Jeffrey P. Lamont

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Optimizing Outcomes in Bariatric Surgery: Outpatient Laparoscopic Gastric Bypass

Background:Roux-en-Y gastric bypass (RYGB) is an effective treatment of severe obesity and one of the fastest growing surgical procedures in the United States. Methods:A single institution prospective database of patients undergoing outpatient laparoscopic (lap) RYGB over a 3-year period was reviewed. Study end points included hospital discharge within 23 hours, 30-day hospital readmission rate, early (<30 day) and late complication rates, and 30-day perioperative mortality. Variables assessed included surgeon experience, patient demographics, comorbidities, operative time, Roux limb pathway, intraoperative steroid bolus, and use of dexmedetomidine. Results:Two thousand consecutive patients undergoing outpatient lap RYGB were identified, and 84% (n = 1669) were discharged within 23 hours. Of these, 1.7% (n = 34) were readmitted within 30 days. The overall early and late complication rates were 1.9% (n = 38) and 4.3% (n = 86), respectively. The 30-day mortality rate was 0.1% (n = 2), and neither patient was discharged before death. Univariate analysis demonstrated surgeon experience (<50 cases), age (<56 years), body mass index (<60 kg/m2), weight (400 lbs), comorbidities (<5), and intraoperative steroid bolus as predictive of successful outpatient discharge. Multivariate analysis revealed surgeon experience, comorbidities, body mass index, and steroid bolus as predictive variables. Conclusions:These data suggest that outpatient lap RYGB can be performed with acceptable perioperative complication rates, hospital readmission, and mortality rates. Surgeon experience, careful patient selection, and the use of intraoperative steroid bolus predicted optimal patient outcomes.

Should locally excised T1 rectal cancer receive adjuvant chemoradiation

BACKGROUND Local excision of low-lying adenocarcinoma of the rectum is increasingly utilized, but the benefit of adjuvant treatment in T1 lesions with otherwise favorable pathology remains controversial. METHODS A retrospective review was performed on patients who underwent local excision of invasive rectal cancer with curative intent from 1991 to 1999. RESULTS Forty-eight patients were treated with local surgical excision. Twenty-seven T1 lesions were identified, 10 received postoperative chemoradiation, and no local recurrences were identified. Seventeen T1 patients did not receive adjuvant treatment and local recurrence occurred in 4 patients (24%). In all cases of local recurrence, the lesions had been excised to negative margins, none were poorly differentiated, and none exhibited vascular or lymphatic invasion. CONCLUSION These data suggest a trend toward improved local control with adjuvant therapy after local excision of T1 rectal cancer. This is an important consideration in patients with negative surgical margins and favorable pathology who are traditionally not treated.

p53 therapy in a patient with Li-Fraumeni syndrome

Li-Fraumeni syndrome is an autosomal dominant disorder that greatly increases the risk of developing multiple types of cancer. The majority of Li-Fraumeni syndrome families contain germ-line mutations in the p53 tumor suppressor gene. We describe treatment of a refractory, progressive Li-Fraumeni syndrome embryonal carcinoma with a p53 therapy (Advexin) targeted to the underlying molecular defect of this syndrome. p53 treatment resulted in complete and durable remission of the injected lesion by fluorodeoxyglucose-positron emission tomography scans with improvement of tumor-related symptoms. With respect to molecular markers, the patients tumor had abnormal p53 and expressed coxsackie adenovirus receptors with a low HDM2 and bcl-2 profile conducive for adenoviral p53 activity. p53 treatment resulted in the induction of cell cycle arrest and apoptosis documented by p21 and cleaved caspase-3 detection. Increased adenoviral antibody titers after repeated therapy did not inhibit adenoviral p53 activity or result in pathologic sequelae. Relationships between these clinical, radiographic, and molecular markers may prove useful in guiding future application of p53 tumor suppressor therapy. [Mol Cancer Ther 2007;6(5):1478–1482

Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer.

Circulating tumor cells (CTCs) have been detected in patients with a variety of metastatic cancers, including colorectal, and may be a significant prognostic variable in patients with liver metastases. This prospective study involved 20 patients (13 men and 7 women) undergoing surgical excision or ablation of liver metastases from a colon or rectal primary tumor. Four 7.5-mL vials of peripheral blood were drawn preoperatively, 2 weeks postoperatively, and during mobilization of the liver or at the beginning of radiofrequency ablation. The samples were centrifuged, the sera combined to a final volume of 7.5 mL, and the CellSearch system used to identify circulating epithelial cells. A CTC count >2 was defined as clinically significant. Preoperative CTC levels averaged 3.9 (range, 0–56) and were significant in 2 patients (10%). Postoperative CTC levels averaged 1.0 (in 18 patients; range, 0–9) and were significant in 1 patient (5%). Intraoperative CTC levels averaged 28.2 (range, 0–315) and were significant in 10 patients (50%). At a median follow-up of 11.5 months (range, 5–25), 6 patients (30%) were dead of disease, 6 patients (30%) showed no evidence of disease, and 8 patients (40%) were alive with disease. Statistical analysis suggested a correlation between the presence of postoperative CTCs and survival (P = 0.036), as well as with disease-free survival (P = 0.036). Thus, CTCs are present and quantifiable in many patients with colorectal hepatic metastases, and peripheral CTCs are present in greater quantity during intraoperative liver manipulation. This preliminary study suggests a relationship between the presence of postoperative CTCs and outcome. Further accrual and follow-up of this group is needed to confirm these findings.

Variables associated with islet yield in autologous islet cell transplantation for chronic pancreatitis

The goal of total pancreatectomy followed by autologous islet cell transplantation is to manage pain and prevent surgical diabetes for patients with severe chronic pancreatitis. We performed this procedure in 17 patients from November 2006 to October 2009 at Baylor University Medical Center. All patients were included in this retrospective study and were divided into two groups based on islet yield in the final product based on patient body weight: a low-yield group (<5000 IE/kg) and a high-yield group (≥5000 IE/kg). There were significant differences between the two groups in the rate of pancreatic findings on computed tomography (low vs high group, 88% vs 22%: P = 0.02), Cambridge classification score for endoscopic retrograde cholangiopancreatography (3.8 ± 0.2 vs 2.1 ± 0.6: P = 0.03), number of positive endoscopic ultrasonography criteria (6.0 ± 0.8 vs 3.5 ± 0.4: P = 0.04), and distension score (1.9 ± 0.4 vs 3.7 ± 0.2: P = 0.006). A significant reduction in narcotics use after the operation was observed in both groups (P = 0.03 and P = 0.009 in the low and high groups, respectively, using a paired t test). Excellent graft function and glycemic control after the transplantation were also demonstrated in both groups. Patients in the high-yield group were in the early stage of chronic pancreatitis, which led to excellent pancreatic distention for islet isolation; however, the excellent clinical outcomes were observed in both low- and high-yield groups.

Summary of bi-shRNAfurin/GM-CSF Augmented Autologous Tumor Cell Immunotherapy (FANG™) in Advanced Cancer of the Liver

Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/106 cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5 × 107 cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC.

Implication of pancreatic image findings in total pancreatectomy with islet autotransplantation for chronic pancreatitis.

Objective: To clarify the implication of pancreatic findings on transabdominal ultrasound and/or abdominal computed tomographic scan on outcomes of islet isolation and endocrine function after total pancreatectomy (TP) with islet autotransplantation (IAT). Methods: Retrospective review of islet isolations and graft functions in a cohort of patients with chronic pancreatitis who received TP with IAT from December 2007 to September 2009. Patients were categorized into the following 2 groups on the basis of their transabdominal ultrasound or computed tomographic findings before IAT: early group (normal or equivocal of Cambridge classification) and advanced group (mild to marked). Results: A total of 12 patients (early group, n = 6; advanced group, n = 6) were included. Total islet yield per pancreas weight and per patient body weight in the early group was significantly higher compared with that in the advanced group (6989 ± 659 vs 3567 ± 615 islet equivalents per gram, P < 0.01; 8556 ± 953 vs 3847 ± 739 islet equivalents per kilogram, P < 0.01, respectively). Four patients (67%) in the early group became insulin-free, whereas 2 patients (33%) in the advanced group obtained insulin independence. However, both groups maintained islet graft function and similar glycated hemoglobin levels after transplantation. Conclusions: Excellent glycemic control was observed in both groups of patients who received TP with IAT, although the early group showed a significantly better outcome of islet isolation.

Management of ampullary lesions

Adenomatous lesions of the ampulla of Vater are relatively rare neoplasms that raise many questions regarding standard management. Adenocarcinoma often will be found in ampullary lesions and should be treated by pancreaticoduodenectomy (PD). Benign-appearing adenomas may be treated by PD, transduodenal ampullectomy (AMP), or endoscopic ampullectomy (EA). AMP and EA have decreased morbidity and mortality compared with PD but are limited by concerns for appropriate resection margins, high recurrence rates, and the need for surveillance endsscopy or additional procedures. Preoperative endoscopic biopsies should be obtained to identify carcinoma, but, they have high false-negative rates and cannot be relied upon to rule out malignancy. Intraoperative frozen section evaluation should be requested routinely during AMP, with conversion to PD if carcinoma is demonstrated. The gold standard management of benign adenomas has not been clarified, but the goal for all treatment modalities is complete resection. Patients with familial adenomatous polyposis may be exceptions to this, and routine surveillance endoscopy and biopsy with selective resection have been advocated by some as an alternative to complete resection. Adjuvant chemoradiation has a very limited role in the treatment of ampullary carcinoma and ideally should be offered in the setting of a clinical trial. Metastatic and locally advanced, unresectable lesions may be palliated by surgical or endoscopic bypass, as well as by celiac plexus blockade.

Improved pancreatic islet isolation outcome in autologous transplantation for chronic pancreatitis.

Total or partial pancreatectomy followed by autologous islet transplantation is a therapeutic option for the treatment of refractory chronic pancreatitis (CP). Maximization of islet yields from fibrotic and inflamed organs is crucial for prevention of posttransplant diabetes. We adapted technical advancements developed for islet allotransplantation toward islet autotransplantation. Eight patients (two men, six women; ages 24–58 years) underwent total (n = 7) or partial (n = 1) pancreatectomy for the treatment of CP refractory to maximal medical management. Pancreata were preserved in UW solution (UW group) in initial three cases and the last five pancreata were preserved with pancreatic ductal injection followed by ET-Kyoto/oxygenated PFC solutions (DI+TLM group). Islets were isolated by modified Ricordi method and were purified only in one case. All islet infusions were performed under general anesthesia via direct vein injection into the portal venous system with pressure monitoring. Total islet yields (129,314 ± 51,627 vs. 572,841 ± 116,934 IEQ, p < 0.04), islet yield/pancreas weight (1,233 ± 359 vs. 6,848 ± 847 IEQ/g, p < 0.003), and islet yield/patient body weight (1,951 ± 762 vs. 7,305 ± 1,531 IEQ/kg, p < 0.05) were significantly higher in the DI+TLM group when compared to the UW group. Pellet size was also higher (5.3 ± 0.3 vs. 13.5 ± 3.4 ml) in the DI+TLM group, suggesting that this method of preservation effectively protected pancreatic tissue against autolysis. First month posttransplant basal C-peptide and the secretory unit of islet transplant objects (SUITO) index were also higher in the DI+TLM group when compared to the UW group (2.0 ± 0.3 vs. 1.4 ± 0.4 ng/ml and 42.6 ± 12.7 vs. 14.6 ± 5.6, respectively). There were no technical complications related to the infusion. Our results suggest that higher islet yields can be achieved even from chronically inflamed and fibrotic organs using DI+TLM. The techniques applied for islet isolations from normal pancreata are showing promise for fibrotic pancreata from CP patients.