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1.
Surg Endosc ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977498

ABSTRACT

BACKGROUND: Excessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer. METHODS: This retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined. RESULTS: AL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45-33.6; P = 0.016). CONCLUSIONS: The presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition.

2.
JMA J ; 5(2): 207-215, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35611234

ABSTRACT

Introduction: Bowel obstruction at the outlet of the stoma, also referred to as "stoma outlet obstruction" (SOO), has been noted to be more common after laparoscopic colorectal surgery with diverting ileostomy than after laparotomy. Thus, the aim of this study is to identify the risk factors for SOO and to evaluate the effectiveness of a modified ileostomy procedure for reducing its incidence. Methods: The medical records of 63 patients who underwent laparoscopic colorectal surgery with diverting ileostomy between January 2014 and July 2021 were retrospectively reviewed. We analyzed the risk factors for SOO using computed tomography findings. Results: In total, 34 patients underwent surgery before modification of the ileostomy procedure (LSa group), and 29 patients underwent surgery after modification (LSb group). In the LSa group, 6 patients have reportedly developed SOO (SOO group), whereas 28 patients did not (non-SOO group). No patients in the LSb group developed SOO. The thickness of the abdominal rectus muscle (ThM) in the SOO group and the non-SOO group was 13.4 mm and 9.6 mm, respectively (p = 0.005). The angle between the ileostomy and the abdominal wall (AIW) was 95.8° in the non-SOO group and 82.2° in the SOO group (p = 0.033). The AIW was 93.4° in the LSa group and 99.7° in the LSb group (p = 0.043). Conclusions: As per our findings, a thick abdominal rectus muscle is predictive of SOO. Correction of the AIW (eliminating medial inclination) by modifying the operative technique has eliminated the occurrence of SOO in our patient population.

3.
J Surg Res ; 152(1): 54-60, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18599084

ABSTRACT

BACKGROUND: Steatosis decreases survival of liver grafts after transplantation due to poorly understood mechanisms. We examined the effect of steatosis on the survival of liver grafts in a rat liver transplantation model and the viability of cultured rat hepatocytes after hypoxia and reoxygenation. MATERIALS AND METHODS: Rats were fed a choline and methionine-deficient diet to induce hepatic steatosis, and the livers were transplanted into recipient rats after 6 h of cold storage. Cultured hepatocytes were made steatotic by incubation for 3 d in fatty acid-supplemented medium. Hypoxia and reoxygenation were induced by placing the cultures in a 90% N(2)/10% CO(2) atmosphere for 4 h, followed by return to normoxic conditions for 6 h. Hepatocyte viability was assessed by lactate dehydrogenase release and mitochondrial potential staining. RESULTS: Transplanted steatotic livers exhibited 0% viability compared with 90% for lean liver controls. When donor choline and methionine-deficient diet rats were returned to a normal diet, hepatic fat content decreased while viability of the grafts after transplantation increased. Cultured steatotic hepatocytes generated more mitochondrial superoxide, exhibited a lowered mitochondrial membrane potential, and released significantly more lactate dehydrogenase after hypoxia and reoxygenation than lean hepatocyte controls. When steatotic hepatocytes were defatted by incubating in fatty acid-free medium, they became less sensitive to hypoxia and reoxygenation as the remaining intracellular triglyceride content decreased. CONCLUSIONS: Hepatic steatosis reversibly decreases viability of hepatocytes after hypoxia and reoxygenation in vitro. The decreased viability of steatotic livers after transplantation may be due to a direct effect of hypoxia and reoxygenation on hepatocytes, and can be reversed by defatting.


Subject(s)
Fatty Liver/physiopathology , Hepatocytes/metabolism , Hypoxia/physiopathology , Liver Transplantation , Mitochondria, Liver/metabolism , Animals , Cell Survival , Cells, Cultured , Female , Male , Membrane Potential, Mitochondrial , Rats , Rats, Inbred Lew , Reperfusion Injury/physiopathology , Superoxides/metabolism
4.
JMA J ; 2(1): 54-59, 2019 Mar 04.
Article in English | MEDLINE | ID: mdl-33681513

ABSTRACT

INTRODUCTION: Open appendectomy for acute appendicitis is a common procedure for surgical residents to perform at the beginning of their training. Recently, many programs have moved to laparoscopic appendectomy as the initial training procedure. However, the feasibility and safety of laparoscopic appendectomy for acute appendicitis performed by surgical residents without any experience of open appendectomy remains controversial. METHODS: The records of patients who underwent laparoscopic appendectomy for acute appendicitis between August 2006 and March 2017 were retrospectively reviewed. Patients were assigned to two groups according to whether their procedure was performed by a surgical resident, with no experience of open appendectomy, or a surgical fellow, with adequate open appendectomy experience but no experience with laparoscopic appendectomy. RESULTS: A total of 130 patients were included. Five residents performed 104 procedures, and three fellows performed 26 procedures. The baseline patient characteristics were comparable between groups. The median operative time was comparable (77.0 min vs. 65.5 min; p = 0.771). There were no significant differences in overall complications; with 14 patients (13%) in the resident group and five patients (19%) in the fellow group experienced complications (p = 0.535). No patient required reoperation, and there were no fatalities. The median length of stay was similar (5.0 days vs. 5.5 days; p = 0.430). CONCLUSIONS: Laparoscopic appendectomy for acute appendicitis is feasible and safe when performed by surgical residents with no prior open appendectomy experience. It may be performed as the first procedure during surgical training with no adverse effect on patients.

5.
J Med Case Rep ; 13(1): 369, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31837708

ABSTRACT

BACKGROUND: A small percentage of patients with foreign body ingestion develop complications, which have a variety of clinical presentations. Less than 1% of cases require surgical intervention. We present a patient with an abdominal wall abscess resulting from a fish bone that pierced the cecum. The patient was treated laparoscopically. CASE PRESENTATION: A 55-year-old Japanese man presented to our hospital with a complaint of right lower abdominal pain. A physical examination revealed tenderness, swelling, and redness at the right iliac fossa. Computed tomography showed a low-density area with rim enhancement in his right internal oblique muscle and a hyperdense 20 mm-long pointed object in the wall of the adjacent cecum. Based on the findings we suspected an abdominal wall abscess resulting from a migrating ingested fish bone. He was administered antibiotics as conservative treatment, and the abscess was not seen on subsequent computed tomography. Two months after the initial treatment, he presented with the same symptoms, and a computed tomography scan showed the foreign body in the same location as before with the same low-density area. We diagnosed the low-density area as recurrence of the abdominal wall abscess. He underwent laparoscopic surgery to remove the foreign body. His appendix, and part of his cecum and the parietal peritoneum that included the foreign body, were resected. He had an uneventful postoperative course, and at 1 year after the surgery, the abdominal wall abscess had not recurred. CONCLUSIONS: An abdominal wall abscess developed in association with the migration of an ingested fish bone. We suggest that a laparoscopic surgical resection of the portion of the bowel that includes the foreign body is a useful option for selected cases.


Subject(s)
Abdominal Abscess/pathology , Anti-Bacterial Agents/therapeutic use , Bone and Bones , Foreign Bodies , Foreign-Body Migration/pathology , Intestinal Perforation/pathology , Abdominal Abscess/diagnostic imaging , Abdominal Abscess/therapy , Abdominal Pain , Animals , Eating , Fishes , Foreign-Body Migration/complications , Humans , Intestinal Perforation/diagnostic imaging , Laparoscopy , Male , Middle Aged , Tomography, X-Ray Computed
6.
Int J Surg Case Rep ; 50: 50-55, 2018.
Article in English | MEDLINE | ID: mdl-30081320

ABSTRACT

INTRODUCTION: Many patients with desmoids have an antecedent trauma, particularly surgical intervention for familial adenomatous polyposis. However, cases of mesenteric desmoid after gastrectomy are extremely rare. We present a case of multiple mesenteric desmoids after total gastrectomy for gastric cancer. PRESENTATION OF CASE: A 70-year-old man had undergone a total gastrectomy for early stage gastric cancer. He had no other relevant medical history or family history. A year after gastrectomy, a computed tomography showed three mesenteric masses, and we performed careful observation. The 2-year postoperative examination indicated slowly growing masses. There were no other lesions except for the three masses. We decided to perform diagnostic surgery to evaluate the tumors. There were three mesenteric masses (1.5 cm, 4 cm and 1.5 cm in diameter). We performed partial small intestinal resections for each mass. Histological examination showed that the tumors were desmoids. A year after surgery, he was doing well with no evidence of recurrence of the desmoids or the gastric cancer. DISCUSSION: Diagnosing intra-abdominal desmoid tumors is often difficult. Especially if a patient has a history of malignancy, it may be extremely difficult to differentiate multiple mesenteric desmoids from a cancer recurrence. In the current case, surgical resection was a useful treatment option as diagnostic therapy. CONCLUSIONS: Multiple mesenteric desmoids could emerge after gastrectomy for gastric cancer, and surgical resection of the tumors is a useful option as a diagnostic therapy.

7.
J Med Case Rep ; 12(1): 347, 2018 Nov 26.
Article in English | MEDLINE | ID: mdl-30474568

ABSTRACT

BACKGROUND: Chylothorax is the accumulation of chyle within the pleural space. Chylothorax can occur as a complication after multiple different types of surgery, most frequently after thoracic surgery, albeit with an incidence rate of less than 1%. Chylothorax after abdominal surgery is extremely rare, and there are only a few case reports. CASE PRESENTATION: A 74-year-old Japanese woman presented with jaundice. She was diagnosed as having hilar cholangiocarcinoma and underwent right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and lymph node dissection after preoperative percutaneous transhepatic portal vein embolization. Postoperative liver function was normal. She developed chylous ascites on postoperative day 5, for which conservative treatment was initially effective. Dyspnea developed suddenly on postoperative day 42, and she had a massive right pleural effusion and a small amount of ascites. Management with pleural drainage, total parenteral nutrition, and octreotide injections decreased the chylothorax. However, the chylous effusion reaccumulated on postoperative day 57. As conservative treatments ultimately failed, lymphangiography was performed on postoperative day 62. Lymphangiography with Lipiodol (ethiodized oil) revealed extravasation into the pleural space, but the location of the leak was not identified. There was neither obstruction nor dilation of the thoracic duct. A lymphatic leak in her abdominal cavity was not demonstrated. A chest tube was placed after lymphangiography, and the chylothorax was diminished by postoperative day 71. She was discharged on postoperative day 72. Two and a half years after surgery, she is doing well with no evidence of recurrence of either chylothorax or cancer. CONCLUSIONS: Chylothorax can occur after hepatectomy and pleural effusion should raise suspicion for chylothorax. Lymphangiography may be effective for both diagnosis and treatment in the case of chylothorax after hepatectomy.


Subject(s)
Bile Duct Neoplasms/surgery , Cholangiocarcinoma/surgery , Chylothorax/therapy , Drainage , Hepatectomy/adverse effects , Lymphography , Postoperative Complications/therapy , Aged , Chest Tubes , Chylothorax/diagnostic imaging , Chylothorax/etiology , Drainage/methods , Ethiodized Oil , Female , Humans , Postoperative Complications/diagnostic imaging , Treatment Outcome
8.
J Med Case Rep ; 12(1): 28, 2018 Feb 06.
Article in English | MEDLINE | ID: mdl-29402298

ABSTRACT

BACKGROUND: Rectal cancer with rectal prolapse is rare, described by only a few case reports. Recently, laparoscopic surgery has become standard procedure for either rectal cancer or rectal prolapse. However, the use of laparoscopic low anterior resection for rectal cancer with rectal prolapse has not been reported. CASE PRESENTATION: A 63-year-old Japanese woman suffered from rectal prolapse, with a mass and rectal bleeding for 2 years. An examination revealed complete rectal prolapse and the presence of a soft tumor, 7 cm in diameter; the distance from the anal verge to the tumor was 5 cm. Colonoscopy demonstrated a large villous tumor in the lower rectum, which was diagnosed as adenocarcinoma on biopsy. We performed laparoscopic low anterior resection using the prolapsing technique without rectopexy. The distal surgical margin was more than 1.5 cm from the tumor. There were no major perioperative complications. Twelve months after surgery, our patient is doing well with no evidence of recurrence of either the rectal prolapse or the cancer, and she has not suffered from either fecal incontinence or constipation. CONCLUSIONS: Laparoscopic low anterior resection without rectopexy can be an appropriate surgical procedure for rectal cancer with rectal prolapse. The prolapsing technique is useful in selected patients.


Subject(s)
Anal Canal/pathology , Colonoscopy , Digestive System Surgical Procedures , Rectal Neoplasms/pathology , Rectal Prolapse/pathology , Rectum/pathology , Anal Canal/surgery , Female , Humans , Laparoscopy , Middle Aged , Rectal Neoplasms/surgery , Rectal Prolapse/surgery , Treatment Outcome
9.
Nagoya J Med Sci ; 80(3): 423-429, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30214092

ABSTRACT

Hepatic carcinosarcoma (HCS) generally presents in advanced stages, demonstrates aggressive behavior, and has a poor prognosis. Other than curative primary resection, no effective treatment options exist. We present a case of resected HCS with four repeat resections for solitary lymph node recurrence followed by chemoradiotherapy with doxorubicin and ifosfamide. A 67-year-old Japanese man was admitted to our hospital for evaluation of an asymptomatic hepatic tumor. The patient underwent right hepatectomy with a presumptive preoperative diagnosis of atypical hepatocellular carcinoma. Based on histopathological and immunohistochemical findings, the tumor was diagnosed as HCS containing osteosarcoma and chondrosarcoma components. After the initial surgery, the patient underwent four additional resections for solitary lymph node HCS recurrence, and then underwent chemoradiotherapy with doxorubicin and ifosfamide for an unresectable lymph node recurrence. Chemotherapy was stopped after two cycles because of severe adverse events, although chemoradiotherapy markedly reduced the size of the lymph node recurrence and provided a progression-free survival of 12 months. Thirty-seven months after the initial surgery, the patient died of cardiac invasion of multiple mediastinal lymph node metastases. The clinical course outlined in this case report suggests that chemoradiotherapy with doxorubicin and ifosfamide for metastatic HCS may prolong survival in patients with unresectable lesions.


Subject(s)
Carcinosarcoma/drug therapy , Carcinosarcoma/surgery , Combined Modality Therapy/methods , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Aged , Antibiotics, Antineoplastic/therapeutic use , Doxorubicin/therapeutic use , Humans , Ifosfamide/therapeutic use , Male , Neoplasm Recurrence, Local , Treatment Outcome
10.
Trials ; 14: 17, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23320901

ABSTRACT

BACKGROUND: Although, in Western countries, oxaliplatin-based regimens have been established as a gold standard treatment for patients with stage III or high risk stage II colon cancer after curative resection, in Japan fluorouracil-based regimens have been widely accepted and recommended in the guidelines for adjuvant settings in patients with stage III colon cancer. S-1, an oral preparation evolved from uracil and tegafur, has equivalent efficacy to uracil and tegafur/leucovorin for treating patients with advanced colorectal cancer and might be a suitable regimen in an adjuvant setting. However, the completion rate of the standard six-week cycle of the S-1 regimen is poor and the establishment of an optimal treatment schedule is critical. Therefore, we will conduct a multicenter randomized phase II trial to compare six-week and three-week cycles to establish the optimal schedule of S-1 adjuvant therapy for patients with stage III colon cancer after curative resection. METHODS/DESIGN: The study is an open-label, multicenter randomized phase II trial. The primary endpoint of this study is three-year disease-free survival rate. Secondary endpoints are the completion rate of the treatment, relative dose intensity, overall survival, disease-free survival, and incidence of adverse events. The sample size was 200, determined with a significance level of 0.20, power of 0.80, and non-inferiority margin of a 10% absolute difference in the primary endpoint. DISCUSSION: Although S-1 has not been approved yet as a standard treatment of colon cancer in an adjuvant setting, it is a promising option. Moreover, in Japan S-1 is a standard treatment for patients with stage II/III gastric cancer after curative resection and a promising option for patients with colorectal liver metastases in an adjuvant setting. However, a six-week cycle of treatment is not considered to be the best schedule, and some clinicians use a modified schedule, such as a three-week cycle to keep a sufficient dose intensity with few adverse events. Therefore, it will be useful to determine whether a three-week cycle has an equal or greater efficacy and tolerance to side-effects compared with the standard six-week cycle schedule, and thus may be the most suitable treatment schedule for S-1 treatment. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000006750.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Colectomy , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery , Oxonic Acid/administration & dosage , Research Design , Tegafur/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Chemotherapy, Adjuvant , Clinical Protocols , Colectomy/adverse effects , Colectomy/mortality , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Disease-Free Survival , Drug Administration Schedule , Drug Combinations , Humans , Japan , Neoplasm Staging , Oxonic Acid/adverse effects , Tegafur/adverse effects , Time Factors , Treatment Outcome
11.
J Surg Res ; 135(1): 92-9, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16600305

ABSTRACT

Heat shock preconditioning (HPc) of fatty donor livers significantly increases recipient survival in rats. We investigated to what extent the blockade of Kupffer cells by gadolinium chloride (GdCl3) can mimic the effect of HPc and the involvement of liver CD4+ T lymphocytes in HPc. Fatty liver was experimentally induced in Lewis rats by a choline- and methionine-deficient diet. Fatty liver donors were pretreated with HPc (42.5 degrees C for 10 min), the Kupffer cell inhibitor GdCl3, or placebo (sham group). Donors were then harvested, stored in University of Wisconsin preservation solution for 12 h at 4 degrees C, and transplanted into normal syngeneic rats. Hepatic injury (alanine aminotransferase) and serum cytokines (interleukin-12p70, tumor necrosis factor-alpha, and interleukin-10) of recipients increased at 3 h, then decreased, and increased again at 24 h after transplantation. HPc treatment diminished both the early and later phases of this biphasic response and improved recipient survival. GdCl3 reduced these cytokines in the early but not the later phase and did not reduce neutrophil accumulation or improve the recipient survival. HPc, but not GdCl3 treatment, also reduced the number of liver CD4+ T lymphocytes and their interferon-gamma production. We conclude that HPc, but not GdCl3 treatment, prevents biphasic liver injury and the activation of liver CD4+ T lymphocytes in transplanted fatty donor livers.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Fatty Liver/surgery , Graft Survival/immunology , Heat-Shock Response , Liver Transplantation , Transplantation Conditioning/methods , Acute Disease , Animals , Anti-Inflammatory Agents/pharmacology , CD4-Positive T-Lymphocytes/metabolism , Cytokines/metabolism , Disease Models, Animal , Gadolinium/pharmacology , Hyperthermia, Induced , Kupffer Cells/drug effects , Kupffer Cells/pathology , Liver/immunology , Liver/pathology , Liver/surgery , Lymphocyte Activation , Male , Rats , Rats, Inbred Lew , Reperfusion Injury/immunology , Reperfusion Injury/prevention & control
12.
Surg Today ; 36(6): 554-8, 2006.
Article in English | MEDLINE | ID: mdl-16715429

ABSTRACT

We report a case of metachronous bilateral adrenal metastases from mucinous adenocarcinoma of the stomach. A 68-year-old man who had undergone surgery for advanced gastric cancer 5 months earlier had a follow-up computed tomography (CT) scan, which showed a right adrenal tumor. We performed a right adrenalectomy, and histopathological examination revealed a mucinous adenocarcinoma with features consistent with those of gastric cancer. A routine follow-up CT scan done 41 months after the right adrenalectomy showed a left adrenal mass. Chemotherapy had no apparent effect, and left adrenalectomy was performed 65 months after the right adrenalectomy. Histopathological examination also revealed a metastasis from gastric cancer. The patient was alive without recurrence 40 months after the left adrenalectomy. This case suggests that resection of adrenal metastasis from gastric cancer is an effective treatment option that may prolong survival in selected patients.


Subject(s)
Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/secondary , Adrenal Gland Neoplasms/secondary , Stomach Neoplasms/pathology , Adenocarcinoma, Mucinous/surgery , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/mortality , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Aged , Humans , Male , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/surgery , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
13.
Liver Transpl ; 10(2): 264-72, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14762865

ABSTRACT

Fatty liver is a common predisposing risk factor for postoperative liver failure and accounts for most discarded livers during triage of donors. We investigated the effect of heat shock preconditioning (HPc) on recipient survival in a rat fatty liver transplantation model. Fatty liver donor rats were exposed to brief whole-body hyperthermia (10 minutes at 42.5 degrees C) and allowed to recover. HPc induced heat shock proteins (HSPs) (HSP72, HSP90, and heme oxygenase [HO]-1) in donor livers, with levels peaking 12 to 48 hours after HPc. Subsequently, donor livers were harvested 24 hours after HPc, placed in cold storage for 10 hours, and transplanted into normal rats. At 3 hours posttransplantation, HPc reduced serum liver enzymes in the recipients and almost completely suppressed the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10. Histologic evaluation 3 and 24 hours after transplantation showed that HPc significantly reduced hepatic inflammation and hepatocellular necrosis without affecting the steatotic appearance of hepatocytes. One week after transplantation, control non-heat-shocked and heat-shocked fatty liver recipients exhibited survival rates of less than 10% and more than 80%, respectively. The evaluation of the survival of recipients receiving fatty livers at different times after HPc showed that the protective effect of HPc was significant when donor livers were transplanted 3 to 48 hours after HPc, with the maximum effect seen 6 to 48 hours after HPc. In conclusion, HPc is a promising avenue to salvage rejected donor fatty livers and enhance the survival rate of fatty liver recipients. We estimate that this technique could increase the annual donor pool by 600 livers.


Subject(s)
Conditioning, Psychological , Fatty Liver/surgery , Hot Temperature , Liver Transplantation , Shock/physiopathology , Tissue Donors , Tissue and Organ Procurement , Animals , Cytokines/blood , Heat-Shock Proteins/metabolism , Liver/pathology , Male , Postoperative Period , Rats , Rats, Inbred Lew , Recovery of Function , Shock/etiology , Survival Analysis , Time Factors
14.
Clin Diagn Lab Immunol ; 9(3): 550-7, 2002 May.
Article in English | MEDLINE | ID: mdl-11986258

ABSTRACT

Intestinal intraepithelial lymphocytes (i-IEL) expressing CD8 alpha are located in the intestine and may confer protection against invasion of intestinal microflora. We found that mice rendered deficient in CD8 alpha molecules by homologous recombination were susceptible to 5-fluorouracil (5-FU)-induced lethality accompanied by translocation of members of the enterobacteria. The number of i-IEL was greatly reduced on day 6 after 5-FU administration in both CD8 alpha(+/-) mice and CD8 alpha(-/-) mice, whereas the recovery of the level of i-IEL thereafter was significantly impaired in CD8 alpha(-/-) mice compared with that in CD8 alpha(+/-) mice. The ability of i-IEL to produce gamma interferon in response to immobilized T-cell receptor (TCR) alpha beta or TCR gamma delta monoclonal antibodies was significantly lower in CD8 alpha(-/-) mice than in CD8 alpha(+/-) mice. Transfer of CD8(+) i-IEL conferred significant protection against 5-FU-induced lethality in CD8 alpha(-/-) mice. The results suggest that CD8(+) i-IEL play an important role in protection against 5-FU-induced lethality with translocation of Enterobacteriaceae.


Subject(s)
Antimetabolites/toxicity , CD8 Antigens/immunology , Fluorouracil/toxicity , Adoptive Transfer , Animals , Antimetabolites/administration & dosage , CD8 Antigens/genetics , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Disease Susceptibility , Enterobacteriaceae/immunology , Fluorouracil/administration & dosage , Interferon-gamma/biosynthesis , Intestinal Mucosa/cytology , Intestinal Mucosa/immunology , Liver/drug effects , Liver/microbiology , Lymphocytes/cytology , Lymphocytes/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Antigen, T-Cell, alpha-beta/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Spleen/drug effects , Spleen/microbiology
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