T2 Gallbladder Carcinoma Research Articles

Letter to the Editor: Early Sonographic Detection of Gallbladder Carcinoma Can Improve Patient Outcomes: A Case Report—by Kimbrow. How is T1 or Shallow T2 Gallbladder Carcinoma Depicted With Sonography?

Letter to the Editor: Early Sonographic Detection of Gallbladder Carcinoma Can Improve Patient Outcomes: A Case Report—by Kimbrow. How is T1 or Shallow T2 Gallbladder Carcinoma Depicted With Sonography?

How Can We Identify T1 or Shallow T2 Gallbladder Carcinoma Using Ultrasound? Comment on Okaniwa, S. How Can We Manage Gallbladder Lesions by Transabdominal Ultrasound? Diagnostics 2021, 11, 784.

I am keenly interested in ultrasound diagnosis of the invasion depth of gallbladder carcinoma (GBC) [...].

Hyperplastic Polyp of the Gallbladder Mimicking a Shallow T2 Gallbladder Carcinoma: A Case Report

Ultrasonography has shown that many T2 gallbladder carcinomas (GBCs) demonstrate a deep hypoechoic area, and many shallow T2 GBCs show a conically thickened, outermost hyperechoic layer. However, this report describes a case of a hyperplastic polyp, of the gallbladder, with similar sonographic findings. This case reviews and analyzes the ultrasonographic imaging, as well as the pathologic correlation. Endoscopic ultrasound (EUS) revealed a thickened, outermost hyperechoic layer beneath a protruding lesion in the gallbladder fundus. The lesion was coupled with a deep hypoechoic area and a pancreaticobiliary maljunction (PBM). Pre-contrast computed tomogram (CT) demonstrated a soft tissue density mass in the fundus. Magnetic resonance imaging (MRI) disclosed no decreased-diffusion lesion under the diffusion-weighted image. Without any finding suggestive of an obvious advanced GBC, a full-thickness laparoscopic cholecystectomy was performed. The histopathology report indicated a hyperplastic polyp, which consisted of hypertrophic muscle, increased fibrosis, and a conically thickened subserosal fatty layer underneath the polyp. A specific benign protruded lesion may, though rarely, demonstrate similar EUS findings to those of shallow T2 carcinoma.

Oncologic safety of laparoscopic radical cholecystectomy in pT2 gallbladder cancer: A propensity score matching analysis compared to open approach.

The role of laparoscopic radical cholecystectomy (LRC) in the surgical management of T2 gallbladder carcinoma (GBC) is still controversial.The medical records of patients with T2 GBC treated with radical cholecystectomy were retrospectively reviewed. In this study, we compare the short- and long-term oncologic outcomes, using propensity score matching analysis, of patients with T2 GBC who underwent LRC and open radical cholecystectomy (ORC).Among 183 patients, 86 were selected by propensity score matching (LRC = 43 and ORC = 43). The ORC group underwent more extensive surgery (liver resections and extended lymph node dissections [ELND]) than the LRC group. The LRC group had less operative blood loss, shorter length of hospital stay, fewer complications, and had the earlier start of adjuvant chemotherapy. There was no significant difference between the laparoscopic and open surgery groups in terms of 5-year overall survival rate (64.6% vs 80.4%, P = .214) and disease-free survival rate (77.1% vs 82.2%, P = .641). A subgroup analyses showed that liver resection and ELND had no survival advantage compared to no liver resection and regional lymph node dissection, respectively.Our LRC approach is safe and effective, with long-term survival comparable to that of ORC.

Is combined extra-hepatic bile-duct resection justified for advanced gallbladder carcinoma?

BackgroundWhether the extra-hepatic bile duct (EHBD) should be routinely resected for gallbladder carcinoma (GBC) remains controversial. The current study aimed to determine the clinical impact of combined EHBD resection during curative surgery for advanced GBC.MethodsIn total, 213 patients who underwent curative surgery for T2, T3 or T4 GBC were enrolled. The clinicopathological features were compared between the patients treated with EHBD resection and those without EHBD resection. Meanwhile, univariable and multivariable Cox-proportional hazards regression models were used to identify risk factors for overall survival (OS).ResultsAmong the 213 patients identified, 87 (40.8%) underwent combined EHBD resection. Compared with patients without EHBD resection, patients with EHBD resection suffered more post-operative complications (33.3% vs. 21.4%, P = 0.046). However, the median OS of the EHBD resection group was longer than that of the non-EHBD resection group (25 vs. 11 months, P = 0.008). Subgroup analyses were also performed according to tumor (T) category and lymph-node metastasis. The median OS was significantly longer in the EHBD resection group than in the non-EHBD resection group for patients with T3 lesion (15 vs. 7 months, P = 0.002), T4 lesion (11 vs. 6 months, P = 0.021) or lymph-node metastasis (12 vs. 7 months, P < 0.001). No survival benefit of EHBD resection was observed in GBC patients with T2 lesion or without lymph-node metastasis. T category, lymph-node metastasis, margin status, pre-operative CA19-9 level and EHBD resection were identified as independent prognostic factors for OS of patients with advanced GBC (all P values <0.05). Conclusions EHBD resection can independently affect the OS in advanced GBC. For GBC patients with T3 lesion, T4 lesion and lymph-node metastasis, combined EHBD resection is justified and may improve OS.

Polypoid gallbladder tumors with a deep hypoechoic area and a conically thickened outermost hyperechoic layer suggest shallow T2 carcinoma.

BackgroundUltrasound findings of shallow T2 gallbladder carcinoma (GBC) with a favorable prognosis are not known.PurposeTo confirm the criteria for ultrasound diagnosis of shallow T2 GBC.Material and MethodsA detailed analysis of ultrasound and pathological correlation was conducted in two patients with pT1 GBC and seven with shallow pT2 GBC (subserosal-invasion depth ≤ 2 mm) at our institution from January 1988 to December 2017.ResultsA polypoid gallbladder tumor with a deep hypoechoic area represented a papillary adenocarcinoma invading the subserosa accompanied by abundant fibrosis and lymphocytic infiltration. Two cases of pT1 GBC did not present a deep hypoechoic area, whereas all seven cases of shallow pT2 GBC did. One case of pT1b GBC and four cases of pT2 GBC showed conical thickening of the outermost hyperechoic layer, whereas one case of pT1a GBC and three cases of pT2 GBC presented no change of the layer thickness. All shallow T2 GBCs showing a conically thickened outermost hyperechoic layer provided good postoperative prognoses.ConclusionUltrasound images of shallow T2 GBC show a deep hypoechoic area with conical thickening or unchanging of an outermost hyperechoic layer. The former demonstrates pulling up the top of the layer at first and then thinning later as carcinoma invades with enlargement of the hypoechoic area, whereas the latter thinning of the layer from the beginning. Polypoid gallbladder tumors with a deep hypoechoic area and a conically thickened outermost hyperechoic layer suggest shallow T2 GBC and may provide good postoperative prognoses.

Lymphatic spread of T2 gallbladder carcinoma: Regional lymphadenectomy is required independent of tumor location

BackgroundThis study aimed to investigate the incidence and distribution of regional lymph node metastasis according to tumor location, and to clarify whether tumor location could determine the extent of regional lymphadenectomy in patients with pathological T2 (pT2) gallbladder carcinoma. MethodsIn total, 81 patients with pT2 gallbladder carcinoma (25 with pT2a tumors and 56 with pT2b tumors) who underwent radical resection were enrolled. Tumor location was determined histologically in each gallbladder specimen. ResultsSurvival after resection was significantly worse in patients with pT2b tumors than those with pT2a tumors (5-year survival, 72% vs. 96%; p = 0.027). Tumor location was an independent prognostic factor on multivariate analysis (hazard ratio, 14.162; p = 0.018). The incidence of regional lymph node metastasis was significantly higher in patients with pT2b tumors than in those with pT2a tumors (46% vs. 20%; p = 0.028). However, the number of positive nodes was similar between the two groups (median, 2 vs. 2; p = 0.910). For node-positive patients with pT2b tumors, metastasis was found in every regional node group (12%–63%), whereas even for node-positive patients with pT2a tumors, metastasis was observed in regional node groups outside the hepatoduodenal ligament. ConclusionsTumor location in patients with pT2 gallbladder carcinoma can predict the presence or absence of regional lymph node metastasis but not the number and anatomical distribution of positive regional lymph nodes. The extent of regional lymphadenectomy should not be changed even in patients with pT2a tumors, provided that they are fit enough for surgery.

Improvement in the diagnosis and treatment of T2 gallbladder carcinoma is pivotal to improvement in the overall prognosis for this disease.

Since the American Joint Committee on Cancer (AJCC) subdivided the T2 stage of gallbladder carcinoma (GBC) into T2a and T2b, the diagnosis and treatment of those stages have been a subject of heated discussion and controversy. T2 is a stage of GBC that might be treatable. Based on the extent of lymph node metastasis and distant metastasis, T2 GBC can be classified into various pathological stages such as IIA, IIB, IIIB, and IVB, leading to controversy in clinical settings. This review aims to discuss the effectiveness of and controversies concerning S4b+5 resection, the acceptable extent of lymph node dissection, the timing for treatment of incidental gallbladder cancer, and adjuvant therapy. This review also aims to suggest directions for and recommendations regarding clinical research in the future.

Revision of nationwide practice patterns in the management of T2 gallbladder carcinoma

Background: National guidelines recommend en-bloc hepatectomy and lymphadenectomy for stage IB and higher gallbladder cancer (GBC). Compliance with these guidelines has been poor. We sought to assess potential changes in the practice patterns in the surgical management of T2 GBC over the last 3 decades. Methods: A contemporary series from National Cancer Database (NCDB) was queried for patients with T2 disease who underwent resection for GBC from 2004 to 2014 (Period 2). This data was compared with an older large series from SEER (Surveillance Epidemiology End-results) database including T2 GBC patients between 1991 and 2005 (Period 1). Kaplan–Meier log-rank analyses assessed the impact of the definitive surgical approach on survival rates. Results: NCDB and SEER databases identified 11,532 and 2,955 patients, respectively. Among them, 618 (5.3%) and 781 (26.4%) T2 GBC were included in this analysis, respectively. Patients undergoing hepatectomy had improved survival in both periods compared to those who did not undergo hepatectomy (51.7 vs. 25.3 months, p < 0.001 and 53.0 vs. 16.0 months, p < 0.001, respectively). Hepatectomy rates increased by 36% from period 1 to period 2 (13.4% vs. 37.2%, p < 0.001). Portal lymphadenectomy increased by 66.4% between period 1 and period 2 (33.3% vs. 50.1%, p < 0.001). Conclusion: Although there was a significant improvement in the compliance with national guidelines over last 3 decades, major disparities yet exist in the current surgical management of GBC. Only one third of patients with T2 GBC currently undergo appropriate hepatectomy and half of them undergo portal lymphadenectomy. Further studies assessing the impact of noncompliance on outcomes of patients with GBC are warranted. Efforts should be directed towards standardization of nationwide practice patterns in GBC.

Adjuvant systemic therapy after resection of node positive gallbladder cancer: Time for a well-designed trial? (Results of a US-national retrospective cohort study)

BackgroundIdeal oncologic management of gallbladder carcinoma (GBCA) after complete surgical resection is unclear. We sought to define benefit of post-resection adjuvant systemic chemotherapy alone in T2 or greater gallbladder carcinoma utilising a large national dataset. Study DesignThe National Cancer Data Base (NCDB) 2004–2012 cohort was retrospectively reviewed for patients with GBCA (T2+) undergoing curative-intent resection and surviving at least 6 weeks. Univariate group comparisons, unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. Results4373 patients were included (N = 2479 T2, N = 1894 T3/4). Overall, 22.1% of patients received adjuvant chemotherapy. Use of multi-agent chemotherapy increased during the study period. Patients receiving adjuvant therapy were younger, had fewer comorbidities, more often node-positive and more likely R1-margins than those receiving surgery alone. Unadjusted overall survival was improved in all patients with node-positive disease as well as for those with inadequate nodal staging. The benefit of chemotherapy persisted after adjustment for patient and tumor factors. ConclusionAdjuvant systemic chemotherapy is associated with survival benefit in patients with T2 or greater GBCA with node positive disease. We recommend a multidisciplinary approach in these patients as less than 1-in-4 of them currently receive adjuvant chemotherapy. Future clinical trials should address adjuvant chemotherapy in node positive GBCA.

The optimal surgical resection approach for T2 gallbladder carcinoma: evaluating the role of surgical extent according to the tumor location

PurposeThe clinical behavior of T2 gallbladder cancer varies among patients. The aims of this study were to identify prognostic factors for survival and recurrence, and to determine the optimal surgical strategy for T2 gallbladder cancer.MethodsWe conducted a retrospective analysis of 78 patients with T2 gallbladder cancer who underwent surgical resection for gallbladder cancer.ResultsTwenty-eight patients (35.9%) underwent simple cholecystectomy and 50 (64.1%) underwent extended cholecystectomy. Among 56 patients without LN metastasis (n = 20) or unknown LN status (no LN dissection, n = 36), the 5-year disease-free survival rates were 81.6%, and 69.8% (P = 0.080). In an analysis according to tumor location, patients with tumors located on the hepatic side (n = 36) had a higher recurrence rate than patients with tumors located on the peritoneal side only (n = 35) (P = 0.043). On multivariate analysis, R1 resection and lymph node metastasis were significant, independent prognostic factors for poor disease-free and overall survival.ConclusionR0 resection and LN dissection are an appropriate curative surgical strategy in patients with T2 gallbladder cancer. Tumors located on the hepatic side show worse prognosis than tumors located on the peritoneal side only, hepatic resection should be considered.

Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma.

AIMTo evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC).METHODSWe performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach.RESULTSThe median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence.CONCLUSIONLCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results.

Hepatectomy of segment 4b and 5 with extrahepatic bile duct resection for pT2 gallbladder carcinoma is valid: a single-institution result.

The results of surgical treatment for T2 gallbladder carcinoma are equivocal, while the precise preoperative TNM staging and localization of gallbladder carcinoma are difficult. The aim of this study was to report the validity of segment 4b and 5 (S4b+5) hepatectomy with extrahepatic bile duct resection for these tumors. We reviewed 30 patients with pT2 gallbladder cancer who underwent S4b+5 hepatectomy with extrahepatic bile duct resection. The median number of lymph nodes retrieved in the S4b+5 hepatectomy group was 11 (0-23) nodes, and lymph node metastasis was observed in 9 of 30 (30%) cases. Although all surgical margins were macroscopically negative, 4 of the 30 patients (13%) had pathologically positive margins. The overall survival rate of patients was 85.1% at 5 years. Of the 30 patients with S4b+5 hepatectomy, surgical margin alone was analyzed as a prognostic factor in univariate and multivariate analysis. The survival rate was comparable between the tumor on the hepatic side and peritoneal side (P = 0.856). Nine patients with additional S4b+5 hepatectomy after simple cholecystectomy because of incidental diagnosis of gallbladder cancer also had comparable survival compared to the remaining 21 patients with simultaneous S4b+5 hepatectomy (P = 0.624). S4b+5 hepatectomy with extrahepatic bile duct resection could be good treatment modality for T2 gallbladder cancers because precise preoperative diagnosis of tumor depth, location, and lymph node metastasis for these tumors is difficult.

Novel strategy for laparoscopic treatment of pT2 gallbladder carcinoma.

This study evaluated our new strategy for treating suspected T2 gallbladder carcinoma (GBC) using a laparoscopic approach. We examined 19 patients with suspected T2 GBC who were treated laparoscopically (LS group) between December 2007 and December 2013; these patients were compared with 14 patients who underwent open surgery (OS group). Laparoscopic staging was initially performed to exclude factors making the patients ineligible for curative resection. Intraoperative pathological examination of the surgical margin of the cystic duct was performed prior to laparoscopic gallbladder bed resection, and pathological examination was again performed to confirm the presence of carcinoma and the depth of tumor invasion. Surgery was completed when the pathological findings indicated that the patient was cancer free. Lymph node dissection was performed according to the depth of tumor invasion. None of the patients required conversion to laparotomy. For three patients with benign lesions, only gallbladder bed resection was required. Additional regional lymph node dissection was performed in 16 patients in the LS group. The mean operative time (309 vs. 324min, p=0.755) and mean number of dissected lymph nodes (12.6 vs. 10.2, p=0.361) were not significantly different between the LS and OS groups. The intraoperative blood loss was significantly lower (104 vs. 584mL, p=0.002) and the postoperative hospital stay was significantly shorter (9.1 vs. 21.6days, p=0.002) for LS patients than for those in the OS group. In the LS group, one patient developed postoperative pneumonia, but all patients survived without recurrence after a mean follow-up of 37months. Our strategy for suspected T2 gallbladder GBC is safe and useful, avoids unnecessary procedures, and is associated with similar oncologic outcomes as the open method.

New strategy for suspected T2 gallbladder carcinoma by laparoscopic approach and its comparison with the conventional open approach

Itano, Osamu MD, PhD; Shinoda, Masahiro; Kitago, Minoru MD, PhD; Abe, Yuta MD, PhD; Hibi, Taizo MD, PhD; Aiko, Satoshi SA. MD, PhD; Yagi, Hiroshi MD, PhD; Kitagawa, Yuko MD, FACS Author Information

Magnetic resonance differentiation between T2 and T1 gallbladder carcinoma: significance of subserosal enhancement on the delayed phase dynamic study

PurposeThe aim of this study is to investigate whether subserosal enhancement on the delayed-phase dynamic magnetic resonance (MR) study (SED) can differentiate T2 from T1 gallbladder carcinoma (GBC). MethodsThe institutional research board approved this retrospective study. Between 1997 and 2006, there were surgically proven 11 T1 and 21 T2 GBC in 30 patients, all of whom had undergone preoperative contrast enhanced dynamic MR study, either with a 2D sequence (n=17) or 3D sequences (n=15). All images were reviewed by two radiologists for the presence of SED, and receiver operating characteristic (ROC) curve analysis was performed. Sensitivity, specificity, positive and negative predictive values were calculated by consensus. ResultsThe areas under the ROC curves of the two readers were 0.91 and 0.86, and the kappa value was 0.78. Of the 21 T2 GBC, 18 and 3 showed positive and negative SED, respectively. Of the 11 T1 GBC, 1 and 10 showed positive and negative SED, respectively. The sensitivity, specificity, positive and negative predictive values of SED for diagnosing T2 lesions were 86%, 88%, 91% and 77%, respectively. ConclusionsIn conclusion, SED may be a useful sign to differentiate T2 from T1 GBC, which would affect the preoperative surgical planning of the patients.

Rational therapeutic strategy for T2 gallbladder carcinoma based on tumor spread

To evaluate the adequacy of surgical treatment of T2 gallbladder carcinoma (GBCa) according to tumor spread in the subserosal layer. A series of 84 patients with GBCa were treated at Saga University Hospital, Japan between April 1989 and October 2008. The tumor stage was graded according to the TNM staging for GBCa from the American Joint Committee on Cancer Manual 6th edition. Tumor staging revealed 30 patients with T2 tumors. T2 GBCa was divided into three groups histologically by the extent of tumor spread in the subserosal layer, using a score of ss minimum (ss min), ss medium (ss med) or ss massive (ss mas). For ss min GBCa, there was no positive pathological factor and patient survival was satisfactory with simple cholecystectomy, with or without extra-hepatic bile duct resection. For ss med GBCa, some pathological factors, h-inf (hepatic infiltration), ly (lymphatic invasion) and n (lymph node metastasis), were positive. For ss mas GBCa, there was a high incidence of positive pathological factors. The patient group with extra-hepatic bile duct resection with D2 lymph node dissection (BDR with D2) and those with S4a5 hepatectomy had significantly better survival rates. We suggest that radical surgery is not necessary for ss min GBCa, and partial hepatectomy and BDR are necessary for both ss med and ss mas GBCa.

Radical Reresection for T2 Gallbladder Cancer Patients Diagnosed following Laparoscopic Cholecystectomy

Purpose: Despite advances in imaging techniques, laparoscopic cholecystectomy (LC) gives many advantages to some patients with suspected gallbladder cancer. The aim of this study was to investigate clinicopathological features and to analyze the risk factors of recurrence after radical reresection for T2 gallbladder cancer patients diagnosed following LC. Methods: From January 2002 to December 2009, the data of 21 consecutive patients for radical reresection for T2 gallbladder cancer were reviewed, retrospectively. The significance of the variables for recurrence was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox’s proportional hazard model. Results: Of the 21 patients studied, 11 were men and 10 were women. Lymph node metastasis was present in 7 patients (33.4%). The 5-year survival rate and disease-free survival rate in those patients were 75.3% and 67.9%, respectively. In the univariate analysis, the male gender (P=0.0047), poorly differentiated tumor (P=0.0169), presence of lymph node metastasis (P=0.0012), presence of lymphovascular invasion (P=0.0259) and presence of perineural invasion (P=0.0096) were significant factors related to recurrence after radical reresection. In the multivariate analysis, the presence of lymph node metastasis was an independently significant factor (5-year disease free survival rate, 20.9% vs. 83.8% in the absence of lymph node metastasis; P=0.015). Conclusion: For patients with T2 gallbladder carcinoma diagnosed following LC, radical reresection is highly recommended and the presence of lymph node metastasis is an unfavorable prognostic factor that calls for additional treatment after radical surgery.

Cancer cells spread through lymph vessels in the submucosal layer of the common bile duct in gallbladder carcinoma

In the present study, we performed immunohistochemical staining with a lymphatic epithelium-specific marker, D2-40, to analyze the status of lymphatic spreading in the hepatoduodenal ligament in T2 gallbladder carcinoma (GC). One hundred and eighty-six paraffin-embedded specimens from 15 T2 GC patients were reviewed. Lymph vessels lined with D2-40 were visualized in the submucosal layer of the common bile duct in all cases. In 3 of 15 patients, clusters of cancer cells were identified in the submucosal lymph vessels of the extrahepatic bile duct, and this lymphatic invasion of cancer cells failed to be detected with only conventional hematoxylin-eosin staining. The frequency of the invasion to the submucosal lymph vessels in T2 GC correlated with presence of microscopic invasion to hepatoduodenal ligament and perineural invasion. There were lymph vessels in the submucosal layer of the common bile duct, and cancer cells can spread through these channels in addition to the large lymph vessels in subserosal layer around the extrahepatic bile duct in GC. The present results would support the concept of en bloc resection of the extrahepatic bile duct in curative resection for T2 GC.

PT2 (ss) 胆嚢癌の根治手術

pT2 (ss) 胆嚢癌の根治手術