Tetsuya Itabashi

Molecular marker identification for relapse prediction in 5-FU-based adjuvant chemotherapy in gastric and colorectal cancers.

To confirm the clinical significance of NF-κB and JNK protein expression from experimentally identified candidates for predicting prognosis for patients with 5-FU treatment, we evaluated the protein expression of surgically removed specimens. A total of 79 specimens were obtained from 30 gastric and 49 colorectal cancer patients who underwent R0 resection followed by postoperative 5-FU based adjuvant chemotherapy. Immunohistochemical examinations of NF-κB and JNK on tissue microarrays (TMAs) revealed that significantly shorter time-to-relapse (TTR) in both NF-κB(+) and JNK(−) subgroups in both gastric (NF-κB(+), p = 0.0002, HR11.7. 95%CI3 3.2–43.4; JNK(−), p = 0.0302, HR4.4, 95%CI 1.2–16.6) and colon (NF-κB(+), p = 0.0038, HR36.9, 95%CI 3.2–426.0; JNK(−), p = 0.0098, HR3.2, 95%CI 1.3–7.7) cancers. These protein expression patterns also show strong discriminately power in gastric cancer patients for overall survival rate, suggesting a potential utility as prognostic or chemosensitivity markers. Baseline expression of these proteins using gastric cancer cell lines demonstrated the reciprocal patterns between NF-κB and JNK, while 5-FU exposure of these cell lines only induced NF-κB, suggesting that NF-κB plays a dominant role in the response to 5-FU. Subsequent siRNA experiments confirmed that gene knockdown of NF-κB increased 5-FU-specific sensitivity, whereas that of JNK did not affect the chemosensitivity. These results suggest that the expression of these proteins may aid in the decisions involved with adjuvant chemotherapy for gastrointestinal tract cancers.

Consensus primers for detecting monoclonal immunoglobulin heavy chain rearrangement in B cell lymphomas

Aims: To demonstrate the usefulness of polymerase chain reaction (PCR) methodology with both the FR2A/LJH/VLJH and the FR1c/LJH/VLJH primer sets for detecting monoclonal immunoglobulin heavy chain (IgH) gene rearrangement in B cell non-Hodgkin lymphomas (B-NHLs). Methods: Eighty three patients with B-NHL were enrolled in this study. DNA was isolated from paraffin wax embedded sections and amplified by PCR to determine the sequences of the rearranged IgH gene. Each PCR product was subcloned. Cycle sequences and sequence analyses were done to determine the clone specific IgH variable region (VH) sequences. Results: Clonal IgH gene rearrangements were detected in 45 cases with FR2a/JH/VLJH and in 14 of the remaining cases with FR1c/JH/VLJH. Most of the cases detectable with FR2a/JH/VLJH were derived from VH3 and VH4 families. Five of six cases in the VH1 family and one in the VH7 family were amplified with the FR1c/JH/VLJH primer set only. Conclusion: The detection rate of IgH rearrangement in B-NHLs can be increased by using both FR2A/LJH/VLJH and FR1c/LJH/VLJH, and these two primer sets are suitable for routine PCR methodology. Moreover, each primer set appears to be closely related to VH family specificity.

Is ultrasound-guided central venous port placement effective to avoid pinch-off syndrome?

Purpose Ultrasound (US)-guided internal jugular vein access has been the standard practice of central venous port (CVP) placement. The subclavian vein (SCV) access has also been preferred, but has potential risk of pinch-off syndrome (POS). The purpose of this study was to examine the effect of US-guided SCV access to avoid POS in patients with CVP. Methods Included in this study were patients who had undergone CVP placement via the SCV. We mainly assessed the computed tomography (CT) findings from two different placement techniques of a CVP via the SCV: (i) venipuncture point described by the ratio between the distance from the venipuncture point to the sternoclavicular joint and the clavicular length; and (ii) presence of direct attachment of the catheter to the clavicle. Secondary outcome was POS rate associated with two different placement techniques of CVP via the SCV. Results A total of 237 patients were included in this study between August 2007 and January 2011. A total of 100 patients (42.2%) underwent CVP placement using the landmark technique while 137 patients (57.8%) underwent CVP placement by US guidance. CT revealed that the US-guided technique tended to be lateral SCV approach compared with the landmark technique (p<0.001). A total of four patients (1.7%) experienced POS, all of them in the landmark group. Conclusion Our results showed that the US-guided technique determines a more lateral SCV approach, with a reduced POS risk than the landmark venipuncture technique.

Development of immunoglobulin variable heavy chain gene consensus probes with conjugated 3′ minor groove binder groups for monitoring minimal residual disease in childhood acute lymphoblastic leukaemia

Aims: To develop immunoglobulin heavy chain variable (VH) gene probes that are shorter and more flexible in position for monitoring minimal residual disease (MRD) in childhood leukaemia (ALL), using minor groove binder (MGB) technology. Methods: All VH germline sequences registered in the database were aligned and the consensus regions were determined. The reliability of the MGB probes was compared with non-MGB probes in all 24 cases of ALL. Results: Ten MGB probes (16 to 18 mers) were designed that enabled all the germline sequences on the database to be analysed, whereas the conventional non-MGB probes (21 to 27 mers) did not allow the analysis of four of the VH1 and five of the VH3 germline sequences. The sequencing results in five of the 24 cases of ALL were not matched to the non-MGB probes. Conclusions: MGB technology allows shorter probes to be designed, enabling MRD to be detected in childhood ALL. This would provide a considerable reduction in cost for a large MRD study.

Central venous port-related infection in patients with malignant tumors: An observational study

Abstract Purpose. We evaluated the characteristics of central venous port (CVP)-related infection with microbiological assessments in patients with malignant tumors. Materials and methods. In a prospective setting, patients with CVP for the treatment of malignant tumors were enrolled in this study. The incidence of CVP-related infection during three months was determined. Microbiological surveillance from skin swab was performed before and after CVP placement. Results. Fifty-nine patients were enrolled in this study, and 60 CVPs were implanted. Thirty-six (61%) patients had head and neck malignancies. Access route was subclavian vein in 43 (71.7%) CVPs and forearm vein in 17 (28.3%). CVP-related infection was observed in three (5.1%) patients: port-pocket infection in one and probable CVP-related infection in two patients, respectively. No definitive CVP-related bloodstream infection was observed. Before the placement of CVP, colonization at the insertion site was observed in ten subclavian CVP patients, while no colonization was observed in the forearm CVP patients. At 1 and 4 weeks, detection rates of colonization were also higher in subclavian CVP patients. No definitive relationship was demonstrated between skin colonization and clinical development of CVP-related infection. Conclusion. The rate of CVP-related infection in this prospective evaluation in patients with malignant tumors was comparable to previous studies. Colonization of the skin was more prominent in the subclavian site than in the forearm site. Although skin colonization was not proven to be a risk factor of infection, these results may draw attention to the adequate maintenance of CVP. (Trial registration: UMIN000003664).

Primary retroperitoneal spindle cell liposarcoma: Pathological and immunohistochemical findings

Spindle cell liposarcoma (SCLS) is presently regarded as a rare variant of well‐differentiated liposarcoma (WDLPS), which has the potential for aggressive clinical behavior. WDLPS occurs most frequently in the limbs and retroperitoneum. The most common site of SCLS occurrence is the upper limbs or shoulder girdle. Herein we report the first case of primary retroperitoneal SCLS. A 60‐year‐old Japanese man presented with a right inferior abdominal mass. Complete excision of the mass displayed a yellowish spherical tumor with a well‐circumscribed appearance measuring 98 × 95 mm. Pathological examination of the tumor revealed a neural‐like spindle cell proliferation set in a fibrous background that was associated with an atypical lipomatous component, which usually included lipoblasts. Mitotic cells were scarce. Immunohistochemical analysis demonstrated that lipoblasts were S100 positive, spindle cells were CD34 positive, and both spindle cells and lipoblasts were MDM2 negative. The Ki‐67 labeling index was <2%. At one year follow up, the patient was alive without local recurrence or metastasis. Although the proliferative activity of this tumor did not indicate strong malignancy, retroperitoneal liposarcoma generally has a poor prognosis. Accumulation of cases of SCLS is necessary to facilitate a more accurate evaluation of the pathology and clinical behavior of this tumor.

Laparoscopic-assisted proctocolectomy with prolapsing technique for familial adenomatous polyposis.

Purpose: The role of laparoscopic total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP) has been controversial, given its technical difficulty of selecting the appropriate distal transection line and achieving safe anastomosis. We herein describe our initial experience with the prolapsing technique for laparoscopic-assisted TPC and IPAA (J-pouch) in the treatment of FAP. Methods: A consecutive series of patients with FAP undergoing laparoscopic-assisted TPC with IPAA were identified from a prospectively collected database between June 2004 and February 2012. Medical records were reviewed for patient demographics, operative outcomes, and follow-up. Results: The surgery was successfully completed in all 6 patients without any conversion to open surgery. The median operating time was 279 minutes (range, 240 to 386 min) and the median blood loss was 17.5 mL (range, 5 to 161 mL). No patient required blood transfusion. The median length of diet resumption and postoperative hospital stay were 7 days (range, 6 to 10 d) and 15 days (range, 13 to 21 d), respectively. A postoperative complication, wound infection, occurred in 1 patient. No anastomotic leakages or small bowel obstructions occurred. At a median follow-up of 59 months (range, 14.2 to 107.5 mo), no carcinoma had developed at the pouch or at the anastomotic site. Sexual function and fertility were unchanged as compared with preoperatively in 2 male patients. None of the patients experienced night-time incontinence or had to use a pad. Conclusions: Our limited experience suggests that this prolapsing technique helps prevent problems with laparoscopic-assisted TPC and IPAA for FAP patients.