Publications by authors named "Michiaki Unno"

588 Publications

A case of intestinal malrotation apparent after laparoscopically total proctocolectomy followed by ileal-pouch-anal anastomosis for ulcerative colitis.

Asian J Endosc Surg 2022 Aug 11. Epub 2022 Aug 11.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Intestinal malrotation (IM) is an abnormality due to a failure of the normal midgut rotation and fixation. We report a case of 46-year-old man with ulcerative colitis whose IM was apparent after laparoscopically total proctocolectomy (TPC) followed by ileal-pouch-anal anastomosis (IPAA) and ileostomy. There was no abnormal anatomy except for mobile cecum/ascending colon during the initial operation. Intestinal obstruction occurred after ileostomy closure. The computed tomography scan showed the duodeno-jejunal transition was located in right abdomen, the superior mesenteric vein was located left of the superior mesenteric artery (SMA) and the obstruction point was the distal ileum near the pouch. We performed an ileo-ileo bypass across the ventral side of the SMA to relieve the intestinal obstruction. The patient would have incomplete IM preoperatively, which became apparent by TPC. In case of TPC for mobile colon, anatomy of small intestine should be checked before IPAA.
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http://dx.doi.org/10.1111/ases.13114DOI Listing
August 2022

A potential preventive method for scar stenosis after esophageal endoscopic mucosal resection using human amniotic epithelial cells in a porcine model.

DEN open 2022 Apr 9;2(1):e104. Epub 2022 Mar 9.

Department of Surgery Tohoku University Graduate School of Medicine Miyagi Japan.

Objectives: The current methods employed for esophageal endoscopic mucosal resection (EMR) involve the risk of adverse postprocedural complications. Therefore, this study aimed to develop a new method to prevent stenosis following a resection procedure using human amniotic epithelial cells in a porcine model.

Methods: With the consent of a woman who underwent a cesarean section, amniotic epithelial cells were isolated from the amniotic membrane of the delivered placenta. Six swine were used for this study. Under general anesthesia, four EMRs using cap-fitted microscope ulcers were performed on each porcine esophagus. Of the four ulcers, the two on the oral side were treated by injecting human amniotic epithelial (AE group) cells, and the remaining two on the anal side were left untreated (control group). One week after the procedure, the swine were sacrificed, and the ulcers were evaluated. The epithelialization rate was calculated by dividing the length of the epithelialized portion of each section by the length of the ulcer, which was determined using an optical microscope. Moreover, the mucosal thickening in each section was measured in terms of diameter.

Results: The epithelialization rate was significantly higher in the AE group than in the control group. Mucosal thickening was not significantly different between the groups.

Conclusions: Transplanting amniotic epithelial cells into the ulcer promoted ulcer epithelialization. Amniotic epithelial cell transplantation is a potential method for the management of ulcer scar stenosis following esophageal endoscopic submucosal dissection.
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http://dx.doi.org/10.1002/deo2.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302276PMC
April 2022

Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan.

Surgery 2022 Jul 9. Epub 2022 Jul 9.

Department of Surgery, Kindai University, Osaka, Japan.

Background: The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy.

Methods: Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study.

Results: Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period.

Conclusion: Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.
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http://dx.doi.org/10.1016/j.surg.2022.04.031DOI Listing
July 2022

Pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline BRCA2 mutation: a case report.

Clin J Gastroenterol 2022 Jul 12. Epub 2022 Jul 12.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Loss of function in the BRCA2 gene exacerbates ovarian, breast, and pancreatic ductal cancer risk. Despite being implicated in the pancreatic ductal epithelium carcinogenesis, the involvement of a germline BRCA2 mutation in acinar and endocrine cells is less reported. A 45-year-old woman with a history of breast cancer was referred to our hospital for a detailed examination of epigastric pain. Her father had pancreatic cancer, and her paternal aunt had a history of breast cancer. Contrast-enhanced computed tomography revealed a round tumor with a contrast effect in the pancreatic head. The patient underwent pancreaticoduodenectomy, and postoperative pathology and genetic testing revealed amphicrine-type mixed acinar-neuroendocrine carcinoma with a germline BRCA2 mutation. Recent studies have reported the BRCA2 mutation in genome sequencing of pancreatic acinar cell carcinoma and neuroendocrine tumor; perhaps, genetic testing for the BRCA2 mutation is feasible for patients with mixed neuroendocrine-non-neuroendocrine neoplasm.
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http://dx.doi.org/10.1007/s12328-022-01668-8DOI Listing
July 2022

A New Strategy of Liver Transplantation for Locally Advanced Unresectable Perihilar Cholangiocarcinoma Using Living Grafts With Simultaneous Resection of Recipients' Hepatic Artery and Portal Vein Without Neoadjuvant Radiation: A Case Report.

Transplant Proc 2022 Jul 6. Epub 2022 Jul 6.

Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan.

Background: Perihilar cholangiocarcinoma (pCCA) is often unresectable, because it includes crucial blood vessels in portal area. The prognosis of locally advanced unresectable cholangiocarcinomas is extremely poor. Recently, there have been several reports of the prognosis improving drastically with transplantation and combined chemoradiation therapy. However, liver transplantation for pCCA has 2 big problems. The first is that pCCA is located at a lethal position and its progress is sometimes rapid; therefore, the optimal timing of transplantation is sometimes lost. The second is vascular complications associated with neoadjuvant radiation, especially in living donor liver transplantation (LDLT). To overcome these problems, we performed conversion surgery using LDLT with simultaneous resection of the hepatic artery and portal vein, instead of neoadjuvant radiation. Herein, we report our experience of interposition reconstruction.

Methods: A 31-year-old man with primary sclerosing cholangitis (PSC) was diagnosed with locally advanced unresectable pCCA. The patient underwent radical chemotherapy (gemcitabine/cisplatin/S-1) and avoided radiation because of PSC. After 6 months, positron emission tomography-computed tomography revealed no lymph node metastasis. There was no time to wait. We immediately performed LDLT with simultaneous resection of hepatic artery and portal vein, and microsurgical reconstruction using auto-vessel grafts.

Results: The recipient recovered and was discharged 31 days posttransplant. His liver function improved, and he has had no recurrence after LDLT.

Conclusion: LDLT with neoadjuvant radiation is associated with high risk of vascular complications. In some cases, conversion surgery after radical chemotherapy using good timing LDLT without radiation may increase chances of transplantation for locally advanced pCCA.
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http://dx.doi.org/10.1016/j.transproceed.2022.03.054DOI Listing
July 2022

A case of refractory esophageal stricture due to occult gastrinoma of the duodenum.

Clin J Gastroenterol 2022 Jul 4. Epub 2022 Jul 4.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-Cho, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan.

Gastrinoma may cause refractory esophageal stricture due to gastro-esophageal reflux disease (GERD), but imaging technologies have limited power in its diagnosis. A 74-year-old female with a history of peptic ulcers suffered from repeated epigastralgia, and she visited a local hospital. An esophago-gastro-duodenoscopy (EGD) demonstrated severe reflux esophagitis and multiple peptic ulcers. Blood examination revealed a high value of fasting serum gastrin. Multi-detector computed tomography showed a hypervascular and tiny nodule in duodenal bulb, although other imaging technologies did not. Short-term medication with a proton pump inhibitor or potassium-competitive acid blocker was intermittently provided, but dysphagia was repeatedly worsened, and she was referred to our division. Serum hypergastrinemia was retained, and EGD reexamination depicted esophageal stricture, treated by multiple sessions of endoscopic balloon dilatation. Primary tumor was not identified by the morphological imaging technologies, but a selective arterial secretagogue injection test suggested its existence in the duodenum or pancreatic head. Pancreaticoduodenectomy was performed, and histological study identified 2 mm-sized microgastrinoma buried in Brunner`s glands on the posterior wall of the duodenum bulb. We reported a case with difficulty in diagnosis of the smallest sporadic gastrinoma of the duodenum, which might cause refractory GERD-associated stricture.
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http://dx.doi.org/10.1007/s12328-022-01657-xDOI Listing
July 2022

Pancreaticoduodenectomy for pancreatic head cancer with cavernous transformation of the portal vein: a case report.

Surg Case Rep 2022 Jun 30;8(1):127. Epub 2022 Jun 30.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seryo-machi, Aoba-ku, Miyagi, 980-8574, Sendai, Japan.

Background: Cavernous transformation of the portal vein (CTPV) due to extrahepatic portal vein obstruction is a rare vascular anomaly. Since its symptoms usually appear in childhood, most of the adult cases are detected unexpectedly with other diseases. Only a few reports have described surgical difficulties in patients with CTPV. We report a case of pancreatic head cancer with CTPV in a patient who underwent pancreaticoduodenectomy.

Case Presentation: A 77-year-old man with epigastric and back pain was referred to our hospital. Computed tomography revealed a tumor in the pancreatic head and a CTPV near the hepatic hilum. CTPV consisted of two main collateral vessels connected by multiple surrounding small vessels. Also, portal vein obstruction was observed near the hepatic hilum, which was far from the pancreatic head tumor. After confirming that there was no distant metastasis by a thorough whole-body search, we performed a pancreaticoduodenectomy following neoadjuvant chemotherapy. During the operation, we carefully manipulated the area of the CTPV and omitted lymph node dissection in the hepatoduodenal ligament to prevent massive venous bleeding and intestinal congestion. Pancreaticoduodenectomy was performed without any intraoperative complications and the postoperative course was uneventful. Complete tumor resection was histologically confirmed.

Conclusion: Although pancreaticoduodenectomy for patients with CTPV involves many surgical difficulties, we successfully performed it by determining specific treatment strategies tailored to the patient and following careful and delicate surgical procedures.
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http://dx.doi.org/10.1186/s40792-022-01463-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247133PMC
June 2022

Comparison of infectious complications after spleen preservation versus splenectomy during laparoscopic distal pancreatectomy for benign or low-grade malignant pancreatic tumors: A multicenter, propensity score-matched analysis.

J Hepatobiliary Pancreat Sci 2022 Jun 29. Epub 2022 Jun 29.

Department of Surgery, Keimyung University Dongsan Hospital, Daegu, South Korea.

Background: Previous studies have reported contrasting results regarding the advantages of spleen preservation during laparoscopic distal pancreatectomy (LDP) for preventing infectious complications.

Methods: A total of 3787 patients who underwent LDP for benign or low-grade malignant pancreatic disease in 92 centers across Korea and Japan were included in this retrospective study. Postoperative infectious complications and other complications were compared between LDP with splenectomy (LDPS) and LDP with spleen preservation (LSPDP) by propensity score matching (PSM) analysis.

Results: After PSM, the LSPDP group had a lower rate of overall infectious complications (P = .079) and a significantly lower rate of intra-abdominal abscess (P = .014) compared with the LDPS group. Within the LSPDP group, the vessel preservation subgroup had a significantly higher rate of infectious complications (P = .002) compared with the vessel resection subgroup. Low-volume centers had a higher rate of intra-abdominal abscess than high-volume centers in the LSPDP group (P = .001) and the splenic vessel preservation subgroup (P = .003).

Conclusions: Spleen preservation in LDP for benign or borderline malignant pancreatic diseases was advantageous in lowering the risk of infectious complications, specifically intra-abdominal abscess. However, the risk of intra-abdominal abscess may differ according to the level of surgeon's experience.
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http://dx.doi.org/10.1002/jhbp.1213DOI Listing
June 2022

Perioperative Administration of Cystine and Theanine Suppresses Inflammation and Facilitates Early Rehabilitation and Recovery after Esophagectomy: A Randomized, Double-Blind, Controlled Clinical Trial.

Nutrients 2022 May 31;14(11). Epub 2022 May 31.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

Oral administration of cystine and theanine (CT) increases glutathione levels to modulate the inflammatory response, which has yet to be sufficiently explored for patients' recovery and early rehabilitation. We planned a randomized, double-blind, placebo-controlled trial to determine whether perioperative oral administration of CT promotes recovery after esophagectomy. Patients were randomized into either CT or placebo groups, who received preoperative and postoperative treatments for 4 and 13 days, respectively. The main outcome measures were triaxial accelerometer readings, inflammation indicators, a 6 min walk test (6MWT), and a quality of life questionnaire (QoR-40). The study involved 32 patients. Although the CT group ( = 16) showed better patient activity across the investigated period, there was no significant difference between the two groups. However, white blood cell count on postoperative days (POD) 2 and 10, neutrophil count (POD 2, 7, and 10), and C-reactive protein level (POD 13) in the CT group were significantly lower than in the placebo group. Furthermore, 6MWT on POD 7 and QoR-40 on POD 13 were significantly higher in the CT group than those in the placebo group. This study suggests that perioperative administration of CT may contribute to early recovery and rehabilitation after esophagectomy via suppression of inflammatory response.
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http://dx.doi.org/10.3390/nu14112319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182838PMC
May 2022

A nationwide certification system to increase the safety of highly advanced hepatobiliary-pancreatic surgery.

J Hepatobiliary Pancreat Sci 2022 May 24. Epub 2022 May 24.

Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.

Background: To ensure that highly advanced hepatobiliary-pancreatic surgery (HBPS) is performed safely, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons established a safety committee to monitor surgical safety.

Methods: We investigated postoperative mortality rates based on summary reports of numbers and outcomes of highly advanced HBPS submitted annually by the board-certified training institutions from 2012 to 2019. We also analyzed summary reports on mortality cases submitted by institutions with high 90-day post-HBPS mortality rates and recommended site visits and surveys as necessary.

Results: Highly advanced HBPS was performed in 121 518 patients during the 8-year period. Thirty-day mortality rates from 2012 to 2019 were 0.92%, 0.8%, 0.61%, 0.63%, 0.70%, 0.59%, 0.48%, and 0.52%, respectively (P < .001). Ninety-day mortality rates were 2.1%, 1.82%, 1.62%, 1.28%, 1.46%, 1.22%, 1.19%, and 0.98%, respectively (P < .001). Summary reports were submitted by 20 hospitals between 2015 and 2019. Mortality rates before and after the start of report submission and audit were 5.72% and 2.79%, respectively (odds ratio 0.690, 95% confidence interval 0.487-0.977; P = .037).

Conclusions: Development of a system for designation of board-certified expert surgeons and safety management improved the mortality rate associated with highly advanced HBPS.
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http://dx.doi.org/10.1002/jhbp.1186DOI Listing
May 2022

Prospective clinical study for claudication after endovascular aneurysm repair involving hypogastric artery embolization.

Surg Today 2022 May 9. Epub 2022 May 9.

Department of Surgery, Division of Vascular Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Purpose: This prospective study aimed to assess the prognosis of claudication after endovascular aneurysm repair (EVAR) involving hypogastric artery (HGA) embolization.

Methods: Patients who were scheduled to undergo EVAR involving bilateral or unilateral HGA embolization (BHE or UHE, respectively) between May 2017 and January 2019 were included in this study. Patients underwent the walk test preoperatively, one week postoperatively, and monthly thereafter for six months. The presence of claudication and the maximum walking distance (MWD) were recorded. A near-infrared spectroscopy monitor was placed on the buttocks, and the recovery time (RT) was determined. A walking impairment questionnaire (WIQ) was completed to determine subjective symptoms.

Results: Of the 13 patients who completed the protocol, 12 experienced claudication in the 6-min walk test. The MWD was significantly lower at one week postoperatively than preoperatively. The claudication prevalence was significantly higher at five and six months postoperatively after BHE than after UHE. BHE was associated with longer RTs and lower WIQ scores than UHE.

Conclusions: We noted a trend in adverse effects on the gluteal circulation and subjective symptoms ameliorating within six months postoperatively, with more effects being associated with BHE than with UHE. These findings should be used to make decisions concerning management strategies for HGA reconstruction.
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http://dx.doi.org/10.1007/s00595-022-02502-xDOI Listing
May 2022

Long-term survival of an adult patient with undifferentiated embryonal sarcoma of the liver with multidisciplinary treatment: a case report and literature review.

Surg Case Rep 2022 May 5;8(1):85. Epub 2022 May 5.

Department of Surgery, Tohoku University Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

Background: Undifferentiated embryonal sarcoma of the liver (UESL) primarily occurs in children; it is rarely seen in adults and appears to have a poor prognosis. However, in recent years, some cases indicated that long-term survival was possible due to a combination of multiple surgeries, chemotherapy, and liver transplantation.

Case Presentation: A 33-year-old female patient presented with a complaint of epigastric pain, for which she underwent a medical examination. Computed tomography (CT) and magnetic resonance imaging showed a cystic tumor in the right hepatic lobe, approximately 10 cm in size. During observation, the abdominal pain worsened, and a contrast-enhanced CT revealed that the tumor's peripheral solid components increased in size and volume, suggesting a malignant tumor threatening hepatic rupture. Subsequently, transcatheter arterial embolization of the anterior and posterior segmental branches of the hepatic artery was performed, followed by right trisectionectomy. Histopathological and immunohistochemical examinations of the lesion revealed UESL. Two months after the surgery, we initiated sarcoma-directed chemotherapy with doxorubicin because of multiple metastases to the liver. After initiating the chemotherapy, she received another regimen using gemcitabine/docetaxel, eribulin, trabectedin, ifosfamide/mesna, pazopanib, and cisplatin. During the chemotherapy, she underwent palliative surgery twice due to the progressive disease. She lived for 49 months after the initial operation.

Conclusions: Improved long-term survival was achieved in an adult patient with UESL after multidisciplinary therapy, involving a combination of three surgical procedures and several chemotherapies.
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http://dx.doi.org/10.1186/s40792-022-01436-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068849PMC
May 2022

Rapidly growing carcinosarcoma of the esophagus following definitive chemoradiotherapy: A case report and the literature review.

Int J Surg Case Rep 2022 May 21;94:107116. Epub 2022 Apr 21.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

Introduction: Esophageal carcinosarcoma is a rare malignancy composed of both carcinoma and sarcoma-like spindle cells. This tumor is usually diagnosed before treatment due to its unique macroscopic appearance but accurate diagnose is difficult even via biopsy if the sarcomatous component is small. Herein, we report a rare case of esophageal carcinosarcoma showing rapid growth after definitive chemoradiotherapy.

Presentation Of Case: A 65-year-old man was diagnosed with locally advanced esophageal squamous cell carcinoma with lymph node metastasis. Following definitive chemoradiotherapy, the primary tumor and metastatic lymph nodes were markedly reduced. However, at 14 weeks after treatment, an ulcerative lesion appeared at the site of the primary tumor and was clinically interpreted as residual cancer. The tumor rapidly grew in a short period of time and new metastatic lesions were clinically detected in the supraclavicular lymph nodes. Salvage esophagectomy was immediately performed and histopathological examination of the resected specimen revealed that the tumor was largely composed of sarcomatous spindle cells harboring the histological transition from squamous cell carcinoma. The final diagnosis was esophageal carcinosarcoma.

Discussion: Due to its characteristics, esophageal carcinosarcoma may occasionally get diagnosed as squamous cell carcinoma by endoscopic biopsy and chemoradiotherapy be performed for latent sarcomatous components unintentionally. There are only a few reports of esophageal carcinosarcoma treated with chemoradiotherapy, with its safety and efficacy not fully verified.

Conclusion: In cases of rapidly growing tumors following chemoradiotherapy, carcinosarcoma should be considered as one of the differential diagnoses, warranting prompt surgical procedures.
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http://dx.doi.org/10.1016/j.ijscr.2022.107116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052132PMC
May 2022

Steroid therapy still plays a crucial role and could serve as a bridge to the next promising treatments in patients with IgG4-related sclerosing cholangitis: Results of a Japanese Nationwide Study.

J Hepatobiliary Pancreat Sci 2022 Apr 22. Epub 2022 Apr 22.

Department of Internal Medicine, Kansai Medical University, Kori Hospital, Neyagawa, Japan.

Objective: The acceptable duration of steroid therapy for patients with IgG4-sclerosing cholangitis (SC) has been under debate. Our aim is to clarify the feasible duration of steroid treatment.

Design: We retrospectively reviewed the data of patients with IgG4-SC and analyzed the following: biliary status during the steroid therapy, incidence of remission, relapse, relapse-free survival rate, and steroid-related complications (SRCs).

Results: Remission was achieved 99.5% (763/767) of patients who received steroid therapy, while remission rate dropped to 63.6% (78/129) of patients who didn't receive it. Relapse was noted in 19.7% (151/763) of the patients who received steroid. Besides, relapse rate went up 38.4% (30/78) of the counterpart. Normalization of the serum total bilirubin and serum alkaline phosphatase (ALP) levels were achieved at two weeks regardless of biliary drainage. Multivariate analysis identified younger onset, MST less than three years, immunosuppressant, and steroid cessation as independent risk factors for relapse. Steroid-free was achieved in the patients underwent MST only 3.4% over 54 months. SRCs were recorded in a total of 99 patients (12.9%) despite sufficient preemptive medications. Multivariate analysis identified history of malignancy and immunosuppressant as independent risk factors for SRCs.

Conclusion: Steroid therapy should be continued for no less than three years to reduce the risk of relapse, with use of preemptive measures taken around five years. The biliary drainage might not be mandatory. Steroid as 1 line therapy could serve as a bridge to further promising treatments.
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http://dx.doi.org/10.1002/jhbp.1157DOI Listing
April 2022

Cotransplantation With Adipose Tissue-Derived Stem Cells Improves Engraftment of Transplanted Hepatocytes.

Transplantation 2022 Apr 11. Epub 2022 Apr 11.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Hepatocyte transplantation is expected to be an alternative therapy to liver transplantation; however, poor engraftment is a severe obstacle to be overcome. The adipose tissue-derived stem cells (ADSCs) are known to improve engraftment of transplanted pancreatic islets, which have many similarities to the hepatocytes. Therefore, we examined the effects and underlying mechanisms of ADSC cotransplantation on hepatocyte engraftment.

Methods: Hepatocytes and ADSCs were cotransplanted into the renal subcapsular space and livers of syngeneic analbuminemic rats, and the serum albumin level was quantified to evaluate engraftment. Immunohistochemical staining and fluorescent staining to trace transplanted cells in the liver were also performed. To investigate the mechanisms, cocultured supernatants were analyzed by a multiplex assay and inhibition test using neutralizing antibodies for target factors.

Results: Hepatocyte engraftment at both transplant sites was significantly improved by ADSC cotransplantation (P < 0.001, P < 0.001). In the renal subcapsular model, close proximity between hepatocytes and ADSCs was necessary to exert this effect. Unexpectedly, ≈50% of transplanted hepatocytes were attached by ADSCs in the liver. In an in vitro study, the hepatocyte function was significantly improved by ADSC coculture supernatant (P < 0.001). The multiplex assay and inhibition test demonstrated that hepatocyte growth factor, vascular endothelial growth factor, and interleukin-6 may be key factors for the abovementioned effects of ADSCs.

Conclusions: The present study revealed that ADSC cotransplantation can improve the engraftment of transplanted hepatocytes. This effect may be based on crucial factors, such as hepatocyte growth factor, vascular endothelial growth factor, and interleukin-6, which are secreted by ADSCs.
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http://dx.doi.org/10.1097/TP.0000000000004130DOI Listing
April 2022

Cholesterol Granuloma of the Liver Mimicking Malignant Tumor: A Case Report.

Tohoku J Exp Med 2022 03;256(3):235-240

Department of Surgery, Tohoku University Graduate School of Medicine.

Cholesterol granuloma is a benign, tumor-like lesion with an accumulation of cholesterol crystals in the tissue and is a consequence of a chronic inflammatory reaction. It commonly occurs in the middle ear but rarely in the liver. There is only one previous case report of cholesterol granuloma of the liver, which was caused by cholesterol hepatolithiasis. We report a case of cholesterol granuloma of the liver in a patient with no intrahepatic cholesterol stones; it was difficult to rule out malignant liver tumor preoperatively. The patient was a 79-year-old woman in whom a lesion in the liver was detected on abdominal ultrasonography. She was referred to our hospital for detailed examination and treatment. Abdominal contrast-enhanced computed tomography showed a 20 mm lesion with ring enhancement in the lateral segment of the liver during the arterial and delayed phases. Since a malignant tumor could not be ruled out radiologically, laparoscopic lateral segment hepatectomy was performed for definitive diagnosis and treatment. The resection specimen showed a yellowish-white lesion measuring 15 mm in diameter. Pathological examination showed a granulomatous lesion with cholesterol crystals surrounded by foreign body giant cells. The lesion was diagnosed as cholesterol granuloma of the liver. The postoperative course was good, and the patient was discharged on postoperative day 5. She was healthy, and no recurrence of the cholesterol granuloma was detected at the 5-month follow-up. This is the first case report of cholesterol granuloma of the liver mimicking a malignant liver tumor in a patient with no intrahepatic cholesterol stones.
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http://dx.doi.org/10.1620/tjem.256.235DOI Listing
March 2022

Clinical features and prognostic impact of asymptomatic pancreatic cancer.

Sci Rep 2022 03 11;12(1):4262. Epub 2022 Mar 11.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8574, Japan.

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and early diagnosis is challenging. Because patients who present with symptoms generally have advanced-stage diseases, analysis of asymptomatic PDAC provides invaluable information for developing strategies for early diagnosis. Here, we reviewed 577 patients with PDAC (372 diagnosed with symptoms [symptomatic group] and 205 without symptoms [asymptomatic group]) diagnosed at our institute. Among the 205 asymptomatic PDAC patients, 109 were detected during follow-up/work-up for other diseases, 61 because of new-onset or exacerbation of diabetes mellitus, and 35 in a medical check-up. Asymptomatic PDAC is characterized by smaller tumor size, earlier disease stage, and higher resectability than those of symptomatic PDAC. In 22.7% of asymptomatic cases, indirect findings, e.g., dilatation of the main pancreatic duct, triggered PDAC detection. Although pancreatic tumors were less frequently detected, overall abnormality detection rates on imaging studies were nearly 100% in asymptomatic PDAC. Asymptomatic PDAC had a better prognosis (median survival time, 881 days) than symptomatic PDAC (342 days, P < 0.001). In conclusion, diagnosis of PDAC in the asymptomatic stage is associated with early diagnosis and a better prognosis. Incidental detection of abnormal findings during the follow-up/work-up for other diseases provides important opportunities for early diagnosis of asymptomatic PDAC.
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http://dx.doi.org/10.1038/s41598-022-08083-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917162PMC
March 2022

Short-term inhalation of isoflurane improves the outcomes of intraportal hepatocyte transplantation.

Sci Rep 2022 03 10;12(1):4241. Epub 2022 Mar 10.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, 980-0872, Japan.

Clinical hepatocyte transplantation (HTx) is only performed without general anesthesia, while inhalation anesthetics are usually used in animal experiments. We hypothesized that isoflurane may be a possible reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx. Syngeneic rat hepatocytes (1.0 × 10) were transplanted to analbuminemic rats with (ISO group) and without (AW group) isoflurane. The serum albumin, AST, ALT, LDH levels and several inflammatory mediators were analyzed. Immunohistochemical staining and ex vivo imaging were also performed. The serum albumin levels of the ISO group were significantly higher in comparison to the AW group (p < 0.05). The serum AST, ALT, LDH levels of the ISO group were significantly suppressed in comparison to the AW group (p < 0.0001, respectively). The serum IL-1β, IL-10, IL-18, MCP-1, RNTES, Fractalkine and LIX levels were significantly suppressed in the ISO group. The ischemic regions of the recipient livers in the ISO group tended to be smaller than the AW group; however, the distribution of transplanted hepatocytes in the liver parenchyma was comparable between the two groups. Isoflurane may at least in part be a reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx.
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http://dx.doi.org/10.1038/s41598-022-08237-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913608PMC
March 2022

Definitive Chemoradiotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil for Advanced Cervical Esophageal Cancer: A Medium-Term Outcome.

Asian Pac J Cancer Prev 2022 Feb 1;23(2):495-499. Epub 2022 Feb 1.

Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Miyagi, Japan.

Background: Definitive chemoradiotherapy (dCRT) is widely considered as a treatment option for cervical esophageal squamous cell carcinoma (ESCC) toward preserving the larynx. We have reported favorable outcomes, including the treatment response rate and short-term survival of dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for advanced cervical ESCC. The aim of this paper was to report the subsequent progress of the study.

Methods: We assessed 18 patients with advanced (clinical stage II-IV, including T4b and/or M1 lymph node) cervical ESCC at our department who received DCF-RT as the first-line treatment between December 2010 and June 2020.

Results: A total of 14 men and 4 women underwent the study regimen. The pretreatment clinical stage included stage II, stage III, stage IVA, and stage IVB cases (including 9 patients with T4b) [8 trachea and 2 thyroids] and 7 patients with the M1 lymph node. The complete response (CR) was achieved in 15 patients, stable disease in 2, and progressive disease in 1. Of 15 patients with CR, 7 experienced recurrence, and 8 had continued CR. Frequent cases of grade ≥3 adverse effects included leucopenia, neutropenia, febrile neutropenia, and pharyngeal pain. The 3-year overall survival rate, disease-free survival rate, and disease-specific survival rate were 44.2%, 47.7%, and 48.6%, respectively.

Conclusion: DCF-RT for advanced cervical esophageal cancer could achieve a favorable prognosis with larynx preservation. Further observations are warranted to establish the long-term prognosis, late complications of radiotherapy, and the significance of salvage surgery.
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http://dx.doi.org/10.31557/APJCP.2022.23.2.495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272611PMC
February 2022

A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study.

Langenbecks Arch Surg 2022 Jun 25;407(4):1345-1356. Epub 2022 Feb 25.

Department of Surgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.

Purpose: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM.

Methods: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS).

Results: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS.

Conclusion: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).
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http://dx.doi.org/10.1007/s00423-022-02434-7DOI Listing
June 2022

A New Preoperative Scoring System for Predicting Aggressiveness of Non-Functioning Pancreatic Neuroendocrine Neoplasms.

Diagnostics (Basel) 2022 Feb 3;12(2). Epub 2022 Feb 3.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.

The management of non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) is still controversial. This study aimed to develop a new scoring system for treatment decisions at initial diagnosis based on the identification of the predictive factors for aggressive NF-PanNENs. Seventy-seven patients who had been pathologically diagnosed with NF-PanNENs were enrolled. We retrospectively reviewed 13 variables that could be assessed preoperatively. Univariate and multivariate stepwise logistic regression analyses were performed to identify factors for the aggressiveness of NF-PanNENs, and a scoring system was developed by assigning weighted points proportional to their β regression coefficient. Tumor size > 20 mm on contrast-enhanced computed tomography, tumor non-vascularity, and Ki-67 labeling index ≥5% on endoscopic ultrasound-guided fine-needle aspiration specimens were identified as independent factors for predicting the aggressiveness of NF-PanNENs. The new scoring system, developed using the identified factors, had an excellent discrimination ability, with area under the curve of 0.92 (95% CI, 0.85-0.99), and good calibration ( = 0.72, Hosmer-Lemeshow test). Ten-year overall survival rates in low-risk (0 point), intermediate-risk (1 to 2 points), and high-risk (3 to 4 points) groups were 100%, 90.9%, and 24.3%, respectively. This new scoring system would be useful for treatment decisions and prognostic prediction at initial diagnosis.
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http://dx.doi.org/10.3390/diagnostics12020397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870938PMC
February 2022

Persistent fecal occult blood due to the small intestinal metastasis of pleomorphic lung carcinoma.

J Surg Case Rep 2022 Feb 19;2022(2):rjac043. Epub 2022 Feb 19.

Department of Thoracic Surgery, Institute of Development Aging and Cancer, Tohoku University, Sendai 980-0872, Japan.

The gastrointestinal tract is one of the locations that lung cancers cause metastasis. A 70-year-old male underwent right lower lobectomy while presenting fecal occult blood with a preoperative colonoscopy showing colon polyps as the cause. The pathological diagnosis was pleomorphic carcinoma of the lung, with stage pT3N0M0. Seven months after the lung surgery, the patient presented with sudden-onset abdominal pain and severe anemia. Computed tomography scanning revealed a large mass in the abdominal cavity, and subsequent intestinal endoscopy demonstrated jejunum tumors. Partial jejunum resection was successfully performed. The patient developed multiple peritoneal nodules suggesting metastatic tumors but well responded to an immune checkpoint inhibitor. It can be challenging to diagnose gastrointestinal metastasis in routine radiography; therefore, endoscopic examination, including the small intestine, might be an important option when a lung cancer patient with advanced clinical stage presents with abdominal symptoms, including fecal occult blood.
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http://dx.doi.org/10.1093/jscr/rjac043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858423PMC
February 2022

Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors.

Cancers (Basel) 2022 Feb 2;14(3). Epub 2022 Feb 2.

Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.

Somatostatin analogues (SSAs) are widely used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatostatin receptor 2 (SSTR2) immunoreactivity serves as a predictive marker of the therapeutic efficacy of SSAs in pancreatic NETs. However, SSTR2 expression profiles in tumor cells and their association with the therapeutic efficacy of SSAs remains virtually unknown in gastrointestinal NETs (GI-NETs). Therefore, we evaluated the association between SSTR2 immunoreactivity and embryological origin and proliferative activity in 132 resected surgical tissues of GI-NETs. The correlation between SSAs' therapeutic efficacy and SSTR2 immunoreactivity was evaluated in 14 GI-NETs treated with SSAs. SSTR2 immunoreactivity was evaluated using Volante scores, immunoreactive scores, and digital image analysis (DIA). SSTR2 immunoreactivity was significantly negatively and positively correlated with the Ki-67 labeling index in foregut and hindgut NETs, respectively. In the normal mucosa, neuroendocrine cells in the rectum had significantly lower positive rates of SSTR2 than those in the stomach and duodenum. SSTR2 expression profiles in GI-NETs could differ by primary sites, while the difference of those between foregut and hindgut NETs might be derived from the SSTR2 status of normal neuroendocrine cell counterparts. In addition, DIA could provide a good alternative for predicting response to SSAs in evaluating SSTR2 immunoreactivity of GI-NETs.
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http://dx.doi.org/10.3390/cancers14030775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834049PMC
February 2022

Optimal Conditions for Oxygenated Subnormothermic Machine Perfusion for Liver Grafts Using a Novel Perfusion Device.

Transplant Proc 2022 Mar 3;54(2):217-224. Epub 2022 Feb 3.

Department of Gastroenterological Surgery, Tohoku University Graduate School, Miyagi, Japan.

Background: Liver transplantation from donors after cardiac death (DCD) resolves donor shortages.

Purpose: We investigated the optimal time for subnormothermic oxygenated perfusion in DCD liver transplantation.

Methods: Ten F1 pigs (body weight: 27-32 kg) were allocated to 2 groups: the heart beating group (n = 6), from which livers were retrieved while the heart was beating, and the donation after cardiac death (DCD) group (n = 4), in which liver retrieval was performed on pigs under apnea-induced cardiac arrest for 20 minutes. In both groups, the livers were kept in cold storage for 2 hours after retrieval and perfused with a subnormothermic oxygenated Krebs-Henseleit buffer for 120 minutes. We used a novel perfusion device, which can set maximum perfusion pressures of arteries and portal vein, developed by Asahikawa Medical University and Chuo Seiko Co. Bile production, liver enzymes, and inflammatory cytokines were measured and the sinusoidal space, using tissue specimens taken from liver grafts, was measured at 30, 60, 90, and 120 minutes after the start of perfusion.

Results: Bile production peaked at 90 minutes. Significantly higher levels of liver enzymes and inflammatory cytokines were found in the DCD group (P < .05). The release of liver enzymes peaked at 60 minutes and that of inflammatory cytokines peaked at 90 minutes. The hepatic sinusoidal space was wide at 90 minutes and narrowed after 120 minutes.

Conclusions: The results suggest that subnormothermic oxygenation perfusion may maintain optimal graft condition until around 90 minutes and perfusion for more than 120 minutes may be counterproductive.
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http://dx.doi.org/10.1016/j.transproceed.2021.12.025DOI Listing
March 2022

Randomized phase III trial of intravenous and intraperitoneal paclitaxel with S-1 versus gemcitabine plus nab-paclitaxel for pancreatic ductal adenocarcinoma with peritoneal metastasis (SP study).

Trials 2022 Feb 5;23(1):119. Epub 2022 Feb 5.

Department of Surgery, Kansai Medical University, 2-3-1, Shin-machi, Hirakata, Osaka, 573-1191, Japan.

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ).
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http://dx.doi.org/10.1186/s13063-022-06049-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8817533PMC
February 2022

High Incidence of Lymph-node Metastasis in a Pancreatic-cancer Patient-derived Orthotopic Xenograft (PDOX) NOG-Mouse Model.

Anticancer Res 2022 Feb;42(2):739-743

AntiCancer, Inc., San Diego, CA, U.S.A.;

Background/aim: Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) model. An important goal of PDOX-model development is facile visualization of metastasis in live mice. In the present report we evaluated tumor growth and metastasis in pancreatic cancer PDOX NOG [Non-obese diabetes (NOD)/Scid/IL2Rγ]-and nude-mouse models using red fluorescent protein (RFP)-expressing tumor stroma to visualize the primary tumor and metastasis.

Materials And Methods: A patient-derived pancreatic cancer was initially implanted in transgenic RFP-expressing nude mice. Then, tumor fragments, which acquired RFP expressing stroma while growing in RFP-expressing nude mice were orthotopically implanted in nude and NOG mice. The primary pancreatic tumor and metastasis were observed 8 weeks after implantation.

Results: Lymph-node metastases expressing red fluorescence were detected only in NOG mice. Significantly faster growth of primary pancreatic tumors and a higher incidence of lymph-node metastasis occurred in NOG mice compared to nude mice.

Conclusion: RFP-expressing tumor stroma, which traffics together with cancer cells to lymph nodes, is useful to observe tumor behavior, such as lymph-node metastasis in a PDOX NOG-mouse model which can be used for evaluation of novel anti-metastatic agents, as well as personalized therapy to identify effective drugs.
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http://dx.doi.org/10.21873/anticanres.15532DOI Listing
February 2022

Usefulness of Preoperative Controlling Nutritional Status in Predicting Prolonged Hospitalization and Incidence of Postoperative Delirium for Elderly Hepatectomy with Hepatocellular Carcinoma.

Tohoku J Exp Med 2022 01;256(1):43-52

Department of Surgery, Tohoku University Graduate School of Medicine.

The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing, but it remains unclear whether hepatectomy can be performed using the same criteria as in younger patients. Furthermore, the appropriate preoperative evaluation for hepatectomy in elderly patients is not yet clearly defined. Here, we investigated the applicability of preoperative assessment using the Controlling Nutritional Status (CONUT) score to help improve hepatectomy outcomes in elderly patients with HCC. This was a single-center retrospective analysis, and the study population comprised 64 consecutive patients who underwent hepatectomy for HCC between January 2012 and August 2016. We compared the preoperative assessment and perioperative outcomes between elderly (≥ 75 years old) and younger (< 75 years old) patients. A total of 61 patients were reviewed. Poor preoperative CONUT score was associated with a longer postoperative hospital stay in elderly patients undergoing hepatectomy for HCC. In addition, although elderly patients had similar perioperative outcomes to younger patients, the incidence of delirium was significantly higher, and univariate analysis confirmed that old age is a risk factor for delirium among the preoperative factors. Hepatectomy for HCC in the elderly can be safely performed with appropriate preoperative nutritional assessment using CONUT score and prevention of postoperative delirium. Preoperative nutritional assessment using the CONUT score was useful in predicting prolonged hospitalization for elderly hepatectomy with HCC.
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http://dx.doi.org/10.1620/tjem.256.43DOI Listing
January 2022

Laparoscopic and robot-assisted surgery for adult congenital biliary dilatation achieves favorable short-term outcomes without increasing the risk of late complications.

Surg Today 2022 Jul 26;52(7):1039-1047. Epub 2022 Jan 26.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

Purpose: Minimally invasive surgery (MIS) is the optimal treatment for congenital biliary dilatation (CBD), but few studies on adults have been reported. We compared the postoperative outcomes of MIS with those of open surgery (OS) in adult patients with CBD.

Methods: The subjects of this retrospective study were 36 adult patients who underwent surgery for CBD. We compared the postoperative outcomes of 20 patients who underwent laparoscopic (n = 15) or robotic (n = 5) surgery with those of 16 patients who underwent OS.

Results: MIS was associated with a significantly higher rate of type I (p < 0.001), significantly less blood loss (p < 0.001), a significantly lower rate of internal stents (p = 0.048), significantly longer operation times (p = 0.009), and a significantly shorter postoperative hospital stay (p = 0.007) than OS. The postoperative outcomes of MIS for type I CBD were similar to those of the whole cohort. There were no significant differences in late complications between the groups. The robotic procedure had a significantly shorter operative time than laparoscopic surgery for hepaticojejunostomy (HJ; p = 0.029).

Conclusions: MIS achieved favorable short-term outcomes without compromising mid-term outcomes compared to OS and is appropriate for adult patients with CBD. Robotic HJ may be more ideal than its laparoscopic counterpart.
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http://dx.doi.org/10.1007/s00595-021-02438-8DOI Listing
July 2022
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