Henry A. Pitt

Pancreaticoduodenectomy for cancer of the head of the pancreas: 201 patients

ObjectiveThis single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. Summary of Background DataIn recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. MethodsTwo hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. ResultsThe overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections: n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, <800 mL intraoperative blood loss, <2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection.

Cholangiocarcinoma: A spectrum of intrahepatic, perihilar, and distal tumors

OBJECTIVEnThe objective of this article is to introduce a simple method for classifying cholangiocarcinomas and to apply this system to analyze a large number of patients from a single institution.nnnSUMMARY BACKGROUND DATAnFor the past 2 decades, most western reports on cholangiocarcinoma have separated intrahepatic from extrahepatic tumors and have subclassified this latter group into proximal, middle, and distal subgroups. However, middle lesions are uncommon and are managed most often either with hilar resection or with pancreatoduodenectomy. The spectrum of cholangiocarcinoma, therefore, is best classified into three broad groups: 1) intrahepatic, 2) perihilar, and 3) distal tumors. These categories correlate with anatomic distribution and imply preferred treatment.nnnMETHODSnThe records of all patients with histologically confirmed cholangiocarcinoma who underwent surgical exploration at The Johns Hopkins Hospital over a 23-year period were reviewed.nnnRESULTSnOf 294 patients with cholangiocarcinoma, 18 (6%) had intrahepatic, 196 (67%) had perihilar, and 80 (27%) had distal tumors. Age, gender, race, and associated diseases were similar among the three groups. Patients with intrahepatic tumors, by definition, were less likely (p < 0.01) to be jaundiced and more likely (p < 0.05) to present with abdominal pain. The resectability rate increased with a more distal location (50% vs. 56% vs. 91%), and resection improved survival at each site. Five-year survival rates for resected intrahepatic, perihilar, and distal tumors were 44%, 11%, and 28%, and median survival rates were 26, 19, and 22 months, respectively. Postoperative radiation therapy did not improve survival. In a multivariate analysis resection (p < 0.001. hazard ratio 2.80), negative microscopic margins (p < 0.01, hazard ratio 1.79), preoperative serum albumin (p < 0.04, hazard ratio 0.82), and postoperative sepsis (p < 0.001, hard ratio 0.27) were the best predictors of outcome.nnnCONCLUSIONSnCholangiocarcinoma is best classified into three broad categories. Resection remains the primary treatment, whereas postoperative adjuvant radiation has no influence on survival. Therefore, new agents or strategies to deliver adjuvant therapy are needed to improve survival.

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

OBJECTIVEnThis study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy.nnnSUMMARY BACKGROUND DATAnBased on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy.nnnMETHODSnFrom October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy.nnnRESULTSnPancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant).nnnCONCLUSIONSnAdjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.

Pyogenic hepatic abscess. Changing trends over 42 years.

OBJECTIVEnThe authors document changes in the etiology, diagnosis, bacteriology, treatment, and outcome of patients with pyogenic hepatic abscesses over the past 4 decades.nnnSUMMARY BACKGROUND DATAnPyogenic hepatic abscess is a highly lethal problem. Over the past 2 decades, new roentgenographic methods, such as ultrasound, computed tomographic scanning, direct cholangiography, guided aspiration, and percutaneous drainage, have altered both the diagnosis and treatment of these patients. A more aggressive approach to the management of hepatobiliary and pancreatic neoplasms also has resulted in an increased incidence of this problemnnnMETHODSnThe records of 233 patients with pyogenic liver abscesses managed over a 42-year period were reviewed. Patients treated from 1952 to 1972 (n = 80) were compared with those seen from 1973 to 1993 (n = 153).nnnRESULTSnFrom 1973 to 1993, the incidence increased from 13 to 20 per 100,000 hospital admissions (p < 0.01. Patients managed from 1973 to 1993 were more likely (p < 0.01) to have an underlying malignancy (52% vs. 28%) with most of these (81%) being a hepatobiliary or pancreatic cancer. The 1973 to 1993 patients were more likely (p < 0.05) to be infected with streptococcal (53% vs. 30%) or Pseudomonas (30% vs. 9%) species or to have mixed bacterial and fungal 26% vs. 1%) infections. The recent patients also were more likely (p < 0.05) to be managed by percutaneous abscess drainage (45% vs. 0%). Despite having more underlying problems, overall mortality decreased significantly (p < 0.01) from 65% (in 1952 to 1972 period) to 31% (in 1973 to 1993 period). The reduction was greatest for patients with multiple abscesses (88% vs. 44%; p < 0.05) with either a malignant or a benign biliary etiology (90% vs. 38%; p < 0.05). Mortality was increased (p < 0.02) in patients with mixed bacterial and fungal abscesses (50%). From 1973 to 1993, mortality was lower (p = 0.19) with open surgical as opposed to percutaneous abscess drainage (14% vs. 26%).nnnCONCLUSIONSnSignificant changes have occurred in the etiology, diagnosis, bacteriology, treatment, and outcome patients with pyogenic hepatic abscesses over the past 4 decades. However, mortality remains high, and proper management continues to be a challenge. Appropriate systemic antibiotics and fungal agents as well as adequate surgical, percutaneous, or biliary drainage are required for the best results.

Postoperative Bile Duct Strictures: Management and Outcome in the 1990s

ObjectiveTo describe the management and outcome after surgical reconstruction of 156 patients with postoperative bile duct strictures managed in the 1990s. Summary Background DataThe 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. MethodsData 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. ResultsOf 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. ConclusionsMajor 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.

Perihilar cholangiocarcinoma: Postoperative radiotherapy does not improve survival

ObjectiveThe aims of this analysis were to determine prospectively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma. BackgroundRetrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma. However, in these reports, patients receiving radiotherapy tended to have smaller, often resectable tumors, and were relatively fit. In comparison, patients who have not received radiotherapy often had unresectable tumors, metastatic disease, or poor performance status. MethodsFrom 1988 through 1993, surgically staged patients with perihilar cholangiocarcinoma and 1) no evidence of metastatic disease, 2) Karnofsky score >60,3) no prior malignancy or radiotherapy, and 4) a patent main portal vein were analyzed. Fifty patients were stratified by resection (n = 31) versus operative palliation (n = 19) and by radiation (n = 23) versus no radiotherapy (n = 27). ResultsPatients undergoing resection had smaller tumors (1.9 ± 2.8 vs. 2.4 ± 2.1 cm, p < 0.01) that were less likely to invade the hepatic artery (3% vs. 42%, p < 0.05) or portal vein (6% vs. 53%, p < 0.05). Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy. Resection improved the length (24.2 ± 2.5 vs. 11.3 ± 1.0 months, p < 0.05) and quality of survival. Radiation had no effect on the length (18.4 ± 2.9 vs. 20.1 ± 2.4 months) or quality of survival or on late toxicity. ConclusionsThis analysis suggests that in patients with localized perihilar cholangiocarcinoma, resection prolongs survival whereas radiation has no effect on either survival or late toxicity. Thus, new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients.

Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients.

Neuroendocrine tumors of the pancreas and peripancreatic area are rare entities with a wide spectrum of clinical presentation. This study retrospectively reviews the patients who underwent surgery for these tumors at The Johns Hopkins Hospital from 1949 to 1996, inclusive There were 125 patients (65 males and 60 females) whose mean age was 51 ± 1 years Fifty-eight patients (48%) had nonfunctional tumors, whereas 64 (52%) had functional tumors 35 (55%) insulinomas, 23 (36%) gastrmomas, three (5%) VIP-omas, two (3 %) glucagonomas, and one (1%) ACTHorna All patients with functional tumors presented with appropriate signs and symptoms of hormonal excess, 86% of patients with nonfunctional tumors presented with weight loss, abdominal pain, or jaundice Preoperaüve computed tomography (CT) correctly localized the tumor in 66 (76%) of 87 patients, angiography in 45 (58%) of 78 patients, and CT plus angiography in 54 (79%) of 68 patients Tumors were benign in 60 patients (48%), malignant m 65 patients (52%), and were located in the head, neck, or uncinate process of the pancreas in 54, body in 14, tail in 18, and duodenum in eight The most common operative procedures performed were 50 pancreaacoduodenectomies (40%), 39 distal pancreatectomies (31%), and 21 tumor enucleations (17%) Nine synchronous hepatic resections were performed for métastases Of the evaluable patients, 46 (43%) had postoperative complications, the most common of which were pancreatic fistula (16%), wound infection (15%), and delayed gastric emptying (8%) There were three in-hospital deaths (2 8%) With a mean follow-up of 55 ±6 months, there have been 30 additional deaths, 23 of which were related to disease progression The overall 2-, 5-, and 10-year actuarial survival rates were 82%, 65%, and 47%, respectively The 5-year survival for patients with functional tumors was 77% compared to 52% for those with nonfunctional tumors (P = 0 025), the 5-year survival for patients with benign tumors was 91% compared to 49% for those with malignant tumors (P = 0 0004) By univanate analysis the most powerful predictor of poor outcome for patients with malignant tumors (n = 60) was positive surgiad margins (P = 0 006) This single-institution experience documents low mortality and moderate morbidity for patients treated operatively for pancreatic and penpancreaac neuroendocrine tumors The most favorable outcomes are observed in patients with benign functional tumors and in those with completely resected malignant tumors

Pancreaticoduodenectomy. Does it have a role in the palliation of pancreatic cancer

OBJECTIVEnThe authors define the role of palliative pancreaticoduodenectomy in patients with pancreatic carcinoma.nnnBACKGROUNDnDecreases in perioperative morbidity and mortality and improved long-term survival associated with pancreaticoduodenectomy for patients with pancreatic carcinoma have clearly established a role for this operation when performed with curative intent. However, most surgeons remain hesitant to perform pancreaticoduodenectomy unless surgical margins are widely clear, choosing rather to perform palliative biliary and gastric bypass.nnnMETHODSnA single-institution retrospective review was performed comparing the outcome of 64 consecutive patients undergoing pancreaticoduodenectomy for pancreatic carcinoma with gross or microscopic evidence of adenocarcinoma at the surgical resection margins, and 62 consecutive patients found to be unresectable at the time of laparotomy because of local invasion without evidence of metastatic disease (stage III). Combined biliary and gastric bypass were performed in 87% of patients not resected.nnnRESULTSnThe two groups were similar with respect to age, gender, race, and presenting symptoms. The hospital mortality rate was identical in both groups (1.6%). Fifty-eight percent of patients undergoing pancreaticoduodenectomy had an uncomplicated postoperative course compared with 68% of patients undergoing palliative bypass (not significant). The length of postoperative hospital stay after pancreaticoduodenectomy was 18.4 days, which was significantly longer (p < 0.05) than for patients undergoing palliative bypass (15.0 days). The overall actuarial survival (Kaplan-Meier) was improved significantly in patients undergoing pancreaticoduodenectomy (p < 0.02). Postoperative chemotherapy and radiation therapy improved survival in both groups.nnnCONCLUSIONSnPancreaticoduodenectomy can be performed with a similar perioperative morbidity and mortality and only a minimal increase in hospital stay when compared with traditional surgical palliation. Pancreaticoduodenectomy with postoperative chemotherapy and radiation therapy is associated with improved long-term survival when compared with patients treated with surgical bypass. These data support the role of palliative pancreaticoduodenectomy in patients with pancreatic carcinoma and with local residual disease.

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 biliaty 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 stems 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 3 5% in those who had stents placed and 30% in those who did not (P = NS), patients with stems 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 fismla 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.

Should pancreaticoduodenectomy be performed in octogenarians

As the population in the United States ages, an increasing number of elderly patients may be considered for pancreaticoduodenal resection. This high-volume, single-institution experience examines the morbidity, mortality, and long-term survival of 727 patients undergoing pancreaticoduodenectomy between December 1986 and June 1996. Outcomes of patients 80 years of age and older (n = 46) were compared to those of patients younger than 80 years. In these older patients, pancreaticoduodenectomy was performed for pancreatic adenocarcinoma (n = 25; 54%), ampullary adenocarcinoma (n = 9; 20%), distal bile duct adenocarcinoma (n = 5; 1 l%), duodenal adenocarcinoma (n = 2; 4%), cystadenocarcinoma (n = 2; 4%), cystadenoma (n = 1; 2%), and chronic pancreatitis (n = 2; 4%). When compared to the 681 concurrent patients younger than 80 years who were undergoing pancreaticoduodenectomy, the two groups were statistically similar with respect to sex, race, intraoperative blood loss, and type of pancreaticoduodenectomy performed. Patients 80 years of age or older had a shorter median operative time (6.4 hours vs. 7.0 hours; P = 0.02) but a longer postoperative length of stay (median = 15 days vs. 13 days; P = 0.01) and a higher complication rate (57% vs. 41%; P = 0.05) when compared to their younger counterparts. Pancreaticoduodenectomy in the older group resulted in a 4.3% perioperative mortality rate compared to 1.6% in the younger group (P = NS). In the subset of patients undergoing pancreati-coduodenectomy for periampullary adenocarcinoma (n = 495), patients 80 years of age or older (n = 41) had a median survival of 32 months and a 5-year survival rate of 19%, compared to 20 months and 27%, respectively, in patients younger than 80 years (n = 4.54; P = 0.77). These data demonstrate that pancreaticoduodenectomy can be performed safely in selected patients 80 years of age or older, with morbidity and mortality rates approaching those observed in younger patients. Based on these data, age alone should not be a contraindication to pancreaticoduodenectomy.