George Z. Li

Hepatic Resection for Hepatocellular Carcinoma: Do Contemporary Morbidity and Mortality Rates Demand a Transition to Ablation as First-Line Treatment?

BACKGROUND Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions. STUDY DESIGN Mortality and morbidity data were extracted from the 2005-2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression. RESULTS Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04-0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22-0.52; p < 0.001). CONCLUSIONS Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible.

TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion

Recent studies implicate a role for cell mechanics in cancer progression. Transforming growth factor β–induced epithelial-to-mesenchymal transition results in decreased stiffness and loss of the normal stiffening response to force applied on integrins.

Erratum to: angiotensin II stimulates canonical TGF-β signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction.

Hypertrophic scar contraction (HSc) is caused by granulation tissue contraction propagated by myofibroblast and fibroblast migration and contractility. Identifying the stimulants that promote migration and contractility is key to mitigating HSc. Angiotensin II (AngII) promotes migration and contractility of heart, liver, and lung fibroblasts; thus, we investigated the mechanisms of AngII in HSc. Human scar and unwounded dermis were immunostained for AngII receptors angiotensin type 1 receptor (AT1 receptor) and angiotensin type 2 receptor (AT2 receptor) and analyzed for AT1 receptor expression using Western blot. In vitro assays of fibroblast contraction and migration under AngII stimulation were conducted with AT1 receptor, AT2 receptor, p38, Jun N-terminal kinase (JNK), MEK, and activin receptor-like kinase 5 (ALK5) antagonism. Excisional wounds were created on AT1 receptor KO and wild-type (WT) mice treated with AngII ± losartan and ALK5 and JNK inhibitors SB-431542 and SP-600125, respectively. Granulation tissue contraction was quantified, and wounds were analyzed by immunohistochemistry. AT1 receptor expression was increased in scar, but not unwounded tissue. AngII induced fibroblast contraction and migration through AT1 receptor. Cell migration was inhibited by ALK5 and JNK, but not p38 or MEK blockade. In vivo experiments determined that absence of AT1 receptor and chemical AT1 receptor antagonism diminished granulation tissue contraction while AngII stimulated wound contraction. AngII granulation tissue contraction was diminished by ALK5 inhibition, but not JNK. AngII promotes granulation tissue contraction through AT1 receptor and downstream canonical transforming growth factor (TGF)-β signaling pathway, ALK5. Further understanding the pathogenesis of HSc as an integrated signaling mechanism could improve our approach to establishing effective therapeutic interventions.Key messageAT1 receptor expression is increased in scar tissue compared to unwounded tissue.AngII stimulates expression of proteins that confer cell migration and contraction.AngII stimulates fibroblast migration and contraction through AT1 receptor, ALK5, and JNK.AngII-stimulated in vivo granulation tissue contraction is AT1 receptor and ALK5 dependent.

Simultaneous Diaphragm and Liver Resection: A Propensity-Matched Analysis of Postoperative Morbidity

BACKGROUND Although a concomitant diaphragm resection might be required at the time of hepatectomy to achieve tumor-free surgical margins, studies addressing its effect on postoperative morbidity and mortality have been inconclusive. The objective of this study was to determine whether the need for diaphragm resection at the time of hepatectomy truly increases 30-day morbidity or mortality using data from the American College of Surgeons National Surgical Quality Improvement Program. STUDY DESIGN Data were obtained from the 2005-2010 American College of Surgeons National Surgical Quality Improvement Program Participant User Files based on CPT coding. All patients undergoing a simultaneous liver and diaphragm resection were propensity-matched to a subset of liver resection patients not undergoing a diaphragm resection. The main outcomes measures were 30-day mortality and morbidity. RESULTS One hundred and ninety-two patients who underwent combined liver and diaphragm resection were matched to 192 patients treated with liver resection alone. The need for concomitant diaphragm resection was associated with a higher overall complication rate (38.54% vs 28.65%; p = 0.048), major complication rate (33.33% vs 23.44%; p = 0.030), and respiratory complication rate (14.06% vs 7.81%; p = 0.058). Postoperative mortality was similar between groups. Combined diaphragm and liver resection was also associated with longer operative times (median 311 minutes vs 247.5 minutes; p < 0.001), higher rates of intraoperative packed RBC transfusion (33.33% vs 23.44%; p = 0.037), and a longer length of hospitalization (median 7 vs 6 days; p = 0.002). CONCLUSIONS The results of this study, when taken into account with those reported previously, suggest that the need for diaphragm resection at time of hepatectomy increases postoperative morbidity but not mortality.

Review of complications associated with endoscopic pancreatic cyst-gastrostomy: a single-institution experience.

Background: Pancreatic fluid collections can form after episodes of pancreatitis, either acute or chronic. The majority will resolve spontaneously but when decompression is mandated, endoscopic drainage is the method of choice. However, it is not void of complications. Methods: We retrospectively reviewed the charts of 65 patients who underwent endoscopic drainage of pancreatic fluid collections in our institution. The primary outcomes examined included the incidence and type of complications associated with the endoscopic approach. Results: Endoscopic ultrasound was utilized in 86.2% and transgastric approach was used in 81.5% of the cases. The complication rate was 17%. Specifically, complications recorded were infection (6%), perforation and acute abdomen necessitating surgical intervention (4.6%), pneumoperitoneum that was managed nonoperatively (3%), upper gastrointestinal bleed in the knife puncture site that resolved spontaneously (1.5%), and stent migration (1.5%). One patient died remotely to the endoscopic drainage after paracentesis of ascites that resulted in hemorrhagic shock. Conclusions: This study is one of the largest studies reporting the associated morbidity and mortality after endoscopic cyst-gastrostomy. Major and minor complications occurred at a rate of 17% in our study. Endoscopic approach is a safe draining method and should remain the approach of choice for pancreatic fluid collection decompression.

Duodenal Stump Blowout

Duodenal stump blowout, while much less common than in previous decades due to a marked reduction in the number of gastrectomies performed, continues to be one of the most dreaded complications following gastric resection. Although mortality following stump blowout has improved substantially since the dismal rates of the 1950s, this devastating complication remains a contemporary concern. In situations where stump blowout nonetheless occurs, rapid diagnosis and intervention are essential in minimizing associated morbidity for the patient. Because of this, prevention and management of stump blowout remains a clinically important consideration for the general surgeon and surgical oncologist performing gastrointestinal surgery.

A medical history of Governor John B. Connally and his gunshot wounds

: On November 22, 1963, the Governor of Texas, John Connally, was injured during the assassination of President John F. Kennedy. Multiple authors have documented President Kennedys injuries, the attempted resuscitation, and the controversies surrounding these events. However, the injuries sustained by Governor Connally have been overlooked by historians predominantly because of the extraordinary importance of the presidential assassination and its impact on the national consciousness. This review discusses the governors political life, the mechanism of injury, his medical care, and the role the injuries had on his subsequent public life.