Woubet T. Kassahun

Focus on parathyroid carcinoma

Parathyroid carcinoma is a malignant neoplasm affecting 05-2 per cent of all patients with primary hyperparathyroidism that was first described by de Quevain in 1904. To day it continues to defy diagnosis and treatment. It is difficult to diagnose in part because of its rarity, lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism. As a result initial surgical treatment is inadequate essentially leading to disease recurrence where complete cure is unlikely. En bloc surgical resection remains the only curative treatment, and high priorities are improving diagnostic methods, and clinical staging for resection once the disease is suspected. Margin status at resection is related to prognosis. Thus, a trend towards aggressive surgical management has improved outcomes. The recurrence rate of parathyroid carcinoma is as high as 80% with survival rates <50% at 10 years. Results of chemotherapy are disappointing. However, recent trials using radiation therapy are promising, but require further study.

Organotypic slice cultures of human gastric and esophagogastric junction cancer

Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6‐well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki‐67 for proliferation, and cleaved caspase‐3 staining for apoptosis. The slices were analyzed under naive conditions and following 2–4 days in vitro exposure to 5‐FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response.

Expression and functional coupling of liver β2 - adrenoceptors in the human hepatocellular carcinoma.

Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. There are now multiple lines of evidence demonstrating that the β-adrenoceptor (β-AR) signaling plays an important role in the progression and metastasis of cancer and may become a novel target for cancer therapy. Little information exists regarding the status of β-ARs and their postreceptor intracellular signaling cascade in the development of human HCC. This study was conducted to detect the expression signal transduction of the β-ARs in liver membranes obtained from patients with HCC and elucidate their possible implication on HCC development. Methods: The β-AR density and subtype distribution were determined by receptor binding studies. Protein levels of the β2-AR and Gsα protein were determined by Western blot analysis. The receptor coupling efficiency and biochemical activities of the adenylate cyclase (AC) was also determined. Results: In HCC liver membranes, the β2-AR density was higher than the density in the nonadjacent nontumor liver membranes. The β2-AR protein expression was 1.5-fold increased as compared with nonmalignant controls, and positively correlated with the receptor density. The Gsα protein expression as well as the receptor, AC and G protein-stimulated activation of the cAMP formation was reduced in HCC. Conclusion: The β2-AR was upregulated in human HCC. Despite this upregulation of the receptor, there was an altered postreceptor signal transduction in HCC liver. The mechanisms responsible for this change in the growth of HCC and the nature of this alteration remain unclear.

A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis

Background. A 59-year-old man presented for a follow-up, 6 years after surgery for a large pheochromocytoma. He had suffered from diabetes mellitus, hypertension and abdominal pain in the right flank region. Previous postoperative follow-up did not reveal tumor recurrence.Investigation. Measurement of plasma free metanephrine and normetanephrine by high-performance liquid chromatography and radioimmunoassay; 123I-metaiodobenzylguanidine (MIBG) scintigraphy; hybrid 123I-MIBG single-photon emission CT (SPECT)–CT; MRI; testing for plasma norepinephrine and epinephrine; intraoperative ultrasonography; histological staining for chromogranin A and synaptophysin; and postoperative 18F-dihydroxyphenylalanine (DOPA) PET scan.Diagnosis. Recurrent pheochromocytoma.Management. Laparotomy with tumor resection. Reduction of antihypertensive medications. Further follow-up by MRI, hybrid 123I-MIBG SPECT–CT and testing for plasma catecholamines and free metanephrines.

Unresolved issues and controversies surrounding the management of colorectal cancer liver metastasis.

Ideally, tumors that might cause morbidity and mortality should be treated, preferably early, with proven, convincing, and effective therapy to prevent tumor progression or recurrence, while maintaining a favorable risk-benefit profile for the individual patient. For patients with colorectal cancer (CRC), this diagnostic, prognostic, and therapeutic precision is currently impossible. Despite significant improvements in diagnostic procedures, a sizable number of patients with CRC have liver metastases either at presentation or will subsequently develop it. And in many parts of the world, most cancer-related deaths are still due to metastases that are resistant to conventional therapy. Metastases to the liver occur in more than 50% of patients with CRC and represent the major determinant of outcome following curative treatment of the primary tumor. Liver resection offers the best chance of cure for metastases confined to the liver. However, due to a paucity of randomized controlled trials, its timing is controversial and a hotly debated topic. This article reviews some of the main controversies surrounding the surgical management of colorectal cancer liver metastases (CRLM).

Psoas abscess secondary to retroperitoneal distant metastases from squamous cell carcinoma of the cervix with thrombosis of the inferior vena cava and duodenal infiltration treated by Whipple procedure: A case report and review of the literature

BackgroundPsoas abscess is a rare clinical disease of various origins. Most common causes include hematogenous spread of bacteria from a different primary source, spondylodiscitis or perforated intestinal organs. But rarely some abscesses are related to malignant metastatic disease.Case presentationIn this case report we present the case of a patient with known squamous cell carcinoma of the cervix treated with radio-chemotherapy three years prior. She now presented with a psoas abscess and subsequent complete inferior vena cava thrombosis, as well as duodenal and vertebral infiltration. The abscess was drained over a prolonged period of time and later was found to be a complication caused by metastases of the cervical carcinoma. Due to the massive extent of the metastases a Whipple procedure was performed to successfully control the local progress of the metastasis.ConclusionAs psoas abscess is an unspecific disease which presents with non-specific symptoms adequate therapy may be delayed due to lack of early diagnostic results. This case report highlights the difficulties of managing a malignant abscess and demonstrates some diagnostic pitfalls that might be encountered. It stresses the necessity of adequate diagnostics to initiate successful therapy. Reports on psoas abscesses that are related to cervix carcinoma are scarce, probably due to the rarity of this event, and are limited to very few case reports. We are the first to report a case in which an extensive and complex abdominal procedure was needed for local control to improve quality of life.

Spectrum of benign lesions mimicking a malignant stricture at the liver hilum.

There is a broad spectrum of benign disorders of the biliary system that resemble hilar cholangiocarcinoma (HCCA) in terms of clinical, pathologic, and imaging findings. No unifying features were found to characterize patients with benign hilar obstruction and distinguish these patients from those with cholangiocarcinoma. Imaging plays a vital role in aiding the differentiation of benign and malignant disease, defining the location and extent of the process, as well as directing biopsy. However, even when lesions at the liver hilum are detected with the highest sensitivity, none of the imaging modalities can reliably characterize and confirm the underlying type of disease. Excessive reliance on cholangiographic or endoscopic biopsy results is dangerous, because tissue sampling is not always diagnostic and a potentially resectable malignancy can be overlooked. Therefore, the preferred treatment option to patients with suspicious hilar lesions should remain resection for presumed malignancy. Local resection with adequate reconstruction excludes a malignant lesion, and provides means of biliary decompression with low mortality and morbidity rate.

Controversies in defining prognostic relevant selection criteria that determine long-term effectiveness of liver resection for noncolorectal nonneuroendocrine liver metastasis

The usefulness of liver resection in the treatment of colorectal liver metastasis and metastases from neuroendocrine tumors of the gastrointestinal tract has been studied extensively. However, the role and utility of surgery in treating patients with noncolorectal nonneuroendocrine liver metastasis (NCNNLM) is poorly defined and controversial. Despite the broadening indications of liver resection for NCNNLM, the group of patients who would benefit from surgery is still unknown. Because tumor biologies among NCNNLM vary widely, it has been difficult to determine which factors influence overall survival. Attempts have been taken in the literature to identify a variety of factors which may influence outcome following liver resection for NCNNLM. Almost all of these data are drawn from retrospective studies, and its relevance to contemporary practice is not known. Many centers have published prognostic factors which influence survival; jet the results are contradictory for these factors. There is no uniformity in the various prognostic factors reported. This review has been undertaken to provide an overview of these important controversies.

Altered liver α1-adrenoceptor density and phospholipase C activity in the human hepatocellular carcinoma.

The human hepatocellular carcinoma (HCC) is a common cancer with high mortality rate. We examined the density and coupling to phospholipase C (PLC) of the α(1)-adrenoceptors. In HCC liver, the α(1)-adrenoceptor density - as assessed by [³H]-Prazosin binding - was significantly reduced to about 75% when compared to non-adjacent non-tumorous liver (NA-NL) (P=0.0002). The decrease in maximal α(1)-adrenoceptor concentration (B(max)) was accompanied by a significant reduction in noradrenaline-stimulated PLC activity (P<0.032 versus NA-NL) (assessed by [³H]-PIP(2) hydrolysis). GTPγS-stimulated PLC activity in HCC livers did not statistically differ from NA-NL livers. NaF, which activates all G-proteins, stimulated PLC in both HCC and NA-NL livers to a similar extent. The altered noradrenaline-induced functional responsiveness of HCC livers was not reflected by changes in the binding affinity of [³H]-Prazosin for α(1)-adrenoceptors (NA-NL: 0.066 ± 0.010 pmol/l; tumour: 0.067 ± 0.020 pmol/l). These results demonstrate that human HCC causes profound alteration of the hepatic α(1)-adrenoceptor signal transduction pathway and may account for a negative cancer related metabolism of carbohydrates and wasting syndrome in tumour patients.

The effects of pre-existing dementia on surgical outcomes in emergent and nonemergent general surgical procedures: assessing differences in surgical risk with dementia

BackgroundThe aim was to assess the morbidity and in-hospital mortality that occur in surgical patients with pre-existing dementia compared with those outcomes in non-dementia patients following emergent and nonemergent general surgical operations.MethodsA total of 120 patients with dementia were matched for sex and type of surgery with 120 patients who did not have dementia, taken from a cohort of 15,295 patients undergoing surgery, in order to assess differences in surgical risk with dementia. Patient information was examined, including sex, body mass index (BMI), prevalence of individual comorbidities at admission, and several other variables that may be associated with postoperative outcomes as potential confounders.ResultsPatients with dementia tended to have a higher overall complication burden compared to those without. This was evidenced by a higher average number of complications per patient (3.30 vs 2.36) and a higher average score on the comprehensive complication index (48.61 vs 37.60), values that were statistically significant for a difference between the two groups. The overall in-hospital mortality in patients with dementia was 28.3% (34 deaths out of 120 patients). During the same period, at our hospital, the overall in-hospital mortality in the control group was 20% (24 deaths out of 120 patients). Patient groups with and without dementia each had 3 and 5 associated risk factors for morbidity and 9 and 12 risk factors for mortality, respectively.ConclusionsPatients with pre-existing dementia have a greater than average risk of early death after surgery, and their incidence of fatal complications is higher than that of surgical patients without dementia.