and viral plaque assays, respectively. Interferon (IFN) responsiveness was determined using MTS assay after ß-IFN pretreatment. Xenografts were established in athymic nude mice and treated with intratumoral M51R-VSV. RESULTS: Cell viability after M51R-VSV infection at a multiplicity of infection of 10 pfu/mL, 48 hours postinfection) ranged between 0 ± 1% and 59 ± 9% (mean ± standard deviation). Sensitive cell lines supported VSV infection, viral protein synthesis, and viral progeny production. In addition, when pretreated with ß-IFN, sensitive cells became resistant to M51R-VSV, suggesting that IFN-mediated antiviral signaling is defective in these cells. In contrast, resistant melanoma cells do not support VSV infection, viral protein synthesis, or viral replication, indicating that antiviral defenses remain intact. In a murine xenograft model, intratumoral M51R-VSV treatment decreased tumor growth relative to controls after 26 days in SK-Mel 5 (-21 ± 19% vs. 2,100 ± 770%; P < .0001) and in SK-Mel 3 (2,000 ± 810% vs. 7,000 ± 3,000%; P = .008) established tumors. CONCLUSION: M51R-VSV is a viable anti-cancer therapy, but susceptibility varies among melanomas. Future work will exploit specific mechanisms of resistance to expand the therapeutic efficacy of M51R-VSV.

Surgical management of colorectal cancer metastases to the liver: multimodality approach and a single institutional experience.

Over the past 30 years, the treatment of metastatic colorectal cancer to the liver has undergone major changes. Once considered terminal and incurable, the prognosis of patients with colorectal hepatic metastases has seen dramatic improvements using modern multimodality therapy and now long-term survival and even cure are possible in some patients. Despite the advances seen in systemic therapy, hepatic resection offers the longest survival potential and remains the only curative option. Based on long-term outcomes and the improved safety of hepatic resection using modern operative techniques and critical care support, an aggressive locoregional approach to colorectal hepatic metastasis has become the standard of care. This article focuses on the management of colorectal hepatic metastases and highlights the importance of multimodality therapy. We also report our 18-year experience treating patients with hepatic resection for colorectal metastases.

A novel antireflux procedure: gastroplasty with restricted antrum to control emesis (GRACE).

PURPOSE: Nissen fundoplication is the most commonly performed operation to treat gastroesophageal reflux disease and vomiting in children with neurologic impairment. However, failure rates of Nissen fundoplication in this population are higher, and alternatives to Nissen fundoplication have technical and functional disadvantages. We hypothesize that the novel gastroplasty with restricted antrum to control emesis (GRACE) would be more effective than Nissen fundoplication at reducing emetic reflux. METHODS: To compare the GRACE with Nissen fundoplication, 15 canine subjects were randomized to Nissen fundoplication or GRACE. All subjects underwent gastrostomy tube placement. Baseline gastric emptying, electrogastrography, and induced vomiting studies were performed. Nissen fundoplication or GRACE was then performed. Postoperatively, gastric emptying and vomiting studies were repeated. RESULTS: Gastric emptying before and after antireflux procedures was not significantly different between groups. Both Nissen fundoplication (38%, P = .04) and GRACE (69%, P < .01) procedures prevented reflux compared with baseline. However, the GRACE procedure significantly reduced reflux when compared with Nissen fundoplication (P = .03). CONCLUSIONS: In this canine model, GRACE appears to be significantly more effective than Nissen fundoplication at reducing emetic reflux. This novel procedure preserves gastric function and is well tolerated. The GRACE procedure may provide an alternative to Nissen fundoplication as a primary or repeat antireflux procedure for children with neurologic impairment.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare and aggressive neoplasm that is largely resistant to traditional anti-cancer therapies. For years it has been considered a terminal condition and once diagnosed, patients generally survived less than a year despite aggressive treatment. Although rare, the worldwide incidence of MPM continues to rise, in part due to its association with asbestos exposure. Patients usually present with non-specific symptoms of abdominal distension and pain making the diagnosis challenging. In recent years, aggressive cytoreductive surgery with the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival in patients with MPM treated at multiple centers worldwide. This review article briefly highlights the presentation, diagnosis, and natural history of MPM. We then explore the available treatment options with primary focus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare, rapidly fatal disease. Because traditional treatments offer little benefit, there has been increasing interest in cytoreductive surgery (CS) with intraperitoneal hyperthermic chemotherapy (IPHC). The most efficacious chemotherapy regimen is not established. Herein we report clinical outcomes of MPM patients treated with CS and IPHC and contrast results using two chemoperfusates: mitomycin and cisplatin. METHODS: Thirty-four patients were treated for MPM. Following CS, 19 patients underwent IPHC with mitomycin and 15 received cisplatin. Overall survival, disease-free survival, and progression-free survival were compared between the two groups. RESULTS: Overall survival was 56 and 17% at 3 and 5 years, with median survival of 40.8 months. Those perfused with cisplatin were more likely to be alive at 1, 2, and 3 years (P < 0.05, 0.05, and 0.04, respectively). Median survival for mitomycin and cisplatin was 10.8 and 40.8 months, respectively (P = 0.22). Median disease-free survival and progression-free survival were 10.3 and 9.1 months, respectively. There was a trend toward improved disease-free and progression-free survival using cisplatin. CONCLUSIONS: CS with IPHC is a promising modality for patients with MPM, and clinical outcomes appear to be improved using cisplatin. We recommend using high-dose intraperitoneal cisplatin following cytoreductive surgery when treating malignant peritoneal mesothelioma.