[SECRETING CARCINOID TUMORS OF TE DIGESTIVE TRACT].
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Appendiceal Neoplasms↗
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High coincidence of Mirizzi syndrome and gallbladder carcinoma.
BACKGROUND: Mirizzi syndrome is a rare complication of long-standing cholelithiasis. It is defined as obstructive jaundice caused by external compression of the common hepatic duct by an impacted stone in the gallbladder neck. Gallstone disease and cholelithiasis-associated chronic biliary inflammation may play a causative role in the pathogenesis of gallbladder carcinoma. The purpose of this study was to investigate the coincidence of gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the diagnostic value of elevated CA 19-9 levels as indicator for a coincidental gallbladder carcinoma in this syndrome was studied. METHODS: Patient demographics, clinical findings, laboratory data, results of diagnostic studies, pathologic reports, and intraoperative findings of 1579 patients undergoing cholecystectomy were obtained from patient records and were retrospectively studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical compression of the common hepatic duct by impacted gallstones, associated chronic cholecystitis, and a history of jaundice) were included in this study. RESULTS: Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed between January 1986 and March 1995 were identified. The seven male patients and 11 female patients had an average age of 74.8 years (range, 32 to 87 years). In five of these patients (27.8%) coincidental cases of gallbladder carcinoma were detected. The incidence of unsuspected malignancies in long-standing gallstone disease was 36 (2%) of 1759 and was statistically significantly different (p < 0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No significant difference was noted in age, gender, duration of jaundice, and type of lesions between these two groups. Tumor-associated antigen CA 19-9 level was elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within 18 months after operation. CONCLUSIONS: There is high association of gallbladder cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are indicative of a coincidental gallbladder malignancy. Because of this high coincidence of Mirizzi syndrome and gallbladder cancer we recommend an intraoperative frozen section of the gallbladder in all patients presenting with Mirizzi syndrome.
Adenocarcinoma↗
Osteomas of the gallbladder.
A 39-year-old woman had multiple osteomas of the gallbladder. She presented with right upper quadrant abdominal pain associated with leukocytosis. An ultrasound showed three small intraluminal gallbladder lesions with no apparent mobility. The lesions proved to be three small polypoid osteomas in the resected gallbladder. A review of the literature showed no previous report of this type of gallbladder neoplasm.
Adult↗
In primary sclerosing cholangitis, gallbladder polyps are frequently malignant.
OBJECTIVE: The management of gallbladder polyps/masses in patients with primary sclerosing cholangitis (PSC) (i.e., cholecystectomy vs observation) remains problematic. Given the risk of biliary tract cancer in PSC in the face of the benign nature of most gallbladder polyps in the general population, our aim was to determine the prevalence of gallbladder cancer in PSC patients with a gallbladder mass who had undergone cholecystectomy. METHODS: The case records of all patients with PSC undergoing a cholecystectomy at the Mayo Clinic between 1977-1999 were reviewed. RESULTS: Of the 102 patients with PSC who underwent a cholecystectomy, 14 of 102 (13.7%) had a gallbladder mass. In the subset of patients with gallbladder masses, eight of 14 (57%) had adenocarcinomas (seven primary adenocarcinomas and one metastatic cholangiocarcinoma); the other six had benign masses (five adenomas and one cholesterol polyp). In those patients with benign masses, 33% had associated epithelial cell dysplasia; in patients with primary gallbladder cancers, 57% had associated dysplasia. The patients with primary gallbladder adenocarcinoma had a favorable outcome after cholecystectomy, with a 36-month survival of 66%. CONCLUSIONS: In conclusion, gallbladder neoplasms in PSC patients are malignant in approximately 40-60% of the cases. The presence of gallbladder epithelial cell dysplasia suggests a dysplasia-carcinoma sequence in PSC similar to that observed in ulcerative colitis. Consideration should be given to performing a cholecystectomy in PSC patients with gallbladder polyps. If a cholecystectomy is not performed, careful interval follow-up is warranted.
Adenocarcinoma↗
European registry comparisons provide evidence of shared risk factors for renal, colon and gallbladder cancer development.
In order to assess links between renal cell cancer (RCCs) and transitional cell cancers (TCCs) of the kidney and cancer development in other organs of the abdominal cavity, incidence data from the Cancer Incidence in Five Continents (Vol VII) were compared between various cancer registries in Europe. Significant correlations which persisted on partial analysis were observed between RCCs and carcinomas of the colon and gallbladder, as well as between the latter themselves. Kidney TCCs, in contrast, were associated with tumours of the urinary bladder. In addition, significant correlations between hepatocellular, but not cholangiocellular carcinomas, and gallbladder and colon cancers were observed. Data for pancreas and gallbladder neoplasms also correlated. Prostate cancer incidences, while positively linked to RCCs, negatively correlated with gallbladder rates. The results point to shared risk factors for RCCs and adenocarcinomas in a number of organs, suggesting a role for humoral agents. The present findings also underline the necessity of distinguishing between tumour types within organs in epidemiological investigations of causal influences.
Adenocarcinoma↗
Clear cell carcinomas of the gallbladder and extrahepatic bile ducts.
Although clear cell carcinomas have been described in numerous anatomic sites, their occurrence in the gallbladder and extrahepatic bile ducts (EHBD) is practically unknown. We report 10 such cases. Seven arose in the gallbladder and three in the EHBD; all patients with gallbladder tumors were females with cholelithiasis whose ages ranged from 56 to 68 years. Patients with EHBD tumors were younger (38 and 40 years of age) and had extrahepatic biliary obstruction and abdominal pain. Two patients with gallbladder carcinomas had elevated serum carcinoembryonic antigen (CEA) levels, and another without hepatic involvement had markedly elevated circulating levels of alpha-fetoprotein (AFP). Histologically, nine tumors were adenocarcinomas and one was a squamous cell carcinoma. Seven adenocarcinomas consisted of cords, sheets, nests, papillae, and trabeculae of clear cells with well-defined cytoplasmic borders. Two were composed predominantly of glands and papillary structures. The cells contained PAS-positive diastase-labile granules and were cytokeratin- and EMA-positive and immunoreactive for erythropoiesis-associated antigen. One gallbladder tumor contained areas of hepatoid differentiation, a feature described in gallbladder neoplasms only once before. These areas were AFP-positive and immunoreactive for CEA. By electron microscopy, they showed hepatoid differentiation with formation of bile canaliculi. In two gallbladder tumors, neoplastic cells contained subnuclear vacuoles reminiscent of early secretory endometrium. Foci of conventional adenocarcinoma or mucinous carcinoma were recognized in all nine tumors. The squamous cell carcinoma showed only foci of squamous differentiation with keratinization. The clear cells of this neoplasm had a trabecular and solid growth pattern. These clear cell neoplasms of the gallbladder and EHBD must be differentiated from metastatic renal cell carcinoma, based upon the presence of areas of conventional adenocarcinoma or foci of squamous differentiation since results of special stains and immunohistochemistry are similar in both neoplasms. One of the patients with EHBD carcinoma is alive and symptom-free 6 years following right hepatic lobectomy. Five patients with gallbladder tumors had direct extension into the liver and died with metastases. Two are living with metastases.
Adenocarcinoma, Clear Cell↗
Fine needle aspiration cytodiagnosis of primary squamous cell carcinoma of the gallbladder. Report of two cases.
BACKGROUND: Cytologic descriptions of the diagnosis of the rare primary carcinoma of the gallbladder are sparse. The obstacles to the diagnosis are ascribed to vague symptoms and inaccessibility of the gallbladder to biopsy. We describe two cases of primary squamous cell carcinoma of the gallbladder that were diagnosed using fine needle aspiration (FNA) cytology. CASES: Both patients were elderly females with vague symptoms of abdominal pain, jaundice, loss of weight, anorexia and mild fever. Imaging studies showed enlargement of the gallbladder with a soft tissue mass in the fundus and abnormally thickened wall, indicative of a tumor. Also, in case 1, gallstones and enlarged, matted paraaortic and porta hepatis lymph nodes were present. FNA of the gallbladder was done after selection of a suitable puncture site and needle positioning, which was confirmed by computed tomography. The aspirated material was collected as needle and syringe washings, and from half the material filter preparations were made and stained for cytologic study, while the remainder was used for making cell blocks for histologic study. Both cases showed cytohistologic features of a moderately well differentiated, necrotizing squamous cell carcinoma characterized by keratinizing malignant cells with orangeophilic cytoplasm. In both cases immunostaining for high-molecular-weight keratins (AE1/AE3) and cytokeratin (CAM 5.2) was positive, while staining for carcinoembryonic antigen, B72.3 and other markers was negative. CONCLUSION: This study further confirmed that with the widespread use of more-sophisticated imaging techniques, the gallbladder is becoming more readily accessible to visualization. In view of this, FNA cytodiagnosis holds promise as a noninvasive technique in the diagnosis of gallbladder neoplasms.
Aged↗
SPECIALIZED ROENTGEN DIAGNOSTIC TECHNICS IN THE INVESTIGATION OF ABDOMINAL DISEASE.
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Abdomen↗
Papillary carcinomas of the gallbladder: analysis of noninvasive and invasive types.
CONTEXT: Although papillary carcinomas have been recognized as distinct morphologic variants of gallbladder neoplasms, they have been lumped together in a single group despite the recognition of noninvasive and invasive types. As a result, the biologic behavior of each type remains undescribed. OBJECTIVE: To compare the biologic behavior of noninvasive and invasive papillary carcinomas of the gallbladder. DESIGN: The clinical and morphologic features of 16 noninvasive papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical behavior was compared with that of 370 invasive papillary carcinomas recorded in the Survey Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1973 through 2001. The biologic behavior of invasive papillary carcinomas was compared with that of invasive nonpapillary carcinomas of the gallbladder recorded in SEER. Hematoxylin-eosin-stained sections were available for review in the 16 noninvasive papillary carcinomas. The number of slides examined per case varied from 3 to 16, with an average of 7. RESULTS: The 16 patients with noninvasive papillary carcinomas included 11 women and 5 men, aged 34 to 83 years (mean age, 61 years). Thirteen patients had cholelithiasis. Laparoscopic cholecystectomy was performed on 12 patients and open cholecystectomy on 4. The tumors measured from 1.3 to 8.6 cm and were well to moderately differentiated. Fourteen noninvasive papillary carcinomas showed biliary phenotype, and 2 showed intestinal phenotype. Follow-up was obtained in 11 patients; 6 were asymptomatic 5 to 11 years after surgery, 2 were symptom free 9 months to 4 years following cholecystectomy, and 3 died of unrelated causes 2 to 3 years after surgery. Three hundred seventy cases of invasive papillary carcinomas were recorded in SEER. The 10-year relative survival rate for 225 patients with invasive papillary carcinomas confined to the gallbladder wall was 52%, while the 10-year relative survival rate for 83 patients with papillary carcinomas that had spread to the lymph nodes was less than 10%. Of the remaining 62 invasive papillary carcinomas, 58 had distant metastases and 4 were not staged. The 10-year relative survival rate for invasive nonpapillary carcinomas confined to the gallbladder wall was 30%. CONCLUSION: Noninvasive papillary carcinomas of the gallbladder-regardless of size, cell phenotype, and degree of differentiation-do not metastasize, and a simple cholecystectomy appears to be a curative procedure. In contrast, invasive papillary carcinomas do metastasize and are associated with a poor prognosis (10-year relative survival rate for tumors confined to the gallbladder wall was 52%, while the 10-year relative survival rate for tumors with lymph node metastasis was <10%). The separation of papillary carcinomas into noninvasive and invasive types is clinically relevant and therefore fully justified.
Adult↗
A case of traumatic neuroma of the gallbladder in the absence of previous surgery and cholelithiasis.
We experienced a patient with traumatic neuroma of the gallbladder with no history of gallbladder surgery or cholelithiasis. A 74-year-old man was referred to our department after a gallbladder tumor was incidentally discovered during a preoperative screening examination for prostate hypertrophy. Ultrasonography, MRI, CT and endoscopic retrograde cholangiography revealed a protuberant lesion of the gallbladder. Laparoscopic cholecystectomy was attempted but adhesion between the liver and duodenum forced us to convert to open laparotomy. Cholecystectomy and adjacent liver tissue resection was performed. Diagnosis was made by frozen histology during operation. It revealed no malignancy. Postoperative pathological examination revealed traumatic neuroma associated with inflammation. To our knowledge, this is the first reported case of gallbladder neuroma without a history of gallstones or surgery in the English and Japanese literature since 1980. This traumatic neuroma should be considered in a differential diagnosis in treating gallbladder neoplasm, even in the absence of an operative history or cholelithiasis.
Aged↗
Cavernous hemangioma of the gallbladder. Case report and review of the literature.
UNLABELLED: Hemangiomas are common benign tumors; they frequently occur in the liver but very rarely in the gallbladder, with only seven cases reported in the scientific literature to date. We here report an additional patient, a 49-year-old white woman presenting with an echogenic lesion of the gallbladder that was incidentally discovered. Cholecystectomy was performed after computed tomography had revealed a gallbladder neoplasm; pathological examination showed the mass to be a cavernous hemangioma. No postoperative complications occurred and the patient is alive and free of recurrence five years after the operation. We present a review of the literature on this topic with special emphasis on the diagnostic and therapeutic challenges these lesions may entail. Hemangiomas of the gallbladder may have extremely variable presentations (from non-specific abdominal pain to acute syndromes resembling cholangitis or choledocholithiasis) and can mimic different lesions (liver tumors, sarcoma). Only surgical exploration can provide a correct diagnosis. Excision is indicated as these lesions may grow to huge sizes, compress adjacent structures or bleed. CONCLUSIONS: Gallbladder hemangiomas are uncommon benign tumors. A preoperative diagnosis is difficult to make. Surgical excision is mandatory both in reaching a final diagnosis and in preventing bleeding or compression of vital structures.
Female↗
Xanthogranulomatous cholecystitis: a radiological study of 12 cases and a review of the literature.
BACKGROUND: Twelve cases of xanthogranulomatous cholecystitis (XGC) are presented, and their radiologic appearance is described. METHODS: Four men and eight women, aged 31-82 years old, with XGC were reviewed. Abdominal ultrasound (US) was performed in all patients. Computed tomography (CT) was performed in five patients, barium enema examination in two, and percutaneously CT-guided fine-needle aspirative biopsy of the gallbladder in one. RESULTS: Barium enema examination showed an indentation of the hepatic flexure. Cholelithiasis was present in all patients, and sludge was present in six. The gallbladder wall was thickened in all patients, irregular in nine, and could not be properly differentiated from surrounding liver parenchyma or from other adjacent structures in most patients. A curvilinear halo, hypoechoic on US and with low attenuation on CT, within the gallbladder wall was found in three patients and pericholecystic fluid in two others. On CT, the pericholecystic fat had streaky soft tissue densities in three cases. Percutaneously CT-guided fine-needle aspirative biopsy of the gallbladder was nondiagnostic. The diagnosis of gallbladder carcinoma was considered preoperatively in three patients. CONCLUSION: Despite the characteristic histologic appearance of XCG, radiologic findings are nonspecific, varying from signs observed in other forms of cholecystitis to the appearance of a gallbladder neoplasm.
Adipose Tissue↗
The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review.
BACKGROUND: Cholangiocarcinoma and gallbladder cancer are difficult to treat curatively. The treatment of choice is surgery, dependent on detection at a resectable stage. No chemotherapy or radiotherapy options have shown substantial activity. Gemcitabine has demonstrated response in similar cancers. Considering the lack of treatment options for cholangiocarcinoma and gallbladder cancer, a systematic review of the evidence on gemcitabine use for these indications was performed. OBJECTIVE: To perform a systematic review to evaluate the role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer. METHODS: The MEDLINE database was searched (1996 to March 2005) using the medical subject headings 'gemcitabine' and 'gallbladder neoplasms' with results limited to English only. Proceedings from the 1998 to 2004 meetings of the American Society of Clinical Oncology, including the 2004 Gastrointestinal Cancers Symposium, were searched for relevant abstracts. The Canadian Medical Association infobase and the National Guidelines Clearinghouse were also searched for practice guideline reports. Reports were selected and reviewed by two reviewers, and the reference lists from those were searched for additional trials. RESULTS: A total of 13 single-arm phase II trial reports were obtained. CONCLUSIONS: In appropriate patients with gallbladder cancer or cholangiocarcinoma, surgery offers the best chance for survival and should remain the first treatment of choice. For patients not considered candidates for surgery, but willing and able to tolerate chemotherapy alone or in combination with a fluoropyrimidine (such as 5-fluorouracil or capecitabine), gemcitabine appears to be a reasonable alternative to best supportive care, although this conclusion has not been confirmed with a randomized controlled trial.
Antimetabolites, Antineoplastic↗
Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma.
This study was designed to test the hypothesis that cyclin D1 overexpression is involved in the multistep process of gallbladder carcinogenesis and can be used to predict poor prognosis for patients with gallbladder carcinoma (GBC). Cyclin D1 expression was examined immunohistochemically in a series of specimens, including 8 normal epithelia, 8 benign adenomyoma lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Four of the 6 (67%) adenomas and 15 of the 37 (41%) adenocarcinomas demonstrated cyclin D1 overexpression (>5% nuclear staining), whereas all normal epithelia and adenomyoma lesions were negative for cyclin D1. Kaplan-Meier curves showed that cyclin D1 overexpression was significantly related to decreased overall survival (P < 0.05) in patients with GBCs. The Cox proportional hazards model identified cyclin D1 overexpression as an independent prognostic marker for death (P = 0.024; risk ratio, 4.2; 95% confidence interval, 1.2-14.7). To test whether cyclin D1 overexpression is a critical event in gallbladder neoplasms, cyclin-dependent kinase inhibitor p27Kip1 was introduced to ascertain how cyclin D1 affects clinical outcomes. Subsequently, neoplasms were divided into three groups on the basis of the combination of cyclin D1 expression and p27Kip1 status, which had been determined previously. Group 1 showed no abnormality in either cyclin D1 or p27Kip1 expression. Group 2 showed aberrant expression of one of the two proteins, whereas group 3 showed concurrent abnormalities in both proteins. Results indicated that overall survival was greatest in group 1, followed by a significant decrease in group 2 and a more precipitous decrease in group 3. In conclusion, cyclin D1 overexpression is an early event in gallbladder carcinogenesis and independently predicts decreased survival for patients with GBC.
Aged↗
[Gallbladder carcinoma. Personal case histories].
BACKGROUND AND AIM: Carcinoma of the gallbladder is a rare pathology which is extremely malignant with a fatal prognosis owing to its difficult and late diagnosis. It represents 3% of all digestive tumours and is predominant in females. The major risk factor is gallbladder stones. METHODS: A total of 14 gallbladder neoplasms were diagnosed in 798 cholecystectomies performed from October 1990 to October 1995, with a male/female ratio of 6: 1 and a mean age of 68 years and 11 months. Biliary colic and jaundice represented approximately 93% of symptoms present in this series. Fourteen cholecystectomies were performed in association with other forms of surgery (1 GEA, 2 drainage acc. Kehr, 1 hemicolectomy, 1 resection of the hepatic bed, 1 hepaticojejunostomy). RESULTS: The operative mortality was nil. Mean survival was 1 year, 4 months and 15 days, and was obviously higher in the early stages. Four patients (all female) are still alive (mean survival 2 years 10 months 9 days). The five-year survival rate reported in the literature does not exceed 5-10%. Surgery does not currently give satisfactory results. In the light of present knowledge it is important to intervene on the risk factors in the form of laparoscopic cholecystectomies for patients with lithiasis or gallbladder polyps. CONCLUSIONS: Diagnosis must be as early as possible during the "early cancer" phase in order to ensure that surgery is oncologically radical and therefore also remedial.
Aged↗
[Cancer of the gallbladder].
A retrospective study was made of cancer of the gallbladder over a 10-year period, during which 874 operations of the biliary tract were performed, 26 for gallbladder neoplasm (2.97%). Of the 26 patients studied, 22 (84.6%) were women, mean age at appearance of the tumor being 63.9 years. In 77% of the patients the time of evolution of the symptoms was less than a year, a men of 3.6 months. The principal symptom was abdominal pain, encountered in 96% of patients, followed by nausea and vomiting (65.4%). Fifty-eight percent of patients had gallstones and 46% had metastases at the time of operation. In 23% of the patients only laparotomy and biopsy could be performed, 42% underwent cholecystectomy and 34% cholecystectomy and drainage of the biliary tract. Of the 26 patients in our study, 24 (92%) had adenocarcinoma.
Adenocarcinoma, Papillary↗
Detection of ras oncogene point mutations and simultaneous proliferative fraction estimation in gallbladder cancer.
Gallbladder cancer is notorious for its poor clinical evolution; so, a study of parameters with any prognostic potential is of particular interest. In this study, we investigated 23 adenocarcinomas regarding both the presence of point mutations in the ras gene family and the quantitative expression of Proliferating Cell Nuclear Antigen (PCNA). We respectively used molecular biology techniques and immunohistochemistry. Our results were related to several clinicopathologic determinators as well as to patients' survival. Mutations in codon 12 of the K-ras gene were detected in four gallbladder neoplasms (17%). This specific type of mutation is likely to be partially involved in this organ's tumourigenesis, particularly since no H-ras codon 12 or K-ras codon 13 (aspartic acid) mutations were detected in any of our specimens. PCNA immunoreactivity was generally limited in all tumours studied except for those morphologically characterized as being particularly aggressive. Notably, the four tumours in which K-ras mutation was detected, demonstrated relatively high PCNA positive immunoexpression in their malignant cells. This finding reinforces a possible correlation between the presence of ras mutations and increased cell growth. Staging was the only factor which was statistically associated with survival (p < 0.01). Therefore, the poor evolution of this cancer is probably due to late diagnosis and not related to a model of increased biologic aggressiveness.
Adult↗
[Anatomoclinical correlations in primary cancer of the gallbladder].
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Gallbladder Neoplasms↗