Differences in subtype distribution between screen-detected and symptomatic invasive breast cancer and their impact on survival

Purpose. Stage shift is considered a major reason for more favorable outcomes in patients with screen-detected breast cancer. However, even after adjusting for clinical stage, unresolved issues concerning the reasons for a survival benefit associated with screening programs remain. This study aims to evaluate differences in subtype distribution and outcomes among patients with screen-detected and symptomatic invasive breast cancer and assess whether variations in subtype distribution could explain differences in prognosis. Methods. Survival analysis was performed to estimate the likelihood of distant recurrence and death in 1132 patients. Subtypes were defined as luminal A [estrogen receptor (ER)+ and/or progesterone receptor (PR)+, human epidermal growth factor receptor 2 (HER2)-, and Ki67 low], luminal B (HER2-) (ER+ and/or PR+, HER2-, and Ki67 high), luminal B (HER2+) (ER+ and/or PR+ and HER2+), HER2 overexpressing (ER-, PR-, and HER2+), and triple negative (ER-, PR-, and HER2-). Results. Screen-detected cancers had favorable clinicopathological characteristics, such as smaller tumor size and a lower frequency of lymph node involvement. Women with screen-detected cancers had a survival advantage. Subtype distribution differed significantly among women with screen-detected and symptomatic cancer. Screen-detected cancers were more likely to be luminal A and less likely to be HER2 overexpressing or triple negative cancer compared with symptomatic cancers (luminal A 61.3 vs. 44.2%, HER2 overexpressing 4.0 vs. 8.0%, triple negative 8.0 vs. 15.9%). Node status, mode of detection, and subtype were independent prognostic factors in the multivariate analysis. Conclusions. Differences in subtype distribution between screen-detected and symptomatic cancer could partially explain differences in outcomes (AU)

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Differences in subtype distribution between screen-detected and symptomatic invasive breast cancer and their impact on survival.

PURPOSE: Stage shift is considered a major reason for more favorable outcomes in patients with screen-detected breast cancer. However, even after adjusting for clinical stage, unresolved issues concerning the reasons for a survival benefit associated with screening programs remain. This study aims to evaluate differences in subtype distribution and outcomes among patients with screen-detected and symptomatic invasive breast cancer and assess whether variations in subtype distribution could explain differences in prognosis. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in 1132 patients. Subtypes were defined as luminal A [estrogen receptor (ER)+ and/or progesterone receptor (PR)+, human epidermal growth factor receptor 2 (HER2)-, and Ki67 low], luminal B (HER2-) (ER+ and/or PR+, HER2-, and Ki67 high), luminal B (HER2+) (ER+ and/or PR+ and HER2+), HER2 overexpressing (ER-, PR-, and HER2+), and triple negative (ER-, PR-, and HER2-). RESULTS: Screen-detected cancers had favorable clinicopathological characteristics, such as smaller tumor size and a lower frequency of lymph node involvement. Women with screen-detected cancers had a survival advantage. Subtype distribution differed significantly among women with screen-detected and symptomatic cancer. Screen-detected cancers were more likely to be luminal A and less likely to be HER2 overexpressing or triple negative cancer compared with symptomatic cancers (luminal A 61.3 vs. 44.2%, HER2 overexpressing 4.0 vs. 8.0%, triple negative 8.0 vs. 15.9%). Node status, mode of detection, and subtype were independent prognostic factors in the multivariate analysis. CONCLUSIONS: Differences in subtype distribution between screen-detected and symptomatic cancer could partially explain differences in outcomes.

Pure laparoscopic hepatectomy for hepatocellular carcinoma patients with severe liver cirrhosis.

Hepatocellular carcinoma often arises in cirrhotic livers. Patients with severe liver cirrhosis who undergo hepatectomy often develop postoperative liver failure, even if the hepatectomy is limited. Here, we report six patients with severe liver cirrhosis (Child-Pugh B/C and indocyanine green retention rate at 15 min ≥ 40%) who underwent pure laparoscopic hepatectomy. Their perioperative course was favorable and comparable to that of other hepatocellular carcinoma patients with mild-moderate liver cirrhosis. In patients with severe liver cirrhosis, pure laparoscopic hepatectomy minimizes the disturbance in collateral blood and lymphatic flow caused by laparotomy and liver mobilization, as well as the mesenchymal injury caused by compression of the liver. It limits complications such as massive ascites, which can lead to severe postoperative liver failure. Good candidates for the procedure include patients with severe liver cirrhosis who have tumors on the liver surface and in whom adaptation to ablation therapy is difficult and/or who experience local recurrence after repeat treatments.

PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft.

The programmed death-1 (PD-1)/B7-H1 pathway acts as an important negative regulator of immune responses. We herein investigated the role of the PD-1/B7-H1 pathway in establishing an immunological spontaneous tolerance status in mouse liver allografting. B7-H1 is highly expressed on the donor-derived tissue cells and it is also associated with the apoptosis of infiltrating T cells in the allografts. Strikingly, a blockade of the PD-1/B7-H1 pathway via anti-B7-H1mAb or using B7-H1 knockout mice as a donor led to severe cell infiltration as well as hemorrhaging and necrosis, thus resulting in mortality within 12 days. Furthermore, the expression of the FasL, perforin, granzyme B, iNOS and OPN mRNA in the liver allografts increased in the antibody-treated group in comparison to the controls. Taken together, these data revealed that the B7-H1 upregulation on the tissue cells of liver allografts thus plays an important role in the apoptosis of infiltrating cells, which might play a critical role of the induction of the spontaneous tolerance after hepatic transplantation in mice.

FK 506 inhibits tolerance induction in mice liver transplantation.

BACKGROUND: In the orthotopic mouse liver transplantation model, allografts are accepted without immunosuppression, and donor-specific tolerance is induced upto 40 days. Although FK 506 is a well-known immunosuppressive agent, its influence on tolerance induction is not known. In this study, we examined the influence of FK 506 on tolerance induction in a mouse liver transplant model. METHODS: Orthotopic liver transplantation was performed from B10.BR (H-2K) to B10.D2 (H-2D mice). In the experimental group, FK 506 (1 mg/kg/d) was given subcutaneously to the recipients from day 0 to day 21, whereas the control group received a placebo (1 mg/kg/d). On day 40, donor skin grafts were transplanted to the recipients to examine the survival times of the recipients and the skin grafts. On day 14, donor-type cells in recipient's blood, spleen, kidney, thymus, and lymph nodes were examined by RT-PCR using specific donor-type MHC class I and II primers. RESULTS: All recipients survived for more than 100 days. The mean survival time of skin grafts in the experimental group was significantly reduced compared to that of controls. On day 14, either donor-type MHC class I- or class II-positive cells were detected in the control group, whereas donor-derived MHC class II-positive cells disappeared in the experimental group. CONCLUSIONS: In the early period after mouse liver transplantation, FK 506 inhibits tolerance induction paradoxically. Some donor-derived MHC class II-positive cells might play an important role in tolerance induction.

Laparoscopic side-to-side esophagogastrostomy using a linear stapler after proximal gastrectomy.

In order to improve anastomotic procedures, we performed laparoscopic side-to-side esophagogastrostomy, using a linear stapler, after proximal gastrectomy in two patients with gastric cancer located in the upper third of the stomach. The patients' postoperative courses were excellent. During postoperative recovery, the patients experienced very little pain, used no analgesic medications, and never experienced reflux esophagitis. This procedure is technically feasible and is an excellent option, given the less involved anastomotic procedure and better postoperative quality of life compared with these features in end-to-side anastomosis using a circular stapler.

Fulminant hepatitis by Fas-ligand expression in MRL-lpr/lpr mice grafted with Fas-positive livers and wild-type mice with Fas-mutant livers.

BACKGROUND: Fulminant hepatitis in mice could be induced by gene-transfection of Fas ligand (FasL). However, the mechanisms of this event still remain controversial as to whether it is mediated by direct Fas/FasL interaction and/or neutrophil migration. To investigate the role of exogenous FasL-expression, we established a simple but clear mouse model on which we performed liver transplantation between Fas-mutant mice (MRL-lpr/lpr) and wild-type mice (MRL+/+). METHODS: The controls were nontransplanted wild-type (group 1) and MRL-lpr/lpr (group 2) mice. We obtained recipients with a Fas defect only in the liver (group 3; MRL-lpr/lpr liver graft in wild-type mice) and Fas-defected recipients with Fas-positive livers (group 4; wild-type graft in MRL-lpr/lpr). We successfully expressed FasL in the liver by cotransfection of two types of adenoviral vectors, AxCALNFasL and AxCANCre, with a Cre-loxP switching system. RESULTS: FasL-expression in the livers in groups 3 and 4 resulted in animal death due to fulminant hepatitis within 48 hr after administration of the vectors. We obtained similar findings in group 1, whereas the mice in group 2 survived without any evidence of hepatitis. Immune staining revealed a marked infiltration of CD11b-positive cells in group 1 and group 3. Despite the number of apoptotic cells, a few infiltration of CD11b-positive cells were seen in group 4. We observed no remarkable findings in the FasL-expressed livers in group 2. CONCLUSION: The results indicated that exogenous FasL-expression induces hepatocyte apoptosis both by direct interaction with Fas and by recruiting Fas-positive inflammatory cells. These findings are important for generating a new strategy to prevent hepatitis as well as for understanding the role of the Fas/FasL interaction in the pathophysiology of hepatitis.

Laparoscopic right hemicolectomy with radical lymph node dissection using the no-touch isolation technique for advanced colon cancer.

The treatment of advanced right-sided colon cancer presents numerous challenges for the surgeon who must aim to minimize the invasiveness of surgery, achieve curative resection, and prevent port-site recurrences. To overcome these issues, we performed a totally intra-abdominal laparoscopic right hemicolectomy with radical lymph node dissection based on a no-touch isolation technique. To perform this no-touch technique, we initially dissected the lymph nodes along the surgical trunk, then transected the transverse colon, terminal ileum, and mesentery without tumor manipulation. Finally, the right side of the colon was freed retroperitoneally. We performed this surgical technique on three patients and no intraoperative complications were encountered. Curative resection was achieved in all three patients, as curability A according to the Japanese Classification of Colorectal Carcinoma, and their postoperative courses were uneventful. Therefore, this novel technique proved to be both feasible and safe. Furthermore, it enabled us to minimize the invasiveness of surgery, while providing clear access to resect the right-sided advanced colon cancer.

Laparoscopic pancreas-preserving total gastrectomy for proximal gastric cancer. A case and technical report.

Although total gastrectomy with distal pancreatectomy has been the standard surgical treatment for advanced gastric cancer, this procedure is frequently complicated by leakage of pancreatic juice and postoperative diabetes mellitus. We present the case of a 74-year-old woman with proximal gastric cancer who underwent a laparoscopic modification of an open pancreas-preserving procedure first described by Maruyama et al. in 1995. With this novel technique, there is no pancreatic leakage, and at 12-month follow-up our patient remains free of diabetes. Herein we give the details of our new method and offer some caveats for its performance.

Gastrointestinal stromal tumor of the stomach successfully treated by laparoscopic proximal gastrectomy with jejunal interposition.

The authors describe a patient with a bleeding gastrointestinal stromal tumor of the stomach who was treated successfully by laparoscopic proximal gastrectomy with jejunal interposition. Immunohistochemically, the tumor was positive for vimentin and CD34 and was diagnosed as a gastrointestinal stromal tumor of low-grade malignancy. Because it is difficult to diagnose this disease preoperatively and a malignant phenotype has been reported, resulting in liver metastasis and peritoneal dissemination, it is desirable to treat this disease with as little manipulation as possible. To achieve this, laparoscopic surgery is a feasible option for the treatment of gastrointestinal stromal tumors.

Identification of the indoleamine 2,3-dioxygenase nucleotide sequence in a rat liver transplant model.

A tryptophan catabolizer, indoleamine 2,3-dioxygenase (IDO) is highly expressed in the placenta and plays an essential role in maternal tolerance. Recent data have shown that the administration of an IDO inhibitor blocked not only maternal tolerance but also liver allograft tolerance. However, little is known about the induction of IDO in liver allografts, although a gene specific for tryptophan 2,3-dioxygenase (TDO) is believed to be expressed in the liver. In the present study, we investigated whether IDO is induced in liver allografts. Synthetic oligonucleotide primers based on the mouse IDO cDNA sequence were used to amplify RNA derived from livers of donor, syngeneic or allogeneic OLT rats. RNA encoding IDO was induced in the rat allogeneic liver after orthotopic liver transplantation (OLT), but not in syngeneic OLT. The rat nucleotide sequence of the RT-PCR products obtained from OLT livers revealed identities of 89% homology to the mouse IDO and of 68% to the human IDO. This study demonstrated the presence of RNA encoding IDO in allogeneic OLT livers, which may be involved in the immune response after liver transplantation.

Precancerous conditions of biliary tract cancer in patients with pancreaticobiliary maljunction: reappraisal of nationwide survey in Japan.

It is widely known that pancreaticobiliary maljunction (PBM), an anomalous arrangement of the pancreaticobiliary ductal system, is frequently associated with biliary tract cancer in patients with or without bile duct dilatation. In 1985, we surveyed patients with PBM who had been operated on at 133 Japanese institutions. A close relationship was shown between biliary tract carcinogenesis and PBM, according to the type of maljunction and age distribution: PBM patients with cystic dilatation had a high risk of bile duct cancer, even in those who were young (aged less than 20 years); the incidence of gallbladder cancer increased markedly in PBM patients over 40 years old with cystic dilatation, while it gradually increased with age in the PBM patients without cystic dilatation. Therefore, we recommend surgical treatment for patients with PBM even if they have no symptoms.

Purely laparoscopic pylorus-preserving gastrectomy with extraperigastric lymphadenectomy for early gastric cancer: a case and technical report.

For the purpose of prevention of postgastrectomy syndrome and a less invasive and yet curative oncological resection, a purely laparoscopic pylorus-preserving gastrectomy with extraperigastric lymphadenectomy was performed for a patient with early gastric cancer located in the middle third of the stomach. The patient's postoperative course was uneventful. During his postoperative recovery, the patient experienced very little pain and used analgesic medication only one time. This operation appeared to be oncologically adequate. As of the seventh postoperative month, the patient never experienced dumping syndrome or alkaline reflux gastritis. This procedure is technically feasible and an excellent option because of its reduced surgical invasiveness and better postoperative quality of life.