Ampullary and periampullary tumors

Ninety-eight consecutive patients with ampullary and periampullary carcinoma diagnosed between 1983-1993 were studied retrospectively. Among these patients, 66 had a carcinoma of the head of the pancreas, 10 a carcinoma of the papilla of Vater, 8 a carcinoma of the duodenum, and 14 a carcinoma of the distal common bile duct. Resectability rate ranged from 12% to 90% according to the tumor location and histologic type. Palliative procedures such as laparotomy, biopsy and bilio-digestive bypasses were performed in 27 patients. Curative resections were performed in 24 cases: 20 pancreatoduodenectomies, 2 total pancreatectomies, 1 duodenectomy, 1 common bile duct resection. The results of the surgical treatment as well as mortality and morbidity rates were compared with those of different and larger series.     

Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors

BACKGROUND: Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms. Specific chemotherapy, interferon-alpha (IFN), and somatostatin analogs are established therapies for these patients, but all of them eventually fail. Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients. METHODS: Between 1981 and 1995, a total of 55 liver embolizations with gel foam powder were performed on 41 patients with histopathologically verified neuroendocrine tumors; 29 had carcinoid tumors and 12 had endocrine pancreatic tumors (EPTs). All patients had received medical treatment, including chemotherapy (n = 18), IFN (n = 31), and octreotide (n = 19), and were experiencing treatment failure when liver embolization was performed at a median of 37 months after diagnosis of liver metastases. Medical treatment was continued after embolization. RESULTS: An overall objective response was noted in 15 of 29 patients with carcinoid tumors (52%). The median duration of effect was 12 months in patients with midgut carcinoid tumors. An overall objective response was observed in 6 of 12 patients with EPTs (50%), with a median duration of effect of 10 months. Adverse events were observed, and, in agreement with earlier reports, the rate of serious complications was 10%. Survival analyses showed a median survival of 80 months and a 5-year survival rate of 60% from the performance of embolization on patients with midgut carcinoid tumors, whereas for patients with EPTs the median survival from embolization was only 20 months. CONCLUSIONS: Liver embolizations performed relatively late in the clinical course in our series appeared to be as effective as "early" embolizations in other series of patients with carcinoid tumors. The results for those with EPTs were poorer, and earlier embolizations may result in better outcomes for these patients. Considering the morbidity associated with the procedure, it is imperative to select patients according to extent of liver involvement, severity of carcinoid heart disease, and somatostatin receptor status.     

Surgical treatment of pancreatic head and periampullary tumors

The aim of this study was the comparison of the postoperative results of standard Whipple pancreatoduodenectomy (WP), pylorus preserving pancreatoduodenectomy (PPPD) and palliative bypass operation performed for treatment of pancreatic head and periampullary tumors. In the period from Jan. 1992 to 1996 106 patients had tumors located in the head of pancreas and 21 patients had periampullary tumors. The diagnosis was established by ERCP, transabdominal ultrasonography and computer tomography. We assessed the morbidity, mortality, prognostical data of the surgery of pancreatic head and periampullary tumors. Tumor markers such as CEA, CA 19-9 and CA 125 were also studied. The operability rate was 26% in case of pancreatic head tumors and 69% in peri ampullary tumors. The mortality rate was 6%. Postoperative complications were in 23 patients(18.1%). There was no significant difference between the survival of WP and PPPD group, but we found much better survival in patients with periampullary tumor. After palliative operation the survival rate was 6.1 months in case of pancreatic head carcinoma and 11 months in case of periampullary tumors. Our data provided many evidences about the advantage of PPPD in the patients with malignant periampullary and pancreas head tumors and the long-term results and quality of life is much better after PPPD.     

Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors

BACKGROUND: Liver metastases from neuroendocrine tumors often present with disabling symptoms due to syndromes of hormonal excess. A locally destructive technique such as hepatic cryotherapy not only alleviates symptoms but may improve survival in this group of patients. METHODS: Six patients with metastatic neuroendocrine tumors were treated with hepatic cryotherapy. Four patients were symptomatic and three of these had elevated tumor markers from ectopic hormone production. RESULTS: All patients are alive and asymptomatic, with a median follow-up of 24 months (range, 6 months to 6 years). All have had a complete radiologic response. All with elevated preoperative markers have had a greater than 89% decrease in tumor markers. Coagulopathy occurred in two patients necessitating additional surgery, but there was no other morbidity attributable to the cryotherapy. CONCLUSION: To the authors' knowledge, this study demonstrates for the first time that hepatic cryotherapy offers supportive treatment for patients with neuroendocrine tumors metastatic to the liver. Cryotherapy alleviates symptoms and may improve survival.     

Evaluation of somatostatin-receptor scintigraphy for detecting neuroendocrine tumors

BACKGROUND: Somatostatin-receptor scintigraphy (SRS) has gained attention as an imaging modality for neuroendocrine tumors (NETs). The purpose of this study was to present one of the first American series evaluating the ability of SRS to detect local and distant disease caused by NETs. METHODS: Medical records were reviewed from 35 patients who underwent a total of 38 studies using 111In-pentetreotide between 1993 and 1995. Twenty-two patients had islet cell tumors, seven had carcinoid tumors, and six had other NETs. RESULTS: The overall sensitivity of SRS was 74% for detecting local disease (primary tumor +/- regional lymph node metastases) in all NETs, excluding insulinoma, 75% in gastrinoma, 0% in insulinoma, 78% in other islet cell tumors, and 50% in carcinoids. For detecting distant disease, the overall sensitivity of SRS was 67% for all NETs, excluding insulinoma, 100% for gastrinoma, 50% for other islet cell tumors, and 80% for carcinoids. Specificity and positive predictive value were 100% for all tumors. Negative predictive value ranged from 33% to 100%. CONCLUSIONS: A positive SRS study strongly predicts the presence of tumor (100% positive predictive value in our study). However, unlike the European reports of very high sensitivity (80% to 88%), we found that SRS had a lower sensitivity (67% for all NETs excluding insulinoma and 71% for noninsulinoma gastroenteropancreatic NETs). Thus negative SRS in patients with NETs must be viewed cautiously, because the false-negative rate is high, and this limits the use of this method in the most difficult patients.     

High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects

Pure geometric isomers of conjugated linoleic acid were prepared from castor oil as the primary starting material. Methyl octadeca-9Z,11E-dienoate (2) and methyl octadeca-9Z,11Z-dienoate (4) were obtained by zinc reduction of methyl santalbate (1, methyl octadec-11E-en-9-ynoate) and methyl octadec-11Z-en-9-ynoate (3), respectively, as the key intermediates. Methyl octadeca-9E,11E-dienoate (8) and methyl octadeca-9E,11Z-dienoate (9) were prepared by demesylation of the mesyloxy derivative of methyl ricinelaidate (6, methyl 12-hydroxy-octadec-9E-enoate). A study of the nuclear magnetic resonance spectral properties was carried-out, and the shifts of the olefinic carbon atoms of 18:2(9Z,11E) (2) and 18:2(9E,11Z) (9) were readily identified by a combination of incredible natural abundance double quantum transfer experiment, heteronuclear multiple bond correlation, and 1H-13C correlation spectroscopy correlation techniques. Doubts remain in the absolute identification of the individual olefinic carbon atoms of the 18:2(9Z,11Z) (4) and 18:2(9E,11E) (8), except the fact that the shifts of the "inner" (C-10 and C-11) and "outer" (C-9 and C-12) positioned olefinic carbon atoms of the conjugated diene system are distinguishable.     

Malignant tumors of the pancreas and periampullary area. Our experience

The authors analyse and evaluate the clinical records of 45 patients treated in the last 4 years for pancreatic cancer and neoplasm of the bilioduodenapancreatic area, comparing the results with data available in the literature. In the group of patients treated with resection (12 cases), postoperative morbidity and mortality were respectively 28% and 6%, and three-years survival was 22%. The authors discuss particularly about reconstruction ways after duodenopancreatectomy, showing good results after reconstruction by Y loop sec. Roux and pancreato-jejunal anastomosis.     

Pancreaticoduodenectomy for benign disease

BACKGROUND: Surgeons are often called upon to perform pancreaticoduodenectomy for either suspicion of malignancy or symptoms due to benign disease. Perioperative morbidity and mortality following pancreaticoduodenectomy have decreased markedly over the last 2 decades. In response, many surgical centers advocate expanding the indications for pancreaticoduodenectomy to include lesions other than periampullary carcinoma. PATIENTS AND METHODS: A retrospective review of medical records for 108 patients undergoing pancreaticoduodenectomy for benign disease at The Johns Hopkins Medical Institutions over 100 months was completed. The subset of patients with a histopathologic diagnosis of chronic pancreatitis was identified and compared with patients undergoing pancreaticoduodenectomy for other benign conditions. RESULTS: The mortality rate for the present series was less than 1%. Perioperative complications, the majority of which were self-limited, occurred in 51% of patients. The most common complication was delayed gastric emptying. Pancreatic anastamotic leak occurred in 18% of patients and developed significantly more frequently in patients with benign diseases other than chronic pancreatitis (31% versus 8%, P < 0.05). CONCLUSION: Among appropriately selected patients, the rates of perioperative mortality and serious morbidity are low, and concerns about mortality and morbidity should not prevent an aggressive approach to surgical resection in patients with benign disease.     

Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors

In vitro studies have shown that gastroenteropancreatic tumors, with the exception of insulinomas, have a high density of somatostatin receptors and can be imaged in vivo using somatostatin receptor scintigraphy (SRS) with either [123I-Tyr3]octreotide or [111In DTPA,DPhe1]octreotide. However, the sensitivity in relation to conventional imaging studies (ultrasound, CT, MRI, angiography) remains unclear. To address this question, we performed a prospective study of 80 patients with gastrinomas where SRS was compared with other conventional imaging techniques for detecting extrahepatic gastrinomas or liver metastases. Extrahepatic gastrinomas were identified by SRS in 58 percent of patients, whereas conventional imaging studies detected gastrinomas in 9 percent to 48 percent of patients. In detecting hepatic metastases in 24 patients with histologically-proven metastases, SRS was positive in 92 percent; ultrasound, CT or angiography in 42 percent to 62 percent; and MRI in 71 percent of patients. These results are compared with other studies in detecting gastrinomas as well as series including other PETs, excluding insulinomas, with insulinomas alone, and with carcinoid tumors. An analysis of the ability of SRS to identify gastrinomas found in different sites at surgery was performed. The role of endoscopic ultrasound (EUS) in detecting various PETs, in comparison to that of SRS, is yet to be established, particularly for extrapancreatic PETs. Therefore, the results of EUS in various studies containing patients with PETs are compared to those with SRS and conventional imaging studies. These data suggest that EUS is the first choice of localization methods for detecting insulinoma, which is an intrapancreatic tumor in almost all cases. In other PETs there still is not sufficient data to establish the relative roles of EUS and SRS.     

Recent data on molecular genetics of neuroendocrine tumors

Between December 1994 and April 1995, a nosocomial outbreak caused by a multi-resistant Acinetobacter baumannii, occurred on a surgical ward in our hospital. The organism was isolated from 13 patients, eight of whom were infected whereas the others were colonized. Twelve isolates were compared by cell envelope protein electrophoretic profiles and AFLP, a recently described DNA fingerprinting method. Both methods indicated that this outbreak was caused by spread of a single strain, which was identified as A. baumannii by amplified ribosomal DNA fingerprinting (ARDRA). A case-control comparison was performed to identify risk factors associated with nosocomial acquisition of A. baumannii. Risk factors for cross-colonization were length of stay, surgery, wounds and treatment with broad-spectrum antibiotics. Cross-infection with A. baumannii among patients occurred despite implementation of stringent infection control measures. The outbreak was controlled after temporary closure of the surgical ward for disinfection purposes. Patients admitted on a general surgical ward colonized or infected with multi-resistant A. baumannii strains should alert the hospital infection control team, and prompt implementation of strict infection prevention measures to prevent further spread is advised.     

Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors

Somatostatin receptor scintigraphy (SRS) has been used for the detection of gastroenteropancreatic (GEP) tumors. This study evaluates the clinical impact of SRS in GEP tumor detection and its therapeutic implications on patient management. METHODS: We prospectively studied 160 patients with biologically and/or histologically proven GEP tumors. Before SRS, patients were classified into three groups: gastrointestinal (Group 1; n = 90) patients without known metastases; (Group 2; n = 59) patients with metastases limited to the liver; (Group 3; n = 11) patients with known extrahepatic metastases. The scintigraphic data were compared to the radiological findings. RESULTS: In Group 1, without known metastases, conventional imaging detected 53 primary sites in 44 patients: SRS was positive in 68% of these sites and discovered 4 additional primary tumors in 3 patients and 16 metastases in 14 patients. Conventional imaging was negative in 46 patients: SRS discovered 47 new sites in 36 patients. In Group 2, SRS confirmed liver metastases in 95% of patients and discovered 45 new sites in 36 of these patients. In Group 3, SRS disclosed 11 new sites in 7 patients. These results modified patient classification in 38 cases (24%). Surgical therapeutic strategy was changed in 40 patients (25%). CONCLUSION: Somatostatin receptor scintigraphy improves tumor detection, has major clinical significance and should be performed systematically for staging and therapeutic decision making in patients with GEP tumors.     

Chorea in fifty consecutive patients with rheumatic fever

Envenomation by the brown recluse spider (Loxosceles reclusa) is associated with shock, significant hemolysis, renal insufficiency, and disseminated intravascular coagulation (DIC). Shock has never been associated with envenomation by L arizonica, a related species indigenous to Arizona, southern California, and northwestern Mexico. We report the case of a 13-year-old girl, bitten by a specimen of L arizonica (the spider was identified by an entomologist), in whom shock and a typical cutaneous lesion developed. She did not experience renal insufficiency or disseminated intravascular coagulation. Infectious causes of shock were excluded. She recovered completely with supportive care.     

Clinical spectrum of hyperglucagonemia associated with malignant neuroendocrine tumors

OBJECTIVE: To review the clinical features associated with hyperglucagonemia in malignant neuroendocrine tumors. MATERIAL AND METHODS: We retrospectively reviewed the medical records of patients with hyperglucagonemia encountered at our institution from Oct. 17, 1988, through February 1993 who had a fasting serum glucagon level of at least 120 pg/mL (twice the normal value). The 71 study patients also had no evidence of a secondary cause of hyperglucagonemia and had pathologic confirmation of a neuroendocrine tumor. RESULTS: The study group consisted of 46 men and 25 women with a median age of 57 years. Two patients had multiple endocrine neoplasia. Forty-nine patients had biochemically polyfunctional tumors, and 22 had hyperglucagonemia only. The most common initial symptoms were weight loss, abdominal pain, diarrhea, nausea, peptic ulcer disease, diabetes, and necrolytic migratory erythema (NME). Diabetes eventually developed in 25 patients and was associated with NME in 11. The highest median serum glucagon values occurred in patients with the glucagonoma syndrome or insulinomas, and the lowest median values were in those with carcinoid syndrome, Zollinger-Ellison syndrome, or diabetes without NME. Fasting glucagon and glucose measurements were not correlated. The most common hormonal syndromes were the Zollinger-Ellison syndrome and the glucagonoma syndrome. All the neuroendocrine tumors were malignant. Several methods of treatment, including surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization, were used. Death occurred in 29 patients at a median of 2.79 years after diagnosis; 42 patients were alive at a median of 2.86 years after diagnosis. CONCLUSION: A mild degree of hyperglucagonemia can commonly be associated with multifunctional neuroendocrine tumors. The glucagonoma syndrome occurs in a few patients with malignant neuroendocrine tumors and hyperglucagonemia and is associated with very high serum glucagon levels. The correlation between serum glucagon levels and the development of diabetes is limited, and other factors such as insulin may be more important than hyperglucagonemia in the development of diabetes.     

Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients

BACKGROUND: Patients with neuroendocrine carcinoma often present with liver metastases not amenable to hepatic resection. For them, liver transplantation has been considered a viable treatment option, especially if hormonal symptoms and pain cannot be controlled medically. Still, little is known regarding potential prognostic factors and long-term survival after liver transplantation for neuroendocrine tumors. METHODS: A search of English, French, and German literature identified patients with liver transplantation for extensive metastases from neuroendocrine carcinoma for whom follow-up data were available. RESULTS: Overall, 2-year and 5-year survival for all 103 patients was 60% and 47%, respectively, but recurrence-free 5-year survival did not exceed 24%. Univariate analysis identified age less than 50 years, primary tumor location in lung or bowel, and pretransplant somatostatin therapy as favorable prognostic factors, whereas extended operations combining liver transplantation with upper abdominal exenteration or Whipple's procedure were associated with poor prognosis. Multivariate analysis identified age greater than 50 years (P<0.03) and transplantation combined with upper abdominal exenteration or Whipple's operation (P<0.001) as adverse prognostic factors. CONCLUSIONS: Liver transplantation may be justified in selected patients to provide immediate relief of otherwise intractable pain or hormone-related symptoms. Transplantation with curative intent appears worthwhile in young patients with only hepatic disease. In older patients with extrahepatic disease requiring extended operations, long-term results are discouraging, and the small benefit achieved by liver transplantation must be weighed against medical treatment options and the natural course of often slowly progressing disease.     

Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors

Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.     

Colectomy as treatment for constipation in selected patients

The aim of this study was to conduct a prospective assessment of the results of total abdominal colectomy and ileorectal anastomosis (TAC) in patients with colonic inertia. Overall, 416 patients were evaluated for chronic constipation. Of the patients 54 (13 per cent) had colonic inertia, defined as diffuse marker delay during transit study without paradoxical puborectalis contraction on cinedefaecography or electromyography. All 54 patients (42 women and 12 men), with a mean age of 49 (range 17-78) years, underwent TAC. Preoperative bowel frequency was a mean of one every 8 days, requiring large doses of laxatives, enemas or both. There was no major postoperative morbidity; five patients were readmitted due to bowel obstruction, three for successful conservative management while the other two required enterolysis. After a mean follow-up of 27 (range 2-51) months these 54 patients reported a mean frequency of spontaneous bowel movements of 3.7 (range 1-10) per day. 'Excellent' or 'good' outcome was reported by 51 patients (94 per cent). TAC can be performed with acceptable morbidity and 94 per cent of patients will have satisfactory improvement in bowel habit.