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Desmoid-type fibromatosis is a relatively rare disease, often associated with familial adenomatous polyposis and a history of abdominal surgery. A 43-year-old male patient presented with abdominal pain and contrast-enhanced CT showed a mass in the lower abdomen. The mass was a 4×4×3 cm white, dense tumor with a wreath-like arrangement of eosinophilic spindle-shaped cells. Immunostaining showed KIT(-), CD34(-), desmin(-), β-catenin(+), SMA(few+), and the diagnosis was desmoid-type fibrosis. Six months after surgery, there was no apparent recurrence.

A 60-year-old woman was not accompanied by any symptom. She had a gallstone which was identified 20 years prior. Ultrasonography performed by a local doctor revealed that the gallbladder was filled with small stones, and the patient was referred to our department for further examination and treatment for gallbladder stone. Tumor markers are elevated. Contrast- enhanced CT revealed gallbladder stones and thickening in the gallbladder body. PET-CT showed abnormal accumulation of FDG-PET with SUVmax 3.6 in the body of the gallbladder. With a diagnosis of gallbladder cancer, extended cholecystectomy and gallbladder bed resection with regional lymph node dissection were performed. The tumor was diagnosed histologically as small cell type neuroendocrine carcinoma of the gallbladder(pT2a[SS], pN0, pStage ⅡA; Japanese society of hepato-biliary-pancreatic surgery, the 7th edition). The postoperative course was uneventful. This patient has been followed up for 8 years without obvious signs of recurrence. R0 resection and lack of lymph node metastasis can allow long- term survival.

This is a case implying a serious infectious complication risk during intensive severe ulcerative colitis treatment. A 26-year-old man developed diarrhea and bloody stool who was diagnosed with ulcerative colitis in 2018. He was managed with 5-aminosalicylic acid, but intolerance reaction resulted in discontinuation of treatment. He relapsed with severe abdominal pain and bloody stools in February 2019. He was referred to our department for intensive therapy. He had been treated with steroids, tacrolimus, granulocyte and monocyte apheresis, infliximab or tofacitinib, which temporarily improved his clinical symptoms. However, his medical condition could not be controlled. Hand-assisted laparoscopic subtotal colectomy was then performed in October 2019. He developed intermittent fever on postoperative day 3. Enhanced computed tomography (CT) revealed multiple deep vein thromboses and pulmonary embolism. Antibiotics and anticoagulation therapy were initiated, but postoperative day 13 CT showed multiple pulmonary cavities containing fluids and air, which were diagnosed as pulmonary abscess. His intermittent fever was over 38.0°C. Severe cough and hemoptysis lasted 3 weeks, the clinical symptoms and laboratory data then gradually improved after the fourth week.

Patients and Methods: Patients with gastric cancer who underwent laparoscopic-assisted pylorus-preserving gastrectomy (LAPPG group)or laparoscopic-assisted distal gastrectomy(LADG group)between January 2010 and December 2019 were reviewed and their postoperative nutritional status and long-term outcomes retrospectively evaluated., Results: In total, 83 patients(LAPPG group, n=23; LADG group, n=60)were included. Weight loss rates 1, 6, 12, and 24 months postoperatively in the LAPPG and LADG groups were 5.7% and 7.1%, 6.6% and 9.6%, 5.8% and 10.1%, and 5.2% and 8.7%, respectively. The LADG group exhibited a significantly higher weight loss than the LAPPG group at 6, 12, and 24 months (p=0.007, 0.002, and 0.022, respectively). No recurrence was observed in either group within 5 years of surgery. The 5- year overall survival rate of patients with pathological Stage Ⅰ cancer( LAPPG group, n=23, LADG group, n=51) was higher in the LAPPG group than in the LADG group(100% vs 82.9%, p=0.027). There were 6 cases of death from other diseases in the LADG group(pneumonia, n=2, other cancer, n=2, postoperative bleeding, n=1, and heart failure, n=1)but none in the LAPPG group., Conclusion: The weight loss after LAPPG was significantly lower than that after LADG. Furthermore, the former showed a good prognosis without death from other diseases, such as pneumonia.

A 70-year-old woman was hospitalized for diarrhea, vomiting, loss of appetite, fatigue, and dyspnea on exertion for the past 3 weeks and treated with intravenous fluid for dehydration. She was receiving prednisolone for polymyositis. She did not have a history of thyroid disease. On day 4 of hospitalization, the patient was diagnosed with congestive heart failure and tachycardiac atrial fibrillation, and treatment with a diuretic agent was initiated. On day 7 of hospitalization, a clinical laboratory evaluation revealed that the level of free thyroxine was 9.95 ng/dL, free triiodothyronine was >30 pg/mL, and thyroid-stimulating hormone was <0.01 μU/mL, and the patient was initially diagnosed with thyrotoxicosis because of Graves' disease. She showed restlessness and had a fever of 39 °C, tachycardia of ≥140 beats/min, pulmonary edema, and frequent diarrhea, all of which were consistent with the symptoms of thyroid storm. Her general condition gradually improved with comprehensive treatment of thyroid storm comprising thiamazole, potassium iodide, hydrocortisone, and landiolol. A reassessment revealed that the patient had already had thyrotoxicosis and thyroid storm on admission. Thyroid storm is a potentially fatal disease that must be urgently addressed; however, its symptoms are difficult to distinguish from those caused by other diseases. Furthermore, elderly individuals may not exhibit typical symptoms of thyroid storm, so the diagnosis is difficult. In this case, the diagnosis was delayed because of the absence of typical symptoms of thyroid storm and the influence of a pre-existing medical condition and medication.

Aim: Low serum carnitine levels have been reported in patients with cancer receiving chemotherapy and are considered one of the factors causing fatigue associated with chemotherapy. We evaluated the effectiveness of L-carnitine in the treatment of fatigue associated with chemotherapy in patients with gastric cancer(GC)., Materials and Methods: We performed a randomized controlled trial between December 2013 and December 2018. Untreated patients with advanced GC were included in the study; 1 patient developed an allergy after receiving the first chemotherapy and was excluded from the study. The primary endpoint was brief fatigue inventory(BFI). Patients were categorized into 2 groups: those who received L-carnitine oral supplements(group C)and those who did not receive L-carnitine oral supplements(group N)., Results: The serum carnitine levels were improved significantly in group C compared with group N. BFIwas more aggravated in group N than group C; however, the difference was not significant., Conclusion: We could not demonstrate the effectiveness of L-carnitine in the treatment of fatigue associated with chemotherapy in patients with GC.

It is well known that the rise of FSH is a hallmark of menopause associated with osteoporosis and visceral adiposity. Recent days, Zahidi's group reported that blocking FSH signals prevents bone loss in ovariectomized mice by inhibiting bone resorption and stimulating bone synthesis. The same research group also showed that blocking FSH action reduces body fat volume by promoting beige fat thermogenesis. These findings open new doors for novel and complementary treatments addressing post-menopausal osteoporosis and metabolic diseases.

We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy for liver metastasis of gastric cancer. A 76- year-old man who had received SOX therapy for metastatic gastric cancer was admitted to our hospital for a chief complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to SOX therapy because of his symptoms and because his laboratory studies showed significant elevation of his serum creatine kinase(CK)level. The symptoms disappeared and the CK level normalized following large-volume transfusions. Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event. This is the first detailed case report of rhabdomyolysis related to SOX therapy.

Calcium-sensing receptor(CaSR)is highly expressed in parathyroid, kidney, bone, and small and large intestines to regulate Ca homeostasis. Calcilytics are allosteric antagonists of CaSR, and stimulate endogenous PTH release. Several calcilytics have been evaluated as anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because the lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders.

A 70-year-old man with left abdominal pain was referred to our hospital, and was diagnosed with type 1 advanced gastric cancer with lymph node metastasis. Neoadjuvant chemotherapy(NAC)with docetaxel and S-1 combination was administered. After 2 courses of chemotherapy, total gastrectomy with D2 lymph node dissection, splenectomy, and cholecystectomy were performed. Pathologically, viable cancer cells were not evident in the primary lesion and lymph nodes. The pathological response of NAC was judged to be Grade 3. On immunohistochemical analysis of the biopsy specimens obtained before treatment, the cancer cells were positive for class III b-tubulin and negative for TS, DPD, and ERCC1. The anti-tumor effect of S-1 may have led to the pCR.

We analyzed the clinicopathological characteristics, preoperative diagnosis, surgical operations, chemotherapy regimens, and prognoses of 6 patients with primary small intestinal carcinomas that were resected at our hospital between January 2004 and December 2014. The patients(3 men and 3 women)were 65 to 77 years old(mean: 70 years old). We were able to diagnose 3 patients pathologically before surgery via double balloon endoscopy and endoscopy of the large intestine. We performed partial resection of the jejunum in 3 patients, partial resection of the ileum in 1 patient, laparoscopic ileocecal resection in 1 patient, and right hemicolectomy in 1 patient. The histological type was well-differentiated adenocarcinoma in 2 patients, moderately differentiated adenocarcinoma in 2 patients, papillary adenocarcinoma in 1 patient, and poorly differentiated adenocarcinoma in 1 patient. The tumor depth was T2 in 1 patient, T3 in 2 patients, and T4 in 3 patients. The pathological stage was I in 1 patient, II A in 1 patients, II B in 2 patient, III A in 1 patient, and III B in 1 patient. The postoperative median duration of follow-up was 44 months(range: 10-127). Regarding prognosis, 5 patients are alive without recurrence, and 1 patient died of peritoneal dissemination. The overall 5-year survival rate was 75%. We suggest that it is very important to perform radical resection with lymph node dissection for patients without distant metastases.

Denosumab is a monoclonal antibody that can be administrated subcutaneously. Although it is not recommended to adjust the dosages for patients with impaired renal function, hypocalcemia has been reported in patients with renal impairment; therefore, it should be administered cautiously. We retrospectively investigated the serum concentrations of calcium after denosumab administration. The results indicated that after continuous administration to patients with a Ccr<40mL/min, serum calcium levels decreased. Grade 2 or above hypocalcemia was detected in 75% of the patients studied. From these results, it is recommended that serum concentrations of calcium be closely monitored in continuous administration of denosu- mab to patients with renal impairment.

We investigated the clinicopathological findings of 90 patients with colorectal perforation who underwent emergency surgery between January 2008 and July 2015.T he patients were divided into 2 groups, namely those with perforation due to colorectal cancer(colorectal cancer group, n=20)and those with perforation due to benign colorectal disease(non-colorectal cancer group, n=70).We investigated the clinicopathological findings of the 2 groups.The SOFA score was significantly lower in the colorectal cancer group than in the non-colorectal cancer group.Of the 20 cases of primary cancer, 11 were located in the sigmoid colon; 5, in the rectum; 2, in the transverse colon; 1, in the ascending colon; and 1, in the cecum.The perforation occurred at the tumor site in 8 patients and at the oral site of cancer in 12.Eleven patients had stage II cancer, 1 had stage IIIa, and 8 had stage IV.Ten patients underwent curability A resection; 1, curability B resection; and 8, curability C resection.Recurrence was observed in 6 of the 10 patients who had undergone curability A resection and in 1 patient who had undergone curability B resection.The initial recurrence site was the liver in 3 cases, the peritoneum in 2 cases, and a local site in 2 cases.Even if the patents underwent curative operation, the recurrence rate was high.Therefore, we conclude that adjuvant chemotherapy is required along with careful follow-up.

Through the studies of patients with hypophosphatemic rickets/osteomalacia, fibroblast growth factor 23(FGF23)has emerged as a humoral factor that reduces serum phosphate. Discovery of FGF23 as an essential regulator of phosphate homeostasis has markedly improved our understanding of phosphate homeostasis and hypophosphatemic or hyperphosphatemic disorders. A nationwide epidemiologic survey of FGF23-related hypophosphatemic diseases indicated that the patients showed FGF23 levels of above 30 pg/mL by intact assay in the presence of hypophosphatemia. The survey also showed that prevalence and biochemical data before and after treatment of the diseases. Novel therapeutic methods for these disorders may be developed by elucidation of the mechanism of action of FGF23.

A 59-year-old man presented with epigastralgia. A diagnosis of advanced gastric cancer MLU, Circ, Type 3, 160 mm, tub2, cT4b (SI: panc), cN1, cM0, cH0, cP0, cCY0, cStage ⅢB was made. Because of difficulty with oral intake due to malignant outlet obstruction and tumor bleeding, endoscopic self-expanding metallic stent placement was performed. We administered chemotherapy involving docetaxel, cisplatin, and S-1(DCS). After 2 courses of chemotherapy, the primary lesion and regional lymph nodes had reduced in size. His response was judged as SD according to the RECIST criteria. The patient elected to undergo explorative laparotomy for assessment of the gastric cancer. The intraoperative findings showed that there was no pancreatic invasion, peritoneal dissemination, or distal metastasis, so a total gastrectomy and D2 lymph node dissection was performed. The pathological findings showed that there were very few cancer cells in the primary lesion, and a lymph node metastasis was found. The final stage was gastric cancer MLU, Circ, Type 3, 100 mm, muc, ypT4a(SE), ypN3a (13/51), ypM0, ypH0, ypP0, ypCY0, ypStage ⅢC. The therapy evaluation was Grade 1b. In summary, we encountered a patient with gastric cancer in whom curative surgery was made possible by undergoing chemotherapy and metallic stent placement.

Background: We investigated the efficacy of nutritional support in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer (LAEC)., Methods: Eleven patients treated with CRT for locally advanced esophageal squamous cell carcinoma were included. Oral intake energy expenditure (OIE) and total energy expenditure (TEE) of all patients were calculated. Oral nutrition supplementations (ONSs) were utilized as nutritional therapy for the patients with malnutrition (OIE/TEE<0.6). Enteral nutrition (EN) was used in the patients with tumor obstruction., Result: Two patients (18.9%) received ONS and 2 other patients received EN. Seven patients were able to take enough energy in the meal. The mean energy charge was increased from 67.9%to 84.9%. Nine patients (81.8%) completed the treatment regimen. During the CRT period, the prognostic nutritional index (PNI) and C-reactive protein level (mg/dL) were not significantly different. The body mass index decreased to 0.39 kg/m2 (p=0.039) and the mean weight loss was 1.57%. The overall response rate was 81.8%., Conclusion: The nutritional support in the patients treated with CRT for LAEC is effective for maintaining nutritional status. Moreover, the response rate is satisfactory.

Following the discovery of the calcium-sensing receptor (CaSR) in 1993, its pivotal role in disorders of calcium homeostasis was demonstrated. Compelling evidence suggests that the CaSR plays multiple roles extending well beyond not only regulating the level of extracellular Ca(2+), but also controlling diverse and crucial roles in human physiology and pathophysiology. This review covers current knowledge of the role of the CaSR in disorders of calcium homeostasis (familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, autosomal dominant hypocalcemia, primary and secondary hyperparathyroidism, hypercalcemia of malignancy) as well as unrelated diseases such as breast and colorectal cancer, Alzheimer's disease and pancreatitis. In addition, it examines the use or potential use of CaSR agonists or antagonists in the management of disorders as diverse as hyperparathyroidism and Alzheimer's disease.

Combination therapy of oral bisphosphonate and vitamin D analogue showed superior anti-osteoporotic effect compare to bisphosphonate mono-therapy for post menopausal, male and glucocorticoid-induced osteoporosis. Furthermore, the degree of success of oral bisphosphonate therapy for osteoporotic patients should depend on the their vitamin D status. It is thought that we have to evaluate severity of osteoporosis and vitamin D status before started therapy. The combination therapy of these drugs will be more efficient for relatively patients with severe osteoporotic patients and with low vitamin D status.

Metabolic bone and joint diseases in adults include osteomalacia, rheumatoid arthritis, gouty arthritis. Recently, the newest molecular biology procedures and the clinical observation studies can produce good results for understanding of these diseases. From this perspective, the author introduced updated information of the pathophysiology, the latest diagnostic criteria and the therapy of these diseases.

The increase of elderly population in Japan suggests the importance of the prevention of osteoporotic fracture. Falls and fractures account for around 10% of the causes for requiring care services in Japan. The Japanese criteria for initiating pharmacological treatment to prevent fragility fracture were revised in 2011. There are many kinds of anti-osteoporosis drugs including bisphosphonates, SERM, teriparatide, and denosumab that have been proven to reduce fractures. Thus, it is important to select drugs appropriate for each osteoporotic patients considering the mechanisms of drug action, their efficacy and side effects. In this article, we review pathophysiology, diagnosis and treatment of osteoporosis.

Intermittent PTH administration stimulates bone formation and counteracts the inhibition of bone formation by glucocorticoid excess. We have previously demonstrated that PTH enhances interleukin (IL) -11 gene transcription by a rapid induction of delta-fosB expression and Smad1/5 phosphorylation. On the other hand, glucocorticoid can suppress osteoblast differentiation and enhance apoptosis of osteoblast cells via down-regulation of IL-11 expression. PTH could reverse glucocorticoid-induced these damage of osteoblast via stimulation of IL-11 expression. Our data also suggested that IL-11 mediates stimulatory and inhibitory signals of osteoblast differentiation by affecting Wnt signaling. These data demonstrates that PTH and glucocorticoid may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression.

A 65-year-old woman with carcinoma of the pancreatic body underwent Whipple's operation. After surgery, adjuvant chemotherapy with gemcitabine alone, and S-1 combined with gemcitabine was conducted. But one year later, a recurrent tumor was detected in the pancreatic tail. We administered FOLFIRINOX treatment for the recurrent tumor. After 6 courses, FOLFIRINOX treatment resulted in a partial response, and after 9 courses, a radiological complete response was achieved. We could then perform total pancreatotectomy and resection of the metastatic liver tumor. FOLFIRINOX as a second-line treat- ment was effective and safe in this case. In cases of gemcitabine and/or S-1 failure, FOLFIRINOX treatment should be considered.

R0 resectability is thought to be one of the important prognostic factors in bile duct cancer. To achieve R0 resection, accurate preoperative diagnosis is essential. However, intraoperative frozen-section diagnosis sometimes reveals positive ductal margins. It is known that nodular infiltrative tumors tend to extend to the subserosal layer. On the other hand, papillary tumors often have extensive intramural extension, the so-called intraepithelial spread. This type of extension remains difficult to diagnose preoperatively. Some investigators query the clinical significance of positive ductal margins with carcinoma in situ or severe dysplasia. However, even in such instances, local recurrence 5 years after the initial surgery was reported in several articles. Middle bile duct cancer often extends to the upper (hilar bile duct) and lower (intrapancreatic bile duct) sections of the bile duct. To achieve R0 resection, a variety of operative procedures should be considered. For example, hepatopancreatoduodenectomy is required in patients with broad tumor extension up to the hilar bile ducts. However, hilar bile duct resection can result in R0 resection for patients with limited tumor extension. Thus, appropriate operative procedures should be selected based on patients' organ function and other possible prognostic factors, such as lymph node metastases.

Differentiation of mesenchymal stem cells to osteoblastic lineage cells is regulated positively by factors such as mechanical strain and parathyroid hormone, and is negatively regulated by factors including aging and glucocorticoids. Wnt/β-catenin pathway plays an important role in controlling the bifurcation of mesenchymal stem cell differentiation between osteoblastic and adipocytic lineages. In this review, we overview the outline of the mechanism of action as well as interrelation of the actions of these factors in controlling osteoblast differentiation, with special reference to the role of interleukin-11 in these processes.

In a rare accident of nature, some families have been found to have dense and strong bones due to a recessive loss of function mutation in the SOST gene that encodes for sclerostin, a protein expressed by osteocytes that downregulates osteoblastic bone formation. Knowledge of this molecule and its actions led rather quickly to the development of anti-sclerostin antibodies that lead to marked increases in bone mass in both animals and human subjects. Blocking sclerostin action with anti-sclerostin antibodies is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis.

Efficacy of circadian chronotherapy for liver metastases from colorectal cancer was evaluated. Chronomodulated infusion of anticancer drugs via the hepatic artery(HAI) was applied for patients with marginally resectable or unresectable liver metastases at initial diagnosis. Response rate of chemotherapy and frequency of liver resection after chemotherapy of patients treated with chronomodulated HAI were higher than those treated with flat HAI. Further, combination of chronomodulated regional HAI and systemic chemotherapy was the most effective prehepatectomy chemotherapy for the treatment of patients with advanced colorectal liver metastases. Based on these results, we are now performing phase II non-randomized open labeled trial of chronomodulated HAI with systemic administration of panitumumab for patients with such advanced liver metastases (ccFLAP trial). Circadian chronotherapy is an effective prehepatectomy chemotherapy for the treatment of patients with advanced and aggressive liver metastases from colorectal cancer.

Here, we report the case of a patient with advanced gastric cancer complicated by pyloric stenosis and direct invasion into the pancreas who underwent curative resection after bi-weekly S-1/docetaxel(DS)therapy after gastrojejunostomy. A 73-year-old man consulted a general practitioner because of indigestibility, and upper gastrointestinal endoscopy indicated gastric cancer. He was referred to our hospital. Gastric cancer, whole stomach tumor(LMU), 150×80 mm, Type 3, T4a(SE), N2, M0, stage III B was diagnosed, and surgery was performed. The tumor was seen to directly invade the pancreas and the middle colic artery intraoperatively, so only a gastrojejunostomy was performed. After the operation, the patient was treated with DS therapy for 13 courses, and the response was defined as non-complete response(CR)and non-progressive disease (PD). During the second laparotomy, a curative operation was performed via distal gastrectomy because frozen-section diagnosis revealed that no cancer cells were present at the oral margin. Postoperatively, the tumor was diagnosed as LM, 10× 7 mm, 10×2.5 mm, pType 4, pT2(MP), pN0, pM0, CY0, stage I B. The patient is now receiving S-1 adjuvant chemotherapy and is still alive 2 years and 4 months after the first operation.

The bone loss due to space flight or prolonged bed rest observes early stage of unloading and causes both decreased bone formation and increased bone resorption. Mechanical unloading induced not only both tarbecular and cortical bone loss but also greater decline bone structure in weight-bearing bone. These findings and further examination concern about pathophysiolosy will allow for better understanding of unloading-associated bone loss and for development of effective countermeasures.

With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Surgery in isolation may be approaching technical limits, but now is likely to help more patients because of success of complementary strategies, particularly newer chemotherapy and targeted therapy. Leaving behind disappearing metastases after chemotherapy, margin-positive resection, staged liver resection, and liver-first reversed management permit potentially curative surgery for patients previously unable to survive resection. Further, survival benefit from maximum debulking surgery, like ovarian cancer, for colorectal liver metastases is uncertain at present, but likely. Individualized multidisciplinary treatment planning using such strategies is essential.

Bone mass and strength are maintained by appropriate weight bearing. The loss of bone mineral due to space flight or prolonged bed rest has been recognized by space scientists and physicians. In spite of the wealth of knowledge obtained thus far, many questions remain unanswered regarding the mechanism of bone loss as well as the factors affecting these skeletal processes. Bisphosphonates have a potential to become countermeasures against space flight-induced or disuse osteoporosis. In this review, the effect and the possible role of biphosphonates on the prevention and treatment of unloading-induced osteoporosis are summarized and future prospects are discussed.

These 2 years, we had had new therapeutic options for osteoporotic patients, for example minodoronate, bazedoxifene, teriparatide and eldecalcitol in Japan. Minodoronate and eldecalcitol came from Japan and they had many clinical evidences on Japanese patients. Teriparatide is a powerful anabolic agent for bone, had been provided as daily or weekly subcutaneous injection. These reagents may become helpful drug for osteoporotic patients. This review shows the character and clinical evidences of these drugs.

Daily subcutaneous self-injection and weekly subcutaneous injection formulas of teriparatide are available as anabolic agents in Japan. These injection formulas are expected to serve as a new treatment choice for high fracture-risk patients with osteoporosis. In addition, studies using new anabolic agents such as PTHrP, calcilytics, and Wnt inhibitor antagonists/antibodies are under way to develop new anabolic agents. These agents may become new treatment drugs for osteoporotic patients especially with low bone turnover.

Eldecalcitol is a new active vitamin D₃ compound, bearing a hydroxypropyloxy residue at the 2β-position of 1α, 25 (OH) ₂D₃. In ovariectomized rats, eldecalcitol increased vertebral bone mass and bone strength by inhibiting bone resorption and maintaining bone formation. In randomized, placebo-controlled, double-blinded clinical trial for osteoporotic subjects, eldecalcitol increased lumber vertebral and hip bone mineral density independent of vitamin D status. Furthermore, in patients with osteoporosis, eldecalcitol treatment was associated with a lower risk of vertebral and wrist fractures, with greater decrease in bone turnover markers compared with alfacalcidol. The incidence of adverse events was similar between the two treatments. Therefore, eldecalcitol can become a new treatment of choice for osteoporosis.

ED-71 is a new vitamin D receptor ligand, bearing a hydroxypropoxy substituent at the 2β-position of 1α, 25 (OH) (2)D(3). In ovariectomized rats, ED-71 increased vertebral bone mass and bone strength by inhibiting bone resorption and maintaining bone formation. In randomized, placebo-controlled, double-blinded clinical trial for osteoporotic subjects, ED-71 increased lumber vertebral and hip bone mineral density independently vitamin D status. Furthermore, ED-71 may have a better osteoprotective effect than alfacalcidol and suggest that ED-71 may serve as a new generation of active vitamin D with anti-fracture efficacy in osteiporotic subjects.

The purpose of this study was to determine the efficacy of hepatic artery infusion (HAI) plus systemic chemotherapy (SYS) as the prehepatectomy chemotherapy for liver metastases from colorectal cancer. Clinicopathologic data were available for 117 patients who were treated with chemotherapy before liver surgery. Response rate of chemotherapy and frequency of liver resection after chemotherapy of patients treated with HAI/SYS (n=26; 65% and 96%, respectively) were higher than those treated with HAI alone (n=63; 41% and 70%) or SYS alone (n=28; 25% and 42%). Histological examination of adjacent nonneoplastic liver confirmed that severe sinusoidal dilatation was less frequent in HAI/SYS group than in SYS group, and moderate to severe steatosis was also less frequent in HAI/SYS group as compared to HAI group. The combination of regional HAI and systemic chemotherapy is an effective prehepatectomy regimen for the treatment of patients with aggressive liver metastases from colorectal cancer.

We report a long-term survival case of metastatic breast cancer treated with trastuzumab and paclitaxel. The patient was a 64-year-old female. She underwent right quadrantectomy with axillary lymphadenectomy for advanced breast cancer. Histological examination showed papillotubular carcinoma, f, t2, n1(6/14), ER(-), PgR(-), HER2(3+). CMF and radiation were performed as adjuvant therapy. One year after the operation she was diagnosed to have liver metastasis and initiated trastuzumab treatment. Paclitaxel was also intermittently administered when the tumor marker was elevated. Four years after the operation, she experienced obstructive jaundice and was diagnosed as hepatic portal region metastasis. Obstructive jaundice was promptly alleviated after receiving trastuzumab and vinorelbin. No adverse events were reported over sixty-eight months of trastuzumab treatment. Long-term trastuzumab and intermittent chemotherapy would be one of the optimal treatments for HER2-positive breast cancer.

For the treatment of osteoporosis, anti-resorptive agents including bisphosphonates and raloxifene are widely used. As new anti-resorptive drugs, anti-RANKL antibody and cathepsin K inhibitor are under development. Among bone anabolic agents, daily subcutaneous injection of teriparatide will soon become available in Japan. In addition, new anabolic agents such as calcilitycs and anti-sclerostin antibody are under clinical or preclinical development for the treatment of osteoporosis.

Hepatocellular carcinoma is the commonest primary liver tumor. It usually occurs in the setting of chronic liver disease and has a poor prognosis. Liver transplantation is the definitive therapy for early, unresectable HCC with poor liver function. After disappointing initial results, the landmark study by Mazzaferro et al. in 1996 established OLT as a suitable treatment for early HCC. Then liver transplantation achieved the best outcomes in well-selected candidates (5-yr survival of around 70%). Up to the present, various groups have attempted to expand these criteria while maintaining long-term survival rates. Even patients whose tumors were beyond Milan criteria showed better long-term survival than the reported 5-yr survival rates of 30-50% in a few large series of non-surgical treatments. Hepatic resection is the treatment of choice for HCC in non-cirrhotic patients. However, ten-year survival of the patients who underwent hepatic resection is lower than that of transplanted patients. This article reviews the expanded indications, disease recurrence and the future direction of liver transplantation for HCC.