Nonocclusive mesenteric ischemia (NOMI) on Roux limb after biliary reconstruction successfully treated by interventional radiology (IVR).

Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder. Early diagnosis is challenging because NOMI lacks specific symptoms. A 52-year-old man who received extended cholecystectomy with Roux-en-Y hepaticojejunostomy for gallbladder cancer (GBC) presented to our hospital with nausea and vomiting. Neither tender nor peritoneal irritation sign was present on abdominal examination. Blood test exhibited marked leukocytosis (WBC:19,800/mm3). A contrast-enhanced abdominal computed tomography (CT) scan revealed remarkable wall thickening and lower contrast enhancement effect localized to Roux limb. On hospital day 2, abdominal arterial angiography revealed angio-spasm at marginal artery and arterial recta between 2nd jejunal artery and 3rd jejunal artery, leading us to the diagnosis of NOMI. We then administered continuous catheter-directed infusion of papaverine hydrochloride until hospital day 7. Furthermore, the patient was anticoagulated with intravenous unfractionated heparin and antithrombin agents for increasing D-dimer level and decreasing antithrombin III level. On hospital day 8, diluted oral nutrition diet was initiated and gradually advanced as tolerated. On hospital day 21, the patient was confirmed of improved laboratory test data and discharged with eating a regular diet. We experienced a rare case of NOMI on Roux limb after 2 years of extended cholecystectomy with hepaticojejunostomy for GBC, promptly diagnosed and successfully treated by interventional radiology (IVR).

International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas.

This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.

Surveillance after resection of non-invasive intraductal papillary mucinous neoplasms (IPMN). A systematic review.

BACKGROUND: The ideal surveillance strategy after partial pancreatectomy for non-invasive IPMN remains undefined and existing guidelines provide conflicting recommendations. The present study was developed in anticipation of the joint meeting of the International Association of Pancreatology (IAP) and the Japan Pancreas Society (JPS) held in Kyoto in July 2022. METHODS: An international team of experts developed the four clinical questions (CQ) to operationalize issues pertaining to surveillance of patients in this context. A systematic review was designed following the PRISMA guidelines and registered in PROSPERO. The search strategy was executed in PubMed/Medline (Ovid), Embase, the Cochrane Library and Web of Science databases. Four investigators individually extracted data from the selected studies and drafted recommendations for each CQ. These were subsequently discussed and agreed upon that the IAP/JPS meeting. RESULTS: From a total of 1098 studies identified through the initial search, 41 studies were included in the review and informed the recommendations. No studies providing level one data were identified in this systematic review, all studies included were cohort or case-control studies. CONCLUSIONS: There is a lack of level 1 data addressing the issue of surveillance of patients following partial pancreatectomy for non-invasive IPMN. The definition of remnant pancreatic lesion in this setting is largely heterogeneous across all studies evaluated. Herein we propose an inclusive definition of remnant pancreatic lesions to guide future prospective efforts for reporting the natural history and long-term outcomes of these patients.

A Prospective Multicenter Phase II Trial of Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer with Arterial Involvement.

BACKGROUND: Only two clinical trials have shown the effects of neoadjuvant treatment for borderline resectable pancreatic cancer with arterial involvement (BRPC-A). Here, we aimed to analyze the efficacy and safety of neoadjuvant gemcitabine plus nab-paclitaxel (GnP) for BRPC-A. PATIENTS AND METHODS: A prospective, single-arm, multicenter phase II trial was conducted. Patients who were radiologically and histologically diagnosed with BRPC-A were enrolled. A central review was conducted to confirm the presence of BRPC-A. Patients received two to four cycles of GnP before surgery. The primary endpoint of the study was the R0 resection rate. Overall survival (OS) was evaluated in an ancillary study. RESULTS: Thirty-five patients were enrolled, of whom 33 were subjected to central review and 28 were confirmed to have BRPC-A. All eligible patients with BRPC-A received neoadjuvant GnP. Nineteen patients underwent pancreatic resections. Postoperative complications of Clavien-Dindo IIIa or lower were observed in 11 patients. No treatment-related mortalities were observed. R0 resection was achieved in 17 patients (89%); the R0 resection rate was 61% in eligible patients. One patient underwent curative resection after termination of the treatment protocol, resulting in an overall R0 resection rate of 64%. The median overall survival (OS) and 2-year OS rate were 24.9 months [95% confidence interval (CI) 19.0 months to not estimatable] and 53.6%, respectively. OS in patients with BRPC-A who achieved overall R0 resection was significantly longer than that in the other patients (p = 0.0255). CONCLUSIONS: Neoadjuvant GnP is a safe and effective strategy for BRPC-A, providing a chance for curative resection and improved survival.

Small and large intestinal cancer in patients with Crohn's disease studied by surgeons.

PURPOSE: The current study summarized the clinical course and treatment outcomes of intestinal cancer in CD seen in our department and explored the steps to take in the future. METHODS: Subjects were patients who had been diagnosed with CD at our hospital and who underwent surgery in our department from 1985 to 2020. RESULTS: Thirty-one patients had CD and intestinal cancer, including 6 with cancer of the small intestine and 25 with cancer of the large intestine. In all six patients with cancer of the small intestine, the site where cancer or a tumor developed was at or near the site of the anastomosis made at a previous surgery. Of the 25 patients with cancer of the large intestine, 22 developed cancer in the rectum or anal region. CONCLUSION: Many of the patients with cancer of the small intestine had previously undergone surgery, and the cancer developed at or near the site of the anastomosis. In patients who have previously undergone resection of the small intestine, the small intestine needs to be examined regularly. Cancer of the large intestine often developed in the rectum or anal region of our patients, so a detailed examination of the same site needs to be performed.

Laparoscopic splenic vessel-preserving distal pancreatectomy after laparoscopic pylorus-preserving gastrectomy: A case report.

A 77-year-old woman who had undergone laparoscopic pylorus-preserving gastrectomy for gastric cancer showed dilatation of the main pancreatic duct in the distal pancreas on ultrasonography during postoperative surveillance. Detailed examination revealed that she had a main-duct type intraductal papillary mucinous neoplasm with high-risk stigmata. As invasive malignancy was not suggested, laparoscopic splenic vessel-preserving distal pancreatectomy was performed to preserve the remnant stomach. Although adhesions around the gastroduodenostomy and splenic artery were severe, the magnified laparoscopic view facilitated the identification of appropriate dissection layers, resulting in limited blood loss. The distal pancreas was successfully resected without sacrificing blood flow to the remnant stomach. The postoperative course was uneventful. The pathological diagnosis was low-grade intraductal papillary mucinous neoplasm. Laparoscopic splenic vessel-preserving distal pancreatectomy for benign or low-grade malignant disease of the distal pancreas can be useful for preserving the remnant stomach in patients with a history of gastrectomy.

Minimally invasive anatomic liver resection: Results of a survey of world experts.

BACKGROUND: Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. METHOD: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). RESULTS: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound. CONCLUSION: Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.

The Tokyo 2020 terminology of liver anatomy and resections: Updates of the Brisbane 2000 system.

BACKGROUND: The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021. METHODS: The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations. RESULTS: This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed. CONCLUSIONS: The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.

Landmarks and techniques to perform minimally invasive liver surgery: A systematic review with a focus on hepatic outflow.

PURPOSE: In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). METHODS: A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A total of 3372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. CONCLUSIONS: This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.

Expert Consensus Guidelines: How to safely perform minimally invasive anatomic liver resection.

BACKGROUND: The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). METHODS: Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. RESULTS: Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. CONCLUSIONS: The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.

Primary gastric synovial sarcoma resected by laparoscopic endoscopic cooperative surgery of the stomach: a case report.

BACKGROUND: Primary gastric synovial sarcoma is extremely rare, only 44 cases have been reported so far, and there have been no reports of laparoscopic endoscopic cooperative surgery for this condition. CASE PRESENTATION: A 45-year-old male patient presented with gastric pain. Esophagogastroduodenoscopy was performed that led to the identification of an 8-mm submucosal tumor in the anterior wall of the antrum, and a kit-negative gastrointestinal stromal tumor was suspected following biopsy. On endoscopic ultrasonography, the boundary of the tumor, mainly composed of the second layer, was depicted as a slightly unclear low-echo region, and a pointless no echo region was scattered inside. A boring biopsy revealed synovial sarcoma. Positron emission tomography did not reveal fluorodeoxyglucose (18F-FDG) accumulation in the stomach or other organs. Thus, the patient was diagnosed with a primary gastric synovial sarcoma, and laparoscopic endoscopic cooperative surgery was performed. The tumor of the antrum could not be confirmed laparoscopically from the serosa, and under intraoperative endoscopy, it had delle on the mucosal surface, which was removed by a method that does not involve releasing the gastric wall. Immunohistochemistry showed that the spindle cells were positive for EMA, BCL-2 protein, TLE-1, and SS18-SSX fusion-specific antibodies but negative for KIT and DOG-1. The final pathological diagnosis was synovial sarcoma of the stomach. The postoperative course was good, and the patient was discharged from the hospital on the 11th postoperative day. CONCLUSION: Resection with laparoscopic endoscopic cooperative surgery (LECS), which has not been reported before, was effective for small synovial sarcomas that could not be confirmed laparoscopically. With the combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (CLEAN-NET) procedure, it was possible to excise the tumor with the minimum excision range of the gastric serosa without opening the stomach.

Laparoscopic distal pancreatectomy for intraductal papillary mucinous neoplasm-associated pancreatic cancer: A case report.

INTRODUCTION AND IMPORTANCE: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often found incidentally during examination for other diseases. In addition to the risk of malignant transformation, patients with IPMN are at risk of developing pancreatic cancer. We report a case of pancreatic tail cancer that developed separately from a preexisting IPMN after minimally invasive esophagectomy for cancer of the esophagogastric junction and was resected successfully by laparoscopic distal pancreatectomy. CASE PRESENTATION: A 72-year-old man underwent thoracoscopic and laparoscopic esophagectomy for esophagogastric junction cancer. He had undergone surgery for ascending colon cancer 20 years ago. At that time, IPMN was confirmed in the pancreatic body by a preoperative examination. Computed tomography was regularly performed for postoperative work-up and follow-up of the IPMN, and a solid lesion with cystic components was detected in the pancreatic tail 9 months after the operation. On detailed examination, pancreatic ductal adenocarcinoma concomitant with IPMN, accompanied by a retention cyst, was considered. Laparoscopic distal pancreatectomy was successfully performed after neoadjuvant chemotherapy. Pathological diagnosis of the lesion in the pancreatic tail was of an invasive intraductal papillary mucinous carcinoma (ypT3ypN0yM0 ypStageIIA). CLINICAL DISCUSSION: If an IPMN is detected during preoperative examination for malignancies of other organs, careful follow-up is necessary due to the high risk of pancreatic cancer development. Furthermore, initial operation with minimally invasive surgery may reduce adhesion and facilitate subsequent surgeries. CONCLUSION: We have provided evidence that supports the importance of a careful follow-up of IPMNs, even if they are low risk.

Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic reaction caused by cancer-associated fibroblasts (CAFs), which provokes treatment resistance. CAFs are newly proposed to be heterogeneous populations with different functions within the PDAC microenvironment. The most direct sources of CAFs are resident tissue fibroblasts and mesenchymal stem cells, however, the origins and functions of CAF subtypes remain unclear. Here, we established allogeneic bone marrow (BM) transplantation models using spontaneous PDAC mice, and then investigated what subtype cells derived from BM modulate the tumor microenvironment and affect the behavior of pancreatic cancer cells (PCCs). BM-derived multilineage hematopoietic cells were engrafted in recipient pancreas, and accumulated at the invasive front and central lesion of PDAC. We identified BM macrophages-derived CAFs in tumors. BM-derived macrophages treated with PCC-conditioned media expressed CAF markers. BM-derived macrophages led the local invasion of PCCs in vitro and enhanced the tumor invasive growth in vivo. Our data suggest that BM-derived cells are recruited to the pancreas during carcinogenesis and that the specific subpopulation of BM-derived macrophages partially converted into CAF-like cells, acted as leading cells, and facilitated pancreatic cancer progression. The control of the conversion of BM-derived macrophages into CAF-like cells may be a novel therapeutic strategy to suppress tumor growth.

Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel Regimen for Borderline Resectable Pancreatic Cancer with Arterial Involvement: A Prospective Multicenter Single-Arm Phase II Study Protocol.

INTRODUCTION: Although neoadjuvant treatment is recommended for patients with borderline resectable pancreatic cancer (BRPC), no standard neoadjuvant regimen has been established for BRPC with arterial involvement (BRPC-A), which is associated with a higher risk of margin-positive resection and poorer prognosis than BRPC with only venous involvement. Gemcitabine plus nab-paclitaxel (GnP) has been reported to significantly reduce tumor size in metastatic pancreatic cancer, and some retrospective studies suggested that neoadjuvant GnP for BRPC improved resectability and survival. METHODS AND ANALYSIS: A prospective multicenter single-arm phase II study is conducted to evaluate the safety and efficacy of GnP as neoadjuvant chemotherapy for BRPC-A. The primary endpoint is the R0 resection rate. The secondary endpoints are the neoadjuvant chemotherapy response rate, resection rate, pathological response rate, incidence rate of adverse events, and quality of life. ETHICS AND DISSEMINATION: This study protocol was approved by the institutional review board of Kyushu University (no. 181). The results will be published in a peer-reviewed journal and will be presented at medical meetings. HIGHLIGHTS: Strategy for borderline resectable pancreatic cancer involving arteries (BRPC-A).There is no standard regimen for neoadjuvant chemotherapy for BRPC-A.Gemcitabine plus nab-paclitaxel (GnP) shows significant tumor shrinkage.Neoadjuvant GnP for BRPC-A increases resectability and margin-negative resection.

Evaluation of relationship between splenic artery and pancreatic parenchyma using three-dimensional computed tomography for laparoscopic distal pancreatectomy.

AIM: Isolating the root of the splenic artery (SPA) is a challenging procedure in laparoscopic distal pancreatectomy (LDP). We investigated the usefulness of evaluation of the relationship between the SPA and pancreatic parenchyma using three-dimensional computed tomography (3D-CT). METHODS: In total, 104 patients were evaluated. The relationship between the SPA and pancreatic parenchyma was classified into two types: buried and non-buried. Video clips of 50 patients who underwent LDP requiring isolation of the SPA root were reviewed to determine whether the classification is related to difficulty of LDP. RESULTS: Of the 50 assessed patients who underwent LDP, the relationship between the SPA and pancreatic parenchyma was the buried type in 30 (60.0%) and non-buried type in 20 (40.0%). The buried type was associated with a significantly longer median operative time than the non-buried type (285.0 vs. 235.5 min, respectively; P < 0.01). The median time required to isolate the SPA in the buried type (25.8 min; range, 4.0-101 min) was significantly longer than that in the non-buried type (7.0 min; range, 1.0-27.0 min) (P < 0.001). CONCLUSION: Preoperative 3D-CT around the pancreas is practical for predicting the difficulty of SPA isolation and determining the safety of the procedure.

Management of postoperative pancreatic fistula after pancreatoduodenectomy: Analysis of 600 cases of pancreatoduodenectomy patients over a 10-year period at a single institution.

BACKGROUND: Although postoperative pancreatic fistula (POPF) is a common and critical complication of pancreatoduodenectomy (PD), effective strategies to prevent POPF have not yet been completely developed. Because appropriate management of POPF is important to reduce the mortality rate after PD, in this study we aimed to evaluate our approach for the management of POPF after PD, including the postoperative course. METHODS: This retrospective study included 605 consecutive patients who underwent PD at our hospital between 2010 and 2020. All patients who developed POPF were first managed conservatively, with drainage tubes placed during surgery retained to manage POPF. In cases wherein conservative treatment was unsuccessful, open drainage, followed by continuous negative pressure and continuous irrigation, was used. For open drainage, the surgical wound was opened bluntly (approximate length, 5 cm) under local anesthesia, and the fluid was directly and completely drained. RESULTS: The prevalence of POPF of grades B and C was 15.4% (n = 93) and 0.33% (n = 2), respectively. Of these patients, 1 required reoperation, 43 recovered with conservative management only, 47 required open drainage, and 4 required image-guided percutaneous drainage. Postoperative hemorrhage with a pseudoaneurysm was identified in 3 (0.66%) patients. The postoperative in-hospital mortality rate was low (n = 1, 0.16%). The rate of successful POPF management was 98.9%. CONCLUSION: Based on our high success rate in POPF management, we consider open drainage to be a safe primary management method for POPF.

Minimally invasive surgery for pancreatic cancer.

Pancreatic cancer is the most lethal malignancy of the digestive organs. Although pancreatic resection is essential to radically cure this refractory disease, the multi-organ resection involved, as well as sequelae such as glucose tolerance insufficiency and severe complications impose a heavy burden on these patients. Since the late twentieth century, minimally invasive surgery has become more popular for the surgical management of digestive disease and pancreatic cancer. Minimally invasive pancreatic resection (MIPR), including pancreaticoduodenectomy and distal pancreatectomy, is now a treatment option for pancreatic cancer. Some evidence suggests that MIPR for pancreatic cancer provides comparable oncological outcomes to open surgery, with some advantages in perioperative outcomes. However, as this evidence is retrospective, prospective investigations, including randomized controlled trials, are necessary. Because neoadjuvant therapy for resectable or borderline-resectable pancreatic cancer and conversion surgery for initially unresectable pancreatic cancer has become more common, the feasibility of MIPR after neoadjuvant therapy or as conversion surgery requires further assessment. It is expected that progress in surgical techniques and devices, as well as the standardization of surgical procedures and widespread educational programs will improve the outcomes of MIPR.

[A Case of Anastomotic Stenosis with Reconstructed Small Intestine Mucosal Damage during Taking S-1 Orally after Gastrectomy for Gastric Cancer].

An 83-year-old woman underwent laparoscopic distal gastrectomy and Billroth Ⅱ reconstruction for gastric cancer. Since histopathological examination revealed that the lesion was Stage ⅢA, she had started taking S-1 as an adjuvant chemotherapy 7 weeks after gastrectomy. Seventeen days later after taking S-1 administration, she felt nauseous and self-interrupted. Nineteen days later, she was urgently hospitalized. Esophagogastroduodenoscopy(EGD)showed anastomotic lumen was open, but reconstructed small intestine mucosal damage was found, and reconstructed small intestine muscle layer was fused to anastomotic region. On 50th day of hospitalization, mucosa was regenerated and endoscopic balloon dilatation (EBD)was performed from 78th day. She was discharged on 151th day of hospitalization after 7 times of EBD. One year later, she does not need EBD and can be taken orally and has no recurrence.