A Path to High-Value Gastric Cancer Surgery Care Delivery.

Objective: To evaluate the feasibility, safety, and effectiveness of a comprehensive regional program, including the Minimally Invasive Recovery and Empowerment Care (MIREC) pathway, that can significantly reduce hospital stays after laparoscopic gastrectomy without increasing adverse events. Background: Cost-effectiveness and improving patient outcomes are crucial in providing quality gastric cancer care worldwide. Methods: To compare the outcomes of gastric cancer surgery using 2 different models of care within an integrated healthcare system from February 2012 to March 2023. The primary endpoint was the length of hospital stay. The secondary endpoints were the need for intensive care unit care, emergency room (ER) visits, readmission, reoperation, and death within 30 days after surgery. Results: There were 553 patients, 167 in the pre-(February 2012-April 2016) and 386 in the post-MIREC period (May 2016-March 2023). Perioperative chemotherapy utilization increased from 31.7% to 76.4% (P < 0.0001). Laparoscopic gastrectomy increased from 17.4% to 97.7% (P < 0.0001). Length of hospitalization decreased from 7 to 2 days (P < 0.0001), with 32.1% and 88% of patients discharged home on postoperative day 1 and postoperative day 2, respectively. When comparing pre- and post-MIREC, intensive care unit utilization (10.8% vs. 2.9%, P < 0.0001), ER visits (34.7% vs. 19.7%, P = 0.0002), and readmission (18.6% vs. 11.1%, P = 0.019) at 30 days were also considerably lower. In addition, more patients received postoperative adjuvant chemotherapy (31.4% to 63.5%, P < 0.0001), and the time between gastrectomy and starting adjuvant chemotherapy was also less (49-41 days; P = 0.002). Conclusion: This comprehensive regional program, which encompasses regionalization care, laparoscopic approach, modern oncologic care, surgical subspecialization, and the MIREC pathway, can potentially improve gastric cancer surgery outcomes. These benefits include reduced hospital stays and lower complication rates. As such, this program can revolutionize how gastric cancer surgery is delivered, leading to a higher quality of care and increased value to patients.

Same-Day Home Recovery for Benign Foregut Surgery.

Importance: Same-day home recovery (SHR) is now the standard of care for many major surgical procedures and has the potential to become standard practice for benign foregut procedures (eg, hiatal hernia repair, fundoplication, and Heller myotomy). Objective: To determine whether SHR for patients undergoing benign foregut surgery is feasible, safe, and effective. Design, Setting, and Participants: This prospective cohort study took place across 19 medical centers within an integrated health care system in northern California from January 2019 through September 2021. Participants included consecutive patients undergoing elective benign foregut surgery. Exposures: Standardized SHR program. Main Outcomes and Measures: The primary end point was the rate of SHR. The secondary end points were 7-day and 30-day rates of postoperative emergency department visits, hospital readmissions, and reoperations. Results: Of 1248 patients who underwent benign foregut surgery from January 2017 through September 2021, 558 were patients before implementation of the SHR program and 690 were patients postimplementation. The mean age of patients was 60 years, and 759 (59%) were female. The preimplementation SHR rate was 64 of 558 patients (11.5%) in 2018 and increased to 82 of 113 patients (72.6%) by 2021 (94/350 [26.9%] in 2019 and 112/227 [49.3%] in 2020; P < .001). There were no statistical differences in the 7-day and 30-day rates of postoperative emergency visits, hospital readmissions, and reoperations or 30-day mortality in the SHR vs non-SHR groups in the postimplementation era. Conclusions and Relevance: In this study, implementation of a regional SHR program among patients undergoing elective benign foregut surgery was feasible, safe, and effective. The changes in perioperative care require comprehensive patient education and full multidisciplinary support. An SHR program for benign foregut procedures has the potential to improve patient care and cost-effectiveness in care delivery.

Clinical Outcomes Following Regionalization of Gastric Cancer Care in a US Integrated Health Care System.

PURPOSE: In 2016, Kaiser Permanente Northern California regionalized gastric cancer care, introducing a regional comprehensive multidisciplinary care team, standardizing staging and chemotherapy, and implementing laparoscopic gastrectomy and D2 lymphadenectomy for patients eligible for curative-intent surgery. This study evaluated the effect of regionalization on outcomes. METHODS: The retrospective cohort study included gastric cancer cases diagnosed from January 2010 to May 2018. Information was obtained from the electronic medical record, cancer registry, state vital statistics, and chart review. Overall survival was compared in patients with all stages of disease, stage I-III disease, and curative-intent gastrectomy patients using annual inception cohorts. For the latter, the surgical approach and surgical outcomes were also compared. RESULTS: Among 1,429 eligible patients with gastric cancer with all stages of disease, one third were treated after regionalization, 650 had stage I-III disease, and 394 underwent curative-intent surgery. Among surgical patients, neoadjuvant chemotherapy utilization increased from 35% to 66% (P < .0001), laparoscopic gastrectomy increased from 18% to 92% (P < .0001), and D2 lymphadenectomy increased from 2% to 80% (P < .0001). Dissection of ≥ 15 lymph nodes increased from 61% to 95% (P < .0001). Surgical complication rates did not appear to increase after regionalization. Length of hospitalization decreased from 7 to 3 days (P < .001). Overall survival at 2 years was as follows: all stages, 32.8% pre and 37.3% post (P = .20); stage I-III cases with or without surgery, 55.6% and 61.1%, respectively (P = .25); and among surgery patients, 72.7% and 85.5%, respectively (P < .03). CONCLUSION: Regionalization of gastric cancer care within an integrated system allowed comprehensive multidisciplinary care, conversion to laparoscopic gastrectomy and D2 lymphadenectomy, increased overall survival among surgery patients, and no increase in surgical complications.

Primary intestinal lymphoma in patients with inflammatory bowel disease: a descriptive series from the prebiologic therapy era.

BACKGROUND: Primary intestinal lymphoma in the setting of inflammatory bowel disease (IBD) is uncommon and may be associated with immune suppressive therapy. We report clinical features and outcomes in patients with both conditions prior to use of biologic therapy. METHODS: All patients with primary intestinal lymphoma and IBD at our institution from 1960-2000 were retrospectively identified. Data reported are frequency (proportion) or median (interquartile range). Kaplan-Meier analysis was performed. RESULTS: Fifteen patients were identified: 14 (93%) were male, 10 (66%) had Crohn's disease. Median age at diagnosis of IBD and lymphoma was 30 (22-51) and 47 (28-68) years, respectively, with bloody diarrhea the most common presenting symptom for each diagnosis. Lymphoma location was colorectal in nine (60%), small bowel in four (27%), and one (6.25%) each: stomach, duodenum, and ileal pouch. Treatments were surgery plus chemotherapy (n = 6), surgery alone (n = 3), chemotherapy alone (n = 2), chemotherapy and radiation (n = 1), surgery and radiation (n = 1); two patients died before treatment. Most patients (n = 11, 73%) were Ann Arbor stages I or II. Large cell B-type histology was most common (n = 9, 60%). Three patients died within 30 days of lymphoma diagnosis. Survival free of death from lymphoma at 1- and 5-years was 78% and 63%, respectively, and was associated with advanced lymphoma stage (P = 0.004). CONCLUSIONS: Diagnosis and treatment of primary intestinal lymphoma in patients with IBD can be challenging and requires a high index of suspicion. Optimal survival requires multimodality therapy.

Laparoscopic central pancreatic resection.

BACKGROUND/AIMS: The reported experience on laparoscopic central pancreatic resection is limited. This paper describes the technical aspects of a total laparoscopic central pancreatic resection. METHODOLOGY: This paper focuses on patient positioning, trocar set up, technical aspect of laparoscopic lesser sac exposure, peripancreatic dissection, proximal pancreatic transection and a Roux-en-Y end to side pancreaticojejunostomy using all intracorporeal technique. CONCLUSIONS: Advanced laparoscopic technique has allowed complex major pancreatic resection including central pancreatic resection to be performed safely. In selected patients, laparoscopic central pancreatic resection can be considered the operation of choice for a non malignant pancreatic neck lesion.

Patient and hospital characteristics on the variance of perioperative outcomes for pancreatic resection in the United States: a plea for outcome-based and not volume-based referral guidelines.

HYPOTHESIS: There is an effect of patient and hospital characteristics on perioperative outcomes for pancreatic resection in the United States. DESIGN: Retrospective cohort study. SETTING: Academic research. PATIENTS: Patient data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project from January 1988 to January 2003. MAIN OUTCOME MEASURES: In-hospital mortality, perioperative complications, and mortality following a major complication. RESULTS: A total of 103 222 patients underwent major pancreatic surgery. The annual number of pancreatic resections increased 15.0% during the 16-year study period. Resection for benign pancreatic disease increased 26.8%. Overall in-hospital mortality, perioperative complications, and mortality following a major complication were 6.5%, 35.6%, and 15.6%, respectively. Multivariate analysis demonstrated that significant independent predictors for these 3 perioperative outcomes were advancing age, male sex, medical comorbidity, and hospital volume for each type of pancreatic resection. The in-hospital mortality for pancreatoduodenectomy increases with age and ranges from 1.7% to 13.8% (P < .001). After adjusting for other confounders, the odds of in-hospital mortality for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy in those 65 years or older were 4.78-fold, 3.84-fold, and 2.60-fold, respectively, lower in the high-volume hospitals compared with those in the lower-volume hospitals. CONCLUSIONS: Perioperative complications derived from this population-based study were higher than those reported in many case series. A significant disparity was noted in perioperative outcomes among surgical centers across the United States. An outcome-based referral guideline may have an immediate effect on improving the quality of care in patients who undergo pancreatic resection for benign and malignant disease.

Minimally invasive repair for pectus excavatum in adults.

BACKGROUND: The purpose of this study is to review the minimally invasive pectus excavatum repair in adults to determine the safety and effectiveness. METHODS: An Institutional Review Board approved chart review identified patients 17 years or older who underwent minimally invasive pectus excavatum repair (MIPER) between January 1999 and January 2004. RESULTS: Nineteen patients underwent MIPER. Indications for surgery were reduced exercise tolerance (13), dyspnea on exertion (17), improve self-perception (10), and chest pain (6). There were no intraoperative complications or conversions to open repair. Twelve patients (63%) required one strut and seven patients (37%) required two struts. Postoperative complications included self-resolving asymptomatic pneumothorax in six patients and pneumonia in one. Pain at six weeks postoperatively was mild to none in most patients and all had no pain at three months postoperatively except one patient with strut displacement. Two patients required removal of one of two struts due to displacement. The mean postoperative pectus index was significantly lower than preoperative value: 2.5 versus 4.6, p = 0.002. Among six patients with strut removal at two years postoperatively, two patients had mild recurrence of their deformity. CONCLUSIONS: Minimally invasive pectus excavatum repair can be performed safely in adults. This approach is technically more challenging in adults with one-third of the patients requiring two struts for optimal repair. The risk of strut displacement is higher than in the pediatric population. The long-term effectiveness and durability of this procedure in adults is still unknown.

Model for End-stage Liver Disease score fails to predict perioperative outcome after hepatic resection for hepatocellular carcinoma in patients without cirrhosis.

BACKGROUND: The Model for End-stage Liver Disease (MELD) score was developed to reflect the hepatocellular reserve in patients with cirrhosis. We hypothesized that the MELD score would not be predictive of perioperative outcome after hepatic resection in patients without cirrhosis. METHODS: We performed a case-control study of all consecutive patients from 1995 through 2005 undergoing hepatic resection for HCC. RESULTS: Group A (21 patients without cirrhosis) had a mean age of 57 years, which was similar to control group B (25 patients with cirrhosis), with a mean age of 60 years. The mean tumor size in group A was 9.8 cm compared with that of group B, which was 4.8 cm (P = .03). The American Joint Committee on Cancer stage in group A was I in 14%, II in 5%, and III in 81% versus I in 48%, II in 16%, and 111 in 36% in group B (P = .002). Eighty-six percent of group A patients had a major hepatic resection (>2 segments) compared with 40% in group B (P = .001). The perioperative morbidity and mortality were 24% and 4.8%, respectively, in group A compared with 64% (P = .006) and 20% (P = .12) in group B. The mean preoperative, postoperative, and delta MELD scores were 7.0, 13.0, and 5.0, respectively, in group A compared with 9.6, 16.8, and 7.2 in group B (P = NS). In group A, none of the MELD score parameters accurately predicted perioperative outcomes despite a higher number of patients who had major hepatic resection. In group B, a preoperative MELD score of 9 or greater was associated with a higher overall perioperative morbidity (84% vs 41%, P = .03). Perioperative mortality (n = 6; 13%) was significantly higher in patients with a postoperative MELD score of 15 or higher (P = .02) and a delta MELD score of 10 or higher (P = .03). CONCLUSIONS: Perioperative MELD score fails to predict perioperative outcomes after hepatic resection for hepatocellular carcinoma in patients without cirrhosis. Other predictive parameters need to be developed for this group of patients.

A suitable animal model for laparoscopic hepatic resection training.

BACKGROUND: There is a growing interest in using laparoscopy for hepatic resection. However, structured training is lacking in part because of the lack of an ideal animal training model. We sought to identify an animal model whose liver anatomy significantly resembled that of the human liver and to assess the feasibility of learning laparoscopic hepatic inflow and outflow dissection and parenchyma transection on this model. METHODS: The inflow and outflow structures of the sheep liver were demonstrated via surgical dissection and contrast studies. Laparoscopic left major hepatic resections were performed. RESULTS: The portal hepatis of all 12 sheep (8 for anatomic study and 4 for laparoscopic hepatic resection) resembled that of human livers. The portal vein (PV) was located posteriorly; the common hepatic artery (CHA) and the common bile duct (CBD) were located anterior medially and anterior laterally with respect to the portal hepatis. The main PV bifurcated into a short right and a long left PV. The extrahepatic right PV then bifurcated into right posterior and anterior sectoral PV. The CBD and CHA bifurcated into left and right systems. The cystic duct originated from the right hepatic duct. The cystic artery originated from the right HA in 11/12 animals. The left hepatic vein drained directly into the inferior vena cava (IVC). The middle and the right hepatic veins formed a short common channel before entering the IVC. Multiple venous tributaries drained directly into IVC. Familiarity with sheep liver anatomy allowed laparoscopic left hepatic lobe (left medial and lateral segments) resection to be performed with accuracy and preservation of the middle hepatic vein. CONCLUSIONS: The surgical anatomy of sheep liver resembled that of human liver. Laparoscopic major hepatic resection can be performed with accuracy using this information. Sheep is therefore an ideal animal model for advanced surgical training in laparoscopic hepatic resection.

Laparoscopic and open distal pancreatic resection for benign pancreatic disease.

The aim of the study is to provide comparisons of the perioperative outcomes between open and laparoscopic distal pancreatic resection (DPR) for benign pancreatic disease. From 2002 and 2005, there were 28 patients (16 open, 12 laparoscopic) with a mean age of 52 who had presumptive diagnoses of benign pancreatic lesions. Pathology was neuroendocrine tumor (nine and five), mucinous cystic neoplasm (three and three), symptomatic pancreatic pseudocyst (two and two), and others (two and two). The mean operative time was 278 vs 212 min (p = 0.05), the estimated blood lost was 609 vs 193 ml (p = 0.01), and the success rate of preoperative intent for splenic preservation was 17 vs 62% (p = 0.08) in the open and laparoscopic groups, respectively. Two patients (16%) were converted to an open procedure. There was no perioperative mortality. The mean hospital stay and total perioperative morbidity were 10.6 vs 6.2 days (p = 0.001) and nine vs two events (p = 0.03) in the open and laparoscopic groups, respectively. Ten of 12 patients (83%) with laparoscopic DPR had adequate oral intake within 72 h post operatively in contrast to 2 of 16 (12.5%) patients in the open DPR group (p = 0.0001). Laparoscopic DPR is technically feasible, safe, and associated with less perioperative morbidity and a shorter hospital stay than open DPR. In centers with the appropriate expertise, laparoscopic DPR should be considered the procedure of choice for putative benign lesions of the pancreatic body and tail.

Inferior vena cava stenting: a safe and effective treatment for intractable ascites in patients with polycystic liver disease.

We performed a retrospective study of seven patients with polycystic liver disease who underwent stenting of the inferior vena cava for intractable ascites. All patients had symptomatic ascites and inferior vena cava stenosis demonstrable by venography. The mean pressure gradient across the inferior vena cava stenosis before stenting was 14.5 mm Hg (range 6-25 mm Hg) and significantly decreased to a mean pressure gradient of 2.8 mm Hg (range 0-6 mm Hg, p = 0.008) after stenting. Two patients also had stenting of hepatic venous stenoses after unsuccessful inferior vena cava stenting. After a mean follow-up of 12.2 months (range 0.5-39.1 months), five of the seven patients have had maintained clinical improvement, defined as decreased symptoms, diuretic requirements, and frequency of paracentesis. Four patients have required no further intervention. The other patient was lost in follow-up. Patients with clinical improvement had an overall larger mean pressure gradient before stenting (19.2 vs. 9.8 mm Hg) and a larger Delta pressure gradient (15.8 vs. 7.8 mm Hg) compared to those in whom stenting was unsuccessful. These results suggest inferior vena cava stenting is safe and effective and should be considered as a first-line intervention in the treatment of medically intractable ascites in select patients with polycystic liver disease.

Aggressive pancreatic resection for primary pancreatic neuroendocrine tumor: is it justifiable?

BACKGROUND: Benign and malignant pancreatic neuroendocrine tumors (PNETs) are rare, and long-term outcome is generally poor without surgical intervention. The aim of the study was to assess whether aggressive pancreatic resection is justifiable for patients with PNET. METHODS: All consecutive patients who had undergone major pancreatic resection from January 1997 through January 2005 were reviewed and analyzed. RESULTS: There were 33 patients (16 male and 17 female) with a mean age of 53 years. Five patients had multiple endocrine neoplasms syndrome, and 1 patient had von Hippel-Lindau syndrome. There were 20 benign (9 functional) and 13 malignant (6 functional) neoplasms. Mean tumor size was 4.2 cm, and multiple tumors were noted in 10 patients. Eight patients (25%) underwent pancreticoduedenectomy, and 25 patients (76%) underwent distal pancreatectomy (extended distal pancreatectomy in 4 and splenectomy in 20 patients). Regional lymph node involvement was present in 10 patients (30%), and 6 patients (18%) had liver metastasis. Four patients (12%) underwent concurrent resection of other organs because of disease extension. Median intraoperative blood loss was 500 mL. Perioperative morbidity was 36%, and mortality was 3%. Symptomatic palliation was complete in 93% (14.15 patients) and partial in 1 patient because of nonresectable hepatic disease. Median hospital stay was 11.5 days. After median follow-up of 36 months, there were no local recurrences. The 1-, 3-, and 5-year overall survival rates for patients with benign versus malignant neoplasms were 100% vs. 92%, 89% vs. 64%, and 89% vs 36% (P = .01), respectively. The 1-, 3-, and 5-year disease progression rates for patients with malignant neoplasms were 13%, 63%, and 100%, respectively (P < .0001). CONCLUSIONS: Aggressive pancreatic resection for PNET can be performed with low perioperative mortality and morbidity. Unlike available nonoperative therapy, this approach offers an excellent means of symptomatic palliation and local disease control. In patients with malignant PNET, metastatic recurrence is not uncommon and will usually require additional multimodality therapy. When possible, an aggressive approach to PNET is justified to optimize palliation and survival.

Diagnosis and management of blunt pancreatic ductal injury in the era of high-resolution computed axial tomography.

BACKGROUND: Blunt pancreatic ductal injury is an uncommon but potentially morbid injury that can be difficult to diagnose and manage. Computed axial tomography (CAT) scan has historically been unreliable for the detection of ductal injury, but the advent of high-resolution CAT should improve diagnostic accuracy. METHODS: From our prospectively maintained trauma registry, consecutive patients who had a diagnosis of blunt pancreatic injury with or without a subsequent laparotomy during the time period from January 1995 through December 2004 were retrospectively reviewed. Pancreatic ductal injury was treated exclusively with distal pancreatic resection (DPR) without adjunctive endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. RESULTS: Of 50 patients with blunt pancreatic injury, 33 patients had both preoperative CAT scan and laparotomy. Although the CAT scan interpretation and operative findings corresponded precisely for all pancreatic injuries in only 55% of cases, CAT scan was 91% sensitive and 91% specific for identifying pancreatic ductal injury. Eleven patients with confirmed pancreatic ductal injury underwent DPR. There were no postoperative pancreas-related deaths and only 1 pancreas-related complication among survivors, a patient with a low-output pancreatic fistula that resolved after 5 weeks. CONCLUSIONS: Blunt pancreatic ductal injury may be accurately diagnosed with preoperative CAT scan, without adjunctive endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography, and is effectively and safely treated with DPR.

Risk factors for mortality after surgery in patients with cirrhosis.

BACKGROUND & AIMS: Current methods of predicting risk of postoperative mortality in patients with cirrhosis are suboptimal. The utility of the Model for End-stage Liver Disease (MELD) in predicting mortality after surgery other than liver transplantation is unknown. The aim of this study was to determine the risk factors for postoperative mortality in patients with cirrhosis. METHODS: Patients with cirrhosis (N = 772) who underwent major digestive (n = 586), orthopedic (n = 107), or cardiovascular (n = 79) surgery were studied. Control groups of patients with cirrhosis included 303 undergoing minor surgical procedures and 562 ambulatory patients. Univariate and multivariable proportional hazards analyses were used to determine the relationship between risk factors and mortality. RESULTS: Patients undergoing major surgery were at increased risk for mortality up to 90 days postoperatively. By multivariable analysis, only MELD score, American Society of Anesthesiologists class, and age predicted mortality at 30 and 90 days, 1 year, and long-term, independently of type or year of surgery. Emergency surgery was the only independent predictor of duration of hospitalization postoperatively. Thirty-day mortality ranged from 5.7% (MELD score, <8) to more than 50% (MELD score, >20). The relationship between MELD score and mortality persisted throughout the 20-year postoperative period. CONCLUSIONS: MELD score, age, and American Society of Anesthesiologists class can quantify the risk of mortality postoperatively in patients with cirrhosis, independently of the procedure performed. These factors can be used in determining operative mortality risk and whether elective surgical procedures can be delayed until after liver transplantation.

Pancreatic pseudocyst in children: the impact of management strategies on outcome.

INTRODUCTION: Persistent pancreatic pseudocysts (PPs) are rare in childhood and management tends to be individualized. The purpose of this review is to determine the impact of different management strategies and to analyze their effects on patient outcomes. METHODS: An institutional review board-approved retrospective chart review was performed on children younger than 18 years who had PP diagnosed between January 1976 and December 2003. RESULTS: There were 24 patients, 13 male and 11 female, with a mean age 10.7 years (range, 2-17 years). The mean PP size was 5.8 cm (range, 1.7-20 cm). Posttraumatic pseudocysts were identified in 11 children. The etiologies of 13 nontraumatic PP were idiopathic (6), familial pancreatitis (4), drug-induced (1), cholelithiasis (1), and bifid duct (1). All patients were symptomatic at diagnosis. Resolution of pseudocysts without operative intervention occurred in 7 (29%) of 24 patients. The mean time to operation for the remaining 17 children (71%) was 13.1 weeks (range, 6-36 weeks), with indications for intervention including persistent/recurrent abdominal pain (17), failure to thrive (9), infected PP (1), and ruptured PP (1). Surgical therapies for 13 of 17 patients consisted of cystogastrostomy (8), cystojejunostomy (2), longitudinal pancreaticojejunostomy (2), and Frey's procedure (1). Four patients underwent pancreatic sphincterotomy and stenting, 2 of whom also had image-guided pseudocyst drainage. The intervention-related mortality and morbidity rates were 0% and 11%, respectively, for children undergoing surgical therapies. The morbidities included pancreatic leak (1) and wound infection (1). Etiology of the PP had a significant influence on the need for intervention (traumatic, 45%; nontraumatic, 92%; P = .02); however, patient age, size, and location of the PP had no significant effect. All 24 patients continued to do well at mean follow-up of 73.3 months (range, 6 weeks-25 years). One patient with idiopathic pancreatitis has since developed insulin-dependent diabetes. All 4 patients with familial pancreatitis had their chronic pain improved without long-term narcotic therapy. CONCLUSION: The treatment of PPs in children is dependent on etiology, where pseudocysts from nontraumatic etiologies are more likely to require and benefit from surgical interventions, whereas pseudocysts from traumatic etiology are more amenable to conservative management. For children with persistent symptoms or interval complication, surgical therapy is safe and effective.

Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: Model of End-Stage Liver Disease (MELD) score predicts perioperative mortality.

Hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis is generally recommended for patients with Child-Turcotte-Pugh (CTP) Class A liver disease and early tumor stage. The Model for End-Stage Liver Disease (MELD) has been shown to accurately predict survival in patients with cirrhosis, but whether MELD is useful for selection of patients with cirrhosis for hepatic resection is unknown. We examined whether MELD was predictive of perioperative mortality and correlated MELD with other potential clinicopathologic factors to overall survival in patients with cirrhosis undergoing hepatic resection for HCC. A retrospective chart review was undertaken of patients with HCC and cirrhosis undergoing hepatic resection between 1993 and 2003. Eighty-two patients (62 men, 20 women; mean age, 62 years) were identified. Forty-five patients had MELD score > or =9 (range, 9-15) and CTP score ranged from 5 to 9 points. Fifty-nine patients underwent minor (<3 segments) hepatic resections (MELD < or =8, n = 29; MELD > or =9, n = 30) and 23 underwent major (> or =3 segments) hepatic resections (MELD < or =8, n = 8; MELD > or =9, n = 15). Perioperative mortality rate was 16%. MELD score < or =8 was associated with no perioperative mortality versus 29% for patients with an MELD score > or =9 (P < 0.01). Multivariate analysis demonstrated that MELD score > or =9 (P < 0.01), clinical tumor symptoms (P < 0.01), and ASA score (P = 0.046) are independent predictors of perioperative mortality. Multivariate analysis showed MELD > or =9 (P < 0.01), tumor size >5 cm (P < 0.01), high tumor grade (P = 0.03), and absence of tumor capsule (P < 0.01) as independent predictors of decreased long-term survival. MELD score was a strong predictor of both perioperative mortality and long-term survival in patients with cirrhosis undergoing hepatic resection for HCC. In patients with cirrhosis, hepatic resection (minor or major) for HCC is recommended if the MELD score is < or =8. In patients with MELD score > or =9, other treatment modalities should be considered.

COX inhibitors modulate bFGF-induced cell survival in MCF-7 breast cancer cells.

Basic fibroblast growth factor (bFGF) serves as a modulator of survival in breast cancer cells. The mechanisms by which bFGF transduces the anti-apoptotic signal and interacts with COX inhibitors were investigated. bFGF reduced apoptosis in MCF-7 breast cancer cells and up-regulated the expression of mitocondrial Bcl-2, whereas COX inhibitors meloxicam (selective COX-2) and aspirin (non-selective), induced apoptosis. bFGF up-regulated survivin protein expression and induced cdc-2 phosphorylation moderately at early (2-6 h), and substantially at late (24 h), time-points. Survivin mRNA expression was up-regulated only at the later time-point. COX inhibitors prevented up-regulation of survivin protein expression at both 2 and 24 h and prevented early modest increases in cdc-2 phosphorylation. Up-regulation of survivin mRNA was not found to be modulated by the COX-2 inhibitor meloxicam. bFGF regulation of survivin expression was found to be ERK1/2 kinase dependent and bFGF-induced phosphorylation of c-raf was prevented by the COX-2 inhibitor. bFGF was, however, unable to induce COX-2 protein expression or modulate COX-2 activity in MCF-7 cells as evidenced by unaltered PGE(2) production. These results indicate that bFGF regulates survivin expression in MCF-7 breast cancer cells by signaling through an ERK1/2 dependent pathway. COX-2 inhibitors can modulate bFGF-induced survivin expression in a COX-2 independent manner.

Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.

BACKGROUND: Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated. MATERIALS AND METHODS: Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody. RESULTS: Plasma endostatin levels, in breast cancer patients, were significantly elevated (P = 0.015) in the post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76 etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival. CONCLUSIONS: Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.