Artificially induced epithelial-mesenchymal transition in surgical subjects: its implications in clinical and basic cancer research.

BACKGROUND: Surgical samples have long been used as important subjects for cancer research. In accordance with an increase of neoadjuvant therapy, biopsy samples have recently become imperative for cancer transcriptome. On the other hand, both biopsy and surgical samples are available for expression profiling for predicting clinical outcome by adjuvant therapy; however, it is still unclear whether surgical sample expression profiles are useful for prediction via biopsy samples, because little has been done about comparative gene expression profiling between the two kinds of samples. METHODOLOGY AND FINDINGS: A total of 166 samples (77 biopsy and 89 surgical) of normal and malignant lesions of the esophagus were analyzed by microarrays. Gene expression profiles were compared between biopsy and surgical samples. Artificially induced epithelial-mesenchymal transition (aiEMT) was found in the surgical samples, and also occurred in mouse esophageal epithelial cell layers under an ischemic condition. Identification of clinically significant subgroups was thought to be disrupted by the disorder of the expression profile through this aiEMT. CONCLUSION AND SIGNIFICANCE: This study will evoke the fundamental misinterpretation including underestimation of the prognostic evaluation power of markers by overestimation of EMT IN past cancer research, and will furnish some advice for the near future as follows: 1) Understanding how long the tissues were under an ischemic condition. 2) Prevalence of biopsy samples for in vivo expression profiling with low biases on basic and clinical research. 3) Checking cancer cell contents and normal- or necrotic-tissue contamination in biopsy samples for prevalence.

[Long survival of a case of unresected duodenal cancer treated by S-1 before and after duodenojejunostomy].

A 52-year-old woman visited our hospital with epigastralgia. Detailed examination revealed a duodenal cancer of the ascending limbs. Since she refused the resection, the administration of S-1 alone was commenced. After one course of this treatment, oral intake became impossible. Duodenography and endoscopy showed duodenal obstruction, and she underwent surgery. The tumor proved to be unresectable due to direct invasion of the inferior vena cava. Duodenojejunostomy was performed. After surgery, she was treated by S-1 and survived 2 years and 11 months, which resulted in 3 years and 2 months' long survival from her first visit. The intervals of the intake and home stay, after the operation, were 2 years and 8 months and 2 years and 5 months, respectively. The combination of S-1 administration and bypass operation provides a useful alternative for the treatment of unresectable duodenal cancer with stenosis.

The validity of sentinel lymph node biopsy using dye technique alone in patients with gastric cancer.

BACKGROUND/AIMS: We investigated whether sentinel lymph node biopsy using dye technique alone is useful or not in decision-making for less invasive surgery in patients with gastric cancer. METHODOLOGY: The subjects were 43 patients who had undergone laparotomy for gastric cancer and consented to undergo sentinel lymph node biopsy using patent blue dye. The patients enrolled were 26 males and 17 females, with a mean age of 62.5 years. The tumor sites were upper third of the stomach in 14, middle third in 16, and lower third in 13 patients. The depth of invasion was mucosa in eight, submucosa in 19, muscularis propria in five, subserosa in five, and serosa in six patients. Total gastrectomy was performed in 12, subtotal gastrectomy in 28, and proximal gastrectomy in three patients. RESULTS: The mean number of sentinel lymph node biopsies per surgery was 3.5 +/- 4.1. We were able to perform blue node biopsy in 40 out of 43 patients, but could not find any blue nodes in three patients. Among the 40 patients in whom blue nodes were identified, 29 patients with no metastasis in blue nodes had no evidence of lymph node metastasis (NO). The depth of invasion was not deeper than subserosa in all these patients. Metastasis was observed in one out of the three patients in whom no blue nodes were found. CONCLUSIONS: When the depth of invasion was not deeper than the subserosa and blue nodes were identified, no metastases in either non-blue nodes or blue nodes could be found in the absence of metastatic blue nodes. Therefore, if the depth of invasion is not deeper than the subserosa in gastric cancer, metastatic search in blue nodes seems sufficient and less invasive surgery can be performed safely. Even when the invasion depth is not deeper than the submucosa, the tumor could be metastatic to Group 2 lymph nodes in patients in whom blue node biopsy revealed metastases. When metastasis is found in lymph nodes by intraoperative frozen section diagnosis, less invasive surgery for gastric cancer is not indicated.

13C-urea breath test in patients having undergone total gastrectomy.

BACKGROUND/AIMS: In this study, we performed 13C-urea breath test in patients who had undergone total gastrectomy and investigated the content of (13)CO2 in the CO2 gas expired after direct influx of 13C-urea into the small intestine. METHODOLOGY: 13C-Urea breath test was performed in 31 patients who had undergone total gastrectomy at this department for the treatment of stomach cancer and consented to participate in this study. The test was performed in two ways, i.e. with and without mouth washing (gargling) on taking 13C-urea. RESULTS: Among 41 measurements, the delta13C was less than 2.5% per hundred in 9 measurements (22.2%) and less than 2.0% per hundred in 6 measurements (14.6%). The delta13C exceeded 50% per hundred, in 4 subjects (9.8%). There were no differences between the methods with and without gargling. CONCLUSIONS: The results of this study suggested the possibility that 13C-urea is decomposed even in the jejunum or the lower part of intestine resulting in absorption of H(13)CO3 and another possibility that 13C-urea is directly absorbed from the intestine and decomposed in the blood.

Bone disorder and vitamin D after gastric cancer surgery.

BACKGROUND/AIMS: The present study was conducted to investigate the relationship between bone metabolic disorder after gastrectomy for gastric cancer and vitamin D metabolites or the hormones involved in calcium metabolism. METHODOLOGY: Twenty-one patients who had undergone gastrectomy for gastric cancer and had been followed for less than 10 years were assessed for bone disorder by microdensitometry. The levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), 24,25-dihydroxy vitamin D (24,25(OH)2VD), N-PTH, calcitonin, estradiol, osteocalcin, and ALP were measured and assessed for correlations with clinicopathological factors, including the operative procedure and the number of years since surgery. RESULTS: Bone disorder was found in 9 out of 21 patients (42.9%). The prevalence was significantly higher in patients who had undergone surgery more than 2 years before assessment, so there was a relationship between the period after surgery and bone disorder. Among the vitamin D metabolites, the level of 1,25(OH)2VD was normal in all patients, whereas 25(OH)VD was reduced in 6 out of 21 patients (28.6%) and 24,25(OH)2VD was reduced in 17 patients (81.0%). The 1,25(OH)2VD was significantly higher in the patients with Grade I to III bone disorder compared to the patients with normal bones or early bone disease. The 1,25(OH)2VD/25(OH)VD ratio was significantly higher in the patients without passage of food through the duodenum due to the reconstructive method, while the 25(OH)VD/24,25(OH)2VD ratio was significantly higher in the patients with remaining of duodenal food passage. PTH was decreased in about 50% of the patients, while calcitonin was normal in all patients. Estradiol was decreased in one female patient, while it was elevated in 10 of the 17 men (58.8%). The osteocalcin level was high in all patients irrespective of the period after surgery. CONCLUSIONS: After gastrectomy, the incidence of bone metabolic disorder increases with time. Changes of vitamin D metabolites, particularly 25(OH)VD and 24,25(OH)2VD, seem to be closely associated with post-gastrectomy bone disease.

Platelet activation in patients after splenectomy with total gastrectomy for gastric cancer.

OBJECTIVE: We investigated change in platelet activation using flow cytometry in patients before and after splenectomy with total gastrectomy for gastric cancer. METHODS: Six patients who underwent splenectomy for lymphadenectomy with total gastrectomy for gastric cancer were the subjects in this study. In the patients, platelet count and platelet activation were evaluated before the operation, 1 week after the operation, and 1 month after the operation. Expression of CD62P (P-selectin) was analysed as a marker of platelet activation using flow cytometry. RESULTS: Although platelet count significantly increased 1 week after the operation, the platelet count 1 month after the operation did not increase significantly. Expression of CD62P (P-selectin) significantly decreased at 1 week and 1 month after the operation, compared with the level before the operation. No postoperative complications occurred in any patient. CONCLUSION: In the present study, platelet activation did not progress after the operation. The results mean that the risk of thrombosis after splenectomy does not increase.

Laparoscopy-assisted distal gastrectomy with 3-cm laparotomy, left hepatic lobe compression technique, and selection of automatic anastomosis device.

In this study, we performed laparoscopy-assisted distal gastrectomy (LADG) and lymph node dissection with an incision of 3 cm aiming at radical cure and low invasiveness. We introduce and discuss this technique of minilaparotomy and recommend a device for anastomosis. In LADG, a skin incision of 5cm or greater is made in order to pull out the stomach in other institutes. Whether function is distinctly better after laparoscopy-assisted surgery than after abdominal section has not been elucidated so far, so we should seek an aesthetic advantage. We have used a 3-cm abdominal wound to date. If the wound is smaller than this, the body of the SDH25 cannot be inserted, and currently a wound less than 3cm may thus not be possible. The shaft of the SDH is straight, making it easy to confirm the direction even through a laparoscope. The shaft of the anvil head of the PPCEEA is too long, so that when it is connected with the body through the 3-cm incision, it is necessary to draw it through the remnant stomach to a great extent.

Successful treatment of multiple small-bowel perforations caused by cytomegalovirus in a patient with malignant lymphoma: report of a case.

We report the successful management of multiple small-bowel perforations caused by cytomegalovirus (CMV) infection in a 60-year-old man, 1 day after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) therapy induction for malignant lymphoma. Emergency laparotomy was performed for perforative peritonitis, but we did not resect the lesions at this time. Instead, we exteriorized the small bowel and then irrigated the peritoneal cavity and intestinal tract. His white blood cell count was low, at 200 cells/microl, so this therapy was continued until it recovered. The intestine was highly edematous, but it improved after irrigation with peritoneal dialysis solution. In the second-stage procedure, we resected the small bowel with the perforations, and constructed a jejunostomy and colostomy, then closed the abdominal cavity. Although the patient needed central venous hyperalimentation, he had a favorable postoperative course and started treatment again for the malignant lymphoma.

Expression profiling of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: clinical implications.

In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT) has a curative potential even in cases of locally advanced carcinoma. However, only about half of the patients benefit from CRT, and an accurate prediction of sensitivity to CRT is eagerly awaited. Using microarrays, we analyzed gene-expression patterns of pretreatment biopsy specimens from 33 patients with CRT alone including long-term survivors, more than 3 years (14 cases) and short-term survivors, less than 1 year (11 cases). The expression patterns of about 12,600 genes were used to identify genes correlated with survival terms. Fifty-seven genes correlating with short-term survival and 120 genes with long-term survival were identified. The genes involved in the immune response were characteristically upregulated in the long-term survivors, and an immunohistochemical staining confirmed an increased CD8-positive T cell number in the long-term survivors over that in the short-term survivors. In the short-term survivors, on the other hand, increased expression of the genes involved in drug resistance was observed. Our gene list should contribute to the elucidation of the mechanisms of CRT response and contains useful markers for predicting the prognosis of individual ESCC patients treated with CRT alone.