[Surgical Outcomes of Laparoscopic Gastrectomy for Upper Gastric Cancer and Verification of the Validity of Laparoscopic Proximal Gastrectomy].

Laparoscopic proximal gastrectomy(LPG)for upper gastric cancer is still inadequate. We verified the validity of LPG by comparing the surgical outcomes of 15 cases who underwent LPG(PG group)and 14 cases who underwent laparoscopic total gastrectomy(TG group)in 29 cases who underwent laparoscopic surgery for upper gastric cancer at our hospital between January 2014 and December 2022. As a patient background, the PG group was significantly older(p=0.03)than the TG group and tended to have more high-risk cases(p=0.12). As a tumor factor, cancer progression tended to be earlier in the PG group(p=0.05). As a surgical(short-term)outcomes, although the range of lymph nodes dissection was narrow (p<0.01)and the amount of blood loss was significantly lower(p=0.01)in the PG group, there was no difference in operation time or postoperative complications between the 2 groups. Furthermore, there was no difference in the rate of weight loss, the rate of change in nutritional indicators in the medium-term(1 year after surgery), or the long-term prognosis.

An innovative approach to bone marrow collection and transplantation in a patient with beta-thalassemia major: marrow collection using a perfusion method followed by intra-bone marrow injection of collected bone marrow cells.

Using small animals (mice and rats) and monkeys, we have found that the combination of bone marrow collection using the perfusion method (PM) and intra-bone marrow-bone marrow transplantation (IBM-BMT) of the collected cells is safe and effective in treating various intractable diseases. Based on these findings, we attempted to apply this method to humans. We report here the first case of a patient (6 years old) with beta-thalassemia major who underwent allogeneic BMT using this new PM + IBM-BMT method. The white blood cell counts of the patient gradually increased to more than 1500/microL by day 47 and continued to increase, reaching the highest level (8600/microL) on day +55. Fluorescence in situ hybridization data on day +33 showed that 98% of the peripheral blood cells were from the donor. Notably, there were no symptoms of graft-versus-host disease (GvHD). However, on day +56, the patient regrettably died of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy. We hope that this case report will help make our new strategies more readily available for the treatment of patients with various intractable diseases.

Treatment of streptozotocin-induced diabetes mellitus in rats by transplantation of islet cells from two major histocompatibility complex disparate rats in combination with intra bone marrow injection of allogeneic bone marrow cells.

BACKGROUND: We have established a new method for the transplantation of allogeneic pancreatic islets obtained from two different rat strains in combination with a newly developed bone marrow transplantation (BMT) method in which bone marrow cells (BMCs) are directly injected into the bone marrow cavity (intra bone marrow BMT [IBM-BMT]). METHODS: Streptozotocin-induced diabetic Brown Norway (BN: RT1A(n)) rats were injected with fludarabine, irradiated with 5.0 Gy x 2, and BMCs from two allogeneic rat strains, Fischer 344 (F344: RT1A(1)) and PVG (PVG: RT1A(c)), were then directly injected into the bone marrow cavity (IBM-BMT). Simultaneously, approximately 600 pancreatic islets (PIs) from F344 and PVG rats were mixed and transplanted into the liver by way of the portal vein. RESULTS: All the recipients thus treated showed normoglycemia 30 days after the treatment. Hematolymphoid cells were completely reconstituted with the two donor-type cells, and immunologic tolerance to F344 and PVG major histocompatibility complex (MHC) determinants were induced. CONCLUSIONS: The transplantation of PIs from two MHC-disparate donors was completely achieved in combination with IBM-BMT, resulting in the improvement of blood glucose levels and the amelioration of diabetes mellitus.

Intra-bone marrow-bone marrow transplantation facilitates hemopoietic recovery including dendritic cells.

In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.

Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells.

A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.