Takanobu Tabuchi

Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients.

Th2‐dominant immunity and high neutrophil/lymphocyte ratios (NLRs) have been reported to reflect tumor progression, and so we examined whether the Th1/Th2 ratio and NLR can act as prognostic indicators or not.

Prognostic Significance of Immunohistochemically Detected Blood and Lymphatic Vessel Invasion in Colorectal Carcinoma: Its Impact on Prognosis

BackgroundThe prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI.MethodsBy immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI.ResultsThe use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival.ConclusionsOur results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.

The perioperative granulocyte/lymphocyte ratio is a clinically relevant marker of surgical stress in patients with colorectal cancer.

PURPOSE This study was to assess the clinical relevance of the blood granulocytes to lymphocytes (G/L) ratio as an early marker of surgical stress in patients with colorectal cancer. METHODS Thirty-three patients with colorectal cancer were prospectively to undergo laparoscopic-assisted (n=12) or open (n=21) surgical resection. Granulocyte and lymphocyte counts were used to calculate the G/L ratios in blood samples from all patients before the operation and post-operatively on days 1, 3 and 7. Additionally, serum inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF were assayed as markers of surgical stress. RESULTS Seven of 33 patients developed unexpected complications. Serum IL-6 (P<0.0001), G-CSF (P=0.0257), and M-CSF (P<0.0001) were higher on day 1 vs before the operation. Similarly, the G/L ratios were higher on days 1-3 vs before the operation (P<0.0001) and then gradually decreased together with the surgical stress levels. The G/L ratios and the numbers of granulocytes and lymphocytes in the blood showed no correlation with serum IL-1β or TNF-α. In contrast, the G/L ratios and the numbers of granulocytes in the blood showed significant correlation with IL-6 (Rs=0.710, P<0.0001, Rs=0.653, P<0.0001, respectively), with G-CSF (Rs=0.626, P<0.0001, Rs=0.578, P<0.0001), with M-CSF (Rs=0.470, P<0.0001, Rs=0.372, P<0.0001). However, the number of lymphocytes showed inverse correlation with IL-6 (Rs=-0.493, P<0.0001), G-CSF (Rs=-0.440, P<0.0001) and M-SCF (Rs=-0.443, P<0.0001). CONCLUSION The G/L ratio appears to be a simple and clinically relevant parameter for the assessment of perioperative stress in patients undergoing colorectal surgery.

Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer

The coexistence of gastric cancer with duodenal ulcer has been found empirically to be rare, but why it is rare is difficult to explain satisfactorily. To elucidate this question, we carried out a literature review of the subject. The frequency with which the two diseases coexist is 0.1–1.7%, and the main factor associated with both gastric cancer and duodenal ulcer is Helicobacter pylori infection. However, there are marked differences between the disorders of hyperchlorhydria in duodenal ulcer, and hypochlorhydria in gastric cancer. The most acceptable view of the reason for the difference may be that the acquisition of H. pylori infection occurs mainly in childhood, so that the time of acquisition of atrophic gastritis may be the most important, and if atrophic gastritis is not acquired early, high levels of gastric acid may occur, and consequently acute antral gastritis and duodenal ulcer may occur in youth, whereas, in elderly individuals, persistent H. pylori infections and the early appearance of atrophic gastritis may be the causes of low gastric acid, and consequently gastric cancer may occur. In patients with duodenal ulcer, factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and dupA-H. pylori strains may contribute to preventing the early acquisition of atrophic gastritis, while acid-suppressive therapy and vascular endothelial growth factor and other entities may inhibit atrophic gastritis. In contrast, in gastric cancer, factors such as excessive salt intake, acid-suppressive therapy, polymorphisms of inflammatory cytokines, and the homB-H. pylori strain may contribute to the early acquisition of atrophic gastritis, while factors such as NSAIDs; fruits and vegetables; vitamins A, C, and E; and good nutrition may inhibit it.

The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression : its clinical applications

Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x105 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x105 cells) and E, F, G and H (1x106 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

Abdominal stapled side-to-end anastomosis (Baker type) in low and high anterior resection: experiences and results in 69 consecutive patients at a regional general hospital in Japan

Objective  The technique of transanally introducing a circular stapled device to accomplish colorectal anastomoses has been widely used. However, the widespread popularity of this technique may have created the potential of anal sphincter injury during transanal insertion of the anastomosing stapler. Thus, to avoid the risk of anal sphincter injury during anal manipulation, we have been performing an abdominal approach, namely abdominal stapled side‐to‐end anastomosis (ASSEA) using a Purstring and premium curved EEA stapler in low and high anterior resection. This study will present our experience and results of consecutive resections.

Overt bone metastasis and bone marrow micrometastasis of early gastric cancer.

Recently we encountered two cases of early gastric cancer (EGC) with bone metastasis after surgery. As they were not accompanied by overt liver, lung, or peritoneal metastasis, we examined the clinical significance of bone metastasis in EGC and its mechanisms by a review of the literature. We found only 10 cases of EGC complicated with overt bone metastasis in the English literature, so we also examined the Japanese reports of such cases. The main histologic type of cases of bone metastasis from EGC was the diffuse type, and there were long intervals between surgery and overt bone metastasis. One reason for such long intervals may have been the tumor dormancy. Two types of dormancy, dynamic and static, and two types of postoperative overt metastases, that of micrometastatic origin (normograde metastatic process) and that of bone marrow origin (retrograde metastatic process), were considered. We speculated that there may be specific routes by which the cancer cells infiltrate the bone marrow directly from EGC or lymph node metastasis. The procedures for diagnosing bone micrometastasis using monoclonal antibodies have recently been improved, but their accuracy rates are still not universally accepted. New, more reliable examinations are required to improve the survival rates of EGC.

Gastric tube perforation after esophagectomy for esophageal cancer.

We searched for cases of perforation of the gastric tube after esophagectomy for esophageal cancer by reviewing the literature. Only 13 cases were found in the English literature, and serious complications were seen in all cases, especially in cases of posterior mediastinal reconstruction. However, in the Japanese literature serious complications were also frequently seen in retrosternal reconstruction. Gastric tubes are at a higher risk of developing an ulcer than the normal stomach, including an ulcer due to Helicobacter pylori infection, insufficient blood supply, gastric stasis, and bile juice regurgitation. H. pylori eradication and acid-suppressive medications are important preventive therapies for ordinary gastric ulcers, but for gastric tube ulcers the effects of such treatments are still controversial. We tried to determine the most appropriate treatment to avoid serious complications in the gastric tubes, but we could not confirm an optimal route because each had advantages and disadvantages. However, at least in cases with severe atrophic gastritis due to H. pylori infection or a history of frequent peptic ulcer treatment, the antesternal route is clearly the best. Many cases of gastric tube ulcers involve no pain, and vagotomy may be one of the reasons for this absence of pain. Therefore, periodic endoscopic examination may be necessary to rule out the presence of an ulcer.

Characteristics of the Serum Pepsinogen (PG) Test, and the Relationship between PG Test Results and Gastric Cancer Outcomes

Background and Aims: The serum pepsinogen (Pg) test is considered to be a high-risk marker for gastric cancer, so that it is intended that it will be gradually adopted for mass surveys in Japan. This manuscript examines the characteristics of the preoperative Pg test and the relationship between its results and the postoperative outcomes of gastric cancer cases in relation to the neutrophil/lymphocyte ratio (NLR) as a prognostic marker. Materials and Methods: Peripheral blood samples were taken within 1 week before gastrectomy for the Pg test and NLR. Results: The Pg test identified 128 (+) cases (59.0%) and 89 (–) cases (41.0%). In three of all cases, cancer had not been detected by an upper gastrointestinal series (UGI) in the previous year (every case showed Pg (+)). Five-year survival was 80.5% in the Pg (+) group, 60.7% in the Pg (–) group, 85.6% in the NLR (< 5.0) group, and 29.9% in the NLR (≥ 5.0) group, but 14.3% in the NLR (≥ 5.0) plus Pg (–) group, and 89.5% in the NLR (< 5.0) plus Pg (+) group. The differences in the 5-year survivals were statistically significant. Conclusions: A mass survey using the Pg test alone is inadequate, but the Pg test may be an important adjunct to the conventional methods. Gastric cancer with Pg (–) may have a higher potential for malignancy than cancer with Pg (+).

Pre-operative granulocyte/lymphocyte ratio as a predictive marker of post-operative complications in patients with colorectal cancer.

The aim of the present study was to assess the clinical relevance of the pre-operative granulocyte/lymphocyte (G/L) ratio as a predictive marker of post-operative complications in patients with colorectal cancer. In total, 85 patients (59 males and 26 females; mean age, 68.9 years) underwent surgery for colorectal cancer at the Department of Surgery, Ibraki Medical Center, Tokyo Medical University (Ami, Japan), and were divided into post-operative complication and non-complication groups. Clinical data, including age, gender, body mass index, tumor localization, tumor pathological type, cancer staging, surgery time, volume of surgical bleeding, pre-operative G/L ratio and further pre-operative laboratory data, including levels of albumin and C-reactive protein, Glasgow Prognostic Score, white blood cell count and levels of hemoglobin, creatine kinase, lactate dehydrogenase, carcinoembryonic antigen and carbohydrate antigen 19-9 were analyzed between these groups. The total post-operative complication rate was 18.8%. On univariate analysis, the amount of surgical bleeding and the pre-operative G/L ratio were significantly higher in the complication group than in the non-complication group (299.8±361.7 vs. 155.6±268.6 ml, P<0.05; and 6.73±10.38 vs. 3.49±2.78, P<0.05, respectively). Multivariate logistic regression analysis for the risk factors of post-operative complications, determined using univariate analysis, demonstrated that the amount of surgical bleeding and the pre-operative G/L ratio were independent risk factors of post-operative complications in patients with colorectal cancer. In conclusion, the G/L ratio may be a clinically relevant pre-operative predictive marker for post-operative complications.