Successful resection of hepatocellular cancer not amenable to Milan criteria and durable complete remission induced by systemic polichemotherapy after development of metastases - should we think about revising the current treatment guidelines in selected patients?

OBJECTIVES: To refresh clinical diagnostic and therapeutic dilemmas in patients presenting with hepatocellular cancer (HCC) and to report a rare success of systemic polichemotherapy in metastatic HCC. METHODS: Case report of a patient with successfully resected HCC although initially deemed inoperable according to current guidelines, and who was successfully treated by systemic polichemotherapy after development of metastatic disease, resulting in a sustained complete remission. RESULTS: We describe a 71-year-old female with HCC initially treated by atypical liver resection, although not amenable to initial surgery according to current treatment guidelines, which resulted in 6 months disease-free interval. After development of pulmonary metastases, the patient was treated by systemic polichemotherapy, due to local unavailability of novel biologic agents. After 3 months of chemotherapy biochemical remission was confirmed, and after 10 months of active treatment complete radiological remission was verified according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, now exceeding 9 months in duration. CONCLUSION: There is an increasing body of evidence that criteria for surgical interventions in HCC should be revised and expanded, and our case is an example of such an approach. Although novel biologic therapies are not widely available in all regions of the world due to their cost, currently there are no hard recommendations for use of chemotherapy in such areas. Since this is a large problem in clinical practice, we conclude that chemotherapy should be offered to selected patients of good performance status if novel agents are unavailable.

Paraneoplastic stiff person syndrome associated with colon cancer misdiagnosed as idiopathic Parkinson's disease worsened after capecitabine therapy.

OBJECTIVES: To refresh clinical diagnostic dilemmas in patients presenting with symptoms resembling to those of parkinsonism, to report rare association of colon cancer and paraneoplastic stiff person syndrome (SPS), and to draw attention on the possible correlation of capecitabine therapy with worsening of paraneoplastic SPS. METHODS: Case report of the patient with paraneoplastic SPS due to colon cancer that was misdiagnosed as idiopathic Parkinson's disease (iPD), whose symptoms worsened after beginning adjuvant capecitabine chemotherapy. RESULTS: We describe a 55-year-old woman with subacute onset of symmetrical stiffness and rigidity of the truncal and proximal lower limb muscles that caused lower body bradykinesia, gait difficulties, and postural instability. Diagnose of iPD was made and levodopa treatment was initiated but failed to provide beneficial effect. Six months later, colon cancer was discovered and the patient underwent surgical procedure and chemotherapy with capecitabine thereafter. Aggravation of stiffness, rigidity, and low back pain was observed after the first chemotherapy cycle and capecitabine was discontinued. Furthermore, levodopa was slowly discontinued and low dose of diazepam was administered which resulted in partial resolution of the patient's symptoms. CONCLUSION: Paraneoplastic SPS is rare disorder with clinical features resembling those of parkinsonian syndrome and making the correct diagnosis remains a challenge. The diagnosis of parkinsonian syndrome should be re-examined if subsequent examinations discover an associated malignant process. Although it remains unclear whether the patients with history of SPS are at the greater risk for symptoms deterioration after administration of capecitabine, clinicians should be aware of capecitabine side effects because recognition and appropriate management can prevent serious adverse outcomes.

[The role of KRAS gene mutation testing in colorectal cancer--a predictive biomarker of response to EGFR inhibitors therapy]. / Uloga mutacije gena KRAS u kolorektalnom karcinomu--prediktivni cimbenik odgovora na lijecenje inhibitorima EGFR-a.

Activation of KRAS oncogene has been implicated in colorectal carcinogenesis. KRAS mutations can be detected in more than 30% of all patients with colorectal cancer (CRC). Most recently, regimens that include anti-epidermal growth factor receptor (EGFR) targeted antibodies, cetuximab and panitumumab, for metastatic CRC have been developed. Several recent studies have shown that patients with KRAS mutations in codons 12 and 13 in metastatic CRC do not benefit from anti-EGFR therapy. With the aim to determine KRAS status as predictive biomarker, 7 known mutations ofKRAS gene in codons 12 or 13 on 44 CRC samples were tested. After DNA extraction from paraffin-embedded tumor tissue blocks, KRAS mutations were analysed using quantitative real-time PCR with internationally certified method, for the first time in Croatia. Mutations were detected in 12 tumor samples: five patients with Gly12Val (GGT>GTT), three with Gly12Asp (GGT>GAT), two patients with Gly13Asp (GGC>GAC), one patient with Gly12Ser (GGT>AGT) and one with Gly12Cys (GGT>TGT) mutation in tumor. Our data about KRAS mutational status in the sample of Croatian population diagnosed with CRC have shown that incidence of KRAS mutation is 27%, which is consistent with results already reported worldwide. The final result must be a proper selection of the correct therapy with EGFR inhibitors for the patients with CRC which is critical for improving clinical outcomes, unnecessary toxicities, side effects and financial cost.

Cochlear potential difference between endolymph fluid and the hair cell's interior: a retold interpretation based on the Goldman equation.

Reported cochlear potential values of near 150 mV are often attributed to endolymph itself, although membrane potentials result from ion fluxes across the adjacent semipermeable membranes due to concentration gradients. Since any two fluids separated by a semipermeable membrane develop potential due to differences in solute concentrations, a proposed interpretation here is that positive potential emanates from the Reissner membrane due to small influx of sodium from perilymph to endolymph. Basolateral hair cell membranes leak potassium into the interstitial fluid and this negative potential inside hair cells further augments the electric gradient of cochlear potential. Taken together as a sum, these two potentials are near the reported values of cochlear potential. This is based on reported data for cochlear fluids used for the calculation of Nernst and Goldman potentials. The reported positive potential of Reissner membrane can be explained almost entirely by the traffic of Na+ that enters endolymph through this membrane. At the apical membrane of hair cells, acoustic stimulation modulates stereocillia permeability to potassium. Potassium concentration gradients on the apical membrane are low (the calculated Nernst value is <+3 mV), suggesting that the potassium current is not caused by the local potassium concentration gradient, but an electric field between the positive sodium generated potential on the Reissner membrane and negative inside hair cells. Potassium is forced by this overall electric field to enter hair cells when stereocilia are permeable due to mechanical bending.

Fluorouracil, leucovorin and irinotecan combined with intra-arterial hepatic infusion of drug-eluting beads preloaded with irinotecan in unresectable colorectal liver metastases: side effects and results of a concomitant treatment schedule. Clinical investigation.

AIM: Safety evaluation of concomitant systemic chemotherapy and liver chemoembolization in patients with colorectal cancer. PATIENTS AND METHODS: Seven patients with metastases confined to the liver were included and stratified into two groups, depending of dosage of systemic chemotherapy. The first group received systemic chemotherapy (FOLFIRI) with 20% dose reduction, and the second group received the full dose of the same chemotherapy. In both groups, chemoembolization of liver metastases with drug-eluting bead irinotecan (DEBIRI) was performed following the application of systemic chemotherapy. The toxicity profiles of the two groups were compared. RESULTS: Of the 7 patients included, 4 received the reduced systemic chemotherapy dose and 3 received the full chemotherapy dose. DEBIRI was performed in all 7 patients. The main toxicities observed in the reduced chemotherapy dose group were leukopenia (25%), anorexia (75%), diarrhea (25%), vomiting (25%), right upper abdominal quadrant pain (100%) and elevated serum amylase level (25%). Main toxicities observed in the full chemotherapy dose group were anorexia (66.6%), vomiting (33.3%), right upper abdominal quadrant pain (100%), and elevated serum amylase level (66.6%). There were no significant differences between the two groups ( P = 0.78541). CONCLUSIONS: Patients with isolated liver metastases from a colorectal primary can safely be treated with DEBIRI chemoembolization and a full dose of systemic chemotherapy (FOLFIRI).