Extensive Hepatic Involvement Research Articles

A Rare Case of Amyloid Light Chain Amyloidosis with Extensive Hepatic Involvement

Abstract Introduction/Objective Amyloid light chain (AL) amyloidosis is a life-threatening disease entity, with an incidence of 10–15 per million per year in the USA. Amyloidosis is caused by the extracellular deposition of insoluble fibrillary amyloid protein resulting in multiorgan damage. Though amyloidosis is primarily a systemic disease, 10%-20% of cases can be localized. Methods/Case Report We present a case of a 37-year-old male admitted with predominant hepatic manifestations, whose liver biopsy led to the diagnosis of amyloidosis. The patient presented with intermittent abdominal pain, weight loss, persistent hypoglycemia, hepatomegaly, and raised liver enzymes. Imaging studies showed hepatomegaly with a heterogeneous lace like appearance of the liver parenchyma. Liver biopsy revealed an extensive deposition of amyloid protein in peri-sinusoidal spaces. The amyloid protein is highlighted by crystal violet stain and revealed apple- green birefringence on polarized microscopy after Congo red staining. On further evaluation, elevated kappa and lambda free light chains with increased kappa-lambda ratio were identified by serum protein electrophoresis. Subsequent bone marrow aspirate and biopsy identified a monoclonal kappa positive plasma cell neoplasm with an amorphous eosinophilic infiltrate. Liquid chromatography-tandem mass spectrometry on bone marrow biopsy detected a peptide profile consistent with AL (kappa) type amyloid deposition. Results (if a Case Study enter NA) NA. Conclusion AL amyloidosis patients with predominant hepatic involvement have a worse prognosis. Rapid diagnosis and prompt clinical intervention prevents further organ damage. This case study aims to promote awareness of the unusual presentations of amyloidosis.

Recurrent Cushing Syndrome Secondary to Metastatic Adrenocortical Carcinoma in a Patient With Previously Resected Adenoma

Background: ACTH-independent causes of Cushing Syndrome (CS) have mostly benign etiologies. For the majority of these conditions, surgery is the recommended treatment and is nearly 100% curative. Current guidelines do not specify follow up imaging recommendations in patients with resected adenomas. We present a case of severe CS secondary to an adrenal adenoma that was completely resected, and presented later as a metastatic adrenocortical carcinoma (ACC). Clinical Case: A 34- year-old woman presented with worsening confusion, weight gain and new onset diabetes and hypertension. Her history was significant for a 7 cm left adrenal mass and ACTH- independent CS previously treated with left adrenalectomy 2 years prior to this presentation. She was following with an endocrinologist who weaned her hydrocortisone to 10-5 mg. She completed a successful pregnancy but had worsening depression. Her steroids were stopped on admission and evaluation showed hypokalemia [2.9 mmol/L (n 3.5-5.1)], hypercortisolemia [29.9 mcg/dL (n 6.7-22.6)], and ACTH <12 pg/mL (n<46). This was followed with 1 and 8 mg dexamethasone suppression tests that she failed with cortisol levels of 37.8 and 41.6 mcg/dL respectively, late-night salivary cortisol of 0.974 ug/dL (n <0.181), and extremely elevated 24-hr urinary cortisol of 3,700.2 ug/d (n<45). Of the steroid hormone precursors, 11 deoxycortisol was elevated at 725 ng/dL (n<32) and DHEA-S was 29mcg/dL (n 35-430). A CT scan revealed multiple liver lesions, and no residual nodularity in the left adrenalectomy bed. Liver lesions were PET-avid, and biopsy confirmed metastatic ACC. Due to the extensive hepatic involvement, she was not a candidate for local therapy. She was started on mitotane and metyrapone for CS. She was treated with doxorubicin, cisplatin and etoposide chemotherapy every 4 weeks. Due to insurance issues; metyrapone was replaced by mifepristone. Over 8 weeks, mitotane level became therapeutic at 20 mcg/mL, hepatic masses decreased in size, and she transitioned form CS to adrenal insufficiency (AI) with am cortisol of 3 mcg/dL with accompanying nausea and improved glycemic control without medication. Next generation sequencing studies of the liver biopsy specimen revealed a frameshift loss of function mutation in FH that encodes the protein fumarase (c.912_918del p.F305fs; variant allele fraction - 67.8%). Conclusion: Metastatic ACC presenting with life-threatening CS presents a diagnostic and management challenge. Combination therapy with mitotane and chemotherapy demonstrated benefit in our patient. The transition from severe CS to AI due to mitotane was challenging to monitor biochemically due to mifepristone use. Loss of function FH mutation is associated with cancer progression. Patients with resected large adrenal adenomas require close monitoring to identify malignant behavior.

Primary biliary neuroendocrine carcinoma: A rare presentation

Presenter: Frances McCarron MD | St. Elizabeth Youngstown Hospital Background: Biliary neuroendocrine carcinomas make up approximately 0.2% of neuroendocrine neoplasm cases per the most recent WHO classification. Previous reports document tumors in the gallbladder and extra-hepatic bile ducts. There has been very little documentation of hepatic involvement of biliary NECs and even fewer reports of intra-hepatic biliary NENs. Given the rarity of these tumors, diagnosis can be mistaken for other malignancies such as cholangiocarcinoma, hepatocellular carcinoma or metastasis. Formal diagnosis, and thus targeted treatment, is usually delayed until post-operative pathology identifies the tumor. We present a rare case of poorly differentiated biliary neuroendocrine carcinoma (G3) with extensive hepatic involvement without evidence of distant metastasis. Methods: A 59-year-old female presented to her primary care office with symptoms of diverticulitis which was confirmed by CT of the abdomen and pelvis. An incidental 9.1cm lesion was identified involving segments 4B, 5, and 8 of the liver. The mass appearing hypodense on non-contrasted phase, with peripheral enhancement in the portal venous phase, was initially concerning for a pyogenic liver abscess secondary to diverticulitis. Differential diagnosis also included intra-hepatic cholangiocarcinoma, and less likely hepatocellular carcinoma or metastasis. A CT guided core biopsy of the lesion suggested a moderately differentiated adenocarcinoma of unknown primary. PET-CT scan showed hypermetabolic uptake of the mass without additional activity to suggest metastatic disease or alternate primary malignancy. Preoperative tumor markers were: CEA = 1.6, Ca 19-9 = 65, AFP = 6. The patient was referred to hepatobiliary surgery for resection. She underwent an en bloc cholecystectomy with central hepatectomy and intra-operative cholangiogram. Total operative time was 346 minutes, estimated blood loss = 600mL, pringle time = 15 minutes with a length of stay of 6 days. Her drain was removed on postoperative day 6. Results: Final pathology revealed a 12.5cm large cell neuroendocrine carcinoma involving the liver of biliary origin. Ki-67 uptake was present in 90% of tumor cells with 25 mitoses per 10 high power fields. An R0 resection was obtained. Pathology was also sent to University of Pittsburgh Medical Center whom concurred with our pathologists. She completed 4 cycles of adjuvant cisplatin and etoposide with no evidence for Conclusion: Biliary tract neuroendocrine neoplasms are exceedingly rare entities. It is estimated that approximately 0.5% of all NENs are of primary gallbladder origin and NEC make up 0.5% of all gallbladder carcinomas. Minimal reports of these tumors, make it difficult to identify the proper treatment modalities. In general, a poor survival rate and increased incidence of metastasis has been associated with G3 biliary NEC. We introduce a case of a rare presentation of a 12.5 cm large cell neuroendocrine carcinoma (G3) of biliary origin with hepatic involvement, no distant metastasis and good response to an R0 resection with 4 cycles of adjuvant chemotherapy. Further research, with long term follow up is needed to identify the optimal treatment plan for these rare tumors. However, this case poses a potential benefit for R0 resection with adjuvant chemotherapy.

Angiosarcoma: A Rare Cause of Acute Liver Failure

We are presenting a case of acute liver failure from angiosarcoma. The patient underwent liver transplant and her explanted liver showed angiosarcoma. She passed away from failure of her transplanted liver with autopsy showing angiosarcoma in her new liver. Hepatic angiosarcoma is difficult to diagnose, is a contraindication to liver transplantation, and carries a poor prognosis with or without liver transplantation. Our patient was a 56-year-old African American female found to have elevated liver function tests as part of bronchitis evaluation. She had no history of alcohol or drug use, or prior history of liver disease. Her acute liver injury rapidly progressed. Liver biopsy at outside hospital showed severe acute hepatitis with confluent necrosis and infiltrate of atypical reactive cells. On our assessment, her Model for End-Stage Liver Disease (MELD) score was greater than 40 and she developed altered mental status. Testing was negative for viral hepatitis. Alpha feto protein level was normal. Abdominal magnetic resonance imaging and CT chest showed a cirrhotic liver with heterogenous parenchyma suggestive of fibrotic changes and no abdominal or thoracic masses. She received orthotopic deceased-donor liver transplantation. Her post-operative course was complicated by liver function test abnormalities and intermittent altered mental status. Three weeks after liver transplant, a CT angiogram showed areas of necrosis and infarct in her liver despite patent hepatic vasculature. Pathology of her explanted liver revealed angiosarcoma with extensive vascular involvement with massive hepatic necrosis. A subsequent CT angiogram of her abdomen revealed worsening hepatic infarcts with diminutive right and left hepatic arteries. She was transitioned to comfort care and passed away. Autopsy revealed angiosarcoma in her liver, with diffuse hepatic necrosis and numerous infarcts.2309_A Figure 1 No Caption available.2309_B Figure 2 No Caption available.2309_C Figure 3 No Caption available.Despite extensive hepatic involvement of angiosarcoma in this patient's explanted liver and autopsy, pre and post transplant imaging were not interpreted as being concerning for malignancy, and pre transplant liver biopsy had nonspecific features without concern for malignancy. Hepatic angiosarcoma is rare, and it rarely results in fulminant liver failure. This atypical presentation poses a clinical dilemna. Hepatic angiosarcoma should be considered in the differential diagnosis in the setting of hepatic necrosis and worsening hepatic infarcts pre- and post-liver transplant.

Theranostics: radionuclide imaging and therapy in neuroendocrine tumours

Neuroendocrine tumours (NETs) are a heterogeneous group with significant variation in morphological characteristics and functional behaviour. This poses challenges in terms of both biochemical and imaging assessment. Somatostatin receptor (sst) overexpression is documented in several malignancies. The sst subtype 2 (sst2) is overexpressed in NETs [1] and can be targeted for both somatostatin receptor scintigraphy and therapy. In-111-octreotide (Octreoscan), a gamma imaging sst agent, binds with relatively high affinity to sst 2.This has good overall sensitivity in the detection of NETs (80-100%) [2]. However, sensitivity varies according to tumour type, grade, and location (e.g. sensitivity 24% in insulinomas) [3]. PET agents such as Ga-68-DOTA-labelled somatostatin analogues have been developed with higher receptor affinity when compared to gamma-based agents. This leads to improved target-to-background ratio and provides the improved imaging characteristics inherent of PET tracers. A 2012 meta-analysis demonstrated pooled sensitivity and specificity in detecting NETs of 93% and 91%, respectively [4] with higher detection rates compared to conventional sst imaging [5]. Whilst other PET tracers such as F-18-DOPA have shown utility and higher sensitivity than conventional sst scintigraphy, their role is limited to problem solving at present. F-18-FDG can, however, provide prognostic information with patients showing uptake having a progression free survival of 0% at 2 years compared with 75±10% in those without uptake [6]. Peptide receptor radionuclide therapy (PRRT) utilises primarily beta-emitting radioisotopes such as Lu-177 and Y-90 linked to somatostatin analogues such as DOTATATE and DOTATOC. Whilst phase 3 data comparing PRRT with other therapies is awaited, treatment with Y-90 and Lu-177 PRRT has been shown to have response rates of approximately 80% and to confer a survival advantage over historical controls [7]. Unsurprisingly, extensive hepatic involvement is an adverse factor for progression free survival, whereas high tumour uptake in pre-therapy imaging confers prolonged survival [8]. Due to the differences in beta particle energy and path length, it has been postulated that Lu-177 PRRT would be best suited to smaller tumour volumes compared with Y-90 which emits a more energetic particle with longer path length. Kunikowska and colleagues have now demonstrated that overall survival is significantly higher in patients treated with combination Y-90/Lu-177-DOTATATE compared with Y-90-DOTATATE alone [9]. Research into the role of sst antagonists is relatively new. Several studies have shown a significantly greater number of binding sites for antagonists when compared to agonists such as Lu-177-DOTATATE. Pilot studies have shown 1.7-10.6 times higher tumour dose with the antagonist Lu-177-DOTA-JR11 when compared to Lu-177-DOTATATE [10]. Encouraging results have also been obtained with the use of radiosensitising chemotherapeutic agents administered together with PRRT. A phase 2 study evaluating capecitabine with Lu-177-octreotate demonstrated a response rate of 94% with no significant increase in toxicity [11]. Further work is required, however, these advances are likely to play a significant role in the future.

Single-Center Experience of Transplantation for Polycystic Liver Disease

BackgroundPolycystic liver disease (PLD) may lead to massive hepatomegaly, abdominal distension, pain, and various degrees of dyspnea. The surgical treatment of this entity remains controversial. MethodsWe report our experience from a retrospective analysis of 23 patients suffering from PLD who were treated with liver transplantation (LT) in our institution. ResultsLiver transplantation for PLD patients with extensive hepatic involvement offers excellent symptoms relief. The actuarial 1-, 3-, and 5-year survival rate after transplantation was 86%. ConclusionsOur experience demonstrates that PLD patients with extensive hepatic involvement and who are treated with LT have good long-term prognosis and excellent symptoms relief. LT might be considered in severe PLD cases where conventional surgery is not a curative option, and it must be balanced against the risks of LT and lifelong commitment to immunosuppression.

FDG Hepatic Superscan Caused by Massive Breast Cancer Invasion

A 46-year-old woman who was treated in the past for locally advanced breast cancer, presented with signs of acute liver failure. FDG PET revealed a massive hot liver with increased activity without any pathologic FDG uptake elsewhere in the body. Therefore, the term hepatic superscan was chosen because intense diffuse hepatic FDG uptake was seen in combination with a surprisingly low cardiac and in minor degree of low brain uptake, similar to the superscan pattern encountered in conventional skeletal scintigraphy. This very unusual finding was the indicator of extensive hepatic involvement caused by breast cancer.

Polycystic Liver Disease: Multimodality Imaging for Complications and Transplant Evaluation

Polycystic liver disease (PLD) is usually associated with polycystic kidney disease but may also occur as an isolated finding in a rarer genetically distinct disease. In either case, the cyst burden will progress over time and, in rare cases, may affect liver function or become symptomatic due to massive hepatomegaly. The character, distribution, location, and size of hepatic cysts are important. Computed tomography, magnetic resonance imaging, or ultrasonography may provide the surgeon with valuable preoperative information, such as the location of infected or hemorrhagic cysts that may be responsible for symptoms. Less invasive cyst aspiration or fenestration may provide temporary relief from dominant or symptomatic cysts, but these cysts will recur in up to 75% of patients. Cyst fenestration with partial hepatic resection and liver transplantation are two therapies that provide more permanent resolution of symptoms in patients with extensive hepatic involvement. However, the higher risk of complications associated with more aggressive surgical therapy must be considered when determining the appropriate therapy for a given patient. Knowledge of the cyst patterns and available treatment options in patients with PLD will help the radiologist provide the referring clinician with important information for therapeutic decision making.

The clinical approach to desmoplastic small round cell tumor

Background and Objectives: Desmoplastic small round cell tumor (DSRCT) is an increasingly recognized entity with a historically poor prognosis. This article describes the present clinical management of these patients. Methods: We retrospectively reviewed our experience with 40 histologically proven cases of desmoplastic small round cell tumor diagnosed between 7/1/72 and 10/1/99. Thirty-five of these patients are the subjects of a previous report. Demographic data, mode of presentation, completeness of resection, and overall survival were assessed. Results: The overall survival from DSRCT remains very poor and in our series was 29% at three years from diagnosis. There is a significant correlation between use of intense alkylator therapy (P6 protocol), and gross total resection with improved overall survival. It is often technically feasible to remove large peritoneal masses using a tangential dissection technique. Extensive hepatic parenchymal or hilar involvement or extensive infiltration of the diaphragm in the region of the septum transversum and hepatic veins usually makes gross total resection impossible with a corresponding worsened prognosis. Conclusion: We recommend induction chemotherapy (P6) followed by aggressive surgical debulking and external beam radiotherapy for the treatment of DSRCT. Further progress will require new forms of treatment.

Effectiveness of Preoperative Transarterial Chemoembolization in Presumed Inoperable Hepatoblastoma

To evaluate the effectiveness and therapeutic role of preoperative transarterial chemoembolization (TACE) of hepatoblastoma. Four patients (one boy, three girls) with unresectable hepatoblastoma were treated twice with preoperative TACE in an effort to improve the surgical and clinical outcome. The patients ranged in age from 8 to 27 months (mean, 15 months). The first TACE was performed superselectively in tumor feeding arteries. The second TACE was performed 3 weeks later. Surgical hepatic resection was performed 1 month after the second TACE. Contrast-enhanced computed tomography (CT) was used to evaluate changes in size, volume, internal texture, and margin of the masses. The toxicity of the chemotherapeutic drugs was evaluated by blood chemistry analysis (AST/ALT, alpha-FP) performed before and after TACE, and after surgery. TACE allowed subsequent surgical resection in all four patients, who remained disease free 16-52 months after operation. There were no major problems related to TACE. There was no chemotherapeutic agent toxicity from TACE. The average largest diameters and volumes of the tumors decreased by 31% (8.3 to 5.6 cm) and 69% (317 to 93 cm2), respectively. TACE provided subsequent successful surgical resection and good long-term results in all four patients. The hepatoblastomas were initially considered inoperable because of extensive hepatic involvement and indistinct margins.

Liver transplantation for adult polycystic liver disease.

Polycystic liver disease, commonly associated with polycystic kidney disease, can result in massive hepatomegaly and debilitating symptoms. Surgical intervention for symptomatic polycystic liver disease has been associated with significant morbidity and inconsistent long-term palliation; it is more appropriate in patients with a single dominant cyst or cysts which is/are confined to one lobe. At our institution, nine patients have undergone orthotopic liver transplantation for symptomatic hepatic cysts with excellent long-term results and minimal morbidity and mortality. Surgical candidates were selected based on severe limitations in daily activities and on sequelae of hepatic cystic involvement. Other factors considered were the extent and pattern of hepatic cystic disease, the degree of hepatic and renal dysfunction, and prior surgical intervention. Three patients (33%) required combined liver and kidney transplantation because of renal cystic involvement with renal insufficiency. The one-year survival rate was 89% with excellent symptomatic relief and improved quality of life in all the surviving patients. One death occurred in a significantly malnourished 62-year-old female. Complications included one case each of hepatic artery thrombosis requiring retransplantation, biliary leak necessitating biliary reconstruction, and postoperative bleeding requiring re-exploration. The mean hospital stay was 23 days and the mean intraoperative blood transfusion requirement was 18 units. Our experience demonstrates that appropriately selected patients with extensive hepatic involvement with adult polycystic liver disease can have an excellent outcome with transplantation, with morbidity comparable with other surgical options.

Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours

Background—Somatostatin receptor scintigraphy (SRS) and octreotide therapy have both changed the management of gastroenteropancreatic endocrine tumours, but very few data are available on the use of SRS and octreotide to...

Une cause peu connue de fièvre prolongée et d'hépatite granulomateuse chez l'enfant: la maladie des griffes du chat

Background. - Extensive hepatic and splenic involvement in cat-scratch disease has rarely been reported. Case report. - A 2 1 2 year-old boy suffered for 2 weeks from high-grade fever, abdominal pain and alteration of his general condition. Ultrasonography revealed multiple hypoechogenic nodules in liver and spleen. The CT scan also showed hypodense lesions. An open liver biopsy was performed 5 weeks after the onset of illness. Histopathology of a resected nodule demonstrated neutrophilic granulomatous inflammation with central abscess formation. Recent cat exposure, suppurated epitrochlear lymph node 15 days before admission were also consistent with cat-scratch disease which was confirmed by elevated anti-Rochalimaea antibody titers. Follow-up showed complete resolution of all hepatic and splenic lesions within 6 months and emergence of splenic calcifications. Conclusion. - Cat-scratch disease should be considered in the diagnosis of fever of unknown origin and hepatosplenic abscesses in children.

Hepatic, pulmonary, and CNS involvement by histiocytosis X in an adult: MRI and CT appearance

Histiocytosis X (HX) is a disease of the lymphoreticular system characterized by histiocytic infiltration of one or more tissues. We present a case with extensive hepatic involvement in an adult visualized on ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). The findings on MRI are strongly suggestive of the correct diagnosis.

Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer.

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.

Antibiotic Therapy for Cat-scratch Disease?

Cat-scratch disease is usually a benign, self-limited disease that causes regional lymphadenopathy. Occasionally, it may present with systemic symptoms and have a prolonged course. To date, antibiotic therapy has not been proved to be of value. We describe three patients with cat-scratch disease who were treated successfully with gentamicin sulfate. Two patients had extensive hepatic involvement, and one patient had regional lymphadenopathy. All three patients responded within 48 hours to intravenous gentamicin. Extensive follow-up has shown no recurrence of symptoms. These cases suggest that gentamicin may be efficacious in shortening the course of cat-scratch disease. Prospective, randomized trials should be performed to confirm these results.

Hepatocellular carcinoma: assessment of resectability by computed tomography and ultrasound.

A retrospective review of the CT and ultrasound scans from examinations of 30 patients who had hepatocellular carcinoma (hepatoma) was undertaken with special emphasis placed on evaluation of hepatic distribution of tumor, vascular invasion, and extrahepatic spread. Although both CT and ultrasound detected hepatoma in 29 of 30 patients (96%), CT showed more extensive hepatic parenchymal involvement in eight of the patients. Vascular invasion was seen more frequently with ultrasound than with CT. Invasion into the main portal vein was seen by ultrasound in 11 of 30 patients (37%). Extrahepatic spread of tumor was much more frequently detected by CT and was present in 21 of 30 patients (70%). A reasoned approach to the diagnostic workup of hepatomas that will minimize invasive procedures and unnecessary surgery is presented.

Metastatic carcinoma of the breast: A cause of obstructive jaundice

Two cases of jaundice are reported that were secondary to obstruction of the common bile duct by metastatic carcinoma of the breast and relieved by palliative surgery. In one case, obstructive jaundice was the first evidence of spread beyond regional lymph nodes, in the other patient it was a late manifestation of the disease. In patients with prior history of carcinoma of the breast, jaundice may be secondary to obstruction of the common bile duct, and, because it is amenable to palliation, this possibility should be investigated before concluding that extensive hepatic involvement is the cause of jaundice.