Association of Familial Fanconi Syndrome with a Novel GATM Variant.

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.

Fracture strength and behavior of resin-faced CAD/CAM anterior crowns.

The fracture strength and behavior of a novel resin-faced computer-aided design/computer-aided manufacturing (CAD/CAM) crown were investigated to evaluate application to the anterior teeth. Resin-faced CAD/CAM crowns were fabricated by arranging a resin composite on a frame prepared from a CAD/CAM resin block. The fracture strength was evaluated after 24 h of complete polymerization (day 0) and after water immersion for 30 days (day 30). Uniaxial loading was applied to the center point between the incisal edge and cingulum (loading point 1) or at 1.5 mm from the incisal edge (loading point 2). There was no significant difference in the fracture strength of the resin-faced CAD/CAM crowns between day 0 and 30 at loading point 1. At loading point 2, they exhibited decreased fracture strength after water immersion; however, the mean strength was still >1 kN. This novel crown showed good mechanical properties to serve as a prosthesis for the anterior teeth.

An anatomical review of various superior mesenteric artery-first approaches during pancreatoduodenectomy for pancreatic cancer.

When pancreatic head cancer invades the superior mesenteric artery (SMA), attempts at curative resection are aborted. Preoperative imaging diagnostics to determine the surgical curability have yet to surpass the intraoperative information acquired via inspection, palpation, and trial dissection. Pancreatoduodenectomy (PD) is a standard measure for treating periampullary cancers. In conventional PD, SMA invasion is usually identified by dissecting the retroportal lamina, which connects the uncinate process and SMA nerve plexus after dividing the neck of the pancreas. During PD for pancreatic head cancer, this retroperitoneal margin frequently vitiates surgical curability. SMA-first approaches during PD are methods where the SMA is dissected first by severing the posterior pancreatic capsule to assess the SMA involvement of pancreatic cancer early in the operation. The first report of such an approach prompted subsequent reports of various maneuvers that are now known collectively as "artery-first" approaches. We herein review those approaches by classifying them according to (1) the side of the mesocolon from where the SMA approach occurs (supracolic or infracolic) and (2) the direction of access (right or left and anterior or posterior). The steps of the reported PD procedures are numbered according to a timeline and summarized using anatomical division of the SMA.

Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome.

Nephrotic syndrome (NS) is a renal disease characterized by severe proteinuria and hypoproteinemia. Although several single-gene mutations have been associated with steroid-resistant NS, causative genes for steroid-sensitive NS (SSNS) have not been clarified. While seeking to identify causative genes associated with SSNS by whole-exome sequencing, we found compound heterozygous variants/mutations (c.524T>C; p.I175T and c.662G>A; p.R221H) of the interleukin-1 receptor accessory protein (IL1RAP) gene in two siblings with SSNS. The siblings' parents are healthy, and each parent carries a different heterozygous IL1RAP variant/mutation. Since IL1RAP is a critical subunit of the functional interleukin-1 receptor (IL-1R), we investigated the effect of these variants on IL-1R subunit function. When stimulated with IL-1ß, peripheral blood mononuclear cells from the siblings with SSNS produced markedly lower levels of cytokines compared with cells from healthy family members. Moreover, IL-1R with a variant IL1RAP subunit, reconstituted on a hematopoietic cell line, had impaired binding ability and low reactivity to IL-1ß. Thus, the amino acid substitutions in IL1RAP found in these NS patients are dysfunctional variants/mutations. Furthermore, in the kidney of Il1rap-/- mice, the number of myeloid-derived suppressor cells, which require IL-1ß for their differentiation, was markedly reduced although these mice did not show significantly increased proteinuria in acute nephrotic injury with lipopolysaccharide treatment. Together, these results identify two IL1RAP variants/mutations in humans for the first time and suggest that IL1RAP might be a causative gene for familial NS.

Pancreaticogastrostomy after pancreaticoduodenectomy without suturing the pancreas.

The aim of the present paper was to describe a new and easy technique for performing pancreaticogastrostomy (PG) through simple pancreatic invagination by a single binding suture without suturing the pancreatic parenchyma. The present study included all consecutive patients who underwent elective pancreaticoduodenectomy from 2007 to 2015. The intraoperative and postoperative outcomes after PG (PG group) were compared with those of patients who underwent pancreaticojejunostomy (PJ) (PJ group). Out of 270 patients, 88 PG and 182 PJ patients were assessed. The rate of clinically significant PF was similar between the PG and PJ groups (10.2% vs. 13.2%, respectively; p = 0.487), despite the risk of pancreatic fistula being higher in the PG group. There were no significant differences in the intraoperative and postoperative outcomes or mortality between the groups. This easy invagination technique for PG is simple, safe and reproducible with a low risk of postoperative pancreatic fistula.

Repeat hepatectomy for patients with recurrent neuroendocrine liver metastasis: Comparison with first hepatectomy.

BACKGROUND: The value of repeat hepatectomy for intrahepatic recurrence after curative resection of neuroendocrine liver metastasis (NELM) remains unclear. The aim of this retrospective cohort study was to determine the significance of repeat hepatectomy for recurrent NELM. METHODS: Patients who underwent hepatectomy for NELM between 1994 and 2016 were identified. The indications for a first hepatectomy were adequate liver remnant volume and no extrahepatic metastasis. The diagnosis of recurrent NELM was based on radiographic examinations. The indications for a repeat hepatectomy were the same as those for the first hepatectomy. Clinicopathologic factors, short-term survival, and long-term survival were investigated using clinical records. RESULTS: Forty-four patients enrolled in this study. Thirty-three patients among them underwent a curative hepatectomy, and 28 of them developed recurrence. Of them, 16 patients underwent a repeat hepatectomy. The overall survival of the repeat hepatectomy cohort (n = 16) was significantly better than that of the no repeat hepatectomy cohort (n = 12) (P < .001). The progression free survival after the first hepatectomy (n = 44) and that after repeat hepatectomy (n = 16) were similar (P = .546). No significant difference was seen between the frequency of major complications (Clavien-Dindo score ≥ 3a) after the first and repeat hepatectomy (P = .279). No repeat hepatectomy (hazard ratio [HR] 5.0, P = .036) was identified as an independent predictive factor of a poor outcome among the recurrent cohort, along with the presence of multiple nodules (HR 26.2, P = .008) and a CA19-9 level ≥40 U/mL (HR 11.2, P = .012). CONCLUSIONS: A repeat hepatectomy is feasible in selected patients with recurrent NELM.

[Portal venous stent placement for variceal hemorrhage in the elevated jejunum caused by portal vein stenosis after pancreatoduodenectomy:a case report].

An 86-year-old male underwent pancreatoduodenectomy with resection and reconstruction of portal vein for pancreatic cancer. He was admitted to our hospital because of severe anemia and dyspnea ten months later. Computed tomography showed varices at the biliary-enteric anastomosis in the elevated jejunum caused by portal venous stenosis, which was suspected as the cause of anemia. Therefore, the patient underwent balloon dilatation of the portal vein followed by stent placement and coil embolization of the collaterals using a transileocolic portal vein approach. After the procedure, portal venous flow was improved, and the collaterals disappeared. The patient has been asymptomatic with no recurrence for three years and four months.

[A Case of Resection of Advanced Pancreatic Adenosquamous Carcinoma in which Multidisciplinary Treatment Was Effective].

A 72-year-old man with general fatigue was referred, and CT and MRI revealed a pancreatic mass with necrosis that was suspected of invading the stomach, splenic artery, celiac artery, liver, and portal vein. Upper gastrointestinal endoscopy showed an extrinsic mass with ulcer formation in the posterior wall of the upper gastric corpus and irregular mucosa in the lower esophagus incidentally. Biopsy showed squamous cell carcinoma from both lesions, leading to the diagnosis of pancreatic adenosquamous carcinoma and early esophageal cancer. We performed distal pancreatectomy with splenectomy, total gastrectomy, partial hepatectomy, superior mesenteric-portal vein resection, and reconstruction. The pathological results revealed pancreatic adenosquamous carcinoma and infiltration of cancer cells at the dissected peripancreatic margin. Therefore, we administered radiotherapy(50.4 Gy to the retroperitoneal region)in postoperative month 2. Endoscopic mucosal resection was performed for the early stage esophageal cancer lesion in postoperative month 5. Three courses of S-1 were administered as adjuvant therapy since postoperative month 7, and he is currently alive without recurrence 1 year and 8 months after surgery. Multidisciplinary treatment can be effective for locally advanced pancreatic adenosquamous carcinoma.

Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment.

No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.

[A Case of Double Cancer of Intrahepatic Cholangiocarcinoma and Gastric Carcinoma with Difficult Diagnosis of the Primary Tumor with Peritoneal Metastasis].

Double cancer of intrahepatic cholangiocarcinoma and gastric cancer is rare. A 62-year-old man underwent gastrectomy for gastric cancer. The pathological findings were tub1>tub2, m, ly0, v0, n0, Stage I A. Two years and a month later, a liver tumor(diameter of 3 cm)and a pelvic mass(diameter of 2.5 cm)were observed. Metastasis from gastric cancer was suspected and chemotherapy(SOX)was administered. However, after 5 courses, CT revealed worseningof the liver tumor (diameter of 12 cm)and pelvic mass(diameter of 3 cm). Intrahepatic cholangiocarcinoma and its peritoneal metastasis were also suspected. There was a limit to treatment with chemotherapy, and it was difficult to judge whether to target gastric cancer or intrahepatic cholangiocarcinoma for chemotherapy. In addition, the lesions were localized in the right lobe of the liver and the pelvis. Therefore, we decided to perform resection. As a second-stage operation, pelvic mass extraction and portal vein embolization were performed first. The pathological result of the pelvic mass assessment was mucinous carcinoma. Subsequently, expansive right hepatectomy was performed. The pathological findings were also suggestive of mucinous carcinoma, which was finally diagnosed as intrahepatic cholangiocarcinoma and peritoneal dissemination. Six months after the surgery, several recurrent nodules were observed in the pelvis and GEM plus CDDP was initiated. Currently, 1 year after surgery, there are no restrictions in the activities of daily life of the patient and he is treated on an outpatient basis.

Dramatic response after functional hemispherectomy in a patient with epileptic encephalopathy carrying a de novo COL4A1 mutation.

We describe the first case of a successful functional hemispherectomy in a patient with epileptic encephalopathy and a de novo collagen type IV alpha 1 (COL4A1) mutation. A 4-year-old girl was COL4A1 mutation-positive and suffered from drug-resistant epilepsy, hemiplegia, and developmental delay. Magnetic resonance imaging detected no porencephaly, and she had no cataract or renal abnormality. Following a presurgical evaluation for epilepsy, she underwent a functional hemispherectomy. She has been seizure free with no intracranial hemorrhage or other perioperative complications. Patients with a COL4A1 mutation have an increased risk for intracranial hemorrhage because of disrupted integrity in the vascular basement membrane due to the mutation. After weighing the risks and benefits to these patients, epilepsy surgery may not be absolutely contraindicated. Furthermore, pediatric neurologists should be aware of an undiagnosed COL4A1 mutation when a patient presents with an unexplained neurological phenotype, such as mild hemiparesis, even in the absence of porencephaly.

Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels.

Hepatocellular carcinoma (HCC) commonly develops in patients with liver fibrosis; in these patients, the blood levels of lysophosphatidic acid (LPA) and its generating enzyme autotaxin (ATX) increase with the liver fibrosis stage. We aimed to examine the potential relevance of ATX and LPA in HCC. Fifty-eight HCC patients who underwent surgical treatment were consecutively enrolled in the study. Among the LPA receptors in HCC, higher LPA2 mRNA levels correlated with poorer differentiation, and higher LPA6 mRNA levels correlated with microvascular invasion, which suggested a higher malignant potential of HCC with increased LPA2 and LPA6 expression. In patients with primary HCC, neither LPA2 nor LPA6 mRNA levels were associated with recurrence. However, when serum ATX levels were combined for analysis as a surrogate for plasma LPA levels, the cumulative intra-hepatic recurrence rate was higher in patients in whom both serum ATX levels and LPA2 or LPA6 mRNA levels were higher than the median. However, the mRNA level of phosphatidic acid-selective phospholipase A1ɑ, another LPA-generating enzyme, in HCC patients was not associated with pathological findings or recurrence, even in combination with the expression of LPA receptors. Higher LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels. ATX and LPA receptors merit consideration as therapeutic targets of HCC.

Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

The surgical management of spontaneous esophageal perforation (Boerhaave's syndrome) ‒ 20 years of experience.

Spontaneous esophageal perforation (Boerhaave's syndrome) is an uncommon and challenging condition with significant morbidity and mortality. Surgical treatment is indicated in the large majority of cases and different procedures have been described in this respect. We present the results of a mono-institutional evaluation of the management of spontaneous esophageal perforation over a 20-year period. The charts of 25 patients with spontaneous esophageal perforation treated at the Surgical Department of the University Hospital of Lausanne were retrospectively studied. In the 25 patients, 24 patients were surgically treated and one was managed with conservative treatment. Primary buttressed esophageal repair was performed in 23 cases. Nine postoperative complications were recorded, and the overall mortality was 32%. Despite prompt treatment postoperative morbidity and mortality are still relevant. Early diagnosis and definitive surgical management are the keys for successful outcome in the management of spontaneous esophageal perforation. Primary suture with buttressing should be considered as the procedure of choice. Conservative approach may be applied in very selected cases.

Genetic heterogeneity in 26 infants with a hypomyelinating leukodystrophy.

T2 hyperintensity of brain white matter lesions detected by magnetic resonance imaging (MRI) are characteristic of a heterogeneous group of diseases. Persistent T2 high intensity in combination with T1 iso- or high intensity of white matter in infants indicates a lack of normal myelination, that is, hypomyelination. However, the precise diagnosis of hypomyelinating leukodystrophy based solely on MRI findings can be difficult, especially in the early stage of the disease. We studied 26 patients who were diagnosed with hypomyelinating leukodystrophy according to MRI findings and clinical features to uncover their genetic etiology through chromosomal analyses, targeted gene analyses, and an array comparative genomic hybridization (aCGH) assay. Then, for the 17 patients with unexplained hypomyelination by traditional analyses, whole-exome sequencing (WES) was performed. The presumptive diagnoses were confirmed in 58 % of the enrolled patients (15/26) and involved 9 different genetic backgrounds. The most frequent backgrounds were 18q deletion syndrome and Pelizaeus-Merzbacher disease, with an incidence of 12 % (3/26) for both. The diagnostic rate of chromosomal analyses, targeted gene analyses, and aCGH was 31 % (8/26), and one patient was clinically diagnosed with Cockayne syndrome. Using WES, the following causative genes of hypomyelination were identified in six individuals (35 %, 6/17): TUBB4A, POLR3B, KCNT1, and MCOLN1, and some of those genes were pathogenic for not only hypomyelination but also dysmyelination or delayed myelination. Our findings suggested heterogeneous genetic backgrounds in patients with persistent white matter lesions. These data also indicate that WES may be a rapid and useful tool for identifying the underlying genetic causes of undiagnosed leukodystrophies.

[Resection of Adrenal Metastasis after Chemotherapy and Radiation Therapy for a Patient with Stage IV B Hepatocellular Carcinoma].

In the treatment of hepatocellular carcinoma, atypical, off guideline multidisciplinary approaches are sometimes effective. A 70-year-old man was diagnosed with multiple hepatocellular carcinomas, multiple bone metastases, and a right adrenal metastasis. Sunitinib was started and the primary hepatic lesions and bone metastases disappeared. However, his adrenal metastasis worsened. Sorafenib, radiotherapy, and some investigational agents were administered, but the adrenal metastasis did not respond. There were no other new lesions except the adrenal lesion 4 years after the initial treatment, so we decided to perform a resection. In the left half lateral decubitus position, the adrenal mass was removed with right thoracolaparotomy. After the surgery, his tumor markers quickly returned to normal. Seven years after the initial treatment(2 years and 4 months after the last surgery), he is alive without any recurrence. Multidisciplinary treatment with chemotherapy, radiotherapy, and surgery may result in long term survival even for patients with advanced hepatocellular carcinoma with multiple extra-hepatic lesions.

[A Case of Solitary Metastasis to the Small Intestine from Sigmoid Colon Cancer after Treatment of Seven Multiple Cancers].

A 75-year-old woman who had undergone a Hartmann's operation for sigmoid colon cancer 2 years ago was hospitalized because she experienced small bowel obstruction several times. She had a treatment history of 6 other cancers, including 5 gastrointestinal tract cancers. However, the obstruction was relieved by conservative therapy each time. In September 2015, she was hospitalized for ileus. Abdominal computed tomography revealed that the lumen of intestine was partially dilated. Subsequently, a long tube was inserted, but the dilatation of the small intestine was not fully recovered. She was diagnosed with small intestinal obstruction due to adhesion, and she underwent an operation in October 2015. During the laparotomy, she was diagnosed with adhesion due to an intestinal tumor, and a partial intestinal resection, including the entire tumor, was performed. Because the tumor appearance and histological findings were very similar to those of sigmoid colon cancer, the tumor was diagnosed as a solitary metastasis of sigmoid colon cancer to the small intestine. Generally, peritoneal dissemination causes metastasis of colon cancer to the small intestine. However, this is a rare case because the lymphatic system or extra-wall invasion was the most likely cause of metastasis. Ileus repeating the improvement exacerbation, an examination must be performed while considering possible intestinal tumors, especially for a patient previously treated for multiple gastrointestinal cancers.

Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome.

West syndrome, which is narrowly defined as infantile spasms that occur in clusters and hypsarrhythmia on EEG, is the most common early-onset epileptic encephalopathy (EOEE). Patients with West syndrome may have clear etiologies, including perinatal events, infections, gross chromosomal abnormalities, or cases followed by other EOEEs. However, the genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. We identified candidate pathogenic variants in 50% of the patients (n = 9/18). The array CGH revealed candidate pathogenic copy number variations in four cases (22%, 4/18), including an Xq28 duplication, a 16p11.2 deletion, a 16p13.1 deletion and a 19p13.2 deletion disrupting CACNA1A. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases (36%, 5/14). Three candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1) (21%, 3/14). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases (14%, 2/14). Evaluating a panel of 67 known EOEE genes failed to identify significant mutations. Despite the heterogeneity of unexplained West syndrome, the combination of array CGH and whole-exome sequencing is an effective means of evaluating the genetic background in unexplained West syndrome. We provide additional evidence for NR2F1 as a causative gene and for CACNA2D1 and BRWD3 as candidate genes for West syndrome.

Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy.

BACKGROUND: Although laparoscopic hepatectomy has increasingly been used to treat cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to that of open surgery because the ability to visualize and palpate the liver surface during laparoscopy is relatively limited. Fluorescence imaging has the potential to provide a simple compensatory diagnostic tool for identification of cancers in the liver during laparoscopic hepatectomy. METHODS: In 17 patients who were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine green (ICG) was administered intravenously within the 2 weeks prior to surgery. Intraoperatively, a laparoscopic fluorescence imaging system obtained fluorescence images of its surfaces during mobilization of the liver. RESULTS: In all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs (75%) and 11 LMs (69%) on the liver surfaces distributed over Couinaud's segments 1-8, including the 17 tumors that had not been identified by visual inspections of normal color images. The 23 tumors that were identified by fluorescence imaging were located closer to the liver surfaces than another nine tumors that were not identified by fluorescence imaging (median [range] depth 1 [0-5] vs. 11 [8-30] mm; p < 0.001). CONCLUSIONS: Like palpation during open hepatectomy, laparoscopic ICG fluorescence imaging enables real-time identification of subcapsular liver cancers, thus facilitating estimation of the required extent of hepatic mobilization and determination of the location of an appropriate hepatic transection line.