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Biomedical subjects

Yuko Kitagawa

Publications and source records attributed to Yuko Kitagawa.

At least 19 recordsLinked to original sources

Release of band cells from the bone marrow is impaired by preoperative chemoradiation in patients with esophageal carcinoma: increased risk of postoperative pneumonia.

PURPOSE: To examine the difference in hematological data and postsurgical course after esophagectomy between patients receiving preoperative chemoradiation and patients without preoperative treatment. METHODS: Twenty-two patients with squamous cell carcinoma of the esophagus who underwent esophagectomy during the past 2 years were retrospectively analyzed in the study. Six patients had preoperative chemoradiation (CRT group) and 16 patients had no preoperative treatment (non-CRT group). The hematological data, postoperative course, and surgical complications were compared between the two groups. RESULTS: Patients in the CRT group were given cisplatin and 5-FU (143 and 6,000 mg on average, respectively) plus an average of 35 Gy of radiation. Although the neutrophil count did not show a significant difference between the two groups, the band cell count was lower in the CRT group compared with the non-CRT group on postoperative day 1 (P<0.05). Postoperative pneumonia was detected in three patients (50%) from the CRT group versus none of the non-CRT group. CONCLUSION: Preoperative CRT may be a risk factor for postoperative pneumonia in patients with esophageal carcinoma who undergo esophagectomy. The normal bone marrow response of releasing band cells from the postmitotic marrow pool after surgery could be disturbed by CRT, which might contribute to an increase in later pulmonary complications.

Aged↗

Role of steroid administration to reduce inflammation after thoracotomy in a rat surgical stress model.

BACKGROUND: Unilateral lung surgical insult can lead to bilateral pulmonary inflammation after transthoracic esophagectomy for esophageal cancer. An inflammatory response of the cytokine network induced by surgical stress followed by neutrophil sequestration is the major mechanism involved in these complications. We examined modulation of the inflammatory cytokine and neutrophil sequestration by preoperative steroid administration in a rat thoracotomy model. METHODS: Adult male rats were subjected to right thoracotomy with pulmonary compression in the surgical stress model. In the another surgical stress model, 10 mg/kg of methylprednisolone (MP) was administered 1 h before the operation intraperitoneally, and peri-operative biological effects of steroid administration to neutrophil sequestration and cytokine-induced neutrophil chemoattractant (CINC) as an inflammatory cytokine were examined. Sham-operated animals were subjected to intubation only. RESULTS: Surgical insult to the unilateral lung increased local CINC concentration followed by an increase in neutrophil sequestration, wet-to-dry weight ratio in bilateral lungs and systemic CINC concentration. Pre-treatment with methylprednisolone reduced CINC concentration as well as neutrophil sequestration and wet-to-dry weight ratio of both lungs. CONCLUSIONS: These data suggest that inflammatory changes induced by the unilateral operative procedure occur in both lungs through local inflammatory response. Pre-operative methylprednisolone administration down-regulates cytokine release and neutrophil sequestration, preventing lung edema, and possibly may act as a prophylactic treatment against acute lung injury caused by a so-called "second attack" theory.

Animals↗

Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis.

BACKGROUND: High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model. METHODS: Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure. RESULTS: Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung. CONCLUSIONS: The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.

Animals↗

Interim results of sentinel node biopsy during laparoscopic gastrectomy: possible role in function-preserving surgery for early cancer.

INTRODUCTION: Intraoperative detection of sentinel nodes (SNs) has been used clinically to predict regional lymph node (LN) metastasis in patients with breast cancer and malignant melanoma. Intraoperative lymphatic mapping and SN biopsy can potentially be combined with minimally invasive surgery. However, few reports have demonstrated the validity of SN biopsy during laparoscopic gastrectomy. The aim of this study was to investigate the feasibility and accuracy of laparoscopic lymphatic mapping in predicting LN status in patients with gastric cancer. METHODS: A total of 35 patients with gastric cancer diagnosed preoperatively as T1, N0 were enrolled. Endoscopic injection of technetium-99m-radiolabeled tin colloid was completed 16 hours before surgery, and radioactive SNs were identified with a gamma probe intraoperatively. Isosulfan blue dye was injected endoscopically during the operation. Laparoscopy-assisted gastrectomy with LN dissection was performed. All resected LNs were evaluated by routine pathology examination. RESULTS: SNs were detected in 33 (94.3%) of 35 patients. The mean number of SNs was 3.9, and the diagnostic accuracy according to SN status was 97.0% (32/33), as one patient with a false-negative result was observed. The patient with the false-negative specimen was finally diagnosed as having advanced gastric cancer with invasion into the proper muscular layer and severe lymphatic vessel invasion, causing destruction of normal lymphatic flow by the tumor. CONCLUSIONS: Radio-guided SN mapping during laparoscopic gastrectomy is an accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer. Validation of this method requires further studies on technical issues, including indications, tracers, methods of lymph node retrieval, and diagnostic modalities of metastasis.

Adult↗

Sentinel lymph node mapping with GI cancer.

Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. The lunchtime symposium focused on the present status of SLN mapping for GI cancer. Dr. Kitigawa proposed a new strategy using sentinel node biopsy for esophageal cancer patients with clinically early stage disease. Dr. Uenosono reported on whether the SLN concept is applicable for gastric cancer through his analysis of more than 180 patients with cT1-2, N0 tumors. The detection rate was 95%, the false negative rate of lymph node metastasis including micro-metastasis was 4%, and accuracy was 99% in gastric cancer patients with cT1N0. Dr. Bilchik recommended the best technique for identifying SLNs in colorectal cancer: a combination of radiotracer and blue dye method, emphasizing that this technique will become increasingly popular because of the SLN concept, with improvement in staging accuracy. He stressed that this novel procedure offers the potential for significant upstaging of GI cancer. Dr. Saha emphasized that SLN mapping for colorectal cancer is highly successful and accurate in predicting the presence or absence of nodal disease with a relatively low incidence of skip metastases. It provided the "right nodes" to the pathologists for detailed analysis for appropriate staging and treatment with adjuvant chemotherapy. Although more evidence from large-scale multicenter clinical trials is required, SLN mapping may be very useful for individualizing multi-modal treatment for esophageal cancer and might be widely acceptable even for GI cancer.

Antineoplastic Agents↗

Gastroesophageal carcinoma: individualized surgical therapy.

During the twentieth century, surgical management of gastroesophageal carcinoma was developed by an establishment of standard procedures with lymph node dissection according to the metastatic distribution. The "fear" of invisible micrometastasis caused surgeons to perform more aggressive resection with lymphadenectomy to control the disease locally. Although several promising results of extensive lymph node dissection have been reported, the prognostic benefits of extensive surgery have not been proven by prospective randomized trials. A novel technology to detect micrometastasis without extensive surgical resection is required to gastroesophageal carcinoma. The lymphatic mapping technique is one of the attractive candidates for a novel tool to approach this issue.

Esophageal Neoplasms↗

Antiangiogenic agent SU6668 suppresses the tumor growth of xenografted A-431 cells.

SU6668 is an antiangiogenic agent that acts as a tyrosine kinase inhibitor for the vascular endothelial growth factor (VEGF) receptor. We treated xenografted A-431, a human squamous cell carcinoma cell line, with SU6668 to investigate the efficacy of tumor dormant therapy using angiogenesis inhibitors for patients with squamous cell carcinoma. A-431 cells were transplanted into severe combined immunodeficient (SCID) mice. The treatment group was given SU6668 at a dose of 200 mg/kg orally twice a day for 3 weeks; the control group was given only the vehicle in the same manner and intervals. SU6668 suppressed tumor growth of A-431 cells in the xenograft model. Furthermore, tumor volume and the number of vessels were significantly reduced in the treatment group compared with those of the control. No significant differences in body weight were found between the treatment and control groups, and no toxic reactions occurred during the experiment. We concluded that this agent was safe, efficient and potentially useful for the treatment of patients with squamous cell carcinoma.

Angiogenesis Inhibitors↗

Diagnostic validity of radio-guided sentinel node mapping for gastric cancer: a review of current status and future direction.

Diagnostic validity of sentinel node (SN) mapping has been recently introduced into the field of various solid tumors, including gastrointestinal (GI) cancer. In gastric cancer, acceptable detection rates of SNs, as well as sensitivity in detecting micrometastasis based on SN status, was reported using the dye-guided method, as well as the radio-guided method. Gastric cancer is currently one of the suitable targets of SN navigation surgery among visceral tumors. Despite the multi-directional and complicated lymphatic flow from gastric mucosa, the anatomical situation of the stomach is relatively suitable for SN mapping in comparison with organs embedded in closed spaces, such as the esophagus and rectum. In particular, clinically T1N0 gastric cancer seems to be a good entity for which to try to modify the therapeutic approach. From the data reported in the literature, micro-metastases tend to be limited within the sentinel basins in cT1N0 gastric cancer. Sentinel basins are, therefore, good targets of selective lymphadenectomy for cT1N0 gastric cancer with the potential risk of micrometastasis. Furthermore, laparoscopic local resection is theoretically feasible for curative treatment of SN negative early gastric cancer. For laparoscopic application of SN mapping of gastric cancer, a radio-guided method is essential. Although recent single institutional studies support the validity of the SN concept, a multi-centric prospective validation study based on a standardized protocol is essential for further clinical application. Currently, two major well-designed clinical trials of SN mapping for gastric cancer open surgery have been initiated in Japan. Radio-guided SN mapping for gastric cancer has a great potential to provide a new paradigm shift for surgical management of an early gastric cancer.

Forecasting↗

Recent advances in sentinel node navigation for gastric cancer: a paradigm shift of surgical management.

The sentinel node (SN) is defined as the first draining node from the primary lesion and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. In the past 5 years, the validity of SN concept for gastric cancer has been demonstrated by a number of single institutional studies. Using a dual tracer method as the optimal procedure, the radio-guided method allows us to confirm the complete harvest of SNs by gamma probing, while the dye procedure enables us to perform real time observation of the lymphatic vessels. From previous reports, clinically staged T1N0 gastric cancer seems to be a good entity on which to try to change the therapeutic approach based on SN biopsy. At present, two large scale prospective multicenter trials are on-going in Japan. To overcome some remaining issues, such as limited sensitivity of intra-operative diagnosis of metastasis, and technical difficulty in laparoscopic SN detection, further technical and instrumental developments will be required. During this transitional phase, focused lymph node dissection targeted to sentinel lymphatic basins and modified resection of the stomach is an acceptable approach. Although there are several remaining issues, SN navigation should provide a paradigm shift for the surgical management of early gastric cancer in near future.

Clinical Trials as Topic↗

Credentialing of nuclear medicine physicians, surgeons, and pathologists as a multidisciplinary team for selective sentinel lymphadenectomy.

There are several possible applications of the sentinel lymph node (SLN) concept with different technological aspects such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. To achieve these clinical applications, multidisciplinary teamwork with surgeons, nuclear medicine physicians, and pathologists would be critically required. Interdisciplinary issues should be resolved in order to develop optimal standard procedures of SLN dissection for various solid tumors.

Credentialing↗

Sentinel lymph node mapping in esophageal and gastric cancer.

In recent years, the sentinel lymph node (SLN) concept has been widely investigated in a variety of solid tumors including gastrointestinal (GI) cancer. This chapter reviews the rationale and refined technical aspects for SLN mapping in upper GI cancer for the intraoperative accurate diagnosis of nodal status to perform individualized minimally invasive surgical approaches. We have described the technical details of the procedure as we have performed it in over 350 consecutive patients with esophageal and gastric cancer and introduced pitfalls and issues remaining. The technical details and clinical applications of SLN mapping differfor patients with esophageal cancer and gastric cancer. Radio-guided method with lymphoscintigraphy using radioisotope-labeled colloid (RI) is essential for SLN mapping for esophageal cancer. Selective lymphadenectomy and SLN-targeted chemoradiotherapy would be feasible and beneficial for the patients with esophageal cancer. For gastric cancer, combined method with dye and RI is recommended for stable and accurate sampling of SLN in the laparoscopic setting. Laparoscopic local resection for superficial gastric cancer with negative SN status would be a reasonable and less-invasive novel procedure based on the SLN concept. We can utilize this procedure not only for an accurate staging but also as a great tool to change the patient care of upper GI cancer by individualized minimally invasive treatments.

Esophageal Neoplasms↗

Oblique view of preoperative lymphoscintigraphy improves detection of sentinel lymph nodes in esophageal cancer.

Because sentinel lymph nodes (SLNs) of esophageal cancer can be widely located between the neck and the upper abdomen, lymphoscintigraphy plays an important role in their detection, but some modifications are required to clearly visualize their locations. Recently, we applied the stereoscopic imaging method by adding the 10-degree oblique view to the conventional lymphoscintigraphy for SLNs, so that we could better determine SLN locations on the basis of depth information. In this report, we describe a case in which the oblique view of the lymphoscintigram contributed to improving the visualization of a mediastinal SLN of esophageal cancer. Evaluation of the patient's chest CT image validated the notion that gamma rays from SLN are less absorbed by the surrounding soft tissues and the sternum in acquisition from the oblique view than from the true anterior view. The additional oblique view of the lymphoscintigram is useful for evaluation of the SLNs of esophageal cancer.

Aged↗

Minimally invasive surgery for gastric cancer--toward a confluence of two major streams: a review.

The minimalization of therapeutic invasiveness in order to preserve quality of life (QOL) is a major topic in the management of early gastric cancer. After laparoscopic surgery for gastric cancer was introduced by Kitano et al. in 1991, an enthusiasm to develop laparoscopic procedures has grown steadily. In the initial phase, early gastric cancer limited to the mucosal layer with no risk of lymph node metastasis was treated by laparoscopic wedge resection or intragastric mucosal resection. Since technical and instrumental advances in endoscopic treatment were achieved by gastroenterologists, these cases can be managed by intraluminal endoscopic approaches. The attention of surgeons then shifted to more radical procedures such as laparoscopic gastrectomy with lymph node dissection, which is comparable to open surgery and can be indicated even in advanced cancer. Although this paradigm shift has already been realized in the field of colorectal surgery, we must pay attention to the particular biological nature of gastric cancer in terms of the potential of peritoneal dissemination. While early-phase recovery after surgery has been improved by laparoscopic surgery, preservation of late-phase QOL by function-preserving surgery is also essential in this regard; therefore, the sentinel node (SN) concept has been a much-discussed topic in gastric cancer surgery to approach this aspect. Recently, the validity of the SN concept has been demonstrated by a number of single institutional studies, and prospective multicenter trials are currently ongoing. Theoretically, various types of function-preserving surgery could be applied in cases of early gastric cancer with negative SNs as less invasive surgery to improve long-term QOL. Although we still have to solve several remaining issues in the treatment of gastric cancers, a confluence of these two major streams, laparoscopic surgery and sentinel node navigation surgery, would enable us to apply a novel individualized minimally invasive approach, both in terms of degree of incisional access and extent of function preservation.

Gastrectomy↗

Increasing age does not affect efficacy of sentinel lymph node biopsy using smaller-sized technetium-99m tin colloids for breast cancer patients.

BACKGROUND: Increasing age of breast cancer patients was reported to cause not only failure of sentinel lymph node (SLN) identification but also false negative results. METHODS: A retrospective review was conducted of breast cancer patients who underwent sentinel lymph node biopsy (SLNB) using small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). A comparison between 82 patients who were less than 60 years and 40 patients who were > or =60 years of age was performed to evaluate the efficacy of SLNB using the small-sized tin colloid in older patients. RESULTS: One hundred twenty-two clinically node-negative breast cancer patients underwent SLNB. Apart from age, there were no statistically significant differences between the younger patients and the older patients in terms of the clinicopathologic characteristics. Successful mapping rates, false negative rates, and accuracy were comparable between the 2 groups. CONCLUSIONS: SLNB using the small-sized tin colloid was not affected by increasing age.

Adult↗