Direct splenic vein reconstruction combined with resection of the portal vein/superior mesenteric vein confluence during pancreaticoduodenectomy.

PURPOSE: Splenic vein (SV) ligation combined with portal vein (PV)/superior mesenteric vein (SMV) confluence resection during pancreaticoduodenectomy (PD) is reported to cause left-side portal hypertension (LPH). The purpose of this study was to present our technique of the SV reconstruction and to evaluate the surgical outcomes with/without SV ligation during PD. METHODS: Twenty-four patients undergoing PD with PV and/or SMV resection and being followed over 4 months after surgery between March 2013 and December 2019 in our hospital were evaluated. Resection of the PV/SMV confluence were performed in 14, and SV reconstruction was successfully performed in 3. Presence of LPH was assessed by examining changes in splenic volume, newly venous collateral formation, and platelet counts before and 4-8 months after PD. Surgical technique is the direct anastomosis between SV and PV. RESULTS: Splenic volume ratio was significantly higher in the SV ligation group (n = 11) than in the SV preservation group (n = 13) (median (range) 1.11 (0.57-1.62) vs. 1.68 (1.05-2.22), p < 0.01), but no significant differences were found in the incidence of newly formed venous collaterals or platelet counts between groups. CONCLUSION: SV ligation may represent the cause of LPH after PD combined with resection of PV/SMV confluence. Our simple procedure may help decrease the incidence of LPH.

Rescue Partial ALPPS for Left Hemihepatectomy with Reconstruction of the Middle Hepatic Vein.

Major hepatectomy in patients with insufficient future liver remnant (FLR) volume and impaired liver functional reserve has considerable risks for posthepatectomy liver failure (PHLF). The patient was a male in his 70s with an intrahepatic cholangiocarcinoma in left hemiliver, involving the middle hepatic vein (MHV). Although FLR volume after left hemihepatectomy was estimated to be 64.4% of the total liver volume, an indocyanine green retention rate at 15 min (ICG-R15) value was 24.2%, thus the patient underwent left portal vein embolization. The FLR volume increased to 71.3%; however, the noncongestive FLR volume was re-estimated as 45.8% after resection of the MHV, the ICG-R15 value was 29.0%, and ICG-Krem was calculated as 0.037. We performed partial rescue Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS) for left hemihepatectomy with the MHV reconstruction. On the first stage, partial liver partition was done along Rex-Cantlie's line, preserving the MHV and sacrificing the remaining branches to segment 8. The FLR volume increased to 77.4% on day 14. The ICG-R15 value was 29.6%, but ICG-Krem after MHV reconstruction was estimated to be 0.059. The second-stage operation on day 21 was left hemihepatectomy with the MHV reconstruction using the left superficial femoral vein graft. The usage of rescue partial ALPPS may contribute to preventing PHLF by introducing occlusion of the portal and/or venous branches in the left hemiliver before curative hepatectomy.

Parenchymal-sparing approaches for resection of tumors located in the paracaval portion of the caudate lobe of the liver-utility of limited resection and central hepatectomy.

PURPOSE: Resection of liver cancer involving the paracaval portion (PC) of the caudate lobe is challenging because the PC is located deepest in the liver. This study aimed to elucidate the utility of two parenchymal-sparing approaches of limited resection and central hepatectomy for resecting tumors located in the PC. METHODS: In 2018 and 2020, 12 out of 143 patients underwent hepatectomy for tumors located in the PC of the liver. In six patients, limited resection (LR) of the PC after full mobilization of the liver off the inferior vena cava (IVC) was performed for tumors excluding the hilar plate or large hepatic veins (large HVs), including major hepatic veins or thick short hepatic veins. In six patients, central hepatectomy (CH) using liver tunnel was performed for tumors involving or close to the hilar plate and/or large HVs. RESULTS: During CH, the surgical view of the cranial side of the hilar plate was wide enough to perform combined resection of the large HVs in front of the IVC. Five of the six CHs were performed with resection of the LHVs. No LRs were accompanied with resection of the LHVs. The CH was associated with longer Pringle's time (76 min vs. 29.5 min, p = 0.015) and blood loss (1104 ml vs. 370 ml, p = 0.041). The preserved liver parenchyma volumes were 82% and 95% of the total liver volume after CH and LR, respectively. CONCLUSION: Our parenchymal-sparing approach for resection of liver cancer located in the PC is feasible for curative resection.

Vascular Anatomy of Mesopancreas in Pancreatoduodenectomy Using an Intestinal Derotation Procedure.

BACKGROUND: Mesopancreas excision in pancreatoduodenectomy is technically complicated because of the anatomical complexity of the mesopancreas with the inferior peripancreatic blood vessels which is caused by intestinal rotation in fetal life. We have developed a novel artery-first approach (the intestinal derotation procedure) for facilitating mesopancreas excision. The aim of this study was to clarify the vascular anatomy of the mesopancreas after derotation. METHODS: The right-sided colon and small intestine are mobilized from the retroperitoneum, and the intestinal loop is then derotated. In 136 cases of pancreatoduodenectomy employing the derotation procedure, we analyzed the vascular anatomy of the mesopancreas. RESULTS: After derotation, the anatomy was simplified. The mesopancreas extended from the right aspect of the superior mesenteric artery (SMA), forming a horizontal plane. The first jejunal trunk (FJT) was situated in parallel with the second jejunal artery and was anterior (91%) or posterior (9%) to the SMA. The inferior pancreaticoduodenal vein (IPDV) entered the right side of the FJT (83%) or the superior mesenteric vein (17%). Besides the IPDV, 1-4 tributaries entered the right wall of the FJT, in 89% of cases. The inferior pancreaticoduodenal artery was observed to originate from the right wall of the SMA, sharing a common stem with the first jejunal artery (70%) or branching directly from the SMA (29%). CONCLUSIONS: Intestinal derotation simplifies the mesopancreas anatomy and reveals the anatomical details of the inferior peripancreatic blood vessels in pancreatoduodenectomy.

Use of intercostal trocars for laparoscopic resection of subphrenic hepatic tumors.

BACKGROUND: The aim of this study was to demonstrate the detailed surgical techniques of laparoscopic hepatectomy using intercostal transthoracic trocars for subcapsular tumors located in segment VII or VIII. METHODS: Intercostal transthoracic trocars were used in patients undergoing laparoscopic hepatectomy for tumors located in segment VII or VIII. Following establishment of pneumoperitoneum and placement of abdominal trocars, balloon-tipped trocars were inserted into the abdominal cavity from the intercostal space and through the pleural space and diaphragm. Upon placement of the intercostal trocars, the lung edge was confirmed by ultrasonography and laparoscopic examination. Following minimal mobilization of the right liver, hemispherical wedge resection of segment VII or VIII was performed using the intercostal trocars as a camera port or for the forceps of the surgeon's left hand. After the hepatectomy, the holes in the diaphragm were sutured closed. RESULTS: Among the 79 patients who underwent laparoscopic hepatectomy, intercostal trocars were used in 14 patients for resection of tumors located in segment VII (4 nodules) or VIII (10 nodules). The median (range) operation time and amount of blood loss for hepatectomy were 225 (109-477) min and 60 (20-310) mL, respectively. No postoperative complications associated with hepatectomy or the use of intercostal trocars occurred. CONCLUSIONS: Use of intercostal transthoracic trocars is safe and effective not only for complicated laparoscopic hepatectomy but also for hemispherical wedge resections of subcapsular hepatic tumors located in segment VII or VIII.

Parenchymal-Sparing Hepatectomy Does Not Increase Intrahepatic Recurrence in Patients with Advanced Colorectal Liver Metastases.

BACKGROUND: Prophylactic impact of major hepatectomy (MH) on liver recurrence has yet to be clarified in patients with advanced colorectal liver metastases (CLMs). METHODS: In our institute, parenchymal-sparing hepatectomy (PSH) is a standard procedure for CLMs consistently throughout initial and repeat resection, and MH is selected only in cases in which CLMs are close to major Glisson's pedicles. We reviewed 145 patients who underwent curative hepatectomy for advanced CLMs (≥4 nodules and ≤50 mm in size) from 1999 to 2012. Surgical outcomes and survival were compared between patients who underwent PSH and MH. RESULTS: PSH was performed in 113 patients (77.9 %) and MH in 32 (22.1 %) patients with advanced CLMs. Tumor characteristics and short-term outcomes did not differ between the 2 groups. Incidence of positive tumor margin (8.8 % in PSH vs 9.4 % in MH; p = .927) and rates of liver-only recurrence (43.4 % in PSH and 50.0 % in MH; p = .505) did not differ. No significant differences were found in 5-year overall survival (37.0 % in PSH vs 29.4 % in MH, p = .473), recurrence-free survival (7.6 vs 6.8 %, p = .597), and liver recurrence-free survival (21.0 vs 21.3 %, p = .691). A total of 65 patients had liver-only recurrence, for which repeat hepatectomy was performed in 81.5 % (53 of 65) following our parenchymal-sparing approach. CONCLUSIONS: In patients with advanced CLM, PSH does not increase positive surgical margin or liver recurrence in comparison with MH. A parenchymal-sparing approach offers a high rate of repeat resection for liver recurrence (salvageability).

Rescue of outflow block of the remnant left liver after extended right hemihepatectomy for resection of a tumor in the caudate lobe.

Outflow block of the liver is a life-threatening event after living donor liver transplantation. Herein, we rescued a patient suffering from the outflow block of the remnant left hemiliver caused by bending of the left hepatic vein (LHV) after right hemihepatectomy plus caudate lobectomy combined with resection of the middle hepatic vein (MHV). A metastatic tumor sized 6 cm in the caudate lobe of the liver involving the root of the MHV was found in a 50's year old patient after resection of a right breast cancer eight years ago. Right hemihepatectomy and caudate lobectomy combined with resection of the MHV was performed using a two-stage hepatectomy (partial TIPE ALPPS). On day 1, the total bilirubin value increased to 4.5 mg/dL, and a dynamic computed tomography (CT) scan showed the bent LHV. On the diagnosis of outflow block of the left liver, a self-expandable metallic stent was placed in the LHV using an interventional approach, and the pressure in the LHV decreased from 27 cmH2O to 12 cmH2O. The bilirubin value decreased to 1.2 mg/dL on day 3. Outflow block of the LHV can happen after extended right hemihepatectomy with resection of the MHV. Early diagnosis and interventional stenting treatment can rescue the patient from congestive liver failure.

Intracellular environment-responsive stabilization of polymer vesicles formed from head-tail type polycations composed of a polyamidoamine dendron and poly(L-lysine).

For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.

Right hemihepatectomy preserving the fluorescently visible paracaval portion of the caudate lobe.

The paracaval portion (PC) of the caudate lobe is a small area of the liver located in front of the inferior vena cava. Conventional right hemihepatectomy (RH) along the Rex-Cantlie line involves resection of not only the anterior and posterior sections but also the PC behind the middle hepatic vein (MHV). However, to preserve the future liver remnant volume as much as possible, PC-preserving RH may be beneficial in selected patients. We injected an indocyanine green (ICG) solution in the PC portal branch under intraoperative ultrasonography (IOUS) guidance and performed an RH preserving the fluorescently visible PC in a patient with liver metastasis. The patient was a 47-year-old male with a 24 ×10 cm metastatic hepatic tumor from sigmoid colon cancer. CT volumetry revealed that the left hemiliver excluding the caudate lobe was 55%, and the caudate lobe was 5.3%. Before hepatic transection, the ICG solution was injected into the PC portal branch under IOUS guidance. During hepatic transection, the PC was identified as a fluorescent area behind the MHV using a near-infrared imaging system. Thus, the anatomical right-side boundary of the caudate lobe was clearly found. Following RH, the PC was preserved as a fluorescently visible area. The patient had an uneventful recovery. RH preserving the fluorescently visible PC of the liver is a feasible procedure.

A multicenter validation study for determining the condition of nonanatomical or minor anatomical hepatectomies satisfying technical difficulty of current high-level hepatectomy certificated by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: The current high-level hepatectomy (HLH) is certified by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS), comprising only anatomical hepatectomies above Couinaud's segmentectomy. This multicenter study aimed to identify the conditions of non-HLH that satisfy equivalent technical difficulties to HLH. METHODS: Between 2018 and 2021, 595 first open hepatectomies without biliary reconstruction (374 HLHs and 221 non-HLHs) were performed in the five institutions. Non-HLHs belonging to at least one of the three conditions; depth of hepatectomy ≥5 cm, number of resections ≥3 locations and at least one location with a depth of hepatectomy ≥3 cm, and hepatectomy involving the paracaval portion of the caudate lobe was proposed as the candidate for difficult non-HLH. The technical difficulty was estimated by the operative time and blood loss. RESULTS: Difficult non-HLHs were neither associated with shorter operative time (373 min vs. 354 min, p = .184) nor lesser blood loss than those with HLHs (503 mL vs. 436 mL, p = .126). Postoperative complications such as Clavien-Dindo classification grade III or more were not significant between the two groups (18.6% vs. 13.4%, p = 0212). CONCLUSIONS: Difficult non-HLHs were associated with no lesser technical difficulty than those with HLH.

A Prospective Study of Neoadjuvant Gemcitabine Plus Nab-paclitaxel in Patients with Borderline-resectable Pancreatic Cancer.

Objectives Neoadjuvant therapy followed by radical resection improves the borderline-resectable pancreatic cancer (BRPC) prognosis; however, the optimal therapeutic regimen remains unclear. Gemcitabine plus nab-paclitaxel (GnP) showed a high anti-tumor effect in primary lesions in a prospective study for metastatic disease. However, evidence concerning its feasibility is still lacking in patients with BRPC. We therefore evaluated the tolerability of neoadjuvant GnP (NAC-GnP) for BRPC. Methods This single-center prospective study evaluated 10 patients with BRPC who were treated with two cycles of NAC-GnP. The primary endpoint was feasibility for NAC-GnP. Treatment feasibility was defined as a successful outcome in at least eight patients. Results Ten patients who had BRPC in contact with the celiac artery (n=5), superior mesenteric artery (n=3), or hepatic artery (n=2) were enrolled. The median age was 75 (range, 40-82) years old. Grade 3 anorexia and grade 2 pneumonia occurred in one patient each, so treatment was feasible in eight patients. The median primary tumor reduction and response rates were 33% (range, 0-68%) and 60%, respectively. Six of eight patients who had abnormal CA19-9 levels at the time of enrolment showed a decrease in CA19-9 levels, with a median decrease of 72%. Five patients underwent radical resection, including R0 resection in four. Postoperative grade IIIa Clavien-Dindo complications occurred in one patient (upper gastrointestinal bleeding and pancreatic fistula). Conclusion Two-cycle NAC-GnP is a feasible treatment for patients with BRPC. Further studies on NAC-GnP in patients with BRPC are warranted.

Trends in the surgical treatment for pancreatic cancer in the last 30 years.

Pancreatic cancer has the poorest prognosis among digestive cancers. During the 1990s, the 5-year survival rate of surgical patients with pancreatic cancer was 14% in Japan. However, survival rates have increased to 40% in the 2020s due to the refinement of surgical procedures and the introduction of perioperative chemotherapy. Several pivotal randomized controlled trials have played an indispensable role to establish each standard treatment strategy. Resectability of pancreatic cancer can be classified into resectable, borderline resectable, and unresectable based on the anatomic configuration, and multidisciplinary treatment strategies for each classification have been revised rapidly. Investigation of superior perioperative adjuvant treatments for resectable and borderline resectable pancreatic cancer and the establishment of optimal conversion surgery for unresectable pancreatic cancer are the progressive subjects.

Predictive factors for subsequent intrahepatic cholangiocarcinoma associated with hepatolithiasis: Japanese National Cohort Study for 18 years.

BACKGROUND: Predictive factors for intrahepatic cholangiocarcinoma in long-term follow-up of hepatolithiasis are unknown. We thus conducted a cohort study to investigate the predictive factors for developing intrahepatic cholangiocarcinoma in hepatolithiasis. METHODS: This cohort is comprised of 401 patients registered in a nationwide survey of hepatolithiasis for 18 years of follow-up. Cox regression analysis was used to elucidate predictive factors for developing intrahepatic cholangiocarcinoma. RESULTS: The median follow-up period of patients was 134 months. Twenty-two patients developed intrahepatic cholangiocarcinoma and all died. Identified independent significant factors were as follows: age 63 years or older (hazard ratio [HR] 3.344), residual stones at the end of treatment (HR 2.445), and biliary stricture during follow-up (HR 4.350). The incidence of intrahepatic cholangiocarcinoma in patients with three factors was significantly higher than that in patients with one or two factors. The incidence in the groups with one or two predictive factors was not different. In 88.9% of patients with both biliary stricture and intrahepatic cholangiocarcinoma, the duration between the diagnoses of biliary stricture and intrahepatic cholangiocarcinoma was ≥ 5 years. However, once intrahepatic cholangiocarcinoma developed, 77.8% of patients died within 1 year. Of 24 patients with no symptoms, no previous choledocoenterostomy, no signs of malignancy, no biliary stricture, and no treatment for hepatolithiasis during follow-up, only one developed intrahepatic cholangiocarcinoma. CONCLUSIONS: Regarding carcinogenesis, complete stone clearance and releasing biliary stricture can prevent the development of intrahepatic cholangiocarcinoma and improve the prognosis of hepatolithiasis.

Bisegmentectomy and venous reconstruction after portal vein embolization for the remnant hemiliver in a patient with recurrent colorectal liver metastases.

Repeat hepatectomy for recurrent colorectal liver metastases (CRLM) for the remnant hemiliver is sometimes challenging due to the insufficient future liver remnant (FLR) volume. We present an aggressive strategy for resection of the recurrent CRLM involving bisegmentectomy of the remnant right hemiliver with the aid of portal vein embolization (PVE) and venous reconstruction. The patient was a 50-year-old woman who had undergone left hemihepatectomy for a CRLM 10 months ago. Three metastatic tumors were found in the remnant segments 7 and 8 (S7&8) of the liver, and one of them involved the right hepatic vein (RHV). Conducting bisegmentectomy of S7&8 with resection of the RHV, the non-congestive FLR volume was calculated as 34.9% of the remnant total liver volume, which was deemed insufficient considering the mild liver damage after repeated chemotherapy. After trans-ileocecal PVE of the portal branches in S7&8 in a hybrid angio room, the non-congestive FLR volume increased to 42.3%, which could be further advanced to 58.0% if the RHV was reconstructed. Segmentectomies of S7&8 with resection and reconstruction of the RHV using the right superficial femoral vein graft was performed. The patient was discharged without any complications, and the postoperative computed tomography (CT) scan showed the good patency of the reconstructed venous graft. Aggressive segmentectomies and venous reconstruction of the remnant hemiliver after PVE might be a new strategy to overcome the insufficient FLR volume.

Trends in the treatment of pancreatic cancer in Japan.

Pancreatic cancer is known to have the poorest prognosis among digestive cancers. With the development of new chemotherapeutic agents and introduction of multidisciplinary therapy, however, the treatment outcomes for pancreatic cancer have dramatically improved over the past two decades. The keys to successful treatment will be accurate assessment of resectability [resectable (R), borderline resectable (BR) or unresectable (UR)] at the time of diagnosis and prompt adoption of an appropriate multidisciplinary treatment strategy. Prep-02/JSAP-05 trial which is an RCT of upfront surgery versus neoadjuvant chemotherapy using GEM and S-1 (GS) and subsequent surgery for R-PDAC in Japan indicated neoadjuvant chemotherapy had a longer overall survival (OS) than those undergoing upfront surgery (36.7M vs. 26.6M, p = 0.015). In a retrospective multicenter study in Japan reported that in BR-PDAC, median survival time (MST) in the pretreatment group was significantly better than that in the upfront surgery group (25.7 months vs. 19.0 months, p = 0.015) according to a propensity score matching analysis. Another retrospective multicenter study with UR-LA PDAC in Japan reported that conversion surgery was more beneficial for patients with more than 8 months of preoperative therapy than those with less than 8 months of that therapy. Various clinical trials on pancreatic cancer are ongoing, and the results of trials on chemotherapeutic regimens and multidisciplinary treatments will be of further interest.

Double-Volume Intraoperative Lavage Reduce Bacterial Contamination After Pancreaticoduodenectomy.

BACKGROUND: To clarify whether double-volume peritoneal lavage can decrease the risk of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy. MATERIALS AND METHODS: Forty-nine patients who underwent pancreaticoduodenectomy and intraoperative peritoneal lavage using 6000 mL of saline before abdominal closure were studied retrospectively. Bacterial cultures of the lavage fluid were taken twice, after irrigation using 3000 mL of saline and then after an additional 3000 mL of saline. Bacterial culture of the drainage fluid was taken on day 1, and the relationship between the results of bacterial cultures and clinically relevant postoperative pancreatic fistula was examined. RESULTS: Double amount of peritoneal lavage significantly decreased the incidence of positive bacterial cultures than single amount of peritoneal lavage (45% vs. 29%, P < .05). Multivariate analysis showed that positive bacterial culture of drainage fluid on day 1 and main pancreatic duct size (<3 mm) were independent risk factors for clinically relevant postoperative pancreatic fistula. A positive bacterial culture of the final lavage fluid and preoperative biliary drainage were independent factors related to a positive bacterial culture on day 1. DISCUSSION: A positive bacterial culture on day 1 is an independent risk factor for clinically relevant postoperative pancreatic fistula during pancreaticoduodenectomy. Double-volume intraperitoneal lavage may be effective for reducing the incidence of clinically relevant postoperative pancreatic fistula.

Optimal Lymphadenectomy of the Mesopancreas Based on Fluorescence Imaging During Pancreaticoduodenectomy.

BACKGROUND: Excision of the mesopancreas with lymphadenectomy is an important component of pancreatoduodenectomy. However, the optimal extent of lymphadenectomy remains unclear. Furthermore, accurate description of the mesopancreatic lymphatic pathways is difficult, probably because of the complex anatomy. Intestinal derotation simplifies the anatomy and facilitates both examination of lymphatic flow and the surgical procedure. The aim of this study was to evaluate lymphatic flow in the mesopancreas using indocyanine green fluorescence imaging with an intestinal derotation technique, and to clarify the optimal extent of mesopancreas excision and lymphadenectomy in pancreatoduodenectomy. METHODS: Indocyanine green solution (2.5 × 10-3 mg) was injected into the pancreatic head parenchyma. After intestinal derotation, the spread of indocyanine green was observed using near-infrared imaging. RESULTS: Participants comprised 10 patients who underwent pancreatoduodenectomy for periampullary neoplasms. With indocyanine green fluorescence imaging, 9 of the 10 patients showed lymphatic flow from the pancreatic head to the superior mesenteric artery via the inferior pancreaticoduodenal artery and first jejunal artery (but not via the second and more distant arteries), with eventual drainage into the paraaortic region. CONCLUSIONS: Lymphatic pathways from the pancreatic head were connected to the superior mesenteric artery via the inferior pancreaticoduodenal artery and first jejunal artery. Excision of the mesopancreas with the inferior pancreaticoduodenal artery and first jejunal artery while preserving the second or more distant arteries appears optimal in pancreatoduodenectomy for periampullary malignancies.