John K. Boitnott

Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer

Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.

Choledochal cyst disease. A changing pattern of presentation.

ObjectiveThe authors compared the presentation, treatment, and long-term outcome of children and adults with choledochal cysts. Summary Background DataThe typical patient with choledochal cyst disease has been the female infant with the triad of jaundice, an abdominal mass, and pain. However, the recent experience of the authors suggested that the disease currently is recognized more commonly in adults. MethodsForty-two patients (11 children, 32 adults) with choledochal cyst disease were treated primarily at this institution between 1976 and 1993. Patient presentation, clinical evaluation, and operative treatment were obtained from existing records. Long-term follow-up was obtained by records, physician, or direct patient contact. ResultsOne child—but no adults—had the classic triad of jaundice, abdominal mass, and pain. Children were more likely to have two of the three signs or symptoms (82% vs. 25%; p = < 0.05). Adult patients most commonly had abdominal pain and were thought to have pancreatitis (23%) or acute biliary tract symptoms, prompting cholecystectomy (50%). The type of choledochal cyst seen in children and adults was similar; the fusiform extrahepatic (Type I) was most common (50%), and the combined intrahepatic and extrahepatic (Type IVA) was the next most prominent (33%). For both children and adults, treatment consisted of excision of the cyst and biliary reconstruction with a hepaticojejunostomy. There was no surgical mortality. Gallbladder or cholangiocarcinoma was identified in three adults (9.7%), two of which were manifest on presentation. Long-term follow-up revealed one patient with a biliary stricture and three patients with Type IVA cysts who had intrahepatic stones. ConclusionsChildren and adults differ in presentation of choledochal cysts, with adults commonly having acute biliary tract or pancreatic symptoms. Surgical treatment with cyst excision and biliary bypass is safe and effective in children and adults with excellent long-term results that minimize the development of malignancy.

Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.

PURPOSE We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION These findings suggest that IVL represents a high-grade non-Hodgkins lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.

Pancreaticoduodenectomy (Whipple resections) in patients without malignancy: Are they all 'chronic pancreatitis'?

Pancreaticoduodenectomy (Whipple resection) has evolved into a safe procedure in major high-volume medical centers for the treatment of pancreatic adenocarcinoma and refractory chronic pancreatitis. However, some Whipple resections performed for a clinical suspicion of malignancy reveal only benign disease on pathologic examination. We evaluated the frequency of such Whipple resections without tumor in a large series of pancreaticoduodenectomies and classified the diverse pancreatic and biliary tract diseases present in these specimens. Of 442 Whipple resections performed during 1999–2001, 47 (10.6%) were negative for neoplastic disease and, in 40 cases, had been performed for a clinical suspicion of malignancy. Most Whipple resections revealed benign pancreatic disease, including 8 (17%) alcohol-associated chronic pancreatitis, 4 (8.5%) gallstone-associated pancreatitis, 1 (2.1%) pancreas divisum, 6 (12.8%) “ordinary” chronic pancreatitis of unknown etiology, and 11 (23.4%) lymphoplasmacytic sclerosing pancreatitis. In particular, patients with lymphoplasmacytic sclerosing pancreatitis were all thought to harbor malignancy, whereas only 13 of 19 (68.4%) of Whipple resections showing histologically “ordinary” forms of chronic pancreatitis were performed for a clinical suspicion of malignancy. Benign biliary tract disease, including three cases of primary sclerosing cholangitis, two cases of choledocholithiasis-associated chronic biliary tract disease, and four fibroinflammatory strictures isolated to the intrapancreatic common bile duct, was a common etiology for clinically suspicious Whipple resections (22.5% of cases). Pancreatic intraepithelial neoplasia (PanIN) was a common finding among all pancreata, whether involved by pancreatitis or histologically normal. Overall, PanIN 1A/1B was present in 68.1%, PanIN 2 in 40.4%, and PanIN 3 in just 2.1%. These findings indicate that “benign but clinically suspicious” Whipple resections are relatively common in high-volume centers (9.2%) and reveal a diverse group of clinicopathologically distinctive pancreatic and biliary tract disease.

Diet and other risk factors for cancer of the pancreas

The findings of a case‐control study of cancer of the pancreas, which was conducted in the Baltimore metropolitan area, are reported. Two hundred one patients with pancreatic cancer were matched on age (±5 years), race, and sex to hospital and non‐hospital controls, the latter selected by random‐digit‐dialing (RDD). All subjects were interviewed regarding diet, beverage consumption, occupational and environmental exposures, and medical and surgical history. Significantly decreased risks were associated with consumption of raw fruits and vegetables and diet soda, and significantly increased risks were associated with consumption of white bread when cases were compared with hospital and RDD controls. A significantly reduced risk was associated with consumption of wine when cases were compared to RDD controls. Risk ratios for consumption of coffee were not significantly different from one, although there appeared to be a dose‐response relationship in women. A moderate but statistically nonsignificant increase in relative odds was found for cigarette smoking, and cessation of smoking was associated with a marked reduction in risk. No significant associations were found with particular occupational exposures. Tonsillectomy was associated with a significantly reduced risk, a finding that has been observed for other cancers as well. The current evidence indicates that pancreatic cancer is likely to result from a complex interaction of factors and suggests that the study of its etiology requires a multidisciplinary approach involving both laboratory and epidemiologic components.

The spectrum of carcinoma arising in Barrett's esophagus. A clinicopathologic study of 26 patients

The clinical and pathologic features of carcinoma arising in Barretts esophagus were studied in resection specimens from 26 patients. White males predominated (73%). A history of symptomatic gastroesophageal reflux was frequently absent, being elicited in only eight of 14 patients (57%) with a carefully obtained history at the time of presentation with carcinoma. Survival was relatively short with a median survival of 23 ± 5 months, and only three patients had a disease-free survival longer than 2 years. A pathologic spectrum of carcinoma was found: differentiation ranged from well to poorly differentiated in the 20 patients with a single adenocarcinoma; two separate carcinomas were found in four patients; and a spectrum of differentiation in a single tumor was found in the other two cases, one an adeno-carcinoid tumor and the other an adenosquamous carcinoma. The tumors were generally far advanced, with extension through the esophageal wall in 23 of 26 cases (88%) and metastases to lymph nodes in 17 of 24 cases (71%). Epithelial dysplasia, including carcinoma in situ in some cases, was found in Barretts mucosa adjacent to the tumor in all 26 patients. Our findings suggest that a surveillance program for dysplasia in patients known to have Barretts esophagus is warranted in an attempt to improve the outcome. However, the impact of surveillance on the incidence of Barretts carcinoma may be lessened by its frequent occurrence in patients with asymptomatic gastroesophageal reflux.

Spectrum of cystic tumors of the pancreas

The pathologic and clinical classification, as well as the behavior, of cystic tumors of the pancreas has been the subject of controversy. We retrospectively reviewed 50 patients with a diagnosis of cystic tumor of the pancreas observed at The Johns Hopkins Hospital from 1984 to 1991. These tumors were classified into three broad groups: I, cystadenoma; II, cystadenocarcinoma; and III, adenocarcinoma with mucin production or an associated cyst. The three groups did not differ with respect to age or sex. The most common clinical presentation was abdominal pain. Symptoms and signs among the three groups were similar except that patients with cystadenomas were less likely (p less than 0.05) to be jaundiced and more likely (p less than 0.05) to be asymptomatic. Radiologic findings on computerized tomography, cholangiography, and arteriography also overlapped, making precise preoperative determination of tumor type difficult. Operative classification was also often not possible. The resectability rate (Group I, 91%; Group II, 67%; Group III, 53%) and 5-year survival rate (Group I, 90%; Group II, 72%; Group III, 14%) correlated with careful pathologic determination. Cystic tumors of the pancreas represent a spectrum of disease ranging from benign cystadenoma to adenocarcinoma masquerading as cystadenocarcinoma. We recommend resection whenever possible, even when preoperative evaluation suggests benign disease.

Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis

Lymphoplasmacytic sclerosing pancreatitis (LPSP) represents a distinctive form of chronic pancreatitis characterized by diffuse fibroinflammatory infiltrates that can involve both the pancreatic ducts and acinar parenchyma. Several cases of inflammatory infiltrates within the gallbladder have been reported in association with LPSP, but the spectrum of gallbladder pathology in patients with LPSP has not been systematically reviewed. Many patients with LPSP have distal CBD fibrosis, strictures, and inflammation, features that overlap somewhat with primary sclerosing cholangitis (PSC). In PSC, a pattern of gallbladder pathology termed “diffuse acalculous lymphoplasmacytic chronic cholecystitis” has been previously described as showing a triad of diffuse, mucosal-based, plasma cell-rich inflammatory infiltrates. We studied 20 gallbladders from patients with LPSP and compared them with 20 gallbladders in PSC, 20 gallbladders with chronic cholelithiasis, and 10 gallbladders from patients with benign (non-LPSP) pancreatic disease. The following features were evaluated: degree and composition of mucosal inflammation and deep (mural) inflammation, lymphoid nodules, metaplasia, dysplasia/neoplasia, fibrosis, muscular hypertrophy, Rokitansky-Aschoff sinuses, and cholesterolosis. The majority (60%) of gallbladders in LPSP contained moderate or marked inflammatory infiltrates and lymphoid nodules, frequencies similar to PSC but significantly higher than in chronic cholelithiasis and benign non-LPSP pancreatic disease. LPSP gallbladders received the highest scores for deep inflammation of all groups, and 35% of LPSP gallbladders showed transmural chronic cholecystitis. Overall, “diffuse lymphoplasmacytic chronic cholecystitis” was present in 50% of PSC cases and 25% of LPSP cases, but in only 5% of chronic cholelithiasis and none of non-LPSP benign pancreatic disease. Mucosal inflammation in LPSP gallbladders correlated significantly with the presence of inflammation in the extrapancreatic portion of the CBD. These findings suggest that inflammatory pathology of the gallbladder is frequently associated with LPSP and that it is part of the spectrum of biliary tract disease in these patients, rather than a simple reflection of the pancreatitis itself.

Malignant transformation of hepatic adenomas

Hepatic adenomas are benign neoplasms of the liver that occur in several well-defined clinical settings, but principally that of excess hormone exposure. They have a small but poorly characterized risk of malignant degeneration. The clinical presentation and pathological findings were reviewed for all hepatic adenomas resected between January 1, 2003 and July 1, 2006. Immunohistochemistry for p53, β-catenin and α-fetoprotein (AFP) were performed on those cases with malignant transformation and exon 3 of β-catenin was amplified and sequenced. A total of 17 hepatic adenomas were resected and 3 showed malignant transformation. All three cases were in women with an age range of 23–33 years. The clinical presentations were vague abdominal pain. Histologically, the malignant transformation occurred within otherwise typical hepatic adenomas. Two of three cases showed patchy atypia throughout the hepatic adenoma. The hepatocellular carcinoma arose as distinct nodules directly within the adenomas, effectively ruling out synchronous lesions. The hepatocellular carcinomas were unifocal in two cases and multifocal in one case with the greatest dimensions of the hepatocellular carcinoma being 2.5, 2.2, and 1 cm. Immunostains for AFP and β-catenin were negative in both the hepatic adenomas and areas of hepatocellular carcinoma. p53 immunostaining was positive within the areas of malignant transformation in one case. No mutations or deletions were seen in exon 3 of the β-catenin gene for either the adenomas or the carcinoma. In conclusion, two of the cases that developed hepatocellular carcinomas showed cytological atypia in the background adenoma. The hepatocellular carcinomas arose as distinct nodules within the adenomas. No common molecular pathway of hepatocellular carcinogenesis was observed by examining AFP, β-catenin, and p53 immunostains and no β-catenin mutations or deletions were found.

The Budd-Chiari syndrome. Treatment by mesenteric-systemic venous shunts

Twelve patients with the Budd-Chiari syndrome have been managed surgically. Ten of the patients were female, two were male, with a mean age of 40 years. Three of the patients had polycythemia vera, two had pre-existing cirrhosis, one had ingested estrogens, one had an occult tumor, and in four there were no associated factors. Ten patients presented with ascites and two with bleeding esophageal varices. The diagnosis was confirmed in all 12 patients by liver biopsy and hepatic vein catheterization. Inferior vena cavography revealed the abdominal vena cava to be thrombosed in six patients. The superior mesenteric vein was used to decompress the congested liver in all 12 patients. In five patients, a mesocaval shunt (MCS) was performed and in seven patients, a mesoatrial shunt (MAS) was carried out. There were four hospital deaths (two MCS, two MAS). One late death (MAS) occurred from liver failure following shunt thrombosis. Two additional patients (one MCS, one MAS) re-developed ascites immediately following surgery and angiography revealed a thrombosed shunt. Ascites has been controlled with a LeVeen shunt in these two patients, but liver biopsies showed progression to cirrhosis. The remaining five patients (three MAS, two MCS) did well, and angiography revealed patent shunts. Two of these patients, however, re-developed ascites at 4 and 10 months following MAS and required a second MAS. Follow-up ranges from 6 to 68 months. In three of the patients (two MCS, one MAS) with patent shunts, liver biopsy shows a remarkable return toward normal liver architecture and histology.