[A Resectable Case of Highly Locally Advanced Cecal Cancer in an Elderly Patient after Bypass Surgery and Chemotherapy].

An 83-year-old woman underwent an examination for right lower abdominal pain and was diagnosed with highly advanced cecal cancer. CT showed no metastasis; thus, we attempted resection or bypass surgery. While no liver metastasis or peritoneal dissemination was observed intraoperatively, the circumflex region was highly infiltrated to the peritoneum and retroperitoneum. Considering the patient's age, resection was deemed overly invasive, so an ileum and transverse colon bypass surgery was performed. To downsize and safely remove the primary lesion, capecitabine plus bevacizumab was started. A CT examination performed after 3 courses revealed that the tumor had decreased in size. After the 4th course, surgery was performed. Intraoperative findings showed no obvious peritoneal dissemination, the tumor size was reduced, and the tumor was movable. A laparoscopic right hemicolectomy plus D3 dissection was performed. She was discharged on postoperative day 5. No obvious recurrence has been observed 6 months after surgery.

Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder: a case report.

BACKGROUND:  Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. CASE PRESENTATION: We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. CONCLUSIONS:  GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.

[Efficacy of Laparoscopic Gastrojejunal Bypass for Unresectable Gastric Cancer with Pyloric Stenosis].

In general, gastrojejunal bypass is performed for unresectable gastric cancers with stenosis. It enables patients to take food and be discharged from the hospital earlier. Previously, we used to primarily perform open gastrojejunal bypass; however, recently, we perform laparoscopic gastrojejunal bypass because it is minimally invasive. We evaluated 31 patients who underwent gastrojejunal bypass for unresectable gastric cancer in our department between December 2009 and December 2019. We retrospectively compared the laparoscopic surgery group(n=7)with the open surgery group(n=24). No significant difference in patient background was found between the study groups. Compared to patients in the open surgery group, those in the laparoscopic group had significantly shorter postoperative hospital stay and time until initiation of oral intake, relatively lesser blood loss, and no postoperative complications. Moreover, more patients in the laparoscopic group than in the open surgery group were administered postoperative chemotherapy. Further, postoperative chemotherapy was administered sooner in the laparoscopic group than in the open surgery group. Laparoscopic gastrojejunal bypass is a safe and less invasive treatment for unresectable gastric cancer with stenosis. It may be superior to the conventional open surgery with regard to early postoperative chemotherapy for cancer.

[Successful Treatment with Nab-Paclitaxel for Stage â £ Gastric Cancer in an Elderly Patient on Hemodialysis].

An 84-year-old man on hemodialysis was referred to our department for an advanced gastric cancer with pyloric stenosis. Pre-operative CT showed thickening of the stomach wall at the primary lesion and regional lymph node metastasis, while no clear peritoneal metastasis was found. However, we found peritoneal disseminations during the operation, so gastrojejunal bypass was performed. After the operation, he hoped chemotherapy despite risk factors such as renal failure and old age. We introduced a reduced dose of weekly nab-paclitaxel to him. After 3 courses, CT showed the primary lesion had decreased in size, and after 6 courses, serum CA19-9 level decreased to 61.8 U/mL from 2,343 U/mL at the before treatment. No serious adverse events were observed during the chemotherapy. However, after 8 courses, the tumor markers was gradually re-increased, and CT showed the primary tumor re-increased after 9 courses. Therefore, he received irinotecan alone as the second-line. He is still alive 1 year and 8 months after diagnosis of gastric cancer. It is generally said that the risk of cancer chemotherapy for dialysis patients and the elderly is high. However, we suggest that it could be safely performed by examining the appropriate drug and dose. Weekly nab-paclitaxel regimen could be one of the promising options for these patients.

Clearance of Intra-graft Donor Specific Anti-HLA Antibodies in the Early Stage of Antibody-Mediated Rejection Following Rituximab and Apheresis Therapy in Renal Transplantation.

BACKGROUND: The management of acute or, in particular, chronic antibody-mediated rejection (AMR) resulting from donor-specific HLA antibodies (DSA) is a critical barrier to obtaining better long-term graft survival. To ascertain the efficacy of anti-AMR therapies, the transition of intra-graft DSA (g-DSA) was assessed. METHODS: Allograft biopsy specimens were analyzed by graft immunocomplex capture fluorescence analysis, as previously described. One hundred recipients who underwent graft biopsies between April 2016 and December 2017 were enrolled for this study. Fifteen recipients diagnosed with g-DSA positive (+) received anti-humoral treatments and underwent follow-up biopsies. g-DSA levels were assessed again by a follow-up biopsy at 6-12 months following the treatments. RESULTS: With anti-humoral treatments, 9 out of 15 recipients comprised a g-DSA negative (-) (3.59 ± 2.82-.58 ± .25): g-DSA6-12- group, while the remaining 6 recipients comprised a g-DSA +(20.6 ± 17.0-14.9 ± 14.1): g-DSA6-12+ group. The initial g-DSA scores were significantly higher in the g-DSA6-12+ group (P = .01). All samples were diagnosed as chronic AMR in the g-DSA+ groups, whereas there were 3 chronic AMR, 4 acute AMR, and 2 incomplete AMR samples in the g-DSA- group. Interestingly, the frequency of responsible DSA belonging to class II tended to be higher in the g-DSA6-12+ group (4/6) compared to the g-DSA6-12- group (2/9) (P = .14). CONCLUSION: These results imply that chronic exposure to DSA causes significant and irreversible damage to the allograft. Timely and adequate anti-humoral intervention might reverse the early phase of AMR with complete clearance of g-DSA.

Upper extremity distal dual bypass enables arteriovenous fistula construction in a critical limb ischemia.

BACKGROUND: Arteriovenous fistula (AVF) trouble in a dialysis patient sometimes results in severe forearm ischemia. CASE PRESENTATION: We present the case of 27-year-old man with severe steal syndrome complained of AVF malfunction. There was a condition where an upstream artery of AVF is occluded and AVF is maintained by regurgitation from the palmar arch with ischemic digits. The patient underwent distal dual bypass: proximal to peripheral artery arterioarterial and arteriovenous bypasses and brachial arterioplasty. His skin perfusion pressure improved from 17 to 90 mmHg with enough quantity of blood: 250 ml/min for hemodialysis. CONCLUSIONS: In severe steal syndrome cases, it is often observed that proximal artery is occluded and AVF inflow was supplied from palmar circulation and collateral vessels. Distal dual bypass is effective to re-establish digital circulation and repair AVF malfunction simultaneously in PAD patients.

Distal Bypass to the Palmar Arch to Rescue Digital Ischemia Due to Peripheral Artery Disease.

Digital ischemia is a serious problem in peripheral artery diseases (PAD) patients. Case 1: A 60-year-old woman with large arteriovenous fistula (AVF) complained of digital ischemia symptoms. The patient underwent dissection of AVF and distal bypass to the palmar arch with successful repair. Case 2: A 47-year-old female, diagnosed with renal failure, and scleroderma, complained of a digital gangrene. A bypass was performed from the left brachial artery to the superficial palmar arch. The digital gangrene showed a complete recovery within 2 months after surgery. Distal bypass to the palmar arch thus appears to be a useful procedure to re-establish digital circulation in PAD patients.

High-dose mizoribine combined with calcineurin inhibitor (cyclosporine or tacrolimus), basiliximab and corticosteroids for renal transplantation: A Japanese multicenter study.

OBJECTIVE: To evaluate the utility and safety of high-dose mizoribine combination therapy using cyclosporine and tacrolimus as calcineurin inhibitors in patients undergoing kidney transplant. METHODS: The present study enrolled 156 patients who received kidney transplants in 18 institutions between 2009 and 2013. ABO-incompatible and/or pre-sensitized recipients were excluded. Immunosuppression used cyclosporine (88) or tacrolimus (68) as a calcineurin inhibitor, and the dosage was adjusted based on blood concentrations. Mizoribine was started at 6 mg/kg/day, and the target trough level was 1-2 ng/mL. Primary efficacy end-points of this study were 2-year patient survival, 2-year graft survival and the acute rejection rate within 2 years after transplantation. RESULTS: The 2-year patient and graft survival rates in the cyclosporine group were 98.9% and 94.3%, respectively, whereas those in the tacrolimus group were 100% and 98.5%, respectively, with no significant difference between groups. Rates of onset of rejection during the observation period were also equivalent, at 22.7% in the cyclosporine group and 17.6% in the tacrolimus group. Furthermore, groups showed no significant differences in transplanted renal function. No notable differences in adverse events were observed between groups. CONCLUSIONS: A regimen of high-dose mizoribine in combination with calcineurin inhibitors basiliximab, and corticosteroids can provide effective immunosuppression while lowering the rate of cytomegalovirus infection in kidney transplant patients.

[A Case of Synchronous Multiple Liver Metastases from Ascending Colon Cancer Showing Pathological Complete Response to CapeOX Treatment].

The patient was a 30-year-old man who underwent a medical examination for shortness of breath.An abdominal computed tomography(CT)scan revealed advanced ascending colon cancer with multiple metastases to the liver.We performed a laparoscopic right hemicolectomy first, due to the obstruction.Postoperatively, the patient received capecitabine plus oxaliplatin( CapeOX)chemotherapy.After 10 courses of CapeOX, the multiple liver metastases had reduced remarkably in size. Colectomy of the anastomosis and partial hepatectomy were then performed.Histological examination of the resected tissue revealed no residual cancer cells, suggestive of a pathological complete response.

Syringomatous adenoma of the nipple: a case report.

INTRODUCTION: Syringomatous adenoma of the nipple is a very rare benign tumor. To the best of our knowledge, there are no reports of a syringomatous adenoma of the nipple metastasizing, although these tumors are known to infiltrate locally and to recur if not totally resected. CASE PRESENTATION: Our patient was a 41-year-old Japanese woman who complained of stiffness of her right nipple with abnormal discharge. Local resection of the tumor was performed. The pathological diagnosis was syringomatous adenoma of the nipple, and the resection margin was found to be positive. Accordingly, additional resection was recommended, but our patient did not allow another operation. After 1.5 years of careful follow-up, no local recurrence or distant metastasis has been observed. CONCLUSION: The optimal initial management of syringomatous adenoma of the nipple demands complete resection with histologically negative margins. However, from a cosmetic viewpoint, nipple-sparing resection could represent an alternative option for the treatment of syringomatous adenoma of the nipple.

Pancreatic cancer: Slow progression in the early stages.

INTRODUCTION: The rates of pancreatic cancer development in the early stages of growth remain unclear; but it is generally believed that they demonstrate a rapid degree of progression. There is evidence to suggest that pancreatic cancers measuring less than 1cm demonstrate better survival rates, hence it is clear that detecting pancreatic cancers less than 1cm in size is of paramount importance. However, to date, there has been no scientifically adequate research to show the growth rate of small pancreatic cancers less than 1cm in the early stages. PRESENTATION OF CASE: We present the case of a 65-year-old woman whose small pancreatic cancer possibly demonstrated a slow progressive rate as it grew to an invasive carcinoma measuring 1cm diameter from over the 29 months. DISCUSSION: It is reasonable to assume that the progression of some pancreatic cancers until 1cm size, can take up to 29 months. During this silent period, it is crucial to detect such a small pancreatic cancer by means of the initial US and subsequent EUS and ERCP. It is clear, therefore, that clinicians have to be aware of the growth rate of small pancreatic cancers and in particular high risk patients should be encouraged to monitor size of the main pancreatic duct by means of US on regular basis. CONCLUSION: This could give better outcomes for pancreatic cancer patients. Hopefully, by detecting these lethal, pancreatic cancers in their early stages, it will give us an extension of time to perform effective therapies.

The beneficial effect of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids on CMV infection in renal transplant recipients.

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent, but has a less potent immunosuppressive effect up to 3 mg/kg/day MZR. Therefore, we investigated whether high-dose MZR, at 6 mg/kg/day, would be effective and safe for kidney transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. METHODS: A total of 40 living related patients were administered MZR (6 mg/kg/day), CsA (7 mg/kg/day), prednisolone (maintenance dose 10 mg/day), and basiliximab (20 mg/body). A control group (n = 38) treated with CsA, mycophenolate mofetil (MMF, 25 mg/kg/day), basiliximab, and corticosteroids was also employed in this study. RESULTS: The 2-year graft survival rates for the MZR and MMF groups were 100 and 94.7 %, respectively. The rejection rate in the MZR group (25 %) was not significantly higher than that in the MMF group (16 %). Serum creatinine level was not significant between the two groups. The number of patients who developed cytomegalovirus (CMV) disease was 0 (0 %) in the MZR group and 7 (18.4 %) in the MMF group (P < 0.05). The number of patients treated with ganciclovir was 3 (7.5 %) and 11 (28.9 %) (P < 0.05), respectively. CONCLUSIONS: The combination of high-dose MZR with CsA, basiliximab, and corticosteroids can establish not only satisfactory immunosuppression but also a low rate of CMV infection in vivo.

Histopathologic evaluation of living kidney donor candidates by pre-operative kidney biopsy.

A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.

A case of living-related renal transplant from the donor with membranous nephropathy.

INTRODUCTION: When a patient who had renal replacement therapy becomes older, an elder donor candidate may be considered as a potential donor for living-related transplantation. Elder donor candidate might have pre-existing disease including mild renal dysfunction, such as proteinuria. Marginally appropriate donors might be considered for renal graft because of the shortage of donors. A successful outcome after kidney transplantation from a living-related donor diagnosed as membranous nephropathy is reported. CASE REPORT: A 38-yr-old male had been on continuous ambulatory peritoneal dialysis (CAPD) since the age of 37. His 63-yr-old father had mild proteinuria, and had been diagnosed with membranous nephropathy by needle biopsy at the age of 60. However, renal function of the father was found to be stable for three yr in a preoperative examination for donor; the father had normal renal function except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father, diagnosed with membranous nephropathy, to his son with a cyclosporine A-based immunosuppression regimen. In both the recipient and the donor, postoperative course was stable without complication such as rejection or infection. At 57 months after transplantation, the serum creatine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. At 39 months after transplantation, allograft needle biopsy showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Decreases in electron-dense deposits and electron-lucent washout lesions with thickening of the GBM were observed using electron microscopy. This was diagnosed as Stage IV membranous nephropathy, showing clearance of the immune complexes and histological repair of the GBM. CONCLUSION: Donation of the kidney did not affect the residual renal function of the father with membranous nephropathy. Pre-existing membranous nephropathy itself might show remission after transplantation in the recipient. However, long-term careful observation for both the donor and recipient is required.

Short- and long-term donor outcomes after kidney donation: analysis of 601 cases over a 35-year period at Japanese single center.

BACKGROUND: The lack of deceased donors in Japan means that living-donor kidney transplantation is necessary in as many as 80% of cases. However, there are few data on perioperative complications and long-term outcome for live kidney donors. METHODS: To determine associated perioperative morbidity and long-term mortality among live kidney donors, we reviewed 601 donor nephrectomies performed at our institution between 1970 and 2006 and attempted to contact all of the donors (or their families) to ascertain their present physical status. The survival rate and causes of death were compared with an age- and gender-matched cohort from the general population. RESULTS: Although three donors (0.5%) experienced major perioperative complications, that is, femoral nerve compression, pulmonary thrombosis, and acute renal failure, all of the donors recovered and left hospital without complications. Among 481 donors (80%) for whom details were available at the time of inspection, 426 (88.5%) were still surviving. Donor survival rates at 5, 10, 20, and 30 years were 98.3%, 94.7%, 86.4%, and 66.2%, respectively. The mean interval between kidney donation and death was 183+/-102 (7-375) months, and the mean age at death was 70+/-11 years. The survival rate of kidney donors was better than the age- and gender-matched cohort from the general population, and the patterns and causes of death were similar. CONCLUSIONS: Our data suggest that continuation of living-donor kidney transplantation programs is justified in short- and long-term donor safety.

BK virus-associated nephropathy in a kidney transplant recipient successfully treated with cidofovir, the first case in Japan.

A 51-year-old female received a kidney transplant, donated by her husband. The patient was induced with tacrolimus, mycophenolate mofetil and prednisolone. After methyl prednisolone pulse therapy without biopsy, allograft biopsy on POD 160 showed severe tubulo-interstitial nephritis with intranuclear inclusions. Urine cytology also showed decoy cells. Blood PCR detected an increase of BK virus DNA. She was diagnosed as having BK virus-associated nephropathy . Reduction of tacrolimus and switching of mycophenolate mofetil to mizoribine were done. Serum Creatinin (sCr) still rose to 3.0 mg/dl with persistent viremia and viruria. From on POD 268, 0.25 mg/kg of cidofovir was administered intravenously every two weeks over about four months. Biopsy on POD 387 revealed the disappearance of tubulitis with intranuclear inclusions, and decoy cells also disappeared from urine cytology. BK virus DNA in the blood decreased under the threshold level. sCr was stable and remained about 2.2 mg/dl for three months after the final treatment of cidofovir.

ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation.

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation. METHODS: Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated. RESULTS: A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045). CONCLUSION: For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.

Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant.

OBJECTIVE: Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We examined the relationships between development of ONF and genetic variations and plasma level of lipoprotein(a) (Lp(a)), which is closely involved in the coagulation and fibrinolytic systems and lipid metabolism. METHODS: The study population consisted of 112 renal transplant patients undergoing corticosteroid treatment. Their apolipoprotein (a) [apo(a)] isoform was determined by Western blotting, and patients were classified into low molecular weight (LMW) or high molecular weight (HMW) groups. The plasma Lp(a) level was measured. Patients were also examined for 3 single-nucleotide polymorphisms (SNP), -773 (G/A), +93 (C/T), and +121 (G/A). Relationships between these 3 genetic factors of Lp(a) and ONF development were examined using statistical methods including multivariate analysis. RESULTS: A strong relationship was observed between the apo(a) molecular weight phenotype and ONF development, with an increased risk of ONF development for the LMW group (adjusted odds ratio 5.75, 95% CI 1.76-18.74, p = 0.0038). No significant relationships were observed between ONF and plasma Lp(a) level and SNP. CONCLUSION: Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment.