Niraj J. Gusani

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis

Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era.

Indications and approach to surgical resection of lung metastases.

Pulmonary metastasectomy is a curative option for selected patients with cancer spread to the lungs. Complete surgical removal of pulmonary metastases can improve survival and is recommended under certain criteria. Specific issues that require consideration in a multidisciplinary setting when planning pulmonary metastasectomy include: adherence to established indications for resection, the surgical strategy including the use of minimally invasive techniques, pulmonary parenchyma preservation, and the role of lymphadenectomy. J. Surg. Oncol. 2010;102:187–195.

Effect of dobutamine on regional left ventricular function measured by tagged magnetic resonance imaging in normal subjects

The effect of inotropic stimulation on the pattern and magnitude of regional left ventricular contraction was studied using tagged magnetic resonance imaging to assess whether dobutamine exacerbates variation in regional contraction at rest. Dobutamine stress testing defines a normal response as a homogeneous increase in regional wall motion. In 8 normal subjects, 4 equally spaced left ventricular short-axis levels were imaged through systole using tagged magnetic resonance imaging. The baseline imaging sequence was repeated with 5-, 10-, 15-, and 20-microg/kg/min dobutamine infusion. Regional myocardial displacement, radial thickening, and circumferential shortening were measured. The left ventricle was analyzed by level (base to apex) and wall (septum, inferior, lateral, anterior). Dobutamine did not alter baseline regional functional heterogeneity. Dobutamine infusion resulted in a uniform increase in displacement, radial thickening, and circumferential shortening from baseline to 10-microg/kg/min infusion without additional increases at higher doses.

A Reduction in Delayed Gastric Emptying by Classic Pancreaticoduodenectomy with an Antecolic Gastrojejunal Anastomosis and a Retrogastric Omental Patch

BackgroundDelayed gastric emptying (DGE) continues to be a major cause of morbidity following pancreaticoduodenectomy (PD). A change in the method of reconstruction following PD was instituted in an attempt to reduce the incidence DGE.MethodsPatients undergoing PD from January 2002 to December 2008 were reviewed and outcomes determined. Pylorus-preserving pancreaticoduodenectomy (PPPD) with a retrocolic duodenojejunal anastomosis (n = 79) or a classic PD with a retrocolic gastrojejunostomy (n = 36) was performed prior to January 2008. Thereafter, a classic PD with an antecolic gastrojejunal anastomosis and placement of a retrogastric vascular omental patch was undertaken (n = 36).ResultsA statistically significant decrease in DGE was noted in the antecolic group compared to the entire retrocolic group (14% vs 40%; p = 0.004) and compared to patients treated by classic PD with a retrocolic anastomosis alone (14% vs 39%; p = 0.016). On multivariate analysis, the only modifiable factor associated with reduced DGE was the antecolic technique with an omental patch, odds ratio (OR) 0.3 (confidence interval (CI) 0.1–0.8) p = 0.022. Male gender was associated with an increased risk of DGE with OR 2.3 (CI 1.1–4.8) p = 0.026.ConclusionA classic PD combined with an antecolic anastomosis and retrogastric vascular omental patch results in a significant reduction in DGE.

Impact of Surgeon and Hospital Volume on Mortality, Length of Stay, and Cost of Pancreaticoduodenectomy

BackgroundImproved mortality rates following pancreaticoduodenectomy by high-volume surgeons and hospitals have been well documented, but less is known about the impact of such volumes on length of stay and cost. This study uses data from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) to examine the effect of surgeon and hospital volume on mortality, length of stay, and cost following pancreaticoduodenectomy while controlling for patient-specific factors.MethodsData included 3,137 pancreaticoduodenectomies from the NIS performed between 2004 and 2008. Using logistic regression, the relationship between surgeon volume, hospital volume, and postoperative mortality, length of stay, and cost was estimated while accounting for patient factors.ResultsAfter controlling for patient characteristics, patients of high-volume surgeons at high-volume hospitals had a significantly lower risk of mortality compared to low-volume surgeons at low-volume hospitals (OR 0.32, p < 0.001). Patients of high-volume surgeons at high-volume hospitals also had a five day shorter length of stay (p < 0.001), as well as significantly lower costs (US

Diagnosis and management of retroperitoneal ancient schwannomas

12,275, p < 0.001).ConclusionsThe results of this study, which simultaneously accounted for surgeon volume, hospital volume, and potential confounding patient characteristics, suggest that both surgeon and hospital volume have a significant effect on outcomes following pancreaticoduodenectomy, affecting not only mortality rates but also lengths of stay and costs.

Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy

BackgroundAncient schwannomas are degenerate peripheral nerve sheath tumors that very rarely occur in the retroperitoneum. They generally reach large proportions before producing symptoms due to mass effect. We describe three cases of retroperitoneal ancient schwannomas and discuss the diagnosis and management of these tumors.Case presentationsThree female patients with retroperitoneal ancient schwannomas were reviewed. One patient presented with several weeks of upper abdominal pain and lower chest discomfort, whereas back pain and leg pain with associated weakness were predominant symptoms in the remaining two. Abdominal imaging findings demonstrated heterogeneous masses in the retroperitoneum with demarcated margins, concerning for malignancy. The patients successfully had radical excision of their tumors. Histological examination showed encapsulated tumors that displayed alternating areas of dense cellularity and areas of myxoid matrix consistent with a diagnosis of ancient schwannoma.ConclusionA diagnosis of ancient schwannoma should be entertained for any heterogeneous, well encapsulated mass in the retroperitoneum. In these cases less radical surgical resection should be considered as malignant transformation of these tumors is extremely rare and recurrence is uncommon following excision.

Cytokine-secreting herpes viral mutants effectively treat tumor in a murine metastatic colorectal liver model by oncolytic and T-cell-dependent mechanisms

Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene γ134.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in response to stressors such as radiation (XRT). By upregulating GADD34, XRT may result in greater oncolytic activity of HSV strains deficient in the γ134.5 gene. The human cholangiocarcinoma cell lines KMBC, SK-ChA-1 and YoMi were treated with NV1023, an oncolytic HSV lacking one copy of γ134.5. Viral proliferation assays were performed at a multiplicity of infection (MOI, number of viral particles per tumor cell) equal to 1, either alone or after XRT at 250 or 500 cGy. Viral replication was assessed by plaque assay. In vitro cytotoxicity assays were performed using virus at MOIs of 0.01 and 0.1, with or without XRT at 250 cGy and cell survival determined with lactate dehydrogenase assay. Established flank tumors in athymic mice were treated with a single intratumoral injection of virus (103 or 104 plaque forming units), either alone or after a single dose of XRT at 500 cGy, and tumor volumes measured. RT-PCR was used to measure GADD34 mRNA levels in all cell lines after a single dose of XRT at 250 or 500 cGy. NV1023 was tumoricidal in all three cell lines, but sensitivity to the virus varied. XRT enhanced viral replication in vitro in all cell lines. Combination treatment with low-dose XRT and virus was highly tumoricidal, both in vitro and in vivo. The greatest tumor volume reduction with combination therapy was seen with YoMi cells, the only cell line with increased GADD34 expression after XRT and the only cell line in which a synergistic treatment effect was suggested. In KMBC and SK-ChA-1 cells, neither of which showed increased GADD34 expression after XRT, tumor volume reduction was less pronounced and there was no suggestion of a synergistic effect in either case. Oncolytic HSV are effective in treating human cholangiocarcinoma cell lines, although sensitivity to virus varies. XRT-enhanced viral replication occurs through a mechanism that is not necessarily dependent on GADD34 upregulation. However, XRT-induced upregulation of GADD34 further promotes tumoricidal activity in viral strains deficient in the γ134.5 gene, resulting in treatment synergy; this effect is cell type dependent. Combined XRT and oncolytic viral therapy is a potentially important treatment strategy that may enhance the therapeutic ratios of both individual therapies.

Multidisciplinary management of malignant pleural effusion.

In this model of hepatic micrometastases, the antitumor efficacy and role of the T-cell and natural killer (NK) cell populations were studied for oncolytic herpes simplex virus type-1 (HSV-1) viral mutants containing the granulocyte-monocyte colony stimulating factor (GM-CSF (NV1034)) or interluken-12 (IL-12 (NV1042)) cytokine genes. These were compared to saline and control virus (NV1023) in vitro and in vivo. HSV-1 mutants were assessed for cytotoxicity, replication and cytokine expression in CT-26 cells. A syngeneic micrometastatic liver model was then established in naive and immune cell-depleted animals to assess the antitumor efficacy of these viruses. In vitro cytotoxicity and viral replication were similar for each virus, resulting in greater than 80 and 98% cytotoxicity at multiplicity of infection of 1 and 10, respectively. Peak viral titers were 25- to 50-fold higher than initial titer and were not significantly different between viruses. In vivo, all three viruses reduced metastases relative to control, but cytokine-secreting viruses did so with greater efficacy compared to NV1023. This effect was abrogated by T-cell depletion, but not NK-cell depletion. Single-agent therapy with oncolytic viral agents containing GM-CSF or IL-12 is effective in a murine model of liver metastases and likely involves direct viral oncolysis and actions of specific immune effector cells.

Multivisceral and extended resections during pancreatoduodenectomy increase morbidity and mortality

Approximately 50% of patients with metastatic disease develop a malignant pleural effusion (MPE). Prompt clinical evaluation and treatment to achieve successful palliation are the main goals of management of MPE. Optimal treatment is still controversial and there is no universal standard approach. Management options include observation, thoracentesis, indwelling pleural catheter (IPC) or chest tube placement, pleurodesis, and surgical pleurectomy. The treatment for each patient should be based on symptoms, general condition, and life expectancy. J. Surg. Oncol. 2012; 105:731–738.