Successful Treatment of γ-Heavy-Chain Disease with Rituximab and Fludarabine

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ?-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgM? monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.     

A case of blastic plasmacytoid dendritic cell neoplasm: Cytomorphological findings of the touch imprint specimen of lymph node

The patient is a 75‐year‐old man with axillary lymphadenopathy presenting an indurated papule on his buttock. Touch imprint cytology of the biopsied axillary lymph node revealed the monotonous appearance of medium‐sized tumor cells. The nuclei had a slightly irregular contour, finely dispersed chromatin, and a conspicuous nucleolus. Some tumor cells had intracytoplasmic microvacuoles. Immunohistochemistry of the imprint specimens showed that the tumor cells were positive for CD56 and CD123. Histological diagnosis of the lesion was blastic plasmacytoid dendritic cell neoplasm (BPDCN). Epstein‐Barr virus‐encoded RNAs were not detected in the tumor cells. Neither immunoglobulin heavy chain genes nor T‐ cell receptor genes was clonally rearranged. BPDCN should be strongly considered during the differential diagnosis of CD56‐positive neoplasms of the skin. We demonstrated a possible contribution of the cytomorphological and immunohistochemical findings of the touch imprint specimens to the diagnosis of BPDCN. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

A randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study

Purpose

The objective of this study was to compare the effects of two types of enteral supplements, an antioxidant-enriched enteral nutrition (AeEN) and an immune-enhancing enteral nutrition (IeEN), on the nutrition, immunoinflammatory response, antioxidant capacity and clinical outcomes in patients after esophagectomy for cancer.

Methods

Patients (n = 20) undergoing esophagectomy for cancer were randomized in this single-center, open-label study. Two types of enteral supplements were used for 5 days before surgery and 7 days after surgery. The circulating levels of nutritional markers, immunoinflammatory markers, oxidative stress markers, and the antioxidant capacity were compared throughout the perioperative period, and the patients’ clinical outcomes were also compared.

Results

The circulating levels of nutritional markers decreased after surgery, but the changes were not significantly different between the AeEN group and the IeEN group throughout the perioperative period. Surgery increased the immunoinflammatory markers, and the levels were not significantly different between the groups after surgery. Surgery also increased the levels of oxidative stress markers, but there were no significant differences between the groups throughout the study period.

Conclusions

The results of this pilot study suggest that AeEN and IeEN have a similar effect on nutrition, the immunoinflammatory response, antioxidant capacity and clinical outcomes after esophagectomy for cancer. These findings, therefore, warrant further studies on a larger scale.     

Clinicopathological Features of Recurrence in Patients After 10-year Disease-free Survival Following Curative Hepatic Resection of Hepatocellular Carcinoma

Background

The present study aimed to clarify the clinicopathologic features of long-term disease-fee survival after resection of hepatocellular carcinoma (HCC).

Methods

This retrospective study identified 940 patients who underwent curative resection of HCC between 1991 and 2000 at five university hospitals. Seventy-four patients with 10 years of recurrence-free survival were identified and followed up. They were divided into two groups, 60 recurrence-free and 14 with recurrence after a 10-year recurrence-free period.

Results

Overall survival rates of recurrence and non-recurrence groups were 68 and 91 % at 16 years, and 34 and 91 % at 20 years (p = 0.02), respectively. There were five (36 %), and two deaths (3 %), respectively, after 10 recurrence-free years. A second resection for recurrence was performed in four patients (29 %), and mean survival was 15.3 years after the first hepatectomy. Although three patients in the non-recurrence group (5 %) developed esophageal and/or gastric varices, seven patients in the recurrence group (50 %) developed varices during 10 years (p < 0.0001). In multivariate analysis, preoperative and 10-year platelet count was identified as a favorable independent factor for maintained recurrence-free survival after a 10-year recurrence-free period following curative hepatic resection of HCC.

Conclusions

Recurrence of HCC may occur even after a 10-year recurrence-free period. Long-term follow-up after resection of HCC is important, and should be life-long. Patients with higher preoperative and 10-year platelet counts are more likely to have long-term survival after resection. A low platelet count, related to the degree of liver fibrosis, is a risk factor for recurrence and survival of HCC after curative resection.     

Hepatectomy based on the tumor hemodynamics for hepatocellular carcinoma: a comparison among the hybrid and pure laparoscopic procedures and open surgery

Purpose

This study was designed to evaluate the surgical parameters and treatment outcomes of tumor hemodynamics-based pure laparoscopic (PURE) and laparoscopy-assisted (HYBRID) hepatectomy for small hepatocellular carcinoma (HCC) compared with those of open hepatectomy.

Methods

Using a prospectively collected database from 1997 to 2011, we analyzed the data of 56 consecutive cases of laparoscopic hepatectomy for HCC (PURE, n = 24; HYBRID, n = 29; HALS, n = 3) from among 102 cases undergoing laparoscopic hepatectomy. We employed 27 cases treated by open hepatectomy during the same period as controls.

Results

PURE was associated with lesser blood loss, lower weight of the resected liver, and a shorter skin incision than HYBRID and open hepatectomy [median blood loss (mL): PURE 7, HYBRID 380, Open 450; P < 0.05]. On the other hand, HYBRID hepatectomy was associated with a longer operation time [operation time (min): HYBRID 232, Open 185; P = 0.0226]. The length of hospitalization in the cases treated by PURE and HYBRID hepatectomy was shorter than that in the cases treated by open hepatectomy [length of hospitalization (days): PURE 11, HYBRID 12, Open 17; P < 0.05]. One case each of transfusion and morbidity was recorded in this series. There was no significant difference of the overall (OS) or disease-free survival (DFS) between the patients treated by laparoscopic and open hepatectomy (3-year OS: 100 vs. 100 %; DFS 50 vs. 62 %, respectively).

Conclusions

Neither the surgical parameters nor the treatment outcomes of hemodynamics-based laparoscopic hepatectomy were inferior to those of open hepatectomy.     

PTK787/ZK222584 Combined with Interferon Alpha and 5-Fluorouracil Synergistically Inhibits VEGF Signaling Pathway in Hepatocellular Carcinoma

Background

The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus remains poor. We previously reported the beneficial effects of interferon alpha (IFN) and 5-fluorouracil (5-FU) combination therapy for these patients. We showed that the mechanism of therapy was regulation of vascular endothelial growth factor (VEGF). Here, we combined IFN/5-FU therapy with the VEGF receptor–selective inhibitor PTK787/ZK222584 (PTK/ZK) and examined the antitumor effects and the mechanism of action.

Methods

We studied two HCC cell lines, PLC/PRF/5 and HuH7, and a human umbilical vein endothelial cell line, HUVEC. We studied the effects of IFN/5-FU with or without PTK/ZK in growth inhibition assays, immunohistochemistry, Western blot analysis, and immunocytochemistry.

Results

In a HuH7 xenograft model, the combination of PTK/ZK and IFN/5-FU significantly inhibited proliferation, induced apoptosis, decreased microvessel density, reduced the number of tumor cells that expressed VEGF receptor 2 (VEGFR-2), and repressed the phosphorylation of Akt in vivo. In HCC cells and HUVECs in vitro, IFN/5-FU plus PTK/ZK repressed the expression of VEGFR-2 and repressed the phosphorylation of VEGFR, Akt, Erk, and p38MAPK.

Conclusions

VEGF signaling inhibition enhanced the antitumor effects of IFN/5-FU therapy on HCC cells and endothelial cells via Erk, Akt, and p38MAPK pathways.