Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma.

HCC remains one of the leading causes of cancer-related death globally. The main challenges in treatments of hepatocellular carcinoma (HCC) primarily arise from high rates of postoperative recurrence and the limited efficacy in treating advanced-stage patients. Various signaling pathways involved in HCC have been reported. Among them, the Sonic hedgehog (SHH) signaling pathway is crucial. The presence of SHH ligands is identified in approximately 60% of HCC tumor tissues, including tumor nests. PTCH-1 and GLI-1 are detected in more than half of HCC tissues, while GLI-2 is found in over 84% of HCC tissues. The SHH signaling pathway (including canonical and non-canonical) is involved in different aspects of HCC, including hepatocarcinogenesis, tumor growth, tumor invasiveness, progression, and migration. The SHH signaling pathway also contributes to recurrence, metastasis, modulation of the cancer microenvironment, and sustaining cancer stem cells. It also affects the resistance of HCC cells to chemotherapy, target therapy, and radiotherapy. Reappraisal of the roles of the SHH signaling pathway in HCC may trigger some novel therapies for HCC.

Case 296: Phlebosclerotic Colitis.

History A 55-year-old woman without systemic underlying disease, such as diabetes mellitus, inflammatory bowel disease, autoimmune disease, or chronic kidney disease, presented with generalized dull abdominal pain of 1-week duration. She had ingested herbal medicine for physical conditioning for several years. Laboratory findings, including biochemistry, electrolyte levels, and complete blood count, were all within normal limits, except for elevated serum C-reactive protein level (7.719 mg/dL; normal range, <1 mg/dL). The patient underwent initial evaluation with conventional abdominal radiography. She underwent subsequent evaluation with noncontrast CT of the abdomen and colonoscopy.

Case 296.

History A 55-year-old woman without systemic underlying disease, such as diabetes mellitus, inflammatory bowel disease, autoimmune disease, or chronic kidney disease, presented with generalized dull abdominal pain of 1-week duration. She had ingested herbal medicine for physical conditioning for several years. Laboratory findings, including biochemistry, electrolyte levels, and complete blood count, were all within normal limits, except for elevated serum C-reactive protein level (7.719 mg/dL; normal range,<1 mg/dL). The patient underwent initial evaluation with conventional abdominal radiography (Fig 1). She underwent subsequent evaluation with noncontrast CT of the abdomen (Figs 2, 3) and colonoscopy (Fig 4).

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease.

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.

Gelsolin decreases actin toxicity and inflammation in murine multiple sclerosis.

Gelsolin is the fourth most abundant protein in the body and its depletion in the blood has been found in multiple sclerosis (MS) patients. How gelsolin affects the MS brain has not been studied. We found that while the secreted form of gelsolin (pGSN) decreased in the blood of experimental autoimmune encephalomyelitis (EAE) mice, pGSN concentration increased in the EAE brain. Recombinant human pGSN (rhp-GSN) decreased extracellular actin and myeloperoxidase activity in the brain, resulting in reduced disease activity and less severe clinical disease, suggesting that gelsolin could be a potential therapeutic target for MS.

Predicting the severity and prognosis of trismus after intensity-modulated radiation therapy for oral cancer patients by magnetic resonance imaging.

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal-Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy.

Primary leptomeningeal melanoma.

Primary melanoma of the central nervous system is a rare melanocytic tumor typically located in the leptomeninges. We report a 57-year-old woman with an intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was completely removed and leptomeningeal melanoma was proven pathologically. Follow-up imaging studies up to 19 months showed no recurrence of the disease. Here we present radiological, gross, and pathological images of leptomeningeal melanoma, discuss its characteristics, and review the relevant literature.

N-butyl cyanoacrylate embolization as the primary treatment of acute hemodynamically unstable lower gastrointestinal hemorrhage.

PURPOSE: To evaluate N-butyl cyanoacrylate (NBCA) embolization as the primary treatment for patients with severe and acute hemodynamically unstable lower gastrointestinal bleeding. MATERIALS AND METHODS: Twenty-seven patients with acute, unstable hemodynamics caused by lower gastrointestinal bleeding underwent therapeutic NBCA microcatheter embolization over a period of 27 months. The inclusion criteria were hematochezia or melena and hypotension refractory to conservative treatment and requiring blood transfusion. Bleeding was localized to the rectum, colon, or small intestine in all nine such cases. Fifteen patients had severe underlying comorbidities, including sepsis, respiratory failure, malignancy, or renal failure. RESULTS: The procedure was technically successful in all patients. Twenty-six patients were treated solely with NBCA, and one required microcoil embolization. Embolization was performed at the level of the arteria recta or as close as possible to the point of bleeding. Immediate hemostasis occurred in all cases. Four patients experienced repeat hemorrhage, one of whom died. The other three were treated successfully with repeat NBCA embolization. None of the surviving patients had evidence of bowel ischemia. In addition, none of the patients with severe underlying disease died during the follow-up period (range, 3 mo to 2 y). CONCLUSIONS: The present findings suggest that NBCA embolization may be a safe alternative treatment for the management of lower gastrointestinal bleeding. Further studies are warranted to confirm the findings.

Clinical manifestations and survival of hepatocellular carcinoma patients with peritoneal metastasis.

BACKGROUND AND AIM: Peritoneal metastasis is an uncommon manifestation of hepatocellular carcinoma (HCC). The aim of the present paper was to investigate the characteristics and survival of HCC patients with peritoneal metastases. METHODS: From January 1985 to December 2004, we retrospectively reviewed the records of 53 Taiwanese HCC patients with peritoneal metastases. RESULTS: Peritoneal metastases were detected at the time of HCC diagnosis (synchronously) in 10 patients and after the initial therapy for the primary tumors (metachronously) in 43 patients. The mean time for development of the metachronous peritoneal metastases was similar whether the primary cancer was treated with surgery (24 months) or transarterial chemoembolization (22.2 months). The single patient whose primary cancer was treated with supportive care alone developed peritoneal metastasis only 7.5 months after detection of the primary cancer. Surgical resection of the peritoneal metastases was possible in two-thirds of the 43 metachronous patients. The median survival for those who received surgery for these metastases was 12.5 months vs. 2.1 months for those without surgery (P = 0.0013). However, there was no difference in survival if patients were stratified to Child-Pugh grade. CONCLUSIONS: Peritoneal metastases of HCC are rare and can occur synchronously or metachronously. Though increased long-term survival was found in patients who had surgical removal of peritoneal metastases, the main determinant of better survival is Child-Pugh grade.

Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method--analysis of 2010 Taiwanese patients.

The aim of this study was to compare six prognostic staging systems (Okuda stage, TNM stage, CLIP score, BCLC stage, JIS score and Tokyo score) in predicting survival in patients with hepatocellular carcinoma (HCC). A total of 2010 Taiwanese HCC patients were included. Demographic, laboratory and tumour characteristics were determined at diagnosis. Predictors of survival included serum levels of albumin, total bilirubin, alkaline phosphatase, alpha-fetoprotein, ascites, tumour size and portal vein invasion. The Tokyo score was the most informative one for predicting the survival of HCC patients as a whole, receiving surgical resection, or receiving transarterial chemoembolisation. CLIP score was the best fit system for HCC patients receiving chemotherapy or supportive care. Each staging system showed a significant difference in predicting the probability of survival across different stages. The applicability of staging systems for patients with HCC was dependent on treatment methods.

Liver resection improves the survival of patients with multiple hepatocellular carcinomas.

BACKGROUND: According to current guidelines of hepatocellular carcinoma (HCC) treatment, multiple HCCs are usually not suitable for surgical resection. However, surgical resection is still possible for patients with multiple HCCs. The role of hepatic resection vs transarterial chemoembolization (TACE) for multiple HCCs should be further clarified. METHODS: We retrospectively enrolled 1065 patients with multiple HCCs. Among them, 294 received surgical resection, 367 received transarterial chemoembolization (TACE), and 404 received chemotherapy or supportive care. Three staging systems (TNM, CLIP, and BCLC) were used for comparison of stage-specific survival between different treatment modalities. RESULTS: The median survival of multiple HCC patients who received surgical resection was 37.9 months, while it was 17.3 months in TACE group, and 2.8 months in supportive group (P < .001). The 1-year, 3-year, 5-year survival rates for surgical group were 77.4%, 51.9%, and 36.6%, respectively. Kaplan-Meier survival analysis demonstrated that patients who received surgical resections had the best survival, followed by TACE and supportive care. For patients of the same stage, surgical resection yields better results than TACE. Surgery could offer better survival than TACE for patients either within or beyond Milan's criteria. CONCLUSIONS: Our results indicate that if patients have preserved liver functions, hepatic resection is helpful, even for patients with multiple HCCs.

On concise 3-D simple point characterizations: a marching cubes paradigm.

The centerlines of tubular structures are useful for medical image visualization and computer-aided diagnosis applications. They can be effectively extracted by using a thinning algorithm that erodes an object layer by layer until only a skeleton is left. An object point is "simple" and can be safely deleted only if the resultant image is topologically equivalent to the original. Numerous characterizations of 3-D simple points based on digital topology already exist. However, little work has been done in the context of marching cubes (MC). This paper reviews several concise 3-D simple point characterizations in a MC paradigm. By using the Euler characteristic and a few newly observed properties in the context of connectivity-consistent MC, we present concise and more self-explanatory proofs. We also present an efficient method for computing the Euler characteristic locally for MC surfaces. Performance evaluations on different implementations are conducted on synthetic data and multidetector computed tomography examination of virtual colonoscopy and angiography.

Balloon occlusion and hypothermic perfusion of the renal artery in laparoscopic partial nephectomy.

OBJECTIVES: We describe our initial experience with renal arterial catheterization for temporary balloon occlusion of renal artery and hypothermic perfusion during laparoscopic partial nephectomy and compare the preoperative and postoperative nephron function. METHODS: Fifteen patients received laparoscopic partial nephrectomy from September 2005 to December 2006. During the operations, the balloons of the arterial catheters were filled with distilled water to achieve pedicle control. Chilled Ringers lactate was continuously infused into the catheters for renal hypothermia. Postoperative Tc-99m diethylenetriamine pentaacetic acid (DTPA) renal scintigraphies were carried out to estimate differential renal function. The volumes of the renal tumors, tumor-bearing and contralateral kidneys from CT scans were measured using commercial software. Estimated creatinine clearance was calculated with Cockroft Gault formula. RESULTS: All procedures were successfully completed. Mean tumor size was 18.4 mL (range 2.14 to 59.0). Estimated mean intraoperative blood loss was 287 mL (range minimal to 1200). Mean estimated creatinine clearance per unit volume of functional renal parenchyma did not change statistically after the operation. Multiple regression analysis revealed that ischemic time was a significant variable which correlated with the value of lost total estimated creatinine clearance of the tumor bearing kidney. CONCLUSIONS: The initial experience shows that renal arterial catheterization for temporary balloon occlusion and hypothermic perfusion of the renal artery in laparoscopic partial nephectomy is safe, feasible and effective. The postoperative kidney function measured by mean estimated creatinine clearance per unit of functional renal volume was similar to the preoperative measurement.

Diffuse intraperitoneal metastasis after spontaneous rupture of hepatocellular carcinoma.

Rupture of hepatocellular carcinoma (HCC) is a fatal complication. Intraperitoneal metastasis after rupture of HCC is rare. We report a case of diffuse intraperitoneal metastases after rupture of HCC. A previously asymptomatic 32-year-old man was admitted because of massive ascites due to ruptured HCC. Poor liver reserve limited the therapeutic options. Transarterial chemoembolization was performed to stop tumor bleeding. Abdominal computed tomography demonstrated multiple large peritoneal metastases 3 months after the rupture episode. Echo-guided fine needle aspiration from the suprapubic area was performed. Cytology was positive for HCC. It is rare for HCC to develop intraperitoneal metastases in as short as 3 months.

Primary liver lymphoma in a patient with chronic hepatitis C.

Primary liver lymphoma is a very rare disease and is frequently overlooked as a possible diagnosis. We report the case of an asymptomatic middle-aged man with chronic hepatitis C who developed primary liver lymphoma (PLL). A large solitary tumor in the left lobe of the liver was incidentally detected on routine ultrasound examination. Imaging studies showed mixed iso- and hypoechogenicity with hypoechoic rim, hypodense in the pre-contrast phase and thick wall enhancement in the post-contrast phase on computed tomographic study, hypointensity on T1WI, and hyperintensity of the central portion and slightly higher intensity in the peripheral wall on T2WI. These pictures were different from focal nodular hyperplasia, hepatocellular carcinoma, cholangiocarcinoma or metastases. Atypical hepatectomy was performed and the pathology of the hepatic tumor revealed non-Hodgkin's lymphoma. Systemic staging revealed no evidence of nodal or bone marrow involvement, so PLL was diagnosed. There was no tumor recurrence more than 4 years after operation and chemotherapy. PLL should be included in the differential diagnosis of solitary hepatic tumor in patients who are hepatitis C virus-positive, and who have atypical imaging and no known malignancy or elevated tumor marker levels.