H. Maschek

Surgical treatment in proximal bile duct cancer. A single-center experience.

OBJECTIVES The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.

Benign Liver Tumors: Differential Diagnosis and Indications for Surgery

Abstract. The differential diagnosis for hemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma may be difficult. Reliable diagnosis is mandatory for the decision of whether to apply surgery or observation. Experience with long-term observation in nonoperated patients with hemangioma and FNH is limited. A group of 437 patients from a single institution were analyzed with regard to a diagnostic algorithm, the indications for surgery, and observation. There were 238 hemangiomas, 150 cases of FNH, 44 adenomas, and 5 mixed tumors. Of the 437 patients, 173 underwent surgery; 103 with hemangioma and 54 with FNH were observed at our own institution, whereas 117 patients underwent follow-up elsewhere or were lost. Among the operated patients with confirmed histology, a good diagnostic yield was found for a combination of ultrasonography (US), contrast (bolus)-enhanced computed tomography (CT), and labeled red blood cell (RBC) scanning: sensitivity 85.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 81.8%, and accuracy 91.3%. For FNH the combination of US and CT plus cholescintigraphy showed a sensitivity 82.1%, specificity 97.1%, PPV 95.8%, NPV 84.6%, and accuracy 90.3%. Surgical mortality was 0.6%. Observation of patients with hemangioma and FNH for a median of 32 months revealed no increase in tumor size in 80% and a decrease in fewer than 7%. There was no tumor rupture and no evidence of malignant transformation. We concluded that liver hemangioma and FNH can be differentiated from adenoma with high sensitivity, specificity, and accuracy by labeled RBC scanning and cholescintigraphy in combination with US and contrast-enhanced CT. In the case of symptoms or an equivocal diagnosis with respect to adenoma or hepatocellular carcinoma, surgery can be performed with very low risk. Because in asymptomatic patients with observed hemangioma or FNH no increase of tumor size can be expected for many years, the indications for surgery must be carefully evaluated.

Recurrence Patterns of Hepatocellular and Fibrolamellar Carcinoma After Liver Transplantation

PURPOSE Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients.

Abstract:  In a retrospective study of 352 patients with primary myelodysplastic syndromes, 61 (17.3%) revealed myelofibrosis in bone marrow biopsies. The fibrosis was observed to occur mostly focally (41/61 cases), and collagen deposits were found very rarely (4/61). The histopathology of bone marrow biopsies revealed hyperplasia and disturbed differentiation in megakaryopoiesis; the frequency and grade of dysplasia in megakaryopoiesis increased with advancing myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelo‐monocytic leukaemia (CMMoL). The frequency of cytogenetic aberrations was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly lower values of haemoglobin and lower platelet counts in MDS with myelofibrosis. Life expectancy was reduced to 9.6 months, compared with 17.4 months in MDS without fibrosis. In refractory anaemia, the survival times were 10.0 months in MDS with myelofibrosis, compared to 28.9 months in MDS without myelofibrosis. 36.6% of the patients with MDS and myelofibrosis developed a transformation into ANLL during the course of the disease. Myelofibrosis therefore seems to herald a poor prognosis.

Hypoplastic myelodysplastic syndrome: incidence, morphology, cytogenetics, and prognosis

SummaryThe present study, based upon the retrospective evaluation of 352 patients with primary myelodysplastic syndrome (pMDS), revealed hypoplastic MDS in 42 patients (11.9%). Median age is similar in hypo- and normo-/hypercellular MDS (72.6 versus 70.7 versus 72.4 years). Hypoplastic MDS occurred significantly more often in women compared with normo- and hypercellular MDS. Sequential biopsies were performed in 14 patients, showing a persistence of hypoplasia over a period of up to 43 months. The proportion of patients showing mesenchymal reaction, especially an increase of mast cells, was significantly higher in hypoplastic MDS, whereas dysplastic features of hematopoiesis occurred less frequently and were of lower grade in comparison to normo-/hyperplastic MDS. Among the subgroup with hypoplastic bone marrow, the classification according to FAB criteria revealed 28 patients with RA (66.7%), three with RARS (7.1%), and eight with RAEB (19.0%), as well as one patient each with RAEB-T and CMMol (2.4% each), and one case which had to be reckoned among the category of unclassifiable MDS (2.4%). Median survival was 21.8 months for hypoplastic MDS, 26.9 months for normoplastic MDS, and 14.2 months for hyperplastic MDS. During follow-up, 14 patients (33%) with hypoplastic MDS developed acute nonlymphatic leukemia. Although not a constant finding, karyotype abnormalities involving particularly chromosome 7 seem to be associated with hypoplastic MDS. The results confirm the existence of a hypoplastic variant of MDS which seems to more frequently affect female patients, and which requires bone marrow biopsy for its accurate diagnosis.

Monoclonal antibodies against inhibin represent key markers of adult granulosa cell tumors of the ovary even in their metastases: a report of three cases with late metastasis, being previously misinterpreted as hemangiopericytoma

Antibodies against human inhibin, a peptide hormone produced by ovarian granulosa cells to inhibit FSH, are widely applied to determine serum inhibin levels. Recently, they were, however, proved also to stain follicle cells in ovarian tissue by immunoreactions in histological sections. The commercially available inhibin antibody produced by Serotec, applied to sections of paraffin blocks, stained follicle epithelia in 6/6 samples of ovarian tissue from females under the age of 40 recruited from the archives. Adult granulosa cell tumor tissue samples from primary tumors of the ovary showed positive reaction in 6/6 cases. No positive reaction was found in staining tissues from hemangiopericytomas from males (0/3), leiomyomas, leiomyosarcomas, and a malignant melanoma (0/5), serving as negative controls. No positive reactions could be observed in tumor cells of 10 ovarian carcinomas, whereas in two of these cases single cells of the specialized ovarian stroma stained positively with inhibin. Positive immunostainings were revealed in three late metastases (two within the liver) from granulosa cell tumors in females, primarily misinterpreted as hemangiopericytomas or leiomyosarcomas, because the previously resected primaries of the ovary were not known at the time of liver surgery. The recognition of granulosa cell tumors, especially the distinction of the sarcomatoid growth type from soft tissue tumors, may be difficult, even if immunostaining for intermediate filaments are applied. Immunostaining by antibodies against inhibin, which can be applied reliably in histopathology, may therefore provide a useful tool to distinguish between granulosa cell tumors and genuine soft tissue tumors. This is also of clinical importance, because treatment of the former by cisplatin-based polychemotherapy and antisex hormone therapy proved to be helpful. Furthermore, the inhibin antibody can be used as an early serum marker for detecting tumor recurrence months before clinical evidence.

Ovarian-like stroma in an invasive mucinous cystadenocarcinoma of the pancreas positive for inhibin. A hint concerning its possible histogenesis.

Abstract A female patient with a mucinous cystadenocarcinoma originating from a mucinous cystadenoma of the pancreas is presented. The cystic tumour was diagnosed 3 years before and was treated with interventional external and internal surgical drainage before radical resection was accomplished by left hemipancreatectomy. Histology showed simultaneous occurrence of mildly dysplastic and invasive malignant epithelium. Immunohistology revealed inhibin-positive cells in the ovarian-like stroma of the tumour. The demonstration of ovarian-like stroma positive for inhibin suggests that this could be a hamartoma with dispersed sex-cord stroma, which would explain the predominance of the female gender in mucinous cystic tumours of the pancreas.

Life expectancy in primary myelodysplastic syndromes: a prognostic score based upon histopathology from bone marrow biopsies of 569 patients.

Abstract:  The retrospective evaluation of bone marrow biopsies of 569 patients with primary myelodysplastic syndrome ‐ pMDS ‐ revealed 256 refractory anemias ‐ RA ‐, 52 refractory anemias with ringed sideroblasts ‐RARS ‐, 133 refractory anemias with excess of blasts ‐ RAEB ‐, 52 refractory anemias with excess of blasts in transformation ‐ RAEB‐t ‐, and 53 chronic myelo‐monocytic leukemias ‐ CMMOL ‐ according to FAB‐criteria, 23 patients were not otherwise specified (myelodysplastic syndrome: not otherwise specified ‐ MDS.NOS ‐). RARS‐patients had the best prognosis (median survival 41.9 months, incidence of leukemia 3.8%), followed by RA‐patients (26.5 months, 16.4%), MDS.NOS‐patients (22.4 months, 21.7%), CMMOL‐patients (12.5 months, 49.1%). RAEB‐and RAEB‐t‐patients had the worst prognosis (median survival time 8.5 and 4.6 months, incidence of leukemia 42.1% and 57.7%, respectively). But the survival times showed a considerable range in each FAB‐subgroup with 0–154 months in RA or 0–52 months in CMMOL. To forecast life expectancy more precisely, a scoring system was developed using nine histopathological parameters, among which the three most important ones were determined: quantity of myeloblasts, myelofibrosis and ALIPs. The scoring system allows a determination of three risk groups with significantly different survival times. It is valid also for patients without increase of myeloblasts (<5% myeloblasts in the bone marrow) and identifies high‐risk MDS patients in this group. By this proposed scoring system, a prognostic approval in primary MDS can be achieved applying histopathology without regarding further methods herewith presenting a system which could be considered independently from hematologic, cytological or laboratory data.

Carcinoma of the ampulla of vater: determinants of long-term survival in 94 resected patients.

This retrospective study details 94 patients after surgical resection of carcinoma of the ampulla of Vater to determine prognostic factors. The tumour was limited to the ampulla of Vater in 32%, invaded the duodenal wall in 34%, infiltrated 2cm or less into the pancreas in 22%, and invaded more than 2cm into the pancreas and/or other adjacent structures in 11%. Curative resection was accomplished in 97% of cases. After exclusion of perioperative deaths the 1-, 5- and 10-year survival rates were 79.6%, 38.2%, and 31.6%, respectively with a median survival of 3.68 years. 26 patients survived more than five and 15 patients more than ten years. In an univariate analysis advanced tumour size, poor tumour grading, lymph node metastases and advanced UICC stage significantly decreased survival. Comparison of short and long survivors confirmed tumour size, lymph node status and UICC stage as significant prognostic factors. In a multivariate analysis (Cox model), only tumour size was a statistically independent predictor of prognosis. The survival probability increased with each year a patient survived after resection. When a patient had already survived five years after resection, the probability to survive another five years was 83%. Careful clinicopathologic staging is important for the prognosis after resection.

Squamous Cell Carcinoma of the Liver Originating from a Solitary Non-Parasitic Cyst: Case Report and Review of the Literature

Squamous cell carcinoma of the liver arising from a non-parasitic cyst is a rare entity of a primary liver tumor with an unfavourable prognosis. We report a case of a patient with a cyst in the right lobe leading to upper abdominal symptoms and respiratory discomfort. Malignancy was not suspected from the clinical findings or repeated cytological examination of the cyst fluid. However, the blood stained brown color of the cyst fluid was unusual. Cyst recurrence after six attempts of conservative treatment with sonography guided drainage over a period for more than one year led to laparotomy with cyst unroofing. Because frozen section from the cyst wall revealed the unexpected finding of squamous cell carcinoma right hemihepatectomy was performed during the same operation. The patient is alive more than four years after surgery without cyst or tumor recurrence. The difficulties in establishing diagnosis are confirmed by the review ofother reports. In the diagnosis and treatment ofsymptomatic non-parasitic liver cysts possible malignancy has to be considered. In case of proven carcinoma radical surgery with partial hepatectomy should be performed.