Satoshi Ogiso

Intraoperative Ultrasonography of Laparoscopic Hepatectomy: Key Technique for Safe Liver Transection

@However, significant bleeding is more difficultto control during laparoscopic hepatectomy than duringan open approach, so prevention of vascular injury iscrucial. This should be achieved not only through anexcellent preoperative understanding of the vascular anat-omy derived from preoperative imaging, but also throughreal-time image guidance during surgery. Some proce-dures, such as posterosuperior segmentectomy (Sg7 orSg8) and limited resection for deeply located liver tumors,require expert laparoscopic hepatectomy techniques. Forthese procedures, accurate real-time imaging of liver anat-omy and a thought-out operative resection plan are neces-sary, and today this is accomplished with the use ofintraoperative ultrasound image.Intraoperative ultrasonography (IOUS) has beenreported as a useful tool for open liver surgery.

Keratin 19, a Cancer Stem Cell Marker in Human Hepatocellular Carcinoma

Purpose: Keratin 19 (K19) is a known marker of poor prognosis and invasion in human hepatocellular carcinoma (HCC). However, the relationship between K19 and cancer stem cells (CSCs) is unclear. Here, we determined whether K19 can be used as a new CSC marker and therapeutic target in HCC. Experimental Design: HCC cell lines were transfected with a K19 promoter–driven enhanced green fluorescence protein gene. CSC characteristics, epithelial–mesenchymal transition (EMT), and TGFb/Smad signaling were examined in FACS-isolated K19+/K19− cells. K19 and TGFb receptor 1 (TGFbR1) expression in 166 consecutive human HCC surgical specimens was examined immunohistochemically. Results: FACS-isolated single K19+ cells showed self-renewal and differentiation into K19− cells, whereas single K19− cells did not produce K19+ cells. K19+ cells displayed high proliferation capacity and 5-fluorouracil resistance in vitro. Xenotransplantation into immunodeficient mice revealed that K19+ cells reproduced, differentiated into K19− cells, and generated large tumors at a high frequency in vivo. K19+ cells were found to be involved in EMT and the activation of TGFb/Smad signaling, and these properties were suppressed by K19 knockdown or treatment with a TGFbR1 inhibitor. The TGFbR1 inhibitor also showed high therapeutic effect against K19+ tumor in the mouse xenograft model. Immunohistochemistry of HCC specimens showed that compared with K19− patients, K19+ patients had significantly poorer recurrence-free survival and higher tumor TGFbR1 expression. Conclusions: K19 is a new CSC marker associated with EMT and TGFb/Smad signaling, and it would thus be a good therapeutic target for TGFbR1 inhibition. Clin Cancer Res; 21(13); 3081–91. ©2015 AACR.

Laparoscopic transabdominal with transdiaphragmatic access improves resection of difficult posterosuperior liver lesions

OBJECTIVE We describe the technical details and evaluate the safety, feasibility, and usefulness of a combined lateral and abdominal (CLA) approach for laparoscopic resection of liver segments 7 and 8. BACKGROUND Laparoscopic resection of lesions in the posterosuperior area of segments 7 and 8 is technically challenging, and currently there is no standardized laparoscopic approach. METHODS Through review of a prospectively maintained database, we identified 44 patients who underwent laparoscopic resection of lesions in segment 7 or 8. Twenty-five patients required the CLA approach because their lesions were more posterosuperior and intraparenchymal; 19 patients underwent resection with a regular abdominal-only approach of more accessible anteroinferior lesions. We reviewed operative details and video footage of these operations and compared the outcomes of the 2 groups. RESULTS In the group treated with the CLA approach, deep location was more frequent (88% vs 42%; P = 0.035), median tumor diameter was larger (24.5 mm vs 15 mm; P = 0.114), and the median weight of the excised parenchyma was greater (56.5 g vs 23 g; P = 0.093). Median operative time was longer in the CLA approach group (217.5 minutes vs 165 minutes; P = 0.046), but blood loss, rate of conversion to open surgery, surgical margin status, morbidity, and mortality were similar between the 2 groups. CONCLUSIONS The CLA approach permits safe laparoscopic resection of lesions in the posterosuperior area of segments 7 and 8, allowing surgeons to overcome the difficulties of limited visualization and access to the target lesions.

SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma.

The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9− cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9− cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9− patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCC-CSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC.

Introduction of laparoscopic low anterior resection for rectal cancer early during residency: a single institutional study on short-term outcomes

BackgroundLaparoscopic surgery for rectal cancer is unpopular because it is technically challenging. Suitable training systems have not been widely studied or established despite the steep learning curve for this procedure. We developed a systematic training program that enables resident surgeons to perform laparoscopic low anterior resection (LLAR) for rectal cancer and evaluated the safety and feasibility of this training program.MethodsWe analyzed prospectively gathered data on all LLARs for rectal cancer performed at a single center over a 7-year period. Patients were assessed for demographic characteristics, tumor characteristics, operative procedure, operative time, blood loss, conversion to open surgery, complications, time to bowel recovery, distal margin, and number of lymph nodes harvested. We compared the early surgical, oncological, and functional outcomes of LLARs performed by expert surgeons with those of LLARs performed by resident surgeons for both intraperitoneal and extraperitoneal rectal cancer. All analyses were performed on an intention-to-treat basis.ResultsA total of 137 patients met the inclusion criteria for this study. Of the 75 LLARs for intraperitoneal rectal cancer, 40 were performed by expert surgeons (I-E group) and 35 by resident surgeons (I-R group). Of the 62 LLARs for extraperitoneal rectal caner, 51 were performed by expert surgeons (E-E group) and 11 by resident surgeons (E-R group). The operative time was longer in the E-R group than in the E-E group. The time to resumption of diet was longer in the I-E group than in the I-R group. The other early outcomes, including blood loss, anastomotic leakage, conversion to open surgery, and number of lymph nodes harvested, were similar in the I-E and I-R groups and in the E-E and E-R groups.ConclusionOur systematic training program on LLAR for rectal cancer enables resident surgeons to perform this procedure safely early during residency, with acceptable short-term outcomes.

Techniques of intragastric laparoscopic surgery

Benign or pre-cancerous lesions and foreign bodies of the stomach not amendable to endoscopic removal often require extensive surgery to address a process that does not necessitate lymph node sampling or formal gastrectomy. These lesions are particularly difficult to address endoscopically when located at the esophagogastric junction as a retroflexed view is needed. From its first description in 1995, intragastric laparoscopic surgery has evolved with respect to both technological advancements and tactical innovations. Here we report the development of four distinct techniques of laparoscopic intragastric surgery which we have developed over time and applied in 11 patients. These techniques consist of a (1) combined gastroscopic/laparoscopic approach when minimal manipulation of the lesion is needed, (2) multiport resection which provides optimal triangulation and allows for resection of more complex lesions, (3) stapled removal of broad-based lesions, and (4) single access technique with the device placed directly through the abdominal wall into the stomach. The techniques expand the surgeon’s armamentarium to address more complex intragastric processes safely, while the typical postoperative benefits of minimal access surgery such as fast recovery time and less pain are preserved. As we gain greater experience with intragastric laparoscopic surgery, this technique holds the promise of becoming a standard surgical technique for benign lesions for which it is oncologically safe to perform a limited resection.

Laparoscopy-Specific Surgical Concepts for Hepatectomy Based on the Laparoscopic Caudal View: A Key to Reboot Surgeons’ Minds

AbstractBackground Despite diffusion of laparoscopic hepatectomy, the acquisition of necessary skills is not easy for open liver surgeons. Concepts and techniques have totally changed in laparoscopic hepatectomy compared with open hepatectomy, which is an underlying cause of a technical hurdle in laparoscopic hepatectomy. This study aimed to illustrate laparoscopy-specific concepts and techniques for hepatectomy.MethodsVideo footages of laparoscopic and open hepatectomies stored in the Institut Mutualiste Montsouris and Kyoto University were reviewed to define the differences in surgical view, surgical concept, and technical details, using left lateral sectionectomy (LLS) and right hepatectomy (RH) as representative examples.ResultsBy comparison with open LLS and RH, laparoscopy-specific procedures were identified with regard to surgical view, parenchymal transection, available landmarks, and vascular dissection. By laparoscopy, the surgical field was constantly viewed and accessed from the caudal side to the cranial side. Similarly, the parenchyma was divided, and intrahepatic vessels were dissected in the same direction. Laparoscopy-specific landmarks were identified for both LLS and RH, behind the liver.ConclusionsThe concepts and techniques in laparoscopic hepatectomy are totally different from those of open hepatectomy because of the different surgical views. Understanding the laparoscopy-specific concepts and techniques would facilitate safe and efficient execution of laparoscopic hepatectomy.

Laparoscopic two-stage hepatectomy for bilobar colorectal liver metastases.

Despite the gradual diffusion of laparoscopic liver resection, the feasibility and results of laparoscopic two‐stage hepatectomy (TSH) for bilobar colorectal liver metastases (CRLM) have not been described frequently. This study aimed to evaluate the feasibility, safety and oncological outcomes of laparoscopic TSH for bilobar CRLM.

Successful treatment of gastric perforation with thyrotoxic crisis

Patients with thyrotoxic crisis presenting with another emergency are at a considerable risk. We report the successful treatment of a 55-year-old woman having gastric perforation with thyrotoxic crisis; the principle of treatment was delayed surgery after rapid preoperative restoration of thyroid function and cardiovascular status. The patient was admitted for severe abdominal pain and nausea with delirium, exophthalmos, diffuse goiter, tremulousness, diaphoresis, tabescence, pretibial edema, and atrial fibrillation. Computed tomography revealed free air over the liver surface. She had been diagnosed with uncontrolled hyperthyroidism 3 days before admission, with a free liothyronine (T(3)) of 23.2 pg/mL, a free levothyroxine sodium (T(4)) of greater than 7.78 ng/dL, and thyrotropin of less than 0.01 ng/mL. She was diagnosed with gastroduodenal perforation and thyrotoxic crisis, and we planned nonoperative management comprising nasogastric aspiration, cefmetazole sodium, omeprazole, thiamazole, and Lugols solution. We also used landiolol, an ultrashort-acting beta(1)-adrenoceptor antagonist, and hydrocortisone. On the third day of admission, her thyroid function had improved with a free T(3) of 4.7 pg/mL and a free T(4) of 2.9 ng/dL; however, perforative peritonitis had worsened, and hence, omental patch repair was performed. She recovered uneventfully and was discharged after radioiodine administration. We discuss the management of a thyrotoxic patient with gastric perforation and focus on the importance of changing the management according to the patients clinical course considering his thyroid function status and comparing the stress of surgery with that of perforative peritonitis in nonoperative management.

Efficient recellularisation of decellularised whole-liver grafts using biliary tree and foetal hepatocytes

A whole-organ regeneration approach, using a decellularised xenogeneic liver as a scaffold for the construction of a transplantable liver was recently reported. Deriving suitable scaffolds was the first step towards clinical application; however, effective recellularisation remains to be achieved. This report presents a strategy for the improvement of the recellularisation process, using novel cell-seeding technique and cell source. We evaluated recellularised liver grafts repopulated through the portal vein or the biliary duct with mice adult hepatocytes or E14.5 foetal hepatocytes. More than 80% of the cells seeded through the biliary tree entered the parenchyma beyond the ductule-lining matrix barrier and distributed throughout the liver lobule. In contrast, about 20% of the cells seeded through the portal tree entered the parenchyma. The gene expression levels of foetal hepatocyte albumin, glucose 6-phosphatase, transferrin, cytokeratin 19, and gamma-glutamyl transpeptidase were increased in three-dimensional cultures in the native liver-derived scaffolds, and the activation of liver detoxification enzymes and formation of biliary duct-like structures were supported. The metabolic functions of liver grafts recellularised with different cell types were similar. These results suggest that biliary tree cell-seeding approach is promising, and that liver progenitor cells represent a good cell source candidate.