Hepatic Nodes Research Articles

Hepatic Arterial Nodal Metastases in Pancreatic Cancer: Is This the Node of Importance?

BackgroundThe hepatic artery lymph node (HALN) is frequently sampled during pancreaticoduodenectomy (PD). Data suggest that survival in the setting of HALN metastases is similar to that of stage IV pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to describe the prognostic significance of HALN metastases and to assess the predictive performance of HALN compared to peripancreatic lymph node status. MethodsPatients undergoing PD for PDAC from January 2000–October 2010 were identified from a prospectively maintained database. Patients were included if during PD the HALN was submitted for pathologic evaluation. Patients were excluded if margins were macroscopically positive, if pathology was found to be consistent with a diagnosis other than PDAC. Overall (OS) and disease-free survival (DFS) were estimated by Kaplan–Meier methods. ResultsOf the 671 patients who underwent PD for PDAC, HALN status was analyzed for 147 patients. HALN was positive in 23 patients (16 %), 38 were peripancreatic lymph node (PPLN) and HALN negative, and 86 were PPLN+/HALN−. Median follow-up for survivors was 10 months. In a multivariable model, lymph node status and tumor differentiation predicted OS and DFS. Hazard of death and relapse/death were highest among the HALN+ patients (hazard ratio [HR] 2.94; p = 0.017 and HR 2.66; p = 0.011, respectively). Kaplan–Meier analysis revealed significant differences in OS (p = 0.017) and DFS (p = 0.013) based on lymph node status. ConclusionsOS and DFS are significantly reduced in patients with a positive HALN. Differentiation and lymph node status were predictors of OS and DFS. In the multivariate models, differentiation and lymph node status remain independent predictors of OS and DFS.

Management of the Hepatic Lymph Nodes During Resection of Liver Metastases from Colorectal Cancer: A Systematic Review

The aim of this review is to assess the role of hepatic lymphadenectomy in patients undergoing liver resection for colorectal metastases. Meta-analysis of trials identified by a systematic literature search of the Medline, Embase and Central databases was performed. There were no randomized controlled trials which assessed the survival benefit to patients undergoing liver resection for colorectal metastases of either a routine or a ‘selective’ lymphadenectomy. The prevalence of nodal metastases after lymphadenectomy was 8.4 %. The overall 3-year and 5-year survival rates in patients with hepatic lymph node metastases undergoing hepatectomy were 21.8 % (63 of 288 patients) and 8.5 % (27 of 315 patients), respectively, compared with 58.2 % (1,366 of 2,346 patients) and 47.5 % (1,717 of 3,609 patients) in patients undergoing hepatectomy who had no hepatic nodal metastases. The odds ratios for 3-year and 5-year mortality in node positive disease compared with node negative disease were 4.54 (95 % confidence interval 3.15–6.54) and 6.33 (95 % confidence interval 4.28–9.36), respectively. In conclusion, long-term survival rates are low in patients undergoing hepatectomy with hepatic lymph node metastases. The poor outcome is irrespective of whether the nodal metastases are discovered following routine lymphadenectomy or are detected because of pathological enlargement. Further trials in this patient group are required.

Microscopic anatomy of the liver.

Microscopic anatomy of the liver.

Down-regulation of programmed cell death 4 leads to epithelial to mesenchymal transition and promotes metastasis in mice

In this study, we demonstrated that knockdown of programmed cell death 4 (Pdcd4), a novel tumour suppressor, decreased the expressions of epithelial-specific proteins and increased the expressions of mesenchymal-specific proteins in vitro and in vivo, suggesting that knockdown of Pdcd4 results in epithelial to mesenchymal transition (EMT). Knockdown of Pdcd4 increased the rate of wound closure and migration capacity in wound-healing assays and Boyden chamber migration assays, respectively, indicating that Pdcd4 knockdown promotes cell migration. Pdcd4 knockdown also altered the adhesion capacity of GEO cells to extracellular matrix including laminin, collagen IV and fibronectin. To test whether knockdown of Pdcd4 promotes metastasis in vivo, parental, control and Pdcd4 knockdown cells were injected into the caecal wall (orthotopic implantation) of nude mice. Tumours are formed on caecum in all injected mice. However, only mice injected with Pdcd4 knockdown cells developed hepatic and local lymph node metastases. Immunohistochemical staining analyses showed that c-Myc and Snail/Slug expressions were up-regulated in the tumours derived from injection of Pdcd4 knockdown cells. These results implicated that promotion of metastasis by Pdcd4 knockdown was contributed by up-regulation of c-Myc and Snail/Slug in nude mice. Taken together, our data demonstrated that knockdown of Pdcd4 leads to EMT, alternation of adhesion and promotion of migration and metastasis.

Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer

Magnetic nanoparticles represent one of the most advanced developments in the application of nanotechnology to human health. To date, their clinical application has been restricted to the diagnosis of hepatic lesions and lymph node metastasis but functionalization of these materials with biomolecules as targeting motifs, and the inclusion of therapeutic drugs in their composition, is certain to make a substantial impact within biomedicine. One of the diseases that could benefit from these advances is cancer, as early diagnosis and effective treatment are crucial for a patient's survival and quality of life. This review will examine the recent uses of magnetic particles in cancer diagnosis and treatment.

Paracoccidioidomycosis simulating cancer diagnosed by endoscopic ultrasound-guided fine needle aspiration

A 57-year-old woman presented with abdominal pain, jaundice, and a 12-kg weight loss over the preceding 6 months. The abdominal computed tomography (CT) scan demonstrated a mass located in the head of pancreas (6.4×5.8cm). Endoscopic retrograde cholangiopancreatography (ERCP) was performed for biliary drainage with the insertion of a single 10-Fr plastic stent in the common bile duct (CBD), which led to an improvement in her jaundice. Furthermore, multiple enlarged lymph nodes were seen in the hepatic hilum on magnetic resonance imaging (MRI; ● Fig.1), but there was no evidence of the previously visualized pancreatic mass. An endoscopic ultrasound (EUS) showed multiple enlarged lymph nodes in the hepatic hilum (● Fig.2), splenic hilum, and celiac trunk, adjacent to the pancreas and CBD, but no pancreatic lesion. During EUS-guided fine needle aspiration (EUS-FNA) of the hepatic hilum lymph nodes using a 22-gauge needle (Echo Tip; Cook Medical, Winston-Salem, North Carolina, USA;● Fig.3), a purulent fluid was released and collected for further analysis. The histopathological analysis revealed Paracoccidioides brasiliensis spores (● Fig.4). Paracoccidioidomycosis is a systemic mycosis caused by the dimorphic fungus P. brasiliensis. The disease is restricted to Latin America. It is the main systemic mycosis seen in Brazil, with higher incidences found in the central and southern regions. The disease is acquired by inhaling fungal propagules [1]. Paracoccidioidomycosis has several clinical presentations depending on the affected organ. Lymph node involvement is usually secondary to a skin and/or visceral primary focus and affects predominantly the cervical and supraclavicular lymph node chains. Other findings are irregularity of the pancreatic head that can simulate cancer, biliary duct dilatation with cholestasis, abscesses, and splenic calcifications, among others [2]. Abdominal lymph node involvement simulating cancer is rare [3]. The use of EUS-FNA to make this diagnosis is even rarer. Our group previously published the first case of adrenal paracoccidioidomycosis diagnosed by EUS-FNA [4]. To our knowledge, this is the first reported case of paracoccidioidomycosis with abdominal lymphadenopathy simulating cancer having been diagnosed by EUS-FNA.

High expression of Dickkopf‐related protein 1 is related to lymphatic metastasis and indicates poor prognosis in intrahepatic cholangiocarcinoma patients after surgery

Dickkopf-related protein 1 (DKK1) has been reported involved in metastasis and invasion in several tumors. This study sought to investigate the prognostic value of DKK1 in intrahepatic cholangiocarcinoma (ICC) and its role in promoting ICC metastasis. Tissue microarrays of 138 ICC patient samples were employed to detect DKK1, vascular endothelial growth factor C (VEGF-C), and matrix metalloproteinase 9 (MMP9) expression using immunohistochemistry. The prognostic significances were assessed by Kaplan-Meier survival estimates. DKK1 expression was measured in an ICC cell line (HCCC-9810) and ICC tissues by immunofluorescence assay, quantitative real-time polymerase chain reaction, and western blot. Serum levels of DKK1 from 37 ICC patients were tested by enzyme-linked immunosorbent assay. The role of DKK1 in proliferation, migration, invasion, and gene expression regulation was assessed by DKK1 depletion using small interfering RNA. Multivariate analyses revealed that DKK1 was an unfavorable predictor for overall survival and time to recurrence. The prognostic significance was retained in ICC patients with low recurrence risk (P < .05). DKK1 expression was elevated in an ICC cell line, tumor samples, and patient sera. High levels of DKK1 in ICC tissues correlated with elevated MMP9, VEGF-C, and metastasis of hepatic hilar lymph nodes. DKK1 depletion caused a decrease in cell migration and invasiveness, and down-regulation of MMP9 and VEGF-C expression. DKK1 is a novel prognostic biomarker for ICC, and it enhances tumor cell invasion and promotes lymph node metastasis of ICC through the induction of MMP9 and VEGF-C. DKK1 may be a potential therapeutic target for ICC.

Hepatocellular carcinomas in Vietnamese pot-bellied pigs (Sus scrofa)

Various neoplasms have been reported in Vietnamese pot-bellied pigs (Sus scrofa) with few reports of hepatocellular tumors. Twenty-two pot-bellied pigs diagnosed with hepatocellular carcinoma at necropsy over a 3-year period at one institution are described, representing 29% of the total pot-bellied pigs necropsied. The average age of affected pigs was 16.6 years with 15 males and 7 females. The most common clinical signs were decreased appetite (16/22) and weight loss (7/22). Grossly, the majority were massive tumors (13/22) with fewer nodular tumors (8/22) and 1 diffuse tumor. Massive tumors were typically multilobulated, very large, and encompassing 1 or more adjacent liver lobes, and were soft to firm and tan-yellow to orange-brown. Nodular tumors had multiple, 1-15 cm in diameter, discrete nodules in multiple liver lobes. Gross evidence of abscesses, necrosis, hemorrhage, or cysts associated with the tumor was occasionally described. Half of the cases had possible intrahepatic metastasis, and extrahepatic metastasis was identified in 3 cases, including to the hepatic lymph node (1/3), lung (2/3), spleen (1/3), and kidney (1/3). Histologically, all tumors had a trabecular or solid pattern, or a combination. An adenoid pattern was only identified in small regions of a few tumors. The neoplastic cells were relatively well-differentiated with moderate pleomorphism and a low mitotic index. Other histologic features within the tumors included intracellular glycogen or lipid accumulation, extramedullary hematopoiesis, foci of coagulative necrosis, and bile stasis. Aged pot-bellied pigs can be predisposed to hepatocellular carcinomas, which are locally aggressive and can metastasize within the liver and to other organs.

Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer

The goals of this retrospective study were to comprehensively evaluate the impact of hepatic lymph node (HLN) involvement on survival in patients with synchronous resectable or unresectable liver metastases from colorectal cancer and to highlight how to deal with such cases in the light of recent advances in chemotherapy. The impact of HLN involvement on survival, along with various clinical, pathological, and therapeutic factors, was retrospectively evaluated in 61 patients with synchronous liver metastases from colorectal cancer (resectable, 26; unresectable, 35), undergoing resection of the primary tumor and histopathological evaluation between July 2000 and April 2008. The proportion with HLN metastasis was 11.5% in resectable cases and 28.6% in unresectable cases. On multivariate analysis using the Cox proportional hazards model, HLN metastasis (P<0.001), along with non-resection of hepatic lesions (P<0.001), larger metastatic tumor volume (P<0.001), non-use of oxaliplatin-based chemotherapy (P<0.001), involvement of 4 or more regional lymph nodes (P<0.001), and excessive lymphatic invasion (P=0.02), was identified as an independent risk factor for shorter survival. To establish a new therapeutic strategy for synchronous liver metastasis of colorectal cancer, the HLNs should be examined histologically in patients undergoing resection of their primary colon and rectal cancer.

Sustained Remission of Multicentric Castleman Disease in Children Treated with Tocilizumab, an Anti-Interleukin-6 Receptor Antibody

Multicentric Castleman Disease (MCD) is an idiopathic lymphoproliferative disorder, reported exceptionally in children and generally believed to be an autoinflammatory disease resulting in an increase of interleukin-6 secretion. Previous studies in adult patients suggested a beneficial role of the anti-interleukin-6 receptor antibody tocilizumab on the clinical and biologic disease manifestations of MCD. Here, we describe the efficacy and safety of tocilizumab in two children with MCD, which was diagnosed on the basis of clinical and histologic findings. In both cases, tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. The tocilizumab treatment alleviated fever and restored growth rate in both patients. The patients' hypergammaglobulinemia, high C-reactive protein, and high erythrocyte sedimentation rates normalized simultaneously. Nevertheless, splenomegaly persisted in the first patient, and a secondary hepatic node appeared in the second patient. The side effects, essentially sustained thrombocytopenia, were mild in both cases. For the first patient, following an initial 10-month period, the interval between infusions was increased. This patient benefited from sustained remission for a period of 3 years. Tocilizumab was effective and safe in these two children with MCD.

Can common hepatic artery lymph node dissection be safely omitted in surgery for clinical T1N0 thoracic esophageal squamous cell carcinoma?

Common hepatic artery lymph node dissection is regarded as a standard procedure in esophageal cancer surgery because of aggressive lymphatic dissemination of esophageal cancer. However, lymph node dissection can prolong operation time and may be associated with complications such as chylous ascites. Here, we aimed to evaluate the effectiveness of common hepatic artery lymph node dissection in clinical T1N0 thoracic esophageal squamous cell carcinoma. Between 1996 and 2009, 1390 patients underwent surgery for esophageal cancer in our institution, and 209 were found to have clinical T1N0 disease. Exclusion criteria were nonsquamous carcinoma, double primary cancer, definite distant metastasis, administration of neoadjuvant treatment, and incomplete abdominal lymph node dissection. We retrospectively analyzed medical records, operative and pathologic data, and follow-up information. Forty-two patients were excluded from the study. Among the 167 enrolled patients, preoperative endoscopic ultrasound evaluation was performed in 160 patients. Fifty-two patients had distal esophageal or esophagogastric junction tumor. Surgery included 2 cases of tri-incisional esophagectomy, 17 cases of transhiatal esophagectomy, and 148 cases of two-field esophagectomy (Ivor Lewis operation). Common hepatic artery lymph node dissection was performed in all cases, and none of the patients had metastasis. Mean follow-up period was 35.4 ± 28.7 months. In-hospital mortality was one, and 5-year survival rate was 80.6%. Among the 15 patients with recurrence, there were two distant metastases and five distant and local recurrences but no intra-abdominal recurrence with common hepatic artery lymph node. Common hepatic artery lymph node dissection may be safely omitted in surgery for clinical T1N0 esophageal squamous cell carcinoma when preoperative evaluations including chest computed tomography, positron emission tomography and computed tomography, and esophagogastroduodenoscopy or endoscopic ultrasound are performed.

External-beam radiotherapy and/or HDR brachytherapy in postoperative endometrial cancer patients: clinical outcomes and toxicity rates

The objectives of this study were to evaluate local disease control, overall survival (OS), disease-free survival (DFS) and local relapse-free survival (LRFS) in patients with endometrial cancer undergoing adjuvant vaginal brachytherapy (VBT )± external-beam radiotherapy (EBRT). From September 2007 to February 2011, 40 patients with endometrial cancer were retrospectively analysed. Surgery consisted of total hysterectomy and bilateral salpingo-oophorectomy without node dissection (16 patients) or with bilateral pelvic node dissection (24 patients). The stage distribution was as follows: two IA, nine IB, 12 IC, five IIA, eight IIB, two IIIA and two IIIC. Thirty-four patients underwent EBRT and VBT. Six patients received VBT alone. Median follow-up was 26 months. The 5-year OS and DFS were 96.4% and 86.9%, respectively. No local recurrence was observed. Four patients presented distant disease (three had lung metastases and one had hepatic node metastases). Acute EBRT-related toxicities were seen in 15 (38%) patients. We recorded late toxicities in 14 patients (35%). There was no evidence of grade 3-4 toxicity. Adjuvant EBRT and/or VBT in patients with endometrial cancer showed good outcomes in terms of local disease control, with an acceptable toxicity profile.

Abstract 1694: Imaging cell cycle progression in gastric cancer lymph node metastasis indicates large fraction of proliferating cancer cells

Abstract We report here a mouse model of lymph node metastasis of stomach cancer and imaging cell cycle progression in the metastasis. FUCCI (fluorescent ubiquitination-based cell cycle indicator)-expressing human MKN45 gastric cancer cells were used to establish the lymph node metastasis nude mouse model. In this model, cell-cycle dynamics of the metastatic cells could be imaged in vivo. FUCCI cells are labeled orange in the G1 phase nuclei (monomeric Kusabira-Orange2: mKO2) and labeled green in the S/G2/M phases (monomeric Azami-Green1: mAG1). FUCCI MKN45 were injected into the mouse stomach mucosa from the serosal side. Lymph node metastasis to the para-aortic or hepatic portal region, left armpit, and brachial lymph nodes were observed. Green-yellow (G2/S) cells were predominant compared to red (G1) fluorescent FUCCI cells as observed in the lymph-node metastases using an FV1000 confocal microscope, indicating that the lymph-node metastatic cells were actively cycling. The origin of lymph node or vessel metastases was confirmed by H.E. staining. Mouse FUCCI gastric metastasis models will be used to visualize cell cycle dynamics in metastasis in lymphoid as well as hematogenous metastasis in order to optimize drug treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1694. doi:1538-7445.AM2012-1694

Serous papillary adenocarcinoma probably arising from epithelial inclusions of the hepatic hilar lymph node

Only three cases of serous adenocarcinoma arising from Mullerian epithelial inclusions of the lymph node have been reported. Herein reported is a case of serous papillary adenocarcinoma arising probably from epithelial (Mullerian) inclusions of the hepatic hilar lymph node. A 73-year-old woman presented with peripheral neuropathy, which was thought to be a paraneoplastic syndrome associated with visceral malignancy. Total body examination, including X-P, US, CT, MRI, PET, and upper and lower gastrointestinal endoscopy was done. As the results, only lymph node swelling was detected in the hepatic hilus. Tumor was not identified in other sites. The physicians considered malignant lymphoma, and laparotomic excision of the hepatic hilar mass was performed. Cytological examination of abdominal cavity washing revealed no malignant cells. Grossly, the mass was firm and white and measured 4 × 5 × 5 cm. Microscopically, the mass showed carcinoma cells arranged in papillary and tubular patterns. The appearances strongly resembled serous papillary adenocarcinoma of the ovary. Lymph node structures were noted in some peripheral areas. No benign epithelial inclusions were recognized. Immunohistochemically, the carcinoma cells were positive for ER, PgR, CA125, WT1, p53. They were negative for TTF-1 and CDX-2. Because the positive ER, PgR, CA125, WT1, p53 and p16 are indicative of gynecologic malignancy, simple hysterectomy and bilateral salpingo-oophorectomy were performed, which showed no abnormalities. Cytological examination of abdominal cavity washing fluid revealed no malignant cells. The patient was treated by paclitaxel and carboplatin, and is now alive without metastasis 2 years after the first manifestation. The author reported a case of serous papillary adenocarcinoma arising probably from epithelial (Mullerian) inclusions of the hepatic hilar lymph node.

The value of dynamic imaging for standardization of abdominal ultrasonography.

Digital video recording of dynamic images is a potential way to improve the reproducibility of abdominal ultrasonography (US). Static US and dynamic US were compared using contrast-enhanced computed tomography (CE-CT) as a reference standard, and the value of stored video images was verified. The subjects were 120 individuals who had undergone CE-CT ≤1month before undergoing US. After static US, dynamic US was carried out according to the Scanning Procedure for Abdominal Ultrasonography described in this paper, and records of 30 separate scans were saved on digital video discs (DVD) as individual video files for interpretation. The findings from static US and dynamic US were compared. With respect to the abdominal US signs covered in this evaluation, dynamic US achieved a detection rate equivalent to or better than that of static US. Detection rates were significantly more frequent on dynamic US for: enlarged hepatic hilum lymph nodes (P<0.001); gallbladder wall thickness (P<0.01); cystic lesions of the liver, bright liver, and splenomegaly (P<0.05). Dynamic US is a valuable tool because it enables repeated evaluation of target organs with playback speed adjustment.

Clinical significance of aberrant hepatic artery arising from superior mesenteric artery in liver cancer and gastric cancer operations

Objective To analyze the clinical significance of aberrant hepatic artery which originated from superior mesenteric artery in liver cancer and gastric cancer operations.Method Four hundred liver cancer patients who underwent digital subtraction angiography (DSA) and multislice spiral computed tomography angiography (MSCTA) and 86 gastric cancer patients who underwent MSCTA between June 2008 and June 2010 and operated at the First Affiliated Hospital of Guangxi Medical University were included in this study.Preoperatively,the origins of the aberrant hepatic arteries from superior mesenteric arteries were detected by medical imaging.Postoperatively,immunohistochemistry of lymphoid tissues around the aberrant hepatic arteries of the gastric cancer patients were performed using recombinant human cytokeratin 20 (CK20) and carcino-embryonic antigen (CEA) to determine the incidence of lymph node metastases around the aberrant arteries.Results Among 486 patients,49 patients with liver cancer and 14 patients with gastric cancer had an aberrant hepatic artery which originated from the superior mesenteric artery.The rate was 12.96％ (63/486).The hepatic artery ran in front of the pancreas in 2 patients (3.17％) and behind the pancreas in 61 patients (96.83％).Immunohistochemical analyses of CK20 and CEA were negative which revealed no metastases in the lymphoid tissues surrounding the aberrant arteries.Conclusions Aberrant hepatic artery originated from the superior mesenteric artery can be classified into the pre-pancreas type and postpancreas type.The majority of aberrant hepatic artery belonged to the post-pancreas type.The clinical significance of aberrant hepatic artery is that the hepatic hilar lymph nodes should be dissected in liver cancer and gastric cancer operations. Key words: Aberrant; Hepatic artery; Tumor; Operation

Anatomia ultrassonográfica dos linfonodos abdominais de furões europeus hígidos

Nos últimos anos o furão (Mustela putorius furo) tornou-se um conhecido animal de estimação sendo observada uma população em constante crescimento no Brasil, e por conseqüência cada vez mais presente em clínicas veterinárias. O presente trabalho teve como objetivo avaliar a anatomia ultrassonográfica dos linfonodos abdominais de furões-europeus hígidos. Foram utilizados 20 animais, dentre os quais nove eram machos e onze fêmeas, com idade média total de três anos. Localizaram-se em 100% dos furões os linfonodos mesentéricos, em 55% dos animais os linfonodos pancreático-duodenal e esplênico, em 20% o linfonodo gástrico e em 5% o linfonodo hepático. Conclui-se que a localização e características ultrassonográfica dos linfonodos abdominais em furões são muito similares aos linfonodos abdominais de gatos, sendo este estudo uma orientação preliminar para a localização dos linfonodos abdominais de furões hígidos.

Significance of Hepatic Lymph Node Metastasis in Patients With Unresectable Synchronous Liver Metastasis of Colorectal Cancer

The frequency and significance of hepatic lymph node (HLN) metastasis were retrospectively evaluated in 43 patients with unresectable synchronous liver metastasis of colorectal cancer who underwent resection of the primary tumor and histopathologic evaluation of HLNs between March 1997 and August 2007. HLN metastasis was detected in 12 patients (27.9%). No significant correlations were observed between the presence of HLN metastasis and any of the 12 clinicopathologic factors examined. On multivariate analysis using the Cox proportional hazards model, the presence of HLN metastasis (P = 0.002), along with a large number (> or = 4) of regional lymph node metastases (P = 0.003), and nonuse of oxaliplatin-based chemotherapy (P = 0.005) were identified as independent risk factors for shorter survival. To establish a new therapeutic strategy for initially unresectable liver metastasis of colorectal cancer, HLNs should be examined histologically in patients undergoing resection of hepatic lesions when they are rendered resectable by effective chemotherapy.

A Rare Case of Erythrodysesthesia of Grafted Skin as an Adverse Reaction of Sorafenib

Purpose: Hand-foot syndrome (palmer-planter erythrodysesthesia) and other adverse reactions relating to administration of sorafenib lead to discontinuation of medication in one third of patients. We describe a rare case of erythrodysesthesia of grafted skin in hepatocellular cancer (HCC) patient treated with sorafenib. 52 year old male presented with complaints of peeling of the skin of hands and burning of tips of fingers. Patient tried different lotions without benefit. Four weeks prior, patient was initiated sorafenib 400 mg twice a day for multifocal HCC with lymph node metastasis. Past medical history was significant for cirrhosis secondary to HCV diagnosed 25 years ago. Patient was diagnosed with multi-focal HCC one year earlier with portal hepatic lymph node positive for poorly differentiated carcinoma cells on EUS-FNA. Patient was treated with transarterial chemoembolization twice as such transplant is not a possibility. Past surgical history was notable for hand surgery of left fingers for electrocution burn with skin graft. Patient is on alprazolam, Docusate® and morphine. No history of drug allergy or allergy to any substance or material. Patient is 1 pack per day active smoker for 30 years. Physical examination revealed redness, tenderness, swelling of hands, peeling of the grafted skin on the palmer surface of left hand fingers. AFP=154, platelets 66,000/ul, slight elevation of ALT&AST with normal total bilirubin, albumin and INR. Sorafenib was reduced to 200 mg one tablet twice a day. All symptoms resolved after one week. Majority of cases of Hand-foot syndrome, like our patient, presented with skin rash, swelling, redness, pain and/or peeling of the skin on the palms of hands and soles of feet. Symptoms are usually mild and start 5-6 weeks after beginning of chemotherapy. For example, 5-Fluouracil, Doxorubincin, Interleukin-2 and Sorafenib can cause this skin reaction for some patients. There are 3 grades of skin toxicity: Grade 1 = above symptoms which do not disrupt normal activities (requires symptomatic treatment with topical therapy), Grade 2 = above symptoms affecting normal activities (requires dose reduction by one dose level), Grade 3 = ulceration, blistering, or severe pain of the hands or feet or severe discomfort that prevents working or performing daily activities (requires discontinuation of treatment). Symptomatic treatment and dose reduction seems to be effective for majority of patients with Hand-foot syndrome including patient with grafted skin.

The role of hilar lymphadenectomy in patients subjected to hepatectomy due to colorectal metastasis

Hepatectomy is the treatment of choice for colorectal liver metastases, and several studies have shown good results, with 5-year survival rates ranging from 40% to 57%. Several clinical and pathological predictive factors for survival after liver resection have been studied. Involvement of the hepatic hilum lymph nodes, the incidence of which varies from 2% to 10%, indicates a poor long-term prognosis. Despite variable results, some authors have reported a not-insignificant improvement in survival rate in liver-metastasis patients with hilar lymph node involvement who undergo combined liver resection and lymphadenectomy. Due to the low rates of morbidity and mortality for liver-resection surgery, several specialized centers perform liver resections combined with lymphadenectomies in selected cases. It should be noted that the therapeutic value of systemic lymphadenectomy is not yet entirely understood, and only controlled studies comparing groups with and without lymphadenectomy can fully resolve the issue. In any case, hilar lymph node dissection has been shown to be a useful tool for improving the accuracy of extra hepatic disease staging, regardless of its impact on survival.