Does preoperative cross-sectional imaging accurately predict main duct involvement in intraductal papillary mucinous neoplasm?

Main pancreatic duct (MPD) involvement is a well-demonstrated risk factor for malignancy in intraductal papillary mucinous neoplasm (IPMN). Preoperative radiographic determination of IPMN type is heavily relied upon in oncologic risk stratification. We hypothesized that radiographic assessment of MPD involvement in IPMN is an accurate predictor of pathological MPD involvement. Data regarding all patients undergoing resection for IPMN at a single academic institution between 1992 and 2012 were gathered prospectively. Retrospective analysis of imaging and pathologic data was undertaken. Preoperative classification of IPMN type was based on cross-sectional imaging (MRI/magnetic resonance cholangiopancreatography (MRCP) and/or CT). Three hundred sixty-two patients underwent resection for IPMN. Of these, 334 had complete data for analysis. Of 164 suspected branch duct (BD) IPMN, 34 (20.7%) demonstrated MPD involvement on final pathology. Of 170 patients with suspicion of MPD involvement, 50 (29.4%) demonstrated no MPD involvement. Of 34 patients with suspected BD-IPMN who were found to have MPD involvement on pathology, 10 (29.4%) had invasive carcinoma. Alternatively, 2/50 (4%) of the patients with suspected MPD involvement who ultimately had isolated BD-IPMN demonstrated invasive carcinoma. Preoperative radiographic IPMN type did not correlate with final pathology in 25% of the patients. In addition, risk of invasive carcinoma correlates with pathologic presence of MPD involvement.

Pancreatic enucleation: improved outcomes compared to resection.

INTRODUCTION: Pancreatic enucleation is associated with a low operative mortality and preserved pancreatic parenchyma. However, enucleation is an uncommon operation, and good comparative data with resection are lacking. Therefore, the aim of this analysis was to compare the outcomes of pancreatic enucleation and resection. MATERIAL AND METHODS: From 1998 through 2010, 45 consecutive patients with small (mean, 2.3 cm) pancreatic lesions underwent enucleation. These patients were matched with 90 patients undergoing pancreatoduodenectomy (n = 38) or distal pancreatectomy (n = 52). Serious morbidity was defined in accordance with the American College of Surgeons-National Surgical Quality Improvement Program. Outcomes were compared with standard statistical analyses. RESULTS: Operative time was shorter (183 vs. 271 min, p < 0.01), and operative blood loss was significantly lower (160 vs. 691 ml, p < 0.01) with enucleation. Fewer patients undergoing enucleation required monitoring in an intensive care unit (20% vs. 41%, p < 0.02). Serious morbidity was less common among patients who underwent enucleation compared to those who had a resection (13% vs. 29%, p = 0.05). Pancreatic endocrine (4% vs. 17%, p = 0.05) and exocrine (2% vs. 17%, p < 0.05) insufficiency were less common with enucleation. Ten-year survival was no different between enucleation and resection. CONCLUSION: Compared to resection, pancreatic enucleation is associated with improved operative as well as short- and long-term postoperative outcomes. For small benign and premalignant pancreatic lesions, enucleation should be considered the procedure of choice when technically appropriate.

Very high serum CA 19-9 levels: a contraindication to pancreaticoduodenectomy?

AIM: To assess the outcome of patients with resectable pancreatic adenocarcinoma (PA) associated with high serum CA 19-9 levels. METHODS: From 2000 to 2007, 344 patients underwent pancreatoduodenectomy for PA. Fifty-three patients (elevated group) had preoperatively elevated serum CA 19-9 levels (>400 IU/ml) after resolution of obstructive jaundice. Of these, 27 patients had high levels (400-899 IU/ml (HL)) and 26 patients had very high levels >or=900 IU/ml (VHL). Fifty patients with normal preoperative serum CA 19-9 levels (<37 IU/ml) comprised the control group. RESULTS: Median survival of the control group (n = 50) versus elevated group (n = 53) was 22 versus 15 months (p = 0.02) and overall 3-year survival was 32% versus 14% (p = 0.03). There was no statistical difference in the median and 3-year overall survival between patients with HL and VHL. Patients in the elevated group who normalized their CA 19-9 levels after surgery (n = 11) had a survival equivalent to patients in the control group. CONCLUSIONS: Patients who normalized their CA19-9 levels postoperatively had equivalent survival to patients with normal preoperative CA 19-9 levels. Preoperative serum CA 19-9 level by itself should not preclude surgery in patients who have undergone careful preoperative staging.

Surgical therapy of iatrogenic lesions of biliary tract.

Iatrogenic injuries of the biliary tract have increased in incidence over the past decade with the introduction of laparoscopic cholecystectomy. Although a number of factors have been identified with a higher risk of injury (male gender, complicated gallstone disease, aberrant anatomy) and a number of technical steps have been emphasized to avoid these injuries, the incidence of bile duct injuries has reached a steady-state at least double the rate observed with open cholecystectomy. Most patients sustaining a bile duct injury are recognized in the weeks following laparoscopic cholecystectomy. Careful preoperative preparation should include control of sepsis by draining any bile collections or fistulas and complete cholangiography. Long-term results are best achieved in specialized hepatobiliary centers performing biliary reconstruction with a Roux-en-Y hepaticojejunostomy. Success rates over 90% have been reported from several centers to date with intermediate follow-up.

Hepatocellular carcinoma: multimodality management.

BACKGROUND: Hepatocellular carcinoma is one of the most common tumors worldwide. Surgical resection has been the standard treatment but can only be applied to a small percentage of patients. In recent years, several other treatment options, including ablative procedures and transplantation, have been used in patients with hepatocellular carcinoma. METHODS: For 6 years, 110 patients with hepatocellular carcinoma were managed at the Medical College of Wisconsin. Fifty-five patients received only chemotherapy (n = 5) or palliative treatment (n = 50) because of advanced cirrhosis (P <.03) or tumor. Thirty-one patients had tumor ablation with percutaneous ethanol injection, cryoablation, radiofrequency ablation, or arterial chemoembolization. Twenty-eight patients underwent surgical resection (n = 18) or hepatic transplantation (n = 10). Relatively more patients (38%; P <.001) were treated with ablation in the second period of the study (1998-2000). RESULTS: Thirty-day mortality was 3% with ablation and 0% with resection. Median survival was 6 months with no treatment, 27 months with ablation (P <.001), and 35 months with resection (P <.001). Patients who underwent liver transplantation had the longest median survival (53 months). A multivariate analysis suggested that treatment modality (ablation or resection; P <.001) and Child-Pugh classification (P <.01) were the most important factors predicting outcome. CONCLUSIONS: This study suggests that treatment of hepatocellular carcinoma requires multidisciplinary expertise and that ablation and operation can be performed safely. Outcome is influenced most by treatment modality and Child-Pugh classification. Patients in Child-Pugh classes A and B should be treated with ablation, surgical resection, or liver transplantation.

Iron deficiency transiently suppresses biliary neuronal nitric oxide synthase.

BACKGROUND: Iron deficiency results in altered gallbladder and sphincter of Oddi (SO) motility and cholesterol crystal formation. In addition, gallbladder neuronal nitric oxide synthase (nNOS) has been shown to be markedly reduced after 8 weeks on an iron-deficient diet. However, the effects of prolonged iron deficiency on gallbladder and SO nNOS as well as crystal formation have not been determined. Therefore, we tested the hypothesis that iron deficiency would downregulate both gallbladder and SO nNOS expression and that nNOS downregulation and cholesterol crystal formation would progress over time. MATERIALS AND METHODS: Thirty-eight adult female prairie dogs were fed either an ironsupplemented (Fe+) (200 ppm) or an iron-deficient (Fe-) (8 ppm) diet for 8 weeks (Fe+ n = 9, Fe- n = 10) or 16 weeks (Fe+ n = 9, Fe- n = 10). Blood hemoglobin (HbG) was measured; gallbladder cholesterol crystals were counted; and cholesterol saturation indices (CSI) were calculated. Gallbladder and SO nNOS levels were measured by Western blot. RESULTS: The Fe+ prairie dogs had significantly higher HbG than the Fe- animals (16.9 +/- 0.6 g/dl vs 15.2 +/- 0.5 g/dl, respectively, P < 0.05) after 8 weeks. This difference was even greater after 16 weeks (16.1 +/- 0.4 g/dl vs 14.0 +/- 0.5 g/dl, P < 0.01). At 8 weeks, more cholesterol crystals per 10 HPF were observed in the Fe- animals (0.4 +/- 0.3 vs 1.6 +/- 0.4 per 10 HPF, P < 0.05). This difference was even greater after 16 weeks (0.0 +/- 0.0 vs 52.6 +/- 25.3 per 10 HPF, P < 0.01). No difference in the CSI was observed in the four groups. Iron deficiency decreased the nNOS/beta-actin protein levels in the gallbladder and SO at 8 weeks (57.0 +/- 29.6 vs 7.4 +/- 2.6, gallbladder, P < 0.05) (98.4 +/- 39.7 vs 29.9 +/- 11.0, SO, P = 0.09), but these levels returned to baseline at 16 weeks. CONCLUSIONS: We conclude that iron deficiency acutely suppresses gallbladder and SO nNOS, and that compensatory mechanisms return nNOS to baseline levels while cholesterol crystal formation increases over time.

Ablation of liver metastasis: is preoperative imaging sufficiently accurate?

The recent introduction of cryotherapy and radiofrequency ablation of liver metastasis has expanded the indications for treatment. As technology has advanced, a percutaneous approach has been developed. Percutaneous treatment, however, requires accurate preoperative imaging. From 1993 to 1999, 179 patients underwent operative exploration for treatment of suspected hepatic metastases from colorectal carcinoma. One hundred seventy-seven patients were staged by preoperative CT, two patients were staged by MRI, and complete data were available in 176. Hepatic tumor count by preoperative imaging was compared to intraoperative tumor count obtained by inspection, palpation, ultrasonographic examination using a 3.5/7.5 MHz T probe, and careful gross sectioning of the resected specimen. Post hoc analysis was performed on 35 CT scans by two radiologists who specialize in abdominal CT. These radiologists were blinded to the intraoperative findings. Their interpretations were compared to the intraoperative counts and to each other. Thirty-four (19%) of 179 patients were deemed untreatable at operation because of unsuspected overwhelming liver involvement in 11 (6%) or extrahepatic metastases in 23 (13%). For the group, CT was accurate in 80 patients (45%), showed more lesions than were found in 16 (9%), and showed fewer metastases than were found in 80 (45%). When the preoperative scan predicted a solitary metastasis, it was correct in 45 (65%) of 69 patients and underestimated disease in 24 (35%). In the post hoc analysis, the mean numbers of lesions reported by the two radiologists did not differ from the mean number of tumors found; however, the radiologists' counts agreed on 16 (59%) and disagreed on 11 (41%) of the scans. The accuracy of CT decreased with increasing numbers of lesions. Regardless of the type of preoperative imaging, intraoperative findings altered the course of the operation in 96 (55%) of 176 patients. Preoperative imaging is not sufficiently accurate to permit adequate percutaneous treatment of hepatic metastases from colorectal carcinoma.

Cholangiocarcinoma.

Despite overall advances in the ability to diagnose and treat patients with cholangiocarcinoma, the prognosis for patients with this malignancy remains poor. Further improvements in the survival of patients with cholangiocarcinoma will come with the early diagnosis of these lesions. New molecular techniques should improve the ability to screen high-risk patients, such as those with primary sclerosing cholangitis, hepatolithiasis, choledochal cysts, and ulcerative colitis. Improvements in imaging will continue, and spiral CT scanning, duplex ultrasonography, MR imaging and, perhaps, PET scans will improve the ability to stage patients with cholangiocarcinoma noninvasively. Complete surgical resection remains the only curative treatment for malignancies of the biliary tract. Aggressive surgical approaches are likely to continue, and the challenge remains in being able to perform these procedures safely in jaundiced and sometimes septic patients. For patients with unresectable lesions, the optimal form of palliation, whether surgical or nonsurgical, remains to be defined. Finally, multicenter, prospective, randomized trials of chemoradiation need to be performed to delineate an effective adjuvant therapy more precisely, and to improve the overall prognosis of patients with cholangiocarcinoma.

Iron deficiency suppresses ileal nitric oxide synthase activity.

Intestinal motility disorders are more common in women of childbearing age who are prone to iron deficiency anemia. The neurotransmitters nitric oxide (NO) and acetylcholine (ACh) play a key role in ileal smooth muscle relaxation and contraction, respectively. Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore we tested the hypothesis that iron deficiency would downregulate ileal NOS activity without affecting the ileum's response to ACh. Twelve adult female prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) (n = 6) or an iron-deficient (Fe-) (8 ppm) (n = 6) diet for 8 weeks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC inhibitory responses are expressed as a percentage of optimal relaxation from EDTA. The excitatory response to ACh was similar in both groups (1.1 +/- 0.3 N/cm(2) vs. 1.5 +/- 0.3 N/cm(2), P = 0.45). The inhibitory response to electrical field stimulation under NANC conditions was greater in the Fe+ group (34.7 +/- 2.9%) compared to the Fe- group (23.9 +/- 3.2%; P<0.01). L-NNA eliminated the inhibitory response in the Fe+ group (0.02 +/- 0.02%) but not in the Fe- group (8.38 +/- 2.15%; P <0.01). VIP(10-28) led to greater relaxation in the Fe+ animals (45.8 +/- 6.6%) than in the Fe- animals (23.4 +/- 5.8%; P <0.05). Both L-NNA and VIP(10-28) had no inhibitory response (0.02 +/- 0.02%) in the Fe+ animals, whereas the Fe- animals had some residual inhibition (2.54 +/- 1.04%; P <0.05). These data suggest that ileal NANC relaxation is due to NOS and that iron deficiency results in (1) decreased NANC relaxation, (2) a compensatory relaxation due to a non-NOS, non-VIP mechanism, and (3) a normal excitatory response. We conclude that iron deficiency suppresses ileal NOS activity.

Quality of life and long-term survival after surgery for chronic pancreatitis.

The objective of this study was to evaluate the short-term and long-term outcome as well as quality of life in patients undergoing surgical management of chronic pancreatitis. Between January 1980 and December 1996, a total of 255 patients underwent surgery for chronic pancreatitis at The Johns Hopkins Hospital. The etiology of the disease, indications for surgery, patient characteristics, and long-term survival were analyzed. A visual analog quality-of-life questionnaire containing 23 items graded on a scale of 0 to 10 (0 = worst and 10 = best) was sent to patients postoperatively. Visual analog responses relating to before and after the chronic pancreatitis surgery were compared using a paired t test. During the17-year review period, 263 operations were performed for chronic pancreatitis in 255 patients. The most common presenting symptoms were abdominal pain (88%), weight loss (36%), nausea/vomiting (30%), jaundice (14%), and diarrhea (12%). The cause of the pancreatitis was resumed to be alcohol in 43%, idiopathic in 38%, pancreas divisum in 5%, ampullary abnormality in 4%, and gallstones in 3%. Pancreaticoduodenectomy was the most common procedure in 96 patients (37%), followed by distal pancreatectomy in 67 (25%), Puestow procedure in 52 (19%), sphincteroplasty in 37 (14%), and Duval procedure in five (2%). The overall mortality and morbidity rates were 1.9% and 35%, respectively. Two hundred twenty-seven (89%) of the 255 patients were alive at last follow-up. For the entire cohort of patients, the 5- and 10-year actuarial survivals were 88% and 82%, respectively. One hundred six (47%) of the 227 living patients responded to the visual analog quality-of-life questionnaire. Patients reported improvements in all aspects of the quality-of-life survey including enjoyment out of life, satisfaction with life, pain, number of hospitalizations, feelings of usefulness, and overall health (P < 0.005). In addition to improved quality of life after surgery, narcotic use was decreased (41% vs. 21%, P < 0.01) and alcohol use was decreased (59% vs. 33%, P < 0.001). However, patients often became insulin-dependent diabetics (12% vs. 41%, P < 0.0001) and required pancreatic enzyme supplementation (34% vs. 55%, P < 0.01) after surgical intervention. These data suggest that surgery for patients with chronic pancreatitis can be performed safely with minimal morbidity and excellent long-term survival. Moreover, this study evaluates quality of life in a standardized analog fashion, with highly significant improvement reported in all quality-of-life measures. We conclude that surgery remains an excellent option for patients with chronic pancreatitis.

p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer.

BACKGROUND: Cell cycle arrest after DNA damage is partly mediated through the transcriptional activation of p21(WAF1) by the p53 tumor suppressor gene. p21(WAF1) and p53 are both critical in maintaining cell cycle control in response to DNA damage from radiation or chemotherapy. Therefore, we examined the role of p21(WAF1) and p53 in the determination of outcome for patients who receive radiation and/or chemotherapy for pancreatic cancer. METHODS: p21(WAF1) and p53 protein expression were determined (with the use of immunohistochemistry) in specimens from 90 patients with pancreatic cancer. Forty-four patients underwent surgical resection, and 46 patients had either locally unresectable tumors (n = 9 patients) or distant metastases (n = 37 patients). Seventy-three percent of the patients who underwent resection and 63% of the patients who did not undergo resection received radiation and/or chemotherapy. RESULTS: p21(WAF1) expression was present in 48 of 86 tumors (56%) and was significantly (P<.05) associated with advanced tumor stage. Median survival among patients with resected pancreatic cancer who received adjuvant chemoradiation with p21(WAF1)-positive tumors was significantly longer than in patients with no p21(WAF1) staining (25 vs. 11 months; P = .01). Fifty of 89 tumors (56%) stained positive for p53 protein. p53 overexpression was associated with decreased survival in patients who did not undergo resection. CONCLUSIONS: Normal p21(WAF1) expression may be necessary for a beneficial response to current adjuvant chemoradiation protocols for pancreatic cancer. Alternate strategies for adjuvant therapy should be explored for patients with pancreatic cancer who lack functional p21(WAF1).

Postoperative bile duct strictures: management and outcome in the 1990s.

OBJECTIVE: To describe the management and outcome after surgical reconstruction of 156 patients with postoperative bile duct strictures managed in the 1990s. SUMMARY BACKGROUND DATA: The management of postoperative bile duct strictures and major bile duct injuries remains a challenge for even the most skilled biliary tract surgeon. The 1990s saw a dramatic increase in the incidence of bile duct strictures and injuries from the introduction and widespread use of laparoscopic cholecystectomy. Although the management of these injuries and short-term outcome have been reported, long-term follow-up is limited. METHODS: Data were collected prospectively on 156 patients treated at the Johns Hopkins Hospital with major bile duct injuries or postoperative bile duct strictures between January 1990 and December 1999. With the exception of bile duct injuries discovered and repaired during surgery, all patients underwent preoperative percutaneous transhepatic cholangiography and placement of transhepatic biliary catheters before surgical repair. Follow-up was conducted by medical record review or telephone interview during January 2000. RESULTS: Of the 156 patients undergoing surgical reconstruction, 142 had completed treatment with a mean follow-up of 57.5 months. Two patients died of reasons unrelated to biliary tract disease before the completion of treatment. Twelve patients (7.9%) had not completed treatment and still had biliary stents in place at the time of this report. Of patients who had completed treatment, 90. 8% were considered to have a successful outcome without the need for follow-up invasive, diagnos tic, or therapeutic interventional procedures. Patients with reconstruction after injury or stricture after laparoscopic cholecystectomy had a better overall outcome than patients whose postoperative stricture developed after other types of surgery. Presenting symptoms, number of stents, interval to referral, prior repair, and length of postoperative stenting were not significant predictors of outcome. Overall, a successful outcome, without the need for biliary stents, was obtained in 98% of patients, including those requiring a secondary procedure for recurrent stricture. CONCLUSIONS: Major bile duct injuries and postoperative bile duct strictures remain a considerable surgical challenge. Management with preoperative cholangiography to delineate the anatomy and placement of percutaneous biliary catheters, followed by surgical reconstruction with a Roux-en-Y hepaticojejunostomy, is associated with a successful outcome in up to 98% of patients.

Iron deficiency diminishes gallbladder neuronal nitric oxide synthase.

BACKGROUND: Iron deficiency has been demonstrated in the prairie dog to result in cholesterol crystal formation and altered biliary motility. Gallbladder filling and emptying are influenced by both inhibitory and excitatory stimuli, with nitric oxide (NO) playing a key role in normal relaxation. Iron is a cofactor for nitric oxide synthase. Therefore, we tested the hypothesis that iron deficiency would result in diminished levels of gallbladder neuronal nitric oxide synthase (nNOS) but would not influence the gallbladder's response to excitatory stimuli. MATERIALS AND METHODS: Twenty adult female prairie dogs were fed either an iron-supplemented (Fe(+)) (200 ppm) control diet (n = 10) or an iron-deficient (Fe-) (8 ppm) diet (n = 10) for 8 weeks. Fasting gallbladder volume was measured. Gallbladder muscle strips were harvested for response to excitatory stimuli and measurement of nNOS protein levels by Western blotting. Muscle strip response to a spectrum of doses of cholecystokinin, acetylcholine, and electrical field stimuli was determined, and the areas under the response curves were calculated. RESULTS: Gallbladder volume increased in the iron-deficient prairie dogs compared with the iron-supplemented group (1.45 +/- 0.27 mL vs 0.80 +/- 0.13 mL, P < 0.05). Iron deficiency diminished the ratio of gallbladder nNOS to beta-actin protein levels (0.05 +/- 0.01 vs 3.48 +/- 1.02, P < 0.05) but resulted in a normal response to excitatory stimuli. CONCLUSIONS: We conclude that diminished gallbladder neuronal nitric oxide synthase contributes to the gallbladder stasis that occurs with iron deficiency. This phenomenon may contribute to the increased incidence of gallstones in premenopausal women.

Do preoperative biliary stents increase postpancreaticoduodenectomy complications?

It has been suggested that the placement of endoscopic or percutaneous biliary stents prior to pancreaticoduodenectomy increases postoperative morbidity. A retrospective review of a prospectively collected database was performed. Patients undergoing preoperative biliary stenting were compared with patients who did not undergo stenting. In addition, outcomes after endoscopic and percutaneous stenting were compared. Patients who had undergone operative biliary bypass prior to pancreaticoduodenectomy were excluded from the analysis. Between January 1994 and December 1997, 567 patients underwent pancreaticoduodenectomy without prior operative biliary bypass. Preoperative biliary stenting was performed in 408 patients (72%), whereas the remaining 159 patients (28%) did not undergo biliary stenting. In the stented group, 64% had stents placed via a percutaneous approach and 36% had stents placed endoscopically. The stented patients were older (mean 63.1 years vs. 61.4 years; P = 0.05) and were more likely to be white (92% vs. 82%; P = 0.005). Those who had stents placed were more likely to have jaundice (67% vs. 38%; P <0.0001) and fever (5% vs. 1%; P = 0.03) as presenting symptoms. There were no differences in multiple intraoperative parameters when the two groups were compared. Patients who had stents placed had a perioperative mortality rate of 1.7% compared to 2.5% in those who did not (P = 0.3). Although the overall complication rates were 35% in those who had stents placed and 30% in those who did not (P = NS), patients with stents experienced a significantly increased incidence of pancreatic fistula (10% vs. 4%; P = 0.02) and wound infection (10% vs. 4%; P = 0.02). The incidences of other postoperative complications were similar between the stented and unstented groups. Eight patients (3%) in the percutaneously stented group developed significant hemobilia after stent placement, whereas none of the patients undergoing endoscopic stent placement developed hemobilia (P = 0.03). There were no statistical differences in other complications between the percutaneously and endoscopically stented groups. Preoperative biliary stenting did not increase the overall complication rate or mortality rate in patients undergoing pancreaticoduodenectomy. Stenting does appear to increase the rate of pancreatic fistula formation, possibly as a result of pancreatic inflammation related to the stenting procedure. Stenting also increases the rate of wound infection, likely secondary to contaminated bile (bactibilia) after instrumentation of the biliary tree. Preoperative biliary stenting is safe but should be used selectively because of the above-mentioned risks. The method of stenting should be based on local expertise.

p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer.

Cholangiocarcinoma occurs frequently in patients with primary sclerosing cholangitis (PSC). We evaluated the incidence and prognostic significance of p53 protein overexpression and K-ras gene mutations in patients with biliary tract cancer and PSC. p53 protein expression was determined in specimens from 12 patients with biliary tract cancer, using the antibody, D07. K-ras mutations were detected using DNA sequencing and a mutation ligation assay. Accumulation of p53 protein was detected in 6 of 12 tumors (50%). K-ras mutations were detected in 4 of 12 tumors (33%). Overall survival in patients with p53-negative tumors was significantly longer (P < 0.05) than that in patients with p53-positive (mutant) tumors. Similarly, overall survival was significantly longer (P < 0.05) in the absence of a K-ras mutation than in patients with a tumor containing a K-ras mutation. Mean interval from the time of diagnosis of PSC until the diagnosis of biliary tract cancer was significantly shorter (P < 0.05) in patients with p53 overexpression than in those patients without p53 overexpression (2 versus 47 months). p53 overexpression and K-ras mutations occur commonly in patients with PSC and biliary tract cancer and are associated with a shortened survival. Patients with longstanding PSC are less likely to have these genetic alterations and may have a better prognosis.

Large cystic pancreatic neoplasms: pathology, resectability, and outcome.

BACKGROUND: Cystic pancreatic neoplasms may be benign, premalignant, or malignant. These lesions may remain asymptomatic for long periods and can be quite large at the time of presentation. METHODS: A retrospective analysis was used to determine whether preoperative evaluation can predict pathology and determine resectability and outcome. RESULTS: Over 12 years, 145 cystic pancreatic neoplasms, of which 24 (17%) were larger than 10 cm, were managed at the Johns Hopkins Hospital. Those 24 large tumors included 9 of 73 cystadenomas (12%), 7 of 27 cystadenocarcinomas (26%), 2 of 35 adenocarcinomas producing mucin or associated with a cyst (6%), 5 of 9 Hamoudi tumors (55%), and 1 dermoid cyst. Clinical symptoms, liver function tests, and computed tomographic scans did not distinguish benign from malignant pathology. On 18 angiograms, 2 malignant and 4 benign neoplasms demonstrated encasement or occlusion; however, 3 of these 6 tumors were resectable. Twenty of 22 patients (91%) who were explored underwent resection with no hospital mortality. For the entire series, 5-year survival for those with cystadenomas, cystadenocarcinomas, and cystic adenocarcinomas was 97%, 38%, and 9%, respectively. Three-year survival for those 7 with cystadenocarcinomas larger than 10 cm was 54%, compared with 51% for those 20 with smaller cystadenocarcinomas. CONCLUSIONS: Preoperative evaluation usually does not predict pathology, resectability, or outcome. Moreover, resectability is high and morbidity is low, irrespective of size. Large cystic pancreatic tumors should be explored to determine pathology, attempt resection, and provide an opportunity for long-term survival.

Clinical pathway implementation improves outcomes for complex biliary surgery.

BACKGROUND: Complex biliary surgery is associated with significant morbidity, prolonged hospital stay, and high cost. Clinical pathway implementation has the potential to standardize treatment and improve outcomes. Therefore the aim of this analysis was to determine whether clinical pathway implementation and/or feedback of outcome data would alter hospital stay, charges, and mortality rates for complex biliary surgery at an academic medical center METHODS: Pre- and postoperative length of stay, hospital charges, and mortality rates were monitored for 36 months before (period 1) and for 2 18-month periods (periods 2 and 3) after implementation of a clinical pathway for hepaticojejunostomy. Outcome data were provided to the surgeons 18 months after pathway implementation to determine whether further clinical practice improvement was possible. RESULTS: From 1991 to 1997, 339 patients underwent hepaticojejunostomy at The Johns Hopkins Hospital for malignant and benign biliary obstruction. Total length of stay was 13.3 +/- 0.9 days for period 1 compared with 12.5 +/- 0.8 days for period 2 (not significant) and 10.1 +/- 0.3 days for period 3 (P < .01 vs period 1; P < .03 vs period 2). Hospital charges averaged $24,446 during period 1 compared with $23,338 during period 2 and $20,240 during period 3 (P < .01 vs periods 1 and 2). Hospital mortality rate was 4.5% during period 1 compared with 0.7% during periods 2 and 3 (P < .05). CONCLUSIONS: These data suggest that implementation of a clinical pathway for hepaticojejunostomy reduces hospital mortality rates and that feedback of outcome data to surgeons results in further clinical practice improvement. Thus clinical pathway implementation and feedback are effective methods to control costs at an academic medical center.

Cryotherapy extends the indications for treatment of colorectal liver metastases.

BACKGROUND: Hepatic resection for colorectal metastases has been established as the best option for patients with 4 or less lesions meeting specified criteria. Recently, the use of intraoperative ultrasound has increased the detection of previously occult liver lesions, and cryotherapy has allowed the treatment of liver lesions in inaccessible areas with less destruction of normal liver in the case of multiple lesions. 14e prospectively performed hepatic resection or cryotherapy to test the hypothesis that more than 4 liver metastases could be safely and successfully treated with improved long-term survival. METHODS: From August 1993 to January 1999, 137 patients with liver metastases from colorectal cancer were treated with hepatic resection or cryotherapy at the Medical College of Wisconsin. Preoperative and postoperative computed tomography scans, intraoperative assessments of lesion number and curability, number of blood transfusions administered, length of stay, complications experienced, and overall survival rates were reviewed. RESULTS: One hundred thirty-seven patients were explored. Treatment consisted of resection alone in 34, cryotherapy alone in 20, both treatments in 52, and no treatment was possible in 31 patients. "Curability" was defined as complete resection or cryotherapy of all identifiable tumor at the conclusion of the operation. A Cox proportional hazards model demonstrated that survival was determined by the destruction of all identifiable metastases (P < . 001) and was not statistically influenced by age, gender type of therapy, or the number of metastases treated. CONCLUSIONS: Surgical treatment of colorectal liver metastases remains the best option for patients with this disease. A key factor in overall survival is the destruction or resection of all identifiable disease and not the number of tumors per se. Using cryotherapy as an addition to the surgical arsenal, patients previously deemed unresectable because of the number of lesions have a chance for long-term survival. This study demonstrates improved long-term survival for "cured" patients with more than 4 metastatic lesions, thereby extending the indications for resection/ablation.

Diagnosis and management of cholangiocarcinoma in primary sclerosing cholangitis.

Cholangiocarcinoma remains difficult to diagnose and is a major cause of death in patients with primary sclerosing cholangitis. Recently serum carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) levels have been reported to improve diagnostic accuracy in patients with cholangiocarcinoma and primary sclerosing cholangitis. We reviewed our experience with cholangiocarcinoma complicating primary sclerosing cholangitis to identify clinical factors associated with cholangiocarcinoma in patients with primary sclerosing cholangitis and to determine the appropriate management of patients with confirmed or suspected cholangiocarcinoma. Between 1984 and 1997, 25 patients (18%) were diagnosed with cholangiocarcinoma among 139 patients with primary sclerosing cholangitis. The diagnosis of primary sclerosing cholangitis was made coincident with the diagnosis of cholangiocarcinoma in 12 patients and preceded it by a mean of 62 months in the remaining 13 patients. The incidence of inflammatory bowel disease was higher (P <0.05) in patients with cholangiocarcinoma (80% vs. 61%). Nine patients (36%) with cholangiocarcinoma were managed with either extrahepatic bile duct resection and/or partial hepatic resection (n = 5) or liver transplantation (n = 4), and the remaining 16 patients were unresectable at presentation. Serum CA 19-9 was elevated in all six patients with cholangiocarcinoma who were analyzed and in none of the eight patients without cholangiocarcinoma who were tested (P <0.01). Actuarial 1- and 3-year survival rates in the resected patients (56% and 28%, respectively) were significantly longer (P <0. 02) than in the unresected patients (13% and 0%, respectively). The 10-year actuarial mortality rates for cholangiocarcinoma among all 139 patients was 25%. In summary, cholangiocarcinoma was the leading cause of death in patients with primary sclerosing cholangitis and was often diagnosed concurrently with or within months of its diagnosis. Early liver transplantation for patients with primary sclerosing cholangitis will not reduce the incidence of cholangiocarcinoma-related mortality in these patients.