Carbonic anhydrase is aberrantly and constitutively expressed in both human and murine erythroleukemia cells.

The levels of the erythrocyte proteins carbonic anhydrase (CA) and hemoglobin (Hb) change coordinately during human ontogeny. To further probe the coordinate gene expression of these two proteins in vitro, we used an immunoblotting technique to measure their levels during erythroid differentiation in normal human and murine erythroid progenitors, in human and murine erythroleukemia cells, and in normal murine erythroid progenitors infected with Friend virus. Levels of CA and Hb seem to gradually increase in normal differentiating stem cells. In contrast, both human and murine erythroleukemia cells show high levels of CA, but not of Hb, prior to induction of differentiation. Friend virus infection of normal murine progenitors appears to stimulate CA synthesis as an initial and integral step in transformation. In addition, both the erythroleukemia cells and the erythroid progenitors transformed with Friend virus seem to contain much higher levels of CA than Hb during the early stages of differentiation. This relationship is in marked contrast to normal erythroid differentiation, in which Hb levels are always higher than CA levels. Thus, neoplastic transformation seems to be associated with aberrant production of CA that does not correspond to a maturation arrest of the normal differentiation sequence.     

MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Purpose

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.

Methods

Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.

Results

High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P?=?0.0257) and poor prognosis (P?=?0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.

Conclusions

MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.     

Intraductal oncocytic papillary neoplasm of the extrahepatic bile duct: report of a case

We report a rare case of an intraductal oncocytic papillary neoplasm (IOPN) of the extrahepatic bile duct. A 66-year-old man was admitted to our hospital for investigation of right-sided back pain. Ultrasonography, computed tomography and magnetic resonance imaging showed a papillary lesion, 3?cm in diameter, in the middle bile duct, invaginating into the cystic duct. We made a provisional diagnosis of middle bile duct cancer and performed substomach-preserving pancreatoduodenectomy. Macroscopically, the middle bile duct contained a two-humped papillary tumor, one tip of which invaginated into the cystic duct. Microscopically, the tumor consisted of cuboidal cells with abundant eosinophilic cytoplasm resembling that of oncocytes and a fine fibrovascular core. The tumor cells were stained strongly with antimitochondria antibody. Based on these findings, the tumor was diagnosed histologically as IOPN of the extrahepatic bile duct. The patient died of prostate cancer 51?months after surgery, but without evidence of recurrence of the IOPN.     

Postoperative cytology for drained fluid from the pancreatic bed after "curative" resection of pancreatic cancers: does it predict both the patient's prognosis and the site of cancer recurrence?

OBJECTIVE: To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer. SUMMARY BACKGROUND DATA: The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy. METHODS: This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence. RESULTS: Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence. CONCLUSIONS: Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.     

Surgical influence on TH1/TH2 balance and monocyte surface antigen expression and its relation to infectious complications

Abstract Malignancy and operation for it cause several alterations in immune function that are considered to be concerned with the development of infectious complications. Forty-three patients who underwent curative surgery for gastrointestinal malignancies were entered into this study and were divided into two groups, those with and those without postoperative infection. Changes in the proportion of Th1/Th2 subsets in CD4⁺ T cells and the expression of human leukocyte antigen (HLA)-DR and CD16a molecules on monocytes were measured by flow cytometry before and after surgery. We performed intracellular cytokine stainings to exactly detect Th1/Th2 subsets. The proportions of interferon-γ-producing CD4⁺ T (Th1) cells in the preoperative state were almost equal in the two groups, and the proportion decreased on postoperative day (POD) 1 in both groups. On POD 7, the proportion of Th1 cells recovered to the preoperative level in the noninfection group, while the suppression was further reinforced in the infection group (26.8% versus 18.3%, p < 0.005). In contrast, the proportion of interleukin-4-producing CD4⁺ T (Th2) cells in the infection group (11.3%) was already suppressed in the preoperative state when compared with the noninfection group (17.3%, p < 0.005). Changes in HLA-DR and CD16a expression on monocytes were similar to the changes in the proportion of Th1 cells. These results indicate that the suppression of Th1 cell and monocyte functions during the early phase of the postoperative course was directly related to the occurrence of infectious complications and that several immunological impairments have already occurred in the preoperative state in cancer patients. Electronic Publication     

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.     

In situ graft-trimming method using polyester vascular prosthesis for inferior vena cava reconstruction after hepatectomy

Hepatectomy for secondary liver cancer that has invaded the inferior vena cava (IVC) can be the only way to achieve long-term survival. We describe a method for hepatectomy combined with partial IVC resection without venous bypass circulation and an in situ graft-trimming method to avoid graft size mismatch after reconstruction. We carried out left hepatectomy extended to segment 1 with partial IVC resection first. During resection and reconstruction of the IVC, it was clamped below the right hepatic vein and above the inferior right hepatic vein to maintain systemic circulation. The graft was trimmed in situ, after a half running suture of the graft was finished to ensure the correct size. Preservation of both inferior right hepatic vein and right hepatic vein helps to maintain systemic circulation during reconstruction of the IVC. The in situ graft-trimming method is an easy and safe method to ensure the correct graft size after IVC reconstruction.     

Intraoperative Identification of the Parathyroid Gland with a Fluorescence Detection System

Background

Intraoperative identification of the difficult-to-spot parathyroid gland is critical during surgery for thyroid and parathyroid disease. Recently, intrinsic fluorescence of the parathyroid gland was identified, and a new method was developed for intraoperative detection of the parathyroid with an original fluorescent detection apparatus. Here, we describe a method for intraoperative detection of the parathyroid using a ready-made photodynamic eye (PDE) system without any fluorescent dye or contrast agents.

Methods

Seventeen patients who underwent surgical treatment for thyroid or parathyroid disease at Kagoshima University Hospital were enrolled in this study. Intrinsic fluorescence of various tissues was detected with the PDE system. Intraoperative in vivo and ex vivo intrinsic fluorescence of the parathyroid, thyroid, lymph nodes and fat tissues was measured and analyzed.

Results

The parathyroid gland had a significantly higher fluorescence intensity than the other tissues, including the thyroid glands, lymph nodes and fat tissues, and we could identify them during surgery using the fluorescence-guided method. Our method could be applicable for two intraoperative clinical procedures: ex vivo tissue identification of parathyroid tissue and in vivo identification of the location of the parathyroid gland, including ectopic glands.

Conclusion

The PDE system may be an easy and highly feasible method to identify the parathyroid gland during surgery.

     

A novel preoperative predictor of pancreatic fistula using computed tomography after distal pancreatectomy with staple closure

Purpose

A thick pancreas has proven to be a conspicuous predictor of pancreatic fistula (PF) following distal pancreatectomy (DP) using staples. Other predictors for this serious surgical complication currently remain obscure. This study sought to identify novel predictors of PF following DP.

Methods

One hundred and twenty-two patients were retrospectively assessed to determine the correlation between PF occurrence and the clinicopathological findings and radiologic data from preoperative computed tomography (CT). CT assessments included the thickness of the pancreas (TP) and pancreatic CT number (pancreatic index; PI), calculated by dividing the pancreatic CT by the splenic CT density.

Results

Twenty-four patients (19.7%) developed a clinically relevant PF. TP was identified as an independent risk factor for PF in multivariate analyses (odds ratio 1.17; P?=?0.0095). In subgroup analyses, a lower PI in a thick pancreas was a significant predictor of PF (P?=?0.032). The combination of these two prediction parameters, known as the TP-to-PI ratio (TPIR), showed a significantly better prediction ability than TP alone (area under the receiver operating characteristic curve for the incidence of PF, TPIR 0.80 vs. TP 0.69; P?=?0.037).

Conclusion

Combining the CT number with TP substantially improves the prediction ability for the incidence of PF following DP with staple use.

     

Neoadjuvant CapeOx therapy followed by sphincter-preserving surgery for lower rectal cancer

Purpose

This retrospective study investigates the safety of neoadjuvant chemotherapy with oxaliplatin capecitabine (CapeOx), followed by laparoscopic surgery, for lower rectal cancer, and its efficacy in preserving the sphincter.

Methods

Ten patients with diagnosed lower rectal cancer received three or four cycles of neoadjuvant CapeOx chemotherapy, prior to undergoing low anterior resection or intersphincteric resection, with total mesorectal excision. The primary outcomes were R0 resection and the rate of sphincter preservation.

Results

Nine patients completed CapeOx as scheduled and a partial response was achieved in four; thus, the overall response rate was 40% (n = 4/10). After surgical intervention, 80% of tumors displayed downstaging. Postoperative anastomosis leakage developed in one patient. The distance from the anal verge to the tumor increased by 60% (median 1.5 cm) after CapeOx treatment. The anal sphincter was preserved in all patients and all pathological distal and radial margins were negative (R0 resections). A pathological complete response was achieved in one patient.

Conclusions

Neoadjuvant CapeOx chemotherapy is a promising approach, because it extended the distance from the anus to the tumor. Subsequent laparoscopic intervention for advanced lower rectal cancer could allow for safe preservation of the sphincter.