Conversion to Complete Resection and/or Ablation Using Hepatic Artery Infusional Chemotherapy in Patients with Unresectable Liver Metastases from Colorectal Cancer: A Decade of Experience at a Single Institution

Background

When feasible, surgical treatment of colorectal liver metastases (CRLM) is the treatment of choice. Regional hepatic artery infusional (HAI) chemotherapy effectively treats CRLM. The combination of HAI and systemic chemotherapy may downsize tumors and allow for complete resection and/or ablation (R/A). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on conversion to complete R/A.

Methods

All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Survival was compared using a landmark analysis to account for bias.

Results

A total of 373 patients were included; 93 patients (25 %) subsequently underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16 % during 2000–2003 to 30 % during 2004–2009. Factors associated with conversion on multivariate analysis were more recent treatment (2004–2009), no prior chemotherapy, clinical risk score <3, treatment on clinical protocol, and younger age. Median and predicted 5-year survival from the time of HAI pump placement was 59 months and 47 %, respectively, in the patients who converted to complete R/A, compared with 16 months and 6 %, respectively in those who did not (p < 0.001).

Conclusions

Despite extensive disease, 25 % of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Combination HAI and systemic chemotherapy is an effective strategy to convert patients to complete resection with an associated excellent long-term survival.     

Predicting Dysplasia and Invasive Carcinoma in Intraductal Papillary Mucinous Neoplasms of the Pancreas: Development of a Preoperative Nomogram

Background

Clinical decision making for patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas is challenging. Even with strict criteria for resection, most resected lesions lack high-grade dysplasia (HGD) or invasive carcinoma.

Methods

We evaluated patients who underwent resection of histologically confirmed IPMN and had preoperative imaging available for review. A hepatobiliary radiologist blinded to histopathologic subtype reviewed preoperative imaging and recorded cyst characteristics. Patients with mixed-type IPMN were grouped with main-duct lesions for this analysis. Based on an ordinal logistic regression model, we devised two independent nomograms to predict the findings of adenoma, high-grade dysplasia (HGD–CIS), and invasive carcinoma, separately in both main and branch-duct IPMN. Bootstrap validation was used to evaluate the performance of these models, and a concordance index was derived from this internal validation.

Results

There were 219 patients who met criteria for this study. Branch-duct IPMN (bdIPMN) comprised 56 % of the resected lesions. The proportion of HGD–CIS was 15 % for bdIPMN and 33 % for main-duct lesions (mdIPMN); P = 0.003. Invasive carcinoma was identified in 15 % of bdIPMN and 41 % of main-duct lesions (P < 0.001). On multivariate regression, patient gender, history of prior malignancy, presence of solid component, and weight loss were found to be significantly associated with the ordinal outcome for patients with mdIPMN and built into the nomogram (concordance index 0.74). For patients with bdIPMN weight loss, solid component, and lesion diameter were associated with the outcome; (concordance index 0.74).

Conclusion

Based on the analysis of patients selected for resection, two nomograms were created that predict a patient’s individual likelihood of harboring HGD or invasive malignancy in radiologically diagnosed IPMN. External validation is ongoing.     

Symptomatic Perihepatic Fluid Collections After Hepatic Resection in the Modern Era

Background

Improvements in liver surgery have led to decreased mortality rates. Symptomatic perihepatic collections (SPHCs) requiring percutaneous drainage remain a significant source of morbidity.

Study Design

A single institution’s prospectively maintained hepatic resection database was reviewed to identify patients who underwent hepatectomy between January 2004 and February 2012.

Results

Data from 2173 hepatectomies performed in 2040 patients were reviewed. Overall, 200 (9 %) patients developed an SPHC, the majority non-bilious (75.5 %) and infected (54 %). Major hepatic resections, larger than median blood loss (≥360 ml), use of surgical drains, and simultaneous performance of a colorectal procedure were associated with an SPHC on multivariate analysis. Non-bilious, non-infected (NBNI) collections were associated with lower white blood cell (WBC) counts, absence of a bilio-enteric anastomosis, use of hepatic arterial infusion pump (HAIP), and presence of metastatic disease, and resolved more frequently with a single interventional radiology (IR) procedure (85 vs 46.5 %, p?<?0.001) more quickly (15 vs 30 days, p?=?0.001).

Conclusions

SPHCs developed in 9 % of patients in a modern series of hepatic resections, and in one third were non-bilious and non-infected. In the era of modern interventional radiology, the need for re-operation for SPHC is exceedingly rare. A significant proportion of minimally symptomatic SPHC patients may not require drainage, and strategies to avoid unnecessary drainage are warranted.

     

The influence of smear layer in lateral channels filling

This in vitro study evaluated the ability of a warm gutta-percha obturation system Thermafil to fill lateral channels in presence/absence of smear layer. Forty single-rooted extracted human teeth were randomly divided into two groups for which different irrigation regimens were used: group A, 5 ml of 5% NaOCl + 2.5 ml of 3.6% H₂O₂; group B, 5 ml of 5% NaOCl 5% + 2.5 ml of 17% ethylenediamine tetraacetic acid. A conventional crown-down preparation technique was employed. Obturation was performed using epoxy resin-based cement (AH Plus) and a warm gutta-percha plastic carrier system (Thermafil). Specimens were cleared in methyl salicylate and analyzed under a stereomicroscope to evaluate the number, length, and diameter of lateral channels. Lateral channels were identified in both groups at medium and apical thirds. Additional samples were prepared for scanning electron microscopy inspection to confirm the presence of smear layer in group A, and the absence of smear layer in group B. All lateral channels resulted filled in both groups. No statistically significant differences regarding number, length, and diameter were observed between the two groups. Smear layer did not prevent the sealing of lateral channels.     

A novel immune competent murine hypertrophic scar contracture model: A tool to elucidate disease mechanism and develop new therapies

Hypertrophic scar (HSc) contraction following burn injury causes contractures. Contractures are painful and disfiguring. Current therapies are marginally effective. To study pathogenesis and develop new therapies, a murine model is needed. We have created a validated immune‐competent murine HSc model. A third‐degree burn was created on dorsum of C57BL/6 mice. Three days postburn, tissue was excised and grafted with ear skin. Graft contraction was analyzed and tissue harvested on different time points. Outcomes were compared with human condition to validate the model. To confirm graft survival, green fluorescent protein (GFP) mice were used, and histologic analysis was performed to differentiate between ear and back skin. Role of panniculus carnosus in contraction was analyzed. Cellularity was assessed with 4′,6‐diamidino‐2‐phenylindole. Collagen maturation was assessed with Picro‐sirius red. Mast cells were stained with Toluidine blue. Macrophages were detected with F4/80 immune. Vascularity was assessed with CD31 immune. RNA for contractile proteins was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Elastic moduli of skin and scar tissue were analyzed using a microstrain analyzer. Grafts contracted to ～45% of their original size by day 14 and maintained their size. Grafting of GFP mouse skin onto wild‐type mice, and analysis of dermal thickness and hair follicle density, confirmed graft survival. Interestingly, hair follicles disappeared after grafting and regenerated in ear skin configuration by day 30. Radiological analysis revealed that panniculus carnosus doesn't contribute to contraction. Microscopic analyses showed that grafts show increase in cellularity. Granulation tissue formed after day 3. Collagen analysis revealed increases in collagen maturation over time. CD31 stain revealed increased vascularity. Macrophages and mast cells were increased. qRT‐PCR showed up‐regulation of transforming growth factor beta, alpha smooth muscle actin, and rho‐associated protein kinase 2 in HSc. Tensile testing revealed that human skin and scar tissues are tougher than mouse skin and scar tissues.     

Pharmacologic Prophylaxis,Postoperative INR,and Risk of Venous Thromboembolism after Hepatectomy

Introduction

Pharmacologic prophylaxis (PP) is recommended for patients undergoing general surgical procedures with at least moderate risk of venous thromboembolism (VTE). The role of PP in patients undergoing hepatectomy is controversial, however, due to concerns regarding postoperative liver dysfunction and bleeding.

Methods

We conducted a retrospective analysis of a prospectively maintained institutional database in order to clarify the relationship between PP, postoperative INR, and risk of VTE.

Results

Postoperative VTE occurred in 55 of 2,147 patients (2.6 %) and was independently associated with advanced age, higher BMI, longer procedure time, and development of a major complication, as well as higher postoperative INR (≥1.5 versus <1.5: OR 2.50, P?=?0.006). Patients undergoing more extensive liver resection with higher postoperative INR were less likely to receive PP, but receipt of PP demonstrated no relationship with either VTE incidence or hemorrhagic complications.

Conclusions

In this large single-institution study, incidence of VTE was not associated with PP but was associated with higher postoperative INR, contrary to the notion that postoperative liver dysfunction is protective against VTE. The interplay between prothrombotic and antithrombotic mechanisms in posthepatectomy patients must be more completely characterized before broad recommendations can be made regarding PP use in these patients.     

Pathologic Grade and Tumor Size are Associated with Recurrence-Free Survival in Patients with Duodenal Neuroendocrine Tumors

Background

Duodenal neuroendocrine tumors are rare and few studies exist to guide surgical management. This study identifies factors associated with recurrence after resection.

Methods

A retrospective, single institution review was performed between 1983 and 2011 on patients with a pathologic diagnosis of duodenal neuroendocrine tumor. Tumor grade was assigned based on WHO 2010 criteria (Ki-67 and mitotic rate).

Results

Seventy-five patients were identified that underwent curative resection. This included 12 patients with endoscopic mucosal resection, 34 that had local resection, and 29 that underwent pancreaticoduodenectomy. Two-year and 5-year recurrence-free survival was 84 and 81 %, respectively. There were 11 tumor recurrences (either local or distant), and four patients died of their disease (3/4 had high-grade lesions) with an overall median follow-up of 27 months. On univariate analysis, tumor size and tumor grade were identified as being associated with recurrence, but not intervention type, lymph node metastases, ampullary location, or margin status.

Conclusions

Tumor grade and size are associated with recurrence-free survival in duodenal neuroendocrine tumors. When feasible, a less aggressive surgical approach to treat low-grade and low-stage duodenal NETs should be considered.