Masahiro Ito

The Prognostic Nutritional Index Predicts Long-term Outcomes of Gastric Cancer Patients Independent of Tumor Stage

PurposeThe aim of this study was to investigate the impact of the prognostic nutritional index (PNI) on the long-term outcomes in gastric cancer patients.MethodsThis study reviewed the medical records of 548 patients with gastric cancer who underwent gastrectomy. The PNI was calculated as 10xa0×xa0serum albumin (g/dl)xa0+xa00.005xa0×xa0total lymphocyte count (per mm3). The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PNI. The multivariate analysis was performed to identify the prognostic factors.ResultsThe mean PNI was significantly lower in patients with T3–T4 tumors (Pxa0<xa00.001) and lymph node metastasis (Pxa0<xa00.001) than in those without such factors. Patients who had a postoperative complication had a lower mean PNI than those without (Pxa0=xa00.023). When the ROC curve analysis was performed, the optimal cutoff value of the PNI for predicting the 5-year survival was 48. In the multivariate analysis, a low PNI was an independent predictor for poor overall survival (Pxa0<xa00.001). In the subgroup analysis, the overall and relapse-free survival rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III disease.ConclusionsThe PNI is a simple and useful marker for predicting the long-term outcomes of gastric cancer patients independent of the tumor stage. Based on our results, we suggest that the PNI should be included in the routine assessment of gastric cancer patients.

Morphologic Characteristics of Chernobyl-Related Childhood Papillary Thyroid Carcinomas Are Independent of Radiation Exposure but Vary with Iodine Intake

BACKGROUNDnThe Chernobyl accident caused an unprecedented increase in papillary thyroid carcinoma (PTC) incidence with a surprisingly short latency and unusual morphology. We have investigated whether unexpected features of the PTC incidence after Chernobyl were radiation specific or influenced by iodine deficiency.nnnMETHODSnPTCs from children from Belarus, Ukraine, and the Russian Federation exposed to fallout from Chernobyl were compared with PTCs from children not exposed to radiation from the same countries, from England and Wales (E&W) and from Japan. The degree and type of differentiation, fibrosis, and invasion were quantified.nnnRESULTSnThere were no significant differences between PTCs from radiation-exposed children from Belarus, Ukraine, and the Russian Federation and PTCs from children from the same countries who were not exposed to radiation. Childhood PTCs from Japan were much more highly differentiated (p < 0.001), showed more papillary differentiation (p < 0.001) and were less invasive (p < 0.01) than Chernobyl tumors, while tumors from E&W generally showed intermediate levels of degree and type of differentiation and invasion. There was a marked difference between the sex ratios of children with PTCs who were radiation exposed and those who were not exposed (F:M exposed vs. unexposed 1.5:1 vs. 4.2:1; chi(2) = 7.90, p < or = 0.01005).nnnCONCLUSIONSnThe aggressiveness and morphological features of Chernobyl childhood PTCs are not associated with radiation exposure. The differences found between tumors from the Chernobyl area, E&W, and Japan could be influenced by many factors. We speculate that dietary iodine levels may have wide implications in radiation-induced thyroid carcinogenesis, and that iodine deficiency could increase incidence, reduce latency, and influence tumor morphology and aggressiveness.

Risk Factors for Esophagojejunal Anastomotic Leakage After Elective Gastrectomy for Gastric Cancer

ObjectiveThe aim of this study was to investigate the correlation between intraoperative anastomotic troubles and the incidence of esophagojejunal anastomotic leakage (EJAL), and to identify risk factors for EJAL after elective gastrectomy for gastric cancer.MethodsThis study reviewed the medical and surgical records of 327 patients who underwent elective gastrectomy followed by esophagojejunostomy. A multivariate analysis was performed to determine the risk factors for EJAL.ResultsAn EJAL occurred in 19 patients (5.8xa0%). A multivariate analysis demonstrated that hemoglobin A1c ≥7.0xa0% (pu2009<u20090.01), chronic renal failure (pu2009<u20090.01), proximal gastrectomy (pu2009<u20090.05), and anastomotic trouble during construction of the esophagojejunostomy (pu2009<u20090.01) were independent predictors for EJAL. Anastomotic trouble during construction of esophagojejunostomy occurred in 20 patients (6.1xa0%), and EJAL occurred in 6 of these 20 patients (30xa0%). Four of ten patients (40xa0%) in whom an incomplete anastomosis was repaired by suturing during surgery had an EJAL, while none of seven patients who underwent re-anastomosis had this complication.ConclusionsEJAL is strongly associated with intraoperative technical errors. To reduce this complication, proper anastomotic techniques are required. Re-anastomosis should be performed when an incomplete anastomosis is discovered during surgery.

Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis.

Defective DNA damage response (DDR) can result in genomic instability (GIN) and lead to the transformation into cancer. P53‐binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules localize at the sites of DNA double strand breaks (DSBs) and rapidly form nuclear foci, the presence of 53BP1 foci can be considered as a cytologic marker for endogenous DSBs reflecting GIN. Although it has been proposed that GIN has a crucial role in the progression of thyroid neoplasms, the significance of GIN during thyroid tumorigenesis remains unclear, particularly in patients. We analyzed, therefore, the level of GIN, as detected with immunofluorescence of 53BP1, in 40 cases of resected thyroid tissues. This study demonstrated a number of nuclear 53BP1 foci in thyroid cancers, suggesting a constitutive activation of DDR in thyroid cancer cells. Because follicular adenoma also showed a few 53BP1 nuclear foci, GIN might be induced at a precancerous stage of thyroid tumorigenesis. Furthermore, high‐grade thyroid cancers prominently exhibited an intense and heterogeneous nuclear staining of 53BP1 immunoreactivity, which was also observed in radiation‐associated cancers and in mouse colonic crypts as a delayed response to a high dose ionizing radiation, suggesting increased GIN with progression of cancer. Thus, the present study demonstrated a difference in the staining pattern of 53BP1 during thyroid carcinogenesis. We propose that immunofluorescence analysis of 53BP1 expression can be a useful tool to estimate the level of GIN and, simultaneously, the malignant potency of human thyroid tumors.

Significance of HER2 and C-MYC oncogene amplifications in breast cancer in atomic bomb survivors: associations with radiation exposure and histologic grade.

It has been postulated that radiation induces breast cancers in atomic bomb (A‐bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A‐bomb survivors with radiation exposure.

Significance of HER2 and C-MYC oncogene amplifications in breast cancer in atomic bomb survivors

It has been postulated that radiation induces breast cancers in atomic bomb (A‐bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A‐bomb survivors with radiation exposure.

Risk Factors for Surgical Site Infections After Elective Gastrectomy

ObjectiveThe aim of this study was to identify the risk factors for surgical site infections (SSIs) after elective gastrectomy.MethodsThis study reviewed the medical records of 842 patients who underwent elective gastrectomy. Multivariate analyses were performed to determine the risk factors for SSIs.ResultsSuperficial incisional, deep incisional, and organ/space SSIs were detected in 50 (5.9%) patients, 2 (0.2%) patients, and 90 (10.7%) patients, respectively. A multivariate analysis demonstrated that female gender (pu2009=u20090.0332) and allogenic blood transfusion (pu2009=u20090.0266) were independent predictors for superficial incisional SSIs, while a male gender (pu2009=u20090.0355), corticosteroid therapy (pu2009=u20090.037), total gastrectomy (pu2009<u20090.0001), and a duration of operation ≥300xa0min (pu2009=u20090.0062) were independent predictors for organ/space SSIs. The median length of postoperative hospital stay was significantly longer in patients with organ/space SSIs in comparison to those without SSIs (pu2009<u20090.0001) and with superficial incisional SSIs (pu2009<u20090.0001). The patients with organ/space SSIs had a significantly higher re-operation rate in comparison to those without SSIs (pu2009<u20090.0001).ConclusionsThe risk factors both for incisional SSIs and for organ/space SSIs are strongly associated with surgical results. Meticulous surgical techniques are therefore required to prevent SSIs.

A novel laparoscopic procedure for treating proximal early gastric cancer: laparoscopy-assisted pylorus-preserving nearly total gastrectomy

PurposePylorus-preserving nearly total gastrectomy (PPNTG) is a function-preserving gastrectomy for treating proximal early gastric cancer that prevents rapid gastric emptying and reflux. In this report, we present a surgical technique for performing laparoscopy-assisted PPNTG (LAPPNTG).MethodsThe resection of the stomach was similar to that during conventional total gastrectomy, with the key difference being that the pyloric cuff was preserved to a length of 3–4xa0cm. Compared with standard total gastrectomy, the lymph node dissection along the right gastric vessels and the infrapyloric vessels were omitted. Reconstruction was performed with a jejunal interposition that was 30xa0cm in length, with preservation of the marginal vessels in a retrocolic fashion.ResultsThirteen patients with cT1 cN0 proximal gastric cancer underwent LAPPNTG at our institution. The median length of the operation and estimated blood loss were 329xa0min and 138xa0ml, respectively. All resected specimens had tumor-free margins, and the median number of removed lymph nodes was 40. There were no serious postoperative complications and no patients underwent conversion to laparotomy.ConclusionsPerforming LAPPNTG with a jejunal interposition is feasible and might be an appropriate treatment for proximal early gastric cancer.

Prognostic impact of RING box protein-1 (RBX1) expression in gastric cancer

BackgroundRING box protein-1 (RBX1) is an essential component of the E3 ubiquitin ligase Skp1/Cullin/RBX1/F-box protein complex. Although an altered expression of RBX1 has been reported in several human cancers, the role of RBX1 in gastric cancer remains unknown.MethodsWe investigated the RBX1 expression in primary gastric cancer tissues from 145 patients by immunohistochemistry, and explored its clinical relevance and prognostic value. Furthermore, the effect of RBX1 expression on cancer cell proliferation was analyzed in vitro using a siRNA silencing technique.ResultsThe RBX1 expression was abundant in gastric cancer tissues. There was a significant difference in the expression level of RBX1 in terms of the tumor depth (Pxa0=xa00.008), presence of distant metastasis (Pxa0=xa00.016) and venous invasion (Pxa0=xa00.005). The postoperative overall (Pxa0<xa00.001) and relapse-free survival (Pxa0<xa00.001) rates were significantly poorer in patients with RBX1-high tumors than in patients with RBX1-low tumors. There was a significant correlation of the RBX1 status with postoperative hematogenous recurrence (Pxa0=xa00.013). Importantly, the RBX1 status was identified as an independent prognostic factor for gastric cancer (Pxa0=xa00.002). Furthermore, RBX1 gene silencing significantly inhibited the proliferation of gastric cancer cells in vitro.ConclusionsThe RBX1 expression has a significant prognostic value in gastric cancer. RBX1 might play an important role in regulating the proliferation of gastric cancer cells and promoting the development of postoperative recurrence. Our data provide a rationale for developing a novel therapy targeting RBX1 for gastric cancer.

Endothelin B receptor expression correlates with tumour angiogenesis and prognosis in oesophageal squamous cell carcinoma.

Background:The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC).Methods:We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed.Results:Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression.Conclusion:Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.