An 82-year-old woman was diagnosed with cholecystitis with a right-sided round ligament. We planned a single-incision laparoscopic cholecystectomy. Based on the findings of fluorescent cholangiography, the running course of the common bile duct was confirmed before dissection of Calot's triangle, and the confluence between the cystic duct and the common bile duct was exposed after the dissection of Calot's triangle. The planned surgery was successful. The operative time and intraoperative blood loss were 157 min and 2 mL, respectively. The patient was discharged from our hospital 3 days after surgery. Application of fluorescent cholangiography during a laparoscopic cholecystectomy for the patients with a right-sided round ligament should be widely accepted.
Abstract Purpose: The negative regulatory programmed death-1/programmed death-1 ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. In this study, we investigated the expression of PD-L1 and PD-L2 in human esophageal cancer to define their clinical significance in patients' prognosis after surgery. Experimental Design: PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR. The protein expression was also evaluated with newly generated monoclonal antibodies that recognize human PD-L1 (MIH1) and PD-L2 (MIH18). Results: The protein and the mRNA levels of determination by immunohistochemistry and real-time quantitative PCR were closely correlated. PD-L–positive patients had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Furthermore, multivariate analysis indicated that PD-L status was an independent prognostic factor. Although there was no significant correlation between PD-L1 expression and tumor-infiltrating T lymphocytes, PD-L2 expression was inversely correlated with tumor-infiltrating CD8+ T cells. Conclusions: These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway.
Right-sided hepatectomy, that is, right hemihepatectomy (H5678, according to the New World terminology)1 or trisectionectomy (H45678)1 is often preferentially used as the resection procedure for perihilar cholangiocarcinoma,2–4 so-called Klatskin tumor, for the following reasons. First, the right hepatic artery runs just behind the common hepatic duct near the porta hepatis. Second, right trisectionectomy is a more common and easier procedure, whereas left trisectionectomy (H23458)1 is demanding and rarely performed. Another reason is the anatomical consideration that the left hepatic duct is longer than the right hepatic duct.2–4 The first 2 reasons are reasonable, but the last one is doubtful. In 1989, Couinaud published a textbook on liver anatomy titled “Surgical anatomy of the liver revisited,”5 in which the length of the hepatic duct was not described. Ten years later, he again published a new book titled “Tell me more about liver anatomy”6 and briefly mentioned the length of the hepatic duct as follows: “the right hepatic duct is short (range, 1–24 mm; mean = 9.005 mm, n = 107) and missing in 46.72% of the cases in which the separate right lateral and right paramedian branches are replaced” (page 33); “the left hepatic duct length is 13.47 ± 1.67 mm when the right hepatic duct is single and 10.89 ± 1.92 mm when the right hepatic duct is duplicated” (page 73). Although this was the first report on the hepatic duct length, Couinaud did not show the definition of the hepatic duct; in other words, there was no description about where the length was measured. It may be very difficult to anatomically define the right or left hepatic duct due to various variations of biliary anatomy.5,6 From a surgical viewpoint, an important matter is not “the length of the extrahepatic portion of the hepatic duct” but rather “the length of the hepatic duct that can be resected.” In this regard, we measured the length of the resected proximal hepatic ducts in 475 patients who underwent major hepatectomy combined with caudate lobectomy for Klatskin tumors.7 In a right-sided hepatectomy, the length from the confluence of the right and left hepatic ducts to the cut end of the left lateral segmental bile duct was measured; in a left-sided hepatectomy, the length from the confluence to the cut end of the right posterior bile duct was measured.7 The length of the resected proximal hepatic duct was 14.1 ± 5.7 mm in left hemihepatectomy (n = 149), 14.9 ± 5.7 mm in right hemihepatectomy (n = 167), 21.3 ± 6.4 mm in left hepatic trisectionectomy (n = 122), and 25.1 ± 6.4 mm in anatomic, not conventional, right hepatic trisectionectomy7,8 (n = 37). In short, the length of the resected hepatic duct can be described as follows: (1) nearly equal between left and right hemihepatectomies (P = 0.626), (2) significantly shorter in right hemihepatectomy than in left hepatic trisectionectomy (P < 0.001), and (3) the longest in anatomic right hepatic trisectionectomy (vs left trisectionectomy, P < 0.005).7 We also measured the “estimated” lengths of the bile duct to be resected in the 4 types of hepatectomy using cholangiograms reconstructed from computed tomography images, taken before biliary drainage, in 61 patients with distal bile duct obstruction. The radiological measurements showed the similar trend to the above-mentioned surgical measurements.7 These observations should be carefully interpreted. Namely, our method of right hepatic trisectionectomy was “anatomic” trisectionectomy, in which the bile ducts of the left lateral sector were divided at the left side of the umbilical fissure.8 In “conventional” right hepatic trisectionectomy which is widely performed in most centers,2–4 the left hepatic duct is divided at the right side of the umbilical fissure which is achievable even in right hemihepatectomy. Overall, an assumption that “the left hepatic duct is longer than the right hepatic duct” lacks scientific validation and is simply the surgeons’ biased view. Considering abovementioned observations, the surgical procedure for Bismuth type IV tumors, particularly tumors with even extension, should be discussed. When liver function is stable and the estimated residual liver volume is sufficient, anatomic right hepatic trisectionectomy is recommended because this hepatectomy approach can provide the longest proximal ductal margin. When right trisectionectomy is deemed high risk, right hemihepatectomy or left trisectionectomy is the next best option. Considering that the resection volume is nearly equal between the 2 hepatectomy methods, the latter procedure is recommended if there is no vascular invasion, because it can offer a significantly longer ductal margin. Practically, the type of hepatectomy is determined by considering the predominant tumor location, the presence or absence of portal vein and/or hepatic artery invasion, the course of the portal vein or hepatic artery, and liver function. Surgeons must also consider that the right hepatic artery is sometimes involved in tumors behind the common hepatic duct. Nevertheless, the surgical strategy based on the previously mentioned biased assumption should be overhauled. In 1999, Neuhaus et al introduced the “no-touch technique,” that is, right-sided hepatectomy with routine portal vein resection for Klatskin tumors, and stressed the oncological superiority of this preemptive procedure.2,3 However, so far there have been no external validation studies showing the oncological superiority. More than 15 years ago, a Japanese center had adopted no-touch technique9 but stopped using this approach 8 years ago, due to disappointing oncological effects (personal communication with Professor Hirano from Hokkaido University). To the best of our knowledge, at present, no centers in Japan use the “no-touch technique.” Previously, we recommended right hemihepatectomy for Bismuth type I/II tumors,10 which are located inevitably near the right hepatic artery, for the following reasons: (1) reported survivals after limited local resection for Bismuth type I/II tumors were dismal due to the high incidence of R1 resection; and (2) right hemihepatectomy is simple without vascular resection. Although this concept is still deemed rational, Sugiura et al have shown that left hemihepatectomy with combined resection and reconstruction of the right hepatic artery is a valid alternative to right hemihepatectomy, especially in patients with an insufficient left liver functional reserve.11 We agree their concept because arterial reconstruction in left hemihepatectomy is relatively easy due to the short range involvement and large caliber of the distal artery, and we have also used this left side approach in such patients with Bismuth type I/II tumors. Finally, the surgical experiences at Nagoya University Hospital need to be briefly mentioned. Between 2001 and 2018, 787 patients underwent resection of Klatskin tumors, including with right trisectionectomy (n = 66, 8.3%), right hemihepatectomy (n = 247, 31.4%), left trisectionectomy (n = 198, 25.1%), left hemihepatectomy (n = 242, 30.7%), and other resection methods (n = 34, 4.3%).12 The 90-day mortality rate was 2.6% (8/313) for right-sided hepatectomy and 1.6% (7/440) for left-sided hepatectomy (P = 0.430). The incidence of positive proximal ductal margin was 11.2% (35/313) in right-sided hepatectomy and 11.6% (51/440) in left-sided hepatectomy (P = 0.862). The overall survival rate at 5 years (including all deaths) was 42% for right-sided hepatectomy and 39% for left-sided hepatectomy (P = 0.121), although the incidence of combined hepatic artery resection was significantly higher in left sided-hepatectomy than in right-sided hepatectomy (30.9% = 136/440 vs 2.9% = 9/313, P < 0.001).12 These results do not support the oncological superiority of right-sided hepatectomy over left-sided hepatectomy. If the resection procedure is flexibly selected, oncological sidedness may not be associated with the type of hepatectomy. Recent studies on the issue of right- or left-sided resections for Klatskin tumors reported a comparable long-term survival,13–16 although mortality was much higher in right-sided hepatectomy.14–16 Hepatobiliary surgeons should abandon the biased assumption that the left hepatic duct is longer than the right hepatic duct and should explode the fallacy that right-sided hepatectomy is oncologically superior. Hepatobiliary surgeons should make an effort to refine their surgical skills to safely and properly perform the demanding method of left hepatic trisectionectomy in which combined vascular resection is often required.12,17 This is a key to ensuring flexibility in the selection of a hepatectomy approach for Klatskin tumors, leading to expanded surgical indications and improved survival of this intractable disease. The most important aim is performance of decent resection with free margins, regardless of the type of hepatectomies.
Recent advances in cancer genomics have led to the identification of many molecular pathways involved in colorectal cancer (CRC) carcinogenesis. Pre-clinical and clinical data have shown that gene mutations involved in several of these pathways have an important prognostic impact, particularly on the outcomes of patients with metastatic CRC. Therefore, specific information on such gene mutational status can be potentially used as biomarkers to guide genome-oriented personalized treatment and ultimately improve patient outcomes. Drosophila protein, mothers against decapentaplegic homolog 4 (SMAD4) has a critical intermediate role in the TGFβ signaling pathway. Loss of SMAD4 expression is associated with both metastatic development and worse response to chemotherapy for patients with CRC. Additionally, it has been reported that the loss of SMAD4 function is independently associated with decreased recurrencefree (RFS) and overall survival (OS) for patients with CRC, especially for patients with advanced stages of disease. Furthermore, among patients who undergo hepatectomy for colorectal liver metastases (CRLM), SMAD4 mutations are associated with a high likelihood of simultaneously carrying RAS mutations, which independently predict worse OS. Although recent evidence highlights the prognostic importance of somatic SMAD4 mutations in CRLM, ongoing research is necessary to untangle the specific molecular mechanisms involved in the complex SMAD4 regulatory network as well as the synergism with other mutations implicated in the pathogenesis of CRC. The detailed elucidation of such mechanisms may potentially aid the development of future trials in establishing novel, targeted therapeutic advances to further guide clinical decision-making for patients with CRC.
Objective: To reappraise whether preoperative autologous blood donation reduces post-hepatectomy liver failure (PHLF) in major hepatectomy for perihilar malignancy. Summary Background Data: Autologous blood storage and transfusion are carried out to reduce the use of allogeneic blood transfusion during hepatectomy and prevent postoperative complications. However, the clinical benefit in major hepatectomy has been controversial. Methods: This randomized clinical trial included patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar malignancy. Eligible patients were randomly assigned (1:1) to undergo surgery with or without the use of autologous blood transfusion. The primary outcome was the incidence of clinically relevant PHLF (grade B/C according to the International Study Group of Liver Surgery definition). Results: Between February 6, 2019, and May 12, 2023, 138 consecutive patients were enrolled in the study (blood storage group n=68, non-storage group n=70). Twenty-five patients who did not undergo resection were excluded; the remaining 113 patients were investigated as the full analysis set (blood storage group n=60, non-storage group n=53). Surgical procedures, operative time, and blood loss were not significantly different between the two groups. The incidence of PHLF was comparable (blood storage group n=10 [17%], non-storage group n=10 [19%]; P =0.760). There were also no between-group differences in other postoperative outcomes, including the incidence of Clavien-Dindo Grade Ⅲ or higher (72% vs. 72%, P =0.997) and median duration of hospital stay (25 vs. 29 d, P =0.277). Conclusions: Autologous blood storage did not contribute to reducing the incidence of PHLF in patients undergoing major hepatectomy.
