[Curative Transanal Resection after Neoadjuvant Chemotherapy for Lower Rectal Cancer-A Case Report].

A 53-year-old woman was referred to our hospital with melena. Examinations revealed advanced rectal cancer involving the anal canal with invasion of the left-sided levator ani muscle. Neoadjuvant chemotherapy was administered to preserve anal function. A first course of capecitabine and oxaliplatin(CapeOX)plus bevacizumab was administered. CapeOX plus panitumumab was administered from the 2nd to the 8th courses after confirming the absence of RAS mutation. Endoscopy and computed tomography confirmed the disappearance of the tumor after completion of the chemotherapy. A biopsy of the scar tissue revealed no cancer cells. However, diffusion weighted-magnetic resonance imaging(MRI-DWI)revealed a suspected residual tumor. To determine the subsequent treatment, a transanal resection was performed. No carcinoma was identified in the specimen. Thus, additional surgical treatment and adjuvant chemotherapy were not administered. The patient was followed-up over 2.5 years post local resection and showed no recurrence.

[Two Cases of Advanced Colorectal Cancer Achieving Complete Response by FOLFOXIRI plus Bevacizumab-A Case Report].

We report 2 cases of advanced colorectal cancer achieving complete response by FOLFOXIRI plus bevacizumab. Case 1 was a 65-year-old male diagnosed with descending colon cancer with multiple liver metastases. Six courses of FOLFOXIRI plus bevacizumab were administered after laparoscopic-assisted left hemicolectomy. Ten partial hepatectomies and 1 radiofrequency ablation were performed as the liver metastases resolved. A pathological complete response was confirmed. Adjuvant chemotherapy was not administered, and recurrence-free survival was 21 months after hepatectomy. Case 2 was a 77-yearold male diagnosed with rectal cancer invading the pelvic wall and sacral foramen with bilateral lateral lymph node metastasis. Additionally, there was a cancer embolism in the right internal iliac vein. Six courses of FOLFOXIRI plus bevacizumab were administered, and the cancer tissue was absent on subsequent CT and MRI. The cancer was scarred by colonoscopy, and the biopsy showed no malignant cells. Six courses of FOLFIRI plus panitumumab were administered as second-line chemotherapy, and the patient survived without any recurrence after 12 months from initiation of chemotherapy.

Pathological Complete Response after Immune-Checkpoint Inhibitor Followed by Salvage Surgery for Clinical Stage IV Pulmonary Adenocarcinoma with Continuous Low Neutrophil-to-Lymphocyte Ratio: A Case Report.

Immune-checkpoint inhibitors (ICIs) play a crucial role in the treatment of advanced nonsmall cell lung cancer (NSCLC); however, most patients fail this treatment after a limited period. We here report a patient with a pathological complete response after treatment with ICI for stage IV pulmonary adenocarcinoma. A 73-year-old man was referred to our hospital because of hoarseness. A roentgenogram and chest CT scan revealed a huge (78-mm diameter) pulmonary tumor in the right upper lobe and a tumor with cavitation in the left lower lobe. A CT scan also showed enlarged upper mediastinal lymph nodes (LNs). Transbronchial lung biopsy of the tumors showed adenocarcinomas in both. The tumor in the right upper lobe was considered to be the primary with mediastinal LNs metastasis and that in the left lower lobe a pulmonary metastasis. The disease was determined to be cT4N2M1a stage IVA. He was treated with first-line chemotherapy comprising cisplatin, pemetrexed, and bevacizumab for 6 cycles. However, 6 months after initial treatment, the primary and metastatic tumors enlarged, and he was treated with second-line anti-programed death 1 therapy for 7 months with a partial response. 18-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed weak accumulation of FDG in the primary tumor only with no accumulation in the left pulmonary metastasis or mediastinal lymph node (LNs), despite the LNs still being enlarged. He was diagnosed as having ycT1bN0M0 stage IA2 disease and underwent right upper lobectomy. Postoperative pathological findings revealed that cancer tissues had been replaced by scar tissue and that CD4-positive T cells, rather than CD8-positive T cells, were predominant. It was also noted that he had a lower neutrophil-to-lymphocyte ratio (NLR) during immunotherapy than before immunotherapy and after surgery. He was diagnosed to be ypT0N0M0 stage 0 (Ef.3). His postoperative course was uneventful, and he remained well for 12 months after surgery with no further treatment. Neoadjuvant chemotherapy with ICIs for advanced NSCLC may be a promising modality, even for clinical stage IV disease, in the near future. Furthermore, NLR during immunotherapy may be a promising biomarker of ICIs treatment.

Laparoscopic repair of an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon.

Here we present the first report of laparoscopic repair of an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon. A 73-year-old woman presented with a 1-week history of a left groin mass below the inguinal ligament with no abdominal symptoms. Abdominal CT demonstrated a 21 × 18-mm oval-shaped, fat-dense structure in the left groin area. The hernia contents were considered potentially associated with the omentum; thus, a left irreducible femoral hernia was diagnosed. Elective laparoscopic surgery revealed an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon, which was then reduced. The reduced epiploic appendage showed no ischemic changes, inflammation, torsion, or swelling, obviating the need for resection. The femoral hernia was laparoscopically repaired via a transabdominal preperitoneal approach with mesh. The patient's postoperative recovery was uneventful, and no recurrence of the femoral hernia was noted at the 6-month follow-up.

Successful Multidisciplinary Treatment for Aggressive Primary Pulmonary Undifferentiated Pleomorphic Sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) was previously known as malignant fibrous histiocytoma (MFH). This sarcoma occurs preferentially in the extremities and retroperitoneal space; primary pulmonary UPS/MFH is rare. We report a 52-year-old woman referred to our hospital with dyspnea and severe cough. Chest computed tomography (CT) revealed a pulmonary mass in the left upper lobe and pleural effusion. Cytology of the effusion showed no malignancy; however, the tumor increased rapidly in size, and the patient's respiratory symptoms worsened. The tumor occupied almost all of the left upper lobe and involved the adjacent pericardium. She underwent left upper lobectomy with pericardial resection and reconstruction. Postoperative pathology of the resected specimen showed undifferentiated pulmonary sarcoma, pT4N0M1a stage IV A, and genetic analyses revealed the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. The patient's dyspnea recurred 1 month postoperatively, and CT showed marked pleural effusion. An 18F-fluorodeoxyglucose positron emission tomography demonstrated abnormal diffuse accumulation of 18F-fluorodeoxyglucose in the left pleural cavity. We initiated five cycles of chemotherapy with doxorubicin and ifosfamide, and the patient has been well without recurrence for 24 months after multidisciplinary treatment with surgery followed by systemic combination chemotherapy. We successfully treated our patient with primary pulmonary UPS/MFH using a multidisciplinary approach, even though this sarcoma carries a poor prognosis and is insensitive to both chemotherapy and radiotherapy.

Wine cup stoma anastomosis after extended sleeve lobectomy for central-type squamous cell lung cancer.

BACKGROUND: Extended sleeve lobectomy is rarely applied to pulmonary surgery for primary lung cancer to avoid a pneumonectomy. As there is a size discrepancy between main bronchus and peripheral bronchus, ingenuity to improve anastomosis is required in the bronchoplasty. We report herein a case in which successful reconstruction of extended sleeve lobectomy with bronchial wall flap. CASE PRESENTATION: We report on a 64-year-old man suffering from hemoptysis, cough, mild fever and dyspnea. His computed tomography (CT) scan showed solid tumor of 40 mm in diameter in left lower bronchus, which obstructed the lower bronchus and caused obstructive pneumonia of left lower lobe and expanded to second carina and pulmonary artery. His bronchoscopy showed that tumor was exposed in the bronchial lumen and infiltrated to left main bronchus and upper bronchus even though the scope could pass through the exposed tumor of upper bronchus. Transbronchial lung biopsy showed squamous cell carcinoma. He had undergone left sleeve lingular segmentectomy and left lower lobectomy. Reconstruction was performed with bronchial wall flap. Pathological findings revealed pT3N0M0 stage IIB according to UICC 8th edition. Postoperative bronchoscopic findings showed no troubles at the anastomotic site. He has been well for eighteen months without recurrence after surgery. CONCLUSIONS: We experienced a successful case who was reconstructed with bronchial wall flap (wine cup stoma) after extended sleeve lobectomy. This technique might be also useful for other types of extended sleeve lobectomy and lung transplantation to adjust caliber changes of bronchi.

Combined laparoscopic resection of intestinal stenosis of Garré and open preperitoneal mesh repair for irreducible femoral hernia.

Intestinal stenosis of Garré is a rare condition caused by a benign fibrous bowel stricture due to complicated strangulated hernia. We present a case of intestinal stenosis of Garré associated with right femoral hernia in an 85-year-old woman. The patient visited our hospital with a 2-day history of vomiting. Her abdomen was slightly distended. A mass was palpated in the right groin region. CT showed prolapse of the small intestine in the right groin region. An incarcerated right femoral hernia was diagnosed and manually reduced. Thirteen days later, the patient complained of abdominal pain. CT revealed dilatation and caliber change in part of the small bowel, indicating a small bowel obstruction due to intestinal stenosis of Garré. Laparoscopic release of the bowel obstruction and femoral hernia repair via an anterior approach were performed simultaneously. No recurrence of femoral hernia or bowel obstruction was noted at the 15-month follow-up.

Brief report on similar mutational changes in neurofibromatosis type 2 gene in minute pulmonary meningothelial-like nodule and meningioma of the central nervous system.

INTRODUCTION: Minute Pulmonary Meningothelial-like Nodules (MPMNs) are usually detected incidentally adjacent to lung cancer tissue. The pathogenesis is unknown. MPMNs reportedly share the status of neurofibromatosis (NF)-2 gene with meningiomas of the central nervous system. RESULTS: Immunohistochemical staining of two MPMNs revealed they were positive for epithelial membrane antigen (EMA), vimentin, CD56, and progesterone. We identified deletion of the NF-2 gene in two MPMNs and one CNS meningioma. CONCLUSIONS: MPMN and CNS meningioma may develop via the same mechanism through NF-2 translocation. Further studies are required to elucidate the genetic similarities between these entities. METHODS: We used fluorescence in situ hybridization to explore the status of the NF-2 gene in MPMNs and compare it with that of CNS meningiomas. We used a commercially available locus-specific probe for the NF-2 region to analyze whole tissue sections of two MPMNs and two CNS meningiomas by fluorescence in situ hybridization.

Case Report of a Small Gastric Neuroendocrine Tumor in a Deep Layer of Submucosa With Diagnosis by Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Treatment With Laparoscopic and Endoscopic Cooperative Surgery.

Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by enterochromaffin-like cells of the stomach. Optimal management of GNETs has not yet been definitively determined. Endoscopic resection is approximately recommended for small GNETs associated with hypergastrinemia. However, endoscopic resection might present risk of perforation or positive vertical margin because neuroendocrine tumors occur in the deep mucosa, with some invading the submucosa. In this case, a patient with type A chronic atrophic gastritis had a small subepithelial lesion in a deep submucosal layer, and we diagnosed it as GNET using endoscopic ultrasound-guided fine-needle aspiration biopsy using a forward-viewing and curved linear-array echoendoscope. Moreover, our results show that laparoscopic and endoscopic cooperative surgery with regional lymph node dissection is a safe and feasible procedure for GNETs, especially those that cross to the muscularis propria. We suggest this approach as one therapeutic option for GNETs because it safely minimizes resection and is less invasive.

Laparoscopic repair of irreducible femoral hernia containing the fallopian tube alone: a case report.

BACKGROUND: We offer the first report of laparoscopic repair of an irreducible femoral hernia containing the fallopian tube alone. CASE PRESENTATION: An 84-year-old woman presented with a 2-week history of a right groin mass with no abdominal symptoms. The mass was located below the inguinal ligament but showed no redness or tenderness. Abdominal computed tomography demonstrated a 4 × 3-cm cystic mass and enhanced cord-like structure in the right groin area. Hernia contents were considered potentially associated with the appendix, and right femoral hernia incarceration was diagnosed. We performed emergency surgery using a laparoscopic approach, revealing an irreducible femoral hernia containing the right fallopian tube, which was reduced laparoscopically. The reduced fallopian tube showed no ischemic changes, obviating the need for resection. No other abdominal organs such as the ovary, fimbriae of the fallopian tube, or appendix were incarcerated. We repaired the femoral hernia laparoscopically using a transabdominal preperitoneal approach with a mesh. CONCLUSIONS: A laparoscopic approach offers ready and accurate confirmation of incarcerated or irreducible organs, rapid recovery, and favorable cosmesis and should therefore be considered for the treatment of incarcerated or irreducible femoral hernia.

Mitomycin C treatment significantly reduces central damage of islets in culture.

OBJECTIVES: We recently reported that mitomycin C (MMC) treatment and subsequent culture of islets significantly prolongs graft survival in allotransplantation and xenotransplantation models. The present study was performed to determine the changes in morphology and signal transduction in pancreatic islets after MMC treatment. METHODS: Freshly isolated rat islets were treated with 10 µg/mL MMC for 30 minutes and then cultured for up to 3 days. The samples were processed for immunohistologic studies and electron microscopic examination at various times after treatment. A DNA fragmentation assay was performed to detect apoptotic cell death. Western blotting was performed to determine the effects of MMC on signal transduction. RESULTS: As early as 4 hours after culture, the islets showed central damage; most cells were necrotic and stained with anti-high mobility group box 1 antibody, and a few were apoptotic. The ratio of the damaged area to the whole area was significantly decreased after MMC treatment. Western blotting showed that MMC treatment increased the levels of activated forms of p53 and p21, whereas levels of the activated forms of Akt and caspase-3 were unchanged. CONCLUSIONS: Mitomycin C treatment protects islets from the progression of central damage during culture. The p53-p21 pathway might be involved in these effects. ABBREVIATIONS: MMC - mitomycin C, HMGB1 - high mobility group box 1.

Mizoribine as sole immunosuppressive agent in islet xenotransplantation models: a candidate immunosuppressant causing no adverse effects on islets.

Mizoribine (MZ) inhibits the differentiation and proliferation of helper T and B cells after antigen recognition by suppressing the purine biosynthesis pathway and nucleic acid synthesis. MZ has been used in kidney transplantation, but distinct data are unavailable for islet transplantation. The present study investigated the efficacy of MZ for islet xenotransplantation. Immunosuppressive effects of MZ were determined by mixed lymphocyte reaction (MLR) assay in vitro. Toxicities for Wistar rat islets were determined by adenosine triphosphate (ATP) contents of islets during 3-day culture and stimulation index in response to glucose after culture. Immunosuppressive effects in vivo were tested in a Wistar-to-B6 islet xenotransplantation model. MZ was administered continuously for 28 days subcutaneously or intramuscularly. MZ inhibited MLR response by approximately 50% at 0.1 µg/ml. ATP contents decreased with MZ >100 µg/ml, while stimulation index was maintained. Continuous infusion of MZ at 10 mg/kg maintained blood concentrations at 0.13-0.19 µg/ml, while intramuscular injection of MZ at 100 mg/kg/day (peak 520 µg/ml at 1 h postinjection) resulted in below measurable levels (<0.03 µg/ml) within 24 h. Graft survival was significantly prolonged following continuous infusion of 10 mg/kg/day compared to controls (31.0 ± 9.5 vs. 13.2 ± 5.2 days; p = 0.002). Furthermore, animals with intramuscular injection at doses of 3.2, 10, or 100 mg/kg/day showed significantly longer graft survival (20.0 ± 7.5, 22.0 ± 7.31, and 24.5 ± 8.1 days, respectively; p < 0.05 each). Histological examination showed significant suppression of lymphocyte infiltration by MZ administration. MZ showed immunosuppressive effects in an experimental islet xenotransplantation model without adverse effects on endocrine function of islet grafts.

A model to evaluate toxic factors influencing islets during collagenase digestion: the role of serine protease inhibitor in the protection of islets.

The recovery of all of the islets contained in a pancreas is the goal of islet isolation for transplantation. This study reveals an environment that injures the isolated islets during digestion and proposes a new model for optimal islet isolation. Islets were isolated from Wistar rat pancreases by stationary collagenase digestion while the digestion time was varied at 15, 30, 60, and 120 min. The digested pancreas and islets were analyzed histologically and adenosine nucleotides were measured. Overnight cultured islets (40 islets) were cocultured for 30 min with the supernatants obtained from pancreatic collagenase digestion at different digestion periods in order to assess the toxic environment. The peak yields of islets were obtained at 30 min of digestion. The histological study of digested pancreas showed that the exocrine cells lost their cellular integrity at 120 min of digestion, but the islet cells were left intact. Accordingly, the ATP levels of the pancreatic tissue decreased during the digestion period. The coculture experiment demonstrated that the islets cultured with the supernatants from the collagenase digestion showed digestion time-dependent disruption of the cellular integrity of islets in accordance with a rapid decrease of ATP levels in the islets. The addition of serine protease inhibitors into this coculture clearly showed protection of islets, which maintained high ATP levels in association with intact membrane integrity as assessed by AO/PI staining. Morphological deterioration of islets as well as a marked ATP decrease was evident in the entire digested pancreas as well as in islets cocultured in the supernatants from the collagenase digestion. Various factors toxic to the islets can therefore be analyzed in future experiments using this coculture model for obtaining a good yield of viable islets.

Adenine nucleotide levels in a closed enzymatic digestion system for porcine islet isolation.

Obtaining viable islets is a crucial step for successful islet transplantation. Adenosine triphosphate (ATP) is a marker of cell viability. However, little is known about any changes in the energy status of the tissues that are being digested during the digestion phase. We herein examined whether the ATP content in serially digested pancreatic tissue samples could be specific objective parameters that signal the optimal point to stop the digestion process. We obtained partial pancreata (body to tail) from 4- to 5-year-old pigs from a slaughterhouse. The tissue samples were preserved in M-Kyoto solution for less than 3 h. They were digested using an automated enzymatic and mechanical dissociation system at 37°C for 90 min following intraductal injection of Liberase HI. Samples were collected from the digestive circuit every 5 or 10 min to determine the ATP level, total adenine nucleotide (TAN) level, islet count (count/g), and yield of islet equivalent (IEQ) in the serial digestive fluids. The ATP and TAN levels, IEQ and islet count were increased and then decreased during digestion process. The profile of these parameters differed from case to case. However, when ATP changing ratio (respective value/precedent value) was compared with IEQ changing ratio, a greater than threefold increase in the ATP changing ratio followed by an increase in the islet count changing ratio within 5 min was consistently observed, indicating the optimal time to stop the digestion. The ATP levels of the handpicked islets in the digested samples were lower in the overdigested phase in comparison to those in the earlier digested phase. These results indicate that the ATP level in digested fluid could be an effective indicator to estimate the viability of cells as well as determine the optimal time to terminate the digestion process in order to obtain viable islets.

Preservation of pancreatic islets in cold UW solution before transplantation.

Culture of islets prior to transplantation needs to be revisited for maintaining functional islet capacity. This study was conducted to compare cold UW (University of Wisconsin) preservation with conventional culture based on insulin secretory capacity in vitro and in vivo. Islets isolated from Wistar rats were either cultured for 24 h at 37°C in RPMI1640 medium or DMEM containing various concentrations of glucose or preserved for the same period in UW solution or in DMEM solution at 4°C. The islet yield in UW group, but not in other groups, was maintained as comparable with that of fresh islets. Insulin secretory capacity in response to glucose was maintained only in the islets of UW group, but not in other groups. SCID mice given 300 IEQ islets of UW group showed gradual restoration of normoglycemia as found in the mice given freshly isolated islets. Meanwhile, those mice given cultured islets for 24 h at 37°C in RPMI1640 medium showed rapid decrease of blood glucose levels on day 1 followed by relatively elevated levels on day 2, suggesting unstable insulin secretory capacity of islets.   Morphological staining with anti-HMGB1 (high mobility group B1) antibody revealed central damage of islets in all culture groups regardless of glucose concentration and in islets of cold DMEM group, whereas those in the UW group were quite intact. These results suggest that cold preservation in UW solution is simple and beneficial in protecting islets morphologically and functionally before transplantation.