Prognosis and predictive factors of conversion surgery for initially unresectable advanced colorectal cancer.

PURPOSE: The aim of this study was to report the outcomes of conversion surgery for initially unresectable advanced colorectal cancer and to identify factors that enable successful conversion surgery. METHODS: We compared the outcomes of patients with colorectal cancer with distant metastases, including extrahepatic metastases, who underwent upfront surgery, neoadjuvant chemotherapy, conversion surgery, and chemotherapy only at our department from 2007 to 2020. In addition, factors influencing the achievement of conversion surgery in patients who were initially unresectable were examined in univariate and multivariate analyses. RESULTS: Of 342 colorectal cancer patients with distant metastases treated during the study period, 239 were judged to be initially unresectable, and 17 (conversion rate: 7.1%) underwent conversion surgery. The prognosis for the conversion surgery group was better than that of the chemotherapy only group but worse than that of the upfront surgery group. In the conversion surgery group, the recurrence-free survival after resection was significantly shorter than that upfront surgery group and neoadjuvant chemotherapy group, and no patients have been cured. Among patients who were initially unresectable, left-sided primary cancer and normal CA19-9 level were identified as independent factors contributing to the achievement of conversion surgery in a multivariate analysis. CONCLUSIONS: Although relapse after conversion surgery is common, and no patients have been cured thus far, overall survival was better in comparison to patients who received chemotherapy only. Among unresectable cases, patients with left-sided primary cancer and normal CA19-9 levels are likely to be candidates for conversion surgery.

[A Case of Resection of Overlapping Ascending Colon Cancer and Primary Malignant Lymphoma of the Cecum].

The patient was a 90-year-old man. He was referred to our department with a diagnosis of ascending colon cancer after lower gastrointestinal endoscopy for a positive stool occult blood test. Lower gastrointestinal endoscopy revealed a type 1 tumor 30 mm in the ascending colon and a type 3 tumor 50 mm in the cecum. Biopsy revealed Group 5(tub1)for the ascending colon lesion, but Group 2 for the cecum lesion. The patient was clinically diagnosed as having overlapping ascending colon cancer and cecum cancer, and a right hemicolectomy of the colon was performed. Histopathological examination revealed ascending colon cancer and primary malignant lymphoma of the cecum.

[A Case of Postoperative Lymph Node Metastatic Recurrence of Ascending Colon Cancer Invading the Primary Branch of Superior Mesenteric Artery during Hemodialysis].

A 58-year-old man with chronic renal disease underwent ileo-cecal resection with lymph node dissection for cancer of the ascending colon at his previous physician. The pathological diagnosis was pT3N0M0, pStage Ⅱa. One year and 7 months after surgery, he was diagnosed with local and lymph node recurrence and referred to our department. Contrast- enhanced CT revealed that an irregular nodal shadow 25 mm in size adjacent to the superior mesenteric artery and the transvers part of duodenum, which was suspicious for lymph node recurrence. We regarded this patient as marginally resectable and neoadjuvant treatment was considered, but because the patient was on dialysis, we decided to operate without pre-operative treatment. Surgical findings showed invasion of a recurrent lymph node into a primary branch of the superior mesenteric artery and vein. We temporarily blocked these vessels and cut off these vessels after checking that blood flow in the intestine was maintained by intravenous injection of ICG. The lymph node was also invading the uncinate process of the pancreas and the transvers part of duodenum, we performed partial resection of those organs. Pathology revealed no tumor exposure on the dissected surface and R0 resection was achieved. The patient received 5 courses of postoperative folinate/ uracil/tegafur therapy and is alive 1 year postoperatively without recurrence.

Clinical utility of transanal indocyanine green near-infrared fluorescence imaging for evaluation of colorectal anastomotic perfusion.

BACKGROUND: Although indocyanine green (ICG) fluorescence imaging has been reported to be useful for assessing colorectal perfusion, unstable quantification remains an issue. We performed ICG fluorescence observation from the luminal side and examined the usefulness of the transanal approach. METHODS: A total of 69 patients who underwent left-side colon surgery were enrolled in this cohort study. After the anastomosis had been constructed, ICG 0.2 mg/kg was injected intravenously. The anastomotic site was then observed by a scope inserted transanally. The following items were examined in the areas of the anastomotic site with the highest- and lowest-fluorescence intensity: maximum fluorescence (Fmax), time from ICG injection to Fmax (Tmax), time from start of dyeing to Fmax (ΔT), and the contrast pattern of the mucosa. RESULTS: Anastomotic leakage (AL) occurred in nine cases. Tmax and ΔT values of the lowest-fluorescence area in the distal intestine showed significant differences in the cases with AL (P = 0.015 and P = 0.040, respectively). Regarding the contrast pattern of the mucosa of the lowest-fluorescence area in the proximal and distal intestine, the patients in whom the vessels were not depicted in the area had a significantly higher incidence of AL than those in whom vessels were depicted in the area (P = 0.031 and P = 0.030, respectively). Some of the areas in which vessels were not depicted by ICG fluorescence observation from the luminal side corresponded to the points of leakage. There were heterogeneous changes that might not be grasped by observation from the serosal side. CONCLUSION: Transanal ICG fluorescence imaging can evaluate perfusion over the entire circumference of the anastomosis in detail and aid in assessing the risk of AL. Therefore, the examination of the detailed low-perfusion area enables us to take measures for AL and to search for safer operative managements.

Positivity rate of interferon-γ release assays for estimating the prevalence of latent tuberculosis infection in renal transplant recipients in Japan.

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and developing active tuberculosis. QuantiFERON®-TB Gold Plus (QFT-Plus) has two TB-specific antigens tubes (TB1 and TB2). TB1 elicits CD4 T-cell response, and TB2 elicits both CD4 and CD8 T-cells responses, with expected increased sensitivity. The aim of this study was to estimate the prevalence of LTBI in renal transplant recipients in Japan. We conducted a cross-sectional study by using two interferon-γ release assays (IGRAs), QFT-Plus and T-SPOT®.TB (TSPOT). One hundred thirty-five recipients were prospectively enrolled. The median age was 49 years (range: 20 to 79). The positivity rates of QFT-Plus and TSPOT were 5.9% (95%CI 3.0-11.3) and 3.7% (95%CI 1.6-8.4), respectively, with no significant difference. The concordance rate was 95.5% (κ coefficient, 0.76). Age of 60 years and higher was related to the higher positivity rate in both QFT-Plus and TSPOT. The positivity rates of TB1 and TB2 were 5.1% (95%CI 2.5-10.2) and 5.9% (95%CI 3.0-11.2), respectively, with no significant difference. The concordance rate was 99.3% (κ coefficient, 0.93). TB2 did not show a higher positivity rate compared with TB1. The estimated prevalence of LTBI by using the both IGRAs was 3.7-5.9% in renal transplant recipients. These results were equivalent to the IGRAs positivity rate in the general Japanese population, even under the condition of immunosuppressive therapy. In consideration of the higher risk of developing active TB from LTBI, we can use both IGRAs as acceptable tools for LTBI diagnosis in renal transplant recipients.

Impact of primary diabetic nephropathy on arteriolar hyalinosis lesions in patients following kidney transplantation.

AIM: Arteriolar hyalinosis (AH) is a common lesion in allograft biopsies taken following kidney transplantation. Recent studies have shown that severe AH may predict transplant outcomes and provide information about previous exposure to certain drugs, such as calcineurin inhibitors (CNI). However, the incidence of AH as a direct result of diabetic nephropathy (DN) after kidney transplantation has not been fully evaluated. This study aimed to assess the impact of primary DN on the development of AH lesions in patients who underwent kidney transplantation. METHODS: Eighty-three patients who underwent living-donor kidney transplantation between April 2005 and June 2015 were enrolled in this study. A total of 33 patients had DN prior to transplantation. Allograft biopsies were scored according to the Banff classification, and the relationship between the individual histological lesions and clinical baseline data was assessed. RESULTS: At early biopsy (3-12 months), there were no differences in the rates of AH lesions between the DN group and the non-DN group (ah ≥ 1: 37% vs. 41.3%, P = 0.719; aah ≥ 1: 14.8% vs. 6.5%; P = 0.453). However, there were significant differences between the groups in biopsies taken more than 3 years after the transplant (ah ≥ 2: 83.3% vs. 36.8%, P = 0.013; aah ≥ 2: 66.7% vs. 21.1%, P = 0.011). Multivariable analysis showed that both the length of time after transplantation and the presence of DN were independent risk factors for ah ≥ 2 (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.47-19.54, P = 0.011) and aah ≥ 2 (OR: 7.55, 95% CI: 1.49-38.33, P = 0.015). CONCLUSION: This is the first report showing that the presence of primary DN disease contributes to the development of severe AH late in the course after kidney allografts.

Comparison of interferon-γ release assays, QuantiFERON TB-GIT and T-Spot.TB, in renal transplantation.

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and progressing to active tuberculosis (TB). This study was conducted in National hospital for tuberculosis and renal transplantation (RT) in Japan. The purpose is to compare two interferon-γ release assays (IGRAs), QuantiFERON®-TB Gold in Tube (QFT) and T-SPOT®.TB (TSPOT), in patients after renal transplantation for detecting latent TB infection (LTBI). Total 92 renal transplant recipients (median age 46 years, range 17-75) were prospectively enrolled, and QFT and TSPOT were concurrently examined. Total subjects were 92 patients (median age 46 years, range 17-75). The positive rate in QFT and TSPOT were 6.5% (95% confidence interval (CI) 3.0-13.5) and 2.2% (95% CI 1.0-7.6), respectively. There was a significant difference in IGRAs positivity (P < 0.05). The negative rate in QFT and TSPOT were 91.3% (95% CI 83.8-95.5) and 95.7% (95% CI 89.3-98.3), respectively. There was no significant difference in IGRAs negativity. No patients among either IGRAs negative patients developed active TB during median follow-up of 994 days. Neither QFT nor TSPOT reaches estimated TB infection rate in Japan, especially elderly recipients aged 60 year-old or more. Therefore, both IGRAs might underestimate LTBI owing to immune suppressive therapy and aging. Physicians for renal transplantation need to understand the characteristics of both IGRAs and pay attention to the possibility of developing active TB even in patients of negative IGRAs results.

Focal segmental glomerular sclerosis recurrence with massive proteinuria and anuria immediately after kidney transplantation.

Here, we report a case of focal segmental glomerular sclerosis (FSGS) recurrence immediately (47 minutes) after transplantation. A 1-hour biopsy specimen showed large periodic acid-Schiff-positive granules within the cells of the swollen proximal tubule, while electron microscopy revealed podocyte swelling and partial foot process effacement. These findings were worse on day 2 biopsy. Massive proteinuria and anuria were then observed. Two courses (2 × 2 times) of plasmapheresis and rituximab were administered, and the graft function gradually recovered. A day 22 biopsy specimen showed improvement in findings compared to those observed on day 2. One year after transplantation, no signs of FSGS recurrence are evident, and graft function remains good.

Reduction of mycophenolate mofetil dosage to limit prolonged viral shedding in solid organ transplant recipients with COVID-19: Two case reports.

Solid organ transplant (SOT) recipients with coronavirus disease-2019 (COVID-19) experience prolonged viral shedding, and they are forced to stay in the hospital because of the requirement for COVID-19 isolation. Here, we present two cases (lung and renal transplant recipients), wherein the isolation period was shortened by reducing the dosage of mycophenolate mofetil (MMF). Both patients recovered well from COVID-19 pneumonia. This case study suggests that a reduction in MMF dosage may lead to a shorter hospitalization period in SOT recipients with COVID-19.

A case of rectal metastasis of prostate cancer mimicking extramural growth-type rectal tumor.

Rectal metastases of prostate cancer are rare and may be difficult to diagnose. In this report, we describe a case in which an extramural growth-type rectal tumor was resected and pathologically diagnosed as prostate cancer metastasis. A 70-year-old man on hormone therapy for prostate cancer with seminal vesicle invasion and pelvic lymph node metastasis was referred to our department after an imaging scan showed an extramural growth-type rectal tumor. Endoscopic ultrasound-guided fine needle aspiration was considered for diagnosis, but the patient preferred an early resection without the exam, so surgery was performed. Histopathological examination revealed that the lesion was in the adventitia of the rectum and metastasis of prostate cancer. Metastatic lesions of prostate cancer are not indicated for resection. A detailed preoperative study with the possibility of prostate cancer metastasis in mind is necessary because it is relevant to choosing the treatment strategy.

Preoperative evaluation of vascular anatomy of right colic vessels using enhanced computed tomographic colonography.

PURPOSE: The purpose of this study is to define the blood vessels from a surgical perspective and show the frequency of vascular anatomical anomalies as well as the positional relationship with the surrounding organs, including the number of jejunal veins that cross the dissection area in our series. MATERIALS AND METHODS: From January 2016 to December 2018, 126 patients who received ileocecal resection or right hemicolectomy for colonic cancer in our institution were retrospectively analyzed by preoperative enhanced computed tomographic colonography images that were obtained using an 80-detector row CT scanner and workstation. The ileocolic artery/vein, right colic artery/vein and middle colic artery/vein were defined as the vessels that flow directly from or into the superior mesenteric artery/vein. All colic veins that flowed into the gastro-colic trunk were defined as accessory right colic veins. RESULTS: The accessory right colonic vein existed more than two in 62.6% of cases. In 11 cases (8.9%), the inflow point of the ileocecal vein was on the ventral side of the pancreas. There was one jejunal vein that straddled the dissection area in 31% and two in 6.3%. CONCLUSION: This study elucidated the vascular anatomy and positional relationship with surrounding organs that is required in central vascular ligation during complete mesocolic excision for right sided colon cancer.

[Current status and future of clinical kidney transplantation in Japan].

Kidney transplantation has been established to be the therapy for an end-stage renal disease. In Japan, living donor kidney transplantation is frequently performed (> 80%) because of a shortage of the deceased donors. The graft survival has been improved to 93.4% (5-year graft survival in living donor kidney transplantation after 2001). ABO-incompatible cases are increasing and more than 20% are ABO-incompatible in Japan (30% in our institution). In our institution, 225 kidney transplantations (182: living donors, 43: deceased donors) have been performed from 2004.4 to 2010.6. Although the graft survival is excellent, posttransplant infections including cytomegalovirus, EB virus and BK virus are problems which should be solved. For the safety of the recipients, we should use kidney grafts from brain-dead donors.

Treatment Outcome of Resection of Disseminated Peritoneal Metastases from Colorectal Cancer.

AIM: To show the treatment outcomes of disseminated nodule resection for peritoneal metastasis of colorectal cancer and describe the details of cured cases. PATIENTS AND METHODS: From January 2001 to December 2016, patients who underwent disseminated nodule resection of colorectal adenocarcinoma with no macroscopic residual tumor in our institution were retrospectively analyzed for clinicopathological factors associated with prognosis. RESULTS: Forty-one cases were included in this study. The 3-year relapse-free survival was 12.5%, and the 5-year overall survival was 38.4%. In a multivariate analysis, lack of post-operative adjuvant chemotherapy and pre-operative carbohydrate antigen 19-9 over 100 IU/l were extracted as independent factors associated with short relapse-free survival, respectively. Among 41 cases, 32 were followed-up 5 years after surgery and five (15.6%) survived without relapse and were regarded as 'cured'. CONCLUSION: More than a few cases of colorectal peritoneal metastasis, which is thought to be difficult to cure, were cured by resection of disseminated nodules without resorting to highly invasive treatment.

Clinical islet transplantation in Japan.

INTRODUCTION: The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems. METHODS: Since the first islet transplantation was performed in 2004, 65 islet isolations and 34 islet transplantations to 18 type 1 diabetic patients have been performed in Japan. RESULTS: Following islet transplantation, patients experienced decreased insulin requirements and lower hemoglobin A1C levels, and positive serum C-peptide levels. All patients achieved stabilized blood glucose levels and the disappearance of hypoglycemic unawareness. Although three patients achieved insulin independency for a limited period, persistent islet graft function was difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7% at 1 year, and 62.9% at 2 years after the first islet transplantation. In our institution, we carried out 23 islet isolations and six islet transplantations to four patients. Although insulin independency was not achieved, all patients showed a disappearance of hypoglycemic unawareness. CONCLUSIONS: Using data from the Japanese Trial of Islet Transplantation, the effectiveness of islet transplantation was shown even when using the pancreata from non-heart-beating donors. Although there are a number of problems to be solved and further improvement is needed, we can state that the introduction of clinical islet transplantation offers hope for type 1 diabetic patients.

A Case of Epstein-Barr Virus-Associated Leiomyosarcoma Concurrently With Posttransplant Lymphoproliferative Disorders After Renal Transplantation.

Epstein-Barr virus (EBV) infection might induce not only posttransplantation lymphoproliferative disorder (PTLD) but also leiomyosarcoma. We report a case of EBV-associated leiomyosarcoma concurrently with PTLD after renal transplantation. The patient was a 30-year-old woman who underwent living donor kidney transplantation at 27 years of age. Preoperative EBV viral capsid antibody immunoglobulin M, immunoglobulin G (IgG), and EBV nuclear antigen IgG were negative. Multiple lung and liver tumors were detected 1.5 years after transplantation. She was diagnosed with PTLD after tumor biopsy. Her EBV DNA was 110 copies/mL detected by real-time polymerase chain reaction when PTLD was diagnosed. She received dose reduction of immunosuppressive therapy and several chemotherapies. Because her hepatic lesion was still progressive while pulmonary lesion was reduced, a liver tumor biopsy was performed, but the biopsy specimens were necrotic. A left lateral segmentectomy was performed as a third biopsy for treatment-resistant hepatic lesion 2.5 years after her first PTLD diagnosis. Pathologically, she was diagnosed with EBV-associated leiomyosarcoma. She was treated with sirolimus, but died 7 months after the operation. This is the first case of the coincidence of leiomyosarcoma associated with EBV and PTLD. This case was exceedingly rare; however, we must consider the coincidence of leiomyosarcoma associated with EBV and PTLD when encountering treatment-resistant PTLD.

Cryopreservation of human pancreatic islets from non-heart-beating donors using hydroxyethyl starch and dimethyl sulfoxide as cryoprotectants.

Although widely used, DMSO is toxic for pancreatic islets. We combined hydroxyethyl starch (HES) with DMSO to simplify the procedure of freezing and thawing, and to decrease the toxicity of DMSO. A preclinical study was performed using islets from beagle dogs. After storage for 4 weeks, the islets were thawed and examined. The islet structure was well maintained after thawing. Although the number of the islets decreased to 71.2 +/- 20.1%, the function of the islets was evaluated by static incubation after thawing and showed a 1.80 +/- 0.78 stimulation index. We have introduced this technique for the cryopreservation of human islets from non-heart-beating donors. Twelve cases of human islet cryopreservation were performed. The sample tube of each human cryopreservation was thawed to evaluate the morphology, contamination, and endocrine function. Although fragmentation was observed in five samples (41.6%), the other seven (58.4%) showed a normal structure when evaluated by microscopic and electron microscopic study. The stimulation index (SI) of static incubation deteriorated from 3.37 +/- 3.02 to 1.34 +/- 0.28 after thawing. We divided the thawed islets into two groups: group 1 (n=8), SI > 1.2; group 2 (n=4), SI < 1.2. The group 1 islets showed a higher rate of normal structure (87%) than did group 2 (25%). Moreover, the SI before cryopreservation was 4.01 +/- 3.57 in group 1, which was higher than the SI of 2.11 +/- 0.72 in group 2. Based on the good results from the preclinical study using a large-animal model, this method was introduced for clinical application. Even from the pancreata of non-heart-beating donors, a successful islet cryopreservation was achieved. However, the isolated islets with poor function should not be cryopreserved for transplantation.

[A case of complete response to combination therapy of S-1 and CDDP for Stage IV gastric cancer with Virchow's lymph node and para-aorta lymph node metastasis].

The patient was a 53-year-old male with Stage IV gastric cancer with Virchow's lymph node and para-aorta lymph node metastasis. The chemotherapy regimen was given S-1 orally at 80 mg/m(2) day on day 1 to 21 and CDDP intravenously at 60 mg/m(2) day on day 8, repeated for 35 days. After two courses and a reduced regimen with S-1 64 mg/m(2) day plus CDDP 35 mg/m(2) day, the tumor lesion became CR and the serum CEA 575 ng/mL level before therapy decreased to the normal level. The patient received six courses of oral S-1(64 mg/m(2) day)for 28 days followed by a 14- day rest as maintenance therapy. The serum CEA elevated 13 months after the treatment, and the patient received a reduced course and two-course S-1/CDDP therapy. The serum CEA decreased to normal level and the patient has now survived 1 year 5 months without recurrence.

Renal Autotransplantation and Extracorporeal Nephron-Sparing Surgery for De Novo Renal Cell Carcinoma in a Kidney Allograft.

De novo renal cell carcinoma (RCC) rarely occurs in kidney allografts; however, the risk of RCC in these patients is 100-fold that of the general healthy population. Although total nephrectomy has been the standard treatment for kidney allograft RCC, several authors have reported that early-stage RCC in kidney allografts was successfully treated with nephron-sparing surgery. We herein describe a new procedure involving renal autotransplantation and extracorporeal nephron-sparing surgery, which was performed to treat de novo RCC near the hilum of a transplanted kidney. In the 22 months since transplantation, the patient's renal function has been favorable, and no recurrence has been observed. In conclusion, renal autotransplantation is a feasible technique for the treatment of RCC in kidney allografts, especially RCC located near the hilum.

Radiofrequency ablation therapy for bone metastasis from hepatocellular carcinoma: case report.

BACKGROUND: Radiofrequency ablation (RFA) is one of the standard percutaneous therapies for hepatocellular carcinoma (HCC), but RFA has not been applied to treat bone metastasis from HCC. CASE: A 65-year-old male patient, who underwent hepatectomy for HCC two and a half years previously, complained of pain in his right thigh. Imaging modalities and a needle biopsy revealed metastatic HCC in his right acetabulum. The first RFA therapy was attempted under computed tomography (CT) guidance with 42 Gy radiation therapy. The second RFA therapy was performed for tumor recurrence in his pelvis at 4 years after the first RFA. CONCLUSION: RFA is a safe, easy, repeatable and effective therapy and should be one of the most important therapeutic modalities for bone metastasis from HCC.

A Review of Autologous Islet Transplantation.

Autologous islet transplantation after total or semitotal pancreatectomy aims to preserve insulin secretory function and prevent the onset of diabetes. The major indication for pancreatectomy is chronic pancreatitis with severe abdominal pain, a benign pancreatic tumor, and trauma. The metabolic outcome of autologous islet transplantation is better than that of allogeneic transplantation and depends on the number of transplanted islets. Achieving islet isolation from a fibrous or damaged pancreas is one of the biggest challenges of autologous islet transplantation; a major complication is portal vein thrombosis after crude islet infusion. However, the incidence of portal vein thrombosis has decreased as islet preparation techniques have improved over time.