Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta-analysis.

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme "HMG CoA reductase" and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta-analysis of 10 studies, statin use was associated with improved recurrence-free survival (RFS; HR 0.64; 95% CI 0.53-0.79, I(2) = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59-0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44-1.46). Statin users similarly showed improved overall survival in a meta-analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44-0.99, I(2) = 89%). Statin users also had improved cancer-specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46-1.06, I(2) = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence-free survival. Statin users also had improved overall survival and cancer-specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.

Selective histology of cholecystectomy specimens--is it justified?

BACKGROUND: Gallbladder cancer (GBC) is rare but the most common malignancy of biliary tract with a dismal prognosis. The early diagnosis and surgical treatment of GBC offers the only chance of long-term survival. Despite advances in radiological imaging, early diagnosis of GBC is still rarely achieved without histopathology. In our hospital, routine histologic examination of all resected gallbladder specimens has been standard practice. This study seeks to define whether selective histologic examination for gallbladder specimens based on preoperative imaging or intraoperative findings is justified. MATERIALS AND METHODS: From September 2008-September 2013, all histopathology reports of gallbladder specimens after elective cholecystectomy were retrospectively analyzed in a single surgical unit. Preoperative imaging, intraoperative findings, and histology notes were analyzed in all cases. RESULTS: Out of 14,369 (60% female and 40% male) patients undergoing cholecystectomy, GBC was found in only 46 cases (0.32%). More than one fifth (10/46) of GBC patients presented with acute cholecutitis (AC). All 10 AC patients coexisted with GBC harbored "significantly inflamed' gallbladders, and about 83.49% AC patients were judged with "significant inflammation." Carcinoma in situ and early GBC (T1a, T1b) accounted for 61% of all cases. Only two patients with Tis and T1a respectively did not show suspicious lesion on preoperative and intraoperative findings, but for the remaining cases (44/46), GBC was suspected either by preoperative imaging and/or intraoperative findings. CONCLUSIONS: Almost all cases of invasive GBC will show macroscopic abnormalities following examination by a simple procedure-a full dissection, inspection, and palpation of the gallbladder. Any patient with early GBCs "missed" on macroscopic examination can still receive the appropriate treatment by the cholecystectomy alone. The gallbladder should be sent for histology only if macroscopic examination raises suspicion. This selective policy is more cost-effective, and does not appear to compromise patients outcome.

Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease.

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty-nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow-up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted.

Effects of epidermal growth factor receptor inhibitor on proliferative cholangitis in hepatolithiasis.

BACKGROUND: There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis (PC), which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC. METHODS: After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls. RESULTS: The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and beta-glucuronidase activity. CONCLUSION: Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.

Histological examination of frozen sections for patients with acute cholecystitis during cholecystectomy.

BACKGROUND: Unexpected gallbladder cancer may present with acute cholecystitis-like manifestations. Some authors recommended that frozen section analysis should be performed during laparoscopic cholecystectomy for all cases of acute cholecystitis. Others advocate selective use of frozen section analysis based on gross examination of the specimen by the surgeon. The aim of the present study was to evaluate whether surgeons could effectively identify suspected gallbladder with macroscopic examination alone. If not, is routine frozen section analysis worth advocating? METHODS: A total of 1162 patients with acute cholecystitis who had undergone simple cholecystectomy in our hospital from February 2009 to February 2014 were enrolled in the study. The data of patients with acute cholecystitis especially those with concurrent gallbladder cancer in terms of clinical characteristics, operative records, frozen section diagnosis and histopathology reports were analyzed. RESULTS: Thirteen patients with acute cholecystitis were found to have concurrent gallbladder cancer, with an incidence of 1.1% in acute cholecystitis. Forty patients with acute cholecystitis were suspected to have gallbladder cancer by macroscopic examination and specimens were taken for frozen section analysis. Six patients with gallbladder cancer were correctly identified by macroscopic examination alone but 7 patients with gallbladder cancer missed, including 3 patients with advanced cancer (2 T3 and 1 T2). Meanwhile, in 6 gallbladder cancer specimens sent for frozen section analysis, 3 early gallbladder cancers (2 Tis and 1 T1a) were missed by frozen section analysis. However, the remaining 3 patients with advanced gallbladder cancers (2 T3 and 1 T2) were correctly diagnosed. CONCLUSIONS: The incidence of comorbidity of gallbladder cancer and acute cholecystitis is higher than that of non-acute cholecystitis. The accurate diagnosis of gallbladder cancer by surgeons is poor and frozen section analysis is necessary.

Applying chemical bile duct embolization to achieve chemical hepatectomy in hepatolithiasis: a further experimental study.

BACKGROUND: Hepatolithiasis is the presence of calculi within the bile ducts of the liver. It represents a significant problem for hepatobiliary surgery because of its high recurrence rate and the associated risk for partial hepatectomy. This study was designed to explore the long-term efficacy of chemical biliary duct embolization (CBDE) to treat recurrent hepatolithiasis. MATERIALS AND METHODS: A rabbit model of hepatolithiasis was established, and CBDE was achieved using oxybenzene and N-butyl-cyanoacrylate. The short-term (6 wk) and long-term (12 wk) efficacy of CBDE treatment was compared by observing the degree of atrophy, fibrosis, proliferation of collagen fibers, and apoptosis of hepatocytes and hepatic stellate cells in the embolized hepatic lobe. Biochemical measurement of ß-glucuronidase was also evaluated to determine the effect of CBDE on stone formation. RESULTS: Six weeks after CBDE, there was liver cell destruction, collagen accumulation, and bile duct proliferation only in the peripheral part of the target lobe. Twelve weeks after CBDE, "self-cut" chemical hepatectomy was achieved, as manifested by the destruction of almost all the hepatocytes in the target lobe, bile duct proliferation, and collagen fiber accumulation. The ß-glucuronidase activity was markedly lower in the embolized lobe than in the nonembolized lobe. In contrast, bax, caspase-3, caspase-9, and α-smooth muscle actin expression was substantially higher in the embolized lobe than in the sham-operation group at 6 wk, but was lower at 12 wk. CONCLUSIONS: CBDE is a potentially effective therapeutic approach for treating and preventing the recurrence of hepatolithiasis.

Sequential embolization of the branches of the bile duct and portal vein to the targeted hepatic lobe in rats.

BACKGROUND: The high recurrence rate of hepatolithiasis and the high operative risk of right posterior, caudate or multiple lobe hepatectomy are the unsettled problems in hepatobiliary surgery. The present study was to investigate the efficacy of chemical hepatectomy performed via applying sequential embolization of the branches of the bile duct and portal vein to the targeted hepatic lobe. METHODS: The bile duct and portal vein branches of the median hepatic lobe of rats were treated with: 1) bile duct embolization followed by portal vein ligation (BDE+PVL) and 2) portal vein ligation followed by bile duct embolization (PVL+BDE). The efficacy of chemical hepatectomy in BDE+PVL and PVL+BDE groups was compared with that of sole BDE by histology and Western blotting analysis of collagen I expression. RESULTS: After six weeks of the chemical hepatectomy, rats in the BDE group showed hepatocyte damages, fibrosis and "self-cut" only in the periphery of the embolized lobe. In contrast, rats in the PVL+BDE and BDE+PVL groups exhibited complete necrosis of hepatocytes and replacement with proliferative ductules and collagen fibers, leading to complete fibrosis and "self-cut" phenomenon in the whole targeted lobe. Collagen I expression in the PVL+BDE group was slightly higher than that in the BDE+PVL group; however, no statistically significant difference was noted. CONCLUSION: The sequential embolization of the bile duct and portal vein branches to the targeted hepatic lobe may be a feasible and effective approach to acheive the ideal effect of chemical hepatectomy in a short period of time.

Bilateral indirect ovarian inguinal hernia in a young female with type 1 Mayer-Rokitansky-Küster-Hauser syndrome: An extremely rare clinical context.

Key Clinical Message: Incidence of bilateral inguinal hernia encompassing bilateral ovaries in adult female is very thin and concomitant association with Mayer-Rokitansky-Küster-Hauser syndrome is out of ordinary. Along with surgical management of hernia, these females need multidisciplinary slant to manage gynecological, social, and emotional issues. Abstract: In mature females, bilateral ovarian inguinal hernias are a rarity. In this situation, ultrasonography is the basic adjunct to confirm the diagnosis. Mayer-Rokitansky-Küster-Hauser syndrome is typically linked to ovarian hernias in grown-up females. The most important ways to avoid problems are early diagnosis and surgical repair. A 25-year-old lady presented to our outpatient clinic with a history of swelling in bilateral inguinal region for 1 month. On the ultrasound examination, the right ovary was visualized in the right high inguinal canal, and the left ovary was seen at the level of deep inguinal ring with no visualization of the uterus in its normal anatomical position. The patient underwent bilateral inguinal exploration under spinal anesthesia, and herniated contents were successfully reduced back to anatomical locations. Clinical care for such a clinical condition must be multifaceted, involving intensive counseling, relocating the uterus, fallopian tube, and ovary to preserve fertility, and preventing consequences like incarceration and strangulation.

Vanishing bile duct syndrome as a presentation of Hodgkin's lymphoma.

Vanishing bile duct syndrome is an uncommon condition characterised by the progressive loss and disappearance of bile ducts. It is an acquired form of cholestatic liver disease presenting with hepatic ductopenia (loss of >50% bile ducts in the portal areas). We present a case of vanishing bile duct syndrome as a presentation of Hodgkin's lymphoma who was treated with standard-of-care chemotherapy-doxorubicin, bleomycin, vinblastine and dacarbazine (along with brief administration of rituximab), which led to complete response and normalisation of liver function.

TACTUM: Trends in Access to Cellular Therapies in Multiple Myeloma, Perspectives of Treating Versus Referring Physicians.

Chimeric antigen receptor T cell therapy (CAR-T) and bispecific T cell engagers (TCE) for multiple myeloma (MM) are readily available at many large US medical centers. However, many potentially eligible patients may not be referred to the specialized centers administering these therapies. Perspectives regarding potential barriers for MM cellular therapy from referring-center oncologists (ROs) versus treating-center oncologists (TOs) have not been reported previously. We conducted TACTUM-23, a survey of US oncologists who treat MM, to identify perceived barriers to these cellular therapies. This 24-question survey, which focused on demographics and perceived barriers to CAR-T and TCE, was conducted between June and August 2023. Of 247 oncologists, 37 (15%) completed the survey including 26 (70%) TOs who prescribed both CAR-T and TCEs, 4 (11%) TOs who only prescribed TCEs, and 7 (19%) ROs who referred patients. The top RO-stated barrier to CAR-T was financial toxicity, while the top TO-stated barrier to CAR-T was leukapheresis/ manufacturing slot availability. The top RO-stated barrier to TCE was financial toxicity, while the top TO-stated barrier to TCE was the hospitalization requirement. In conclusion, financial concerns are perceived by ROs to be the top barrier to both CAR-T and TCEs in myeloma. In contrast, TOs perceive logistical concerns to be the top barrier. Interventions to lower financial toxicity during these therapies, and outreach to raise awareness of such interventions among ROs, are needed alongside strategies to streamline manufacturing (for CAR-T) and monitoring.

Post-operative Tumor Lysis Syndrome in High-Grade Uterine Sarcoma.

Tumor lysis syndrome (TLS) is a well-known oncologic emergency. It is a constellation of metabolic derangements usually observed in hematological malignancies due to rapid cell lysis, typically due to chemotherapy or radiotherapy initiation. Spontaneous TLS is an unusual complication in solid malignancies, and only a few cases have previously been reported for spontaneous TLS in gynecological malignancies. We report a case of TLS in a 50-year-old female patient shortly after resection of high-grade uterine sarcoma. We review previous TLS cases in uterine malignancies and the associated morbidity and mortality.

Renin-Angiotensin Blockade Reduces Readmission for Acute Chest Syndrome in Sickle Cell Disease.

Rationale Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD. Acute chest syndrome appears similar to pulmonary fat embolism (PFE), a complication of severe skeletal trauma or orthopedic procedures from pulmonary micro-vessel blockage by bone marrow fat. Vascular obstruction and bone marrow necrosis occur in PFE and ACS.  Pulmonary fat embolism rat models have shown that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) mitigate damage in PFE. These medications could work similarly in ACS. We hypothesize that time to readmission after one hospitalization for ACS will be reduced in patients taking ACEI or ARB compared to patients who are not. Methods This is a retrospective cohort study. Inclusion criteria are adults (18 to 100 years) with sickle cell anaemia (HbSS), hemoglobin SC (HbSC) disease, sickle cell thalassemia (HbSßThal), hospitalized with ACS over 16 years (January 1, 2000, to March 31, 2016); patients who take and don't take ACEI or ARB. Children (<18 years old), elderly adults (>100 years old), pregnant patients, and patients with sickle cell trait were excluded. Data was collected from the Health Facts database, which contains de-identified information from the electronic medical records of hospitals in which Cerner© has a data use agreement. Kaplan-Meier estimates explored a time-to-event model of ACS readmission. Multivariable analysis (age, gender, smoking history) was conducted using Cox proportional hazards regression. Results were reported around a 95% confidence interval. Results There were 6972 patients in total. Of which, 9.6% (n = 667) reported taking ACEI or ARB. Results for the covariates were: average age of 38 years old; 63% female (n = 4366/6969); 16% smokers (n = 1132). Readmission rates were higher for patients not taking ACEI/ARB than those who did: 0.44 (95% CI 0.43, 0.46) versus 0.28 (95% CI 0.24, 0.31) at one year, and 0.56 (95% CI 0.55, 0.58) versus 0.33 (95% CI 0.29, 0.37) at two years. Age had the strongest effect on readmission rates for patients taking ACEI/ARB (adjusted hazards ratio 0.78 [95% CI 0.68, 0.91]). Conclusion Patients with SCD who reported taking ACEI or ARB had lower readmission rates for ACS; age was the strongest covariate. Our results may have a significant impact on the prevention of ACS. Prospective studies comparing ACEI or ARB therapy versus placebo are needed to confirm this preventative effect.

Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer.

Triple-negative breast cancer (TNBC) is classically defined by estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry expression <1% and absence of HER2 amplification/overexpression. HER2-negative breast cancer with low ER/PR expression (1-10%) has a gene expression profile similar to TNBC; however, real-world treatment patterns, chemotherapy response, endocrine therapy benefit, and survival outcomes for the Low-ER group are not well known. 516 patients with stage I-III HER2-negative breast cancer and ER/PR expression ≤10% who were enrolled in a multisite prospective registry between 2011 and 2019 were categorized on the basis of ER/PR expression. TNBC (ER and PR < 1%) and Low-ER (ER and/or PR 1-10%) groups comprised 87.4% (n = 451) and 12.6% (n = 65) of patients, respectively. Demographic, clinical, and treatment characteristics, including prevalence of germline BRCA1/2 mutation, racial and ethnic distribution, and chemotherapy use were not different between TNBC and Low-ER groups. No difference was observed in recurrence-free survival (RFS) and overall survival (OS) between TNBC and Low-ER groups (3-year RFS 82.5% versus 82.4%, respectively, p = 0.728; 3-year OS 88.0% versus 83.4%, respectively, p = 0.632). Among 358 patients receiving neoadjuvant chemotherapy, rates of pathologic complete response were similar for TNBC and Low-ER groups (49.2% vs 51.3%, respectively, p = 0.808). The HER2-negative Low-ER group is often excluded from TNBC clinical trials assessing novel treatments (immunotherapy and antibody-drug conjugates), thus limiting efficacy data for newer effective therapies in this group. Given that HER2-negative Low-ER disease displays clinical characteristics and outcomes similar to TNBC, inclusion of this group in TNBC clinical trials is encouraged.

Docetaxel-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome-related complex in a patient with metastatic prostate cancer?

A 63-year-old African American man was diagnosed with prostate cancer by biopsy for elevated prostrate-specific antigen. He was initially treated with radiation and then with intermittent androgen ablation because of biochemical relapse. He continued to have rising prostrate-specific antigen and he was thought to have hormone-resistant prostate cancer. So he received chemotherapy with docetaxel. He returned to the hospital within 3 days of the first cycle of treatment with fever, altered mental status, acute renal failure, anemia, and thrombocytopenia. He was started on empiric antibiotics but his cultures from most sites were negative. His platelets dropped from 119,000 to a nadir of 10,000 during hospital stay. Patient had microangiopathic hemolytic anemia suggested by elevated lactate dehydrogenase, decreased haptoglobin, increased indirect bilirubin, and schistocytes in peripheral smear. His coagulation profile was normal. A presumptive diagnosis of chemotherapy-related thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome was made and patient was started on fresh frozen plasma infusion and hemodialysis for renal failure and steroids. Patient improved symptomatically, platelet count was stable, and lactate dehydrogenase was in a declining trend after 5 days of fresh frozen plasma infusion. The ADAMS TS-13 activity was 37% suggestive of chemotherapy-related TTP. Patient also had sickle cell beta thalassemia disease and glucose 6 phosphate dehydrogenase deficiency. Docetaxel, like some other vascular endothelial growth factor inhibiting chemotherapeutic drugs may cause TTP-hemolytic uremic syndrome.

Efficacy and Safety of Andexanet Alfa for Bleeding Caused by Factor Xa Inhibitors: A Systematic Review and Meta-Analysis.

Direct oral anticoagulants (DOAC) including factor Xa inhibitors are associated with bleeding events which can lead to severe morbidity and mortality. Reversal agents like andexanet alfa (AA) and 4F-PCC (Four-factor prothrombin concentrate complex) are available for treating bleeding that occurs with DOAC therapy but a comparison on their efficacy is lacking. In this study, we analyzed the efficacy and safety of patients treated with andexanet alfa for bleeding events from DOAC. Databases were searched for relevant studies where AA was used to determine efficacy and safety in bleeding patients who were on factor Xa inhibitors. Published papers were screened independently by two authors. RevMan 5.4 (The Cochrane Collaboration, 2020) was used for data synthesis. Odds ratio (OR) and mean difference (MD) was used to estimate the outcome with a 95% confidence interval (CI). Among 1245 studies were identified after a thorough database search and three studies were included for analysis. AA resulted in lower odds of mortality compared to 4F- PCC (OR, 0.37; 95% CI, 0.20-0.71) among patients with intracerebral hemorrhage. There was no difference in thrombotic events between patients receiving AA and 4F-PCC (OR, 2.40; 95% CI, 0.36-15.84). No differences in length of hospital stay and intensive care unit (ICU) stay were seen between patients receiving AA and 4F-PCC. In conclusion, andexanet alfa reduced in-hospital mortality in patients who had bleeding due to factor Xa inhibitors compared to 4F-PCC. However, there were no differences in thrombotic events, length of ICU, and hospital stay between patients treated with AA and 4F-PCC.

Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I-III Triple-negative Breast Cancer (NeoSTOP).

PURPOSE: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens. PATIENTS AND METHODS: Patients aged ≥18 years with stage I-III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B). Stromal tumor-infiltrating lymphocytes (sTIL) were assessed. Primary endpoint was pCR in breast and axilla. Other endpoints included residual cancer burden (RCB), toxicity, cost, and event-free (EFS) and overall survival (OS). RESULTS: One hundred patients were randomized; arm A (n = 48) or arm B (n = 52). pCR was 54% [95% confidence interval (CI), 40%-69%] in arm A and 54% (95% CI, 40%-68%) in arm B. RCB 0+I rate was 67% in both arms. Median sTIL density was numerically higher in those with pCR compared with those with residual disease (20% vs. 5%; P = 0.25). At median follow-up of 38 months, EFS and OS were similar in the two arms. Grade 3/4 adverse events were more common in arm A compared with arm B, with the most notable differences in neutropenia (60% vs. 8%; P < 0.001) and febrile neutropenia (19% vs. 0%; P < 0.001). There was one treatment-related death (arm A) due to acute leukemia. Mean treatment cost was lower for arm B compared with arm A (P = 0.02). CONCLUSIONS: The two-drug CbD regimen yielded pCR, RCB 0+I, and survival rates similar to the four-drug regimen of CbP → AC, but with a more favorable toxicity profile and lower treatment-associated cost.

Predictive factors of early recurrence after R0 resection of hilar cholangiocarcinoma: A single institution experience in China.

Prediction of early postoperative recurrence is of great significance for follow-up treatment. However, there are few studies available that focus on high-risk factors of early postoperative recurrence or even the definition the exact time of early recurrence for hilar cholangiocarcinoma. Thus, we aimed to examine the optimal cut-off value for defining the early in patients with R0 resection of hilar cholangiocarcinoma and to investigate prognostic factors associated with early recurrence. Two hundred and fifty-eight patients with R0 resection of hilar cholangiocarcinoma between 2000 and 2015 were included. The minimum P value approach was used to define the optimal cut-off of early recurrence. The prognostic factors associated with early recurrence were investigated. The optimal cut-off value for dividing patients into early and non-early recurrence groups after R0 resection of hilar cholangiocarcinoma was 12 months. Sixty-two patients were recorded as early recurrence, and the remaining 196 patients were labeled as non-early recurrence. Multivariate logistic regression analysis indicated lymph node metastasis (OR = 2.756, 95% CI 1.409-5.393; P = 0.003), poor differentiation (OR = 1.653; 95% CI 1.040-2.632; P = 0.034), increased postoperative CA 19-9 levels (OR = 1.965, 95% CI 1.282-3.013; P = 0.002), neutrophil-to-lymphocyte ratio > 3.41 (OR = 5.125, 95% CI 2.419-10.857; P < 0.001) and age > 60 years (OR = 2.018, 95% CI 1.032-3.947; P = 0.040) were independent determinants of early and non-early recurrence. Poor differentiation (HR = 2.609, 95% CI 1.600-4.252; P < 0.001), Bismuth classification type III/IV (HR = 2.510, 95% CI 1.298-4.852; P = 0.006) and perineural invasion (HR=2.380, 95% CI 1.271-4.457; P = 0.007) were independent factors of overall survival in the subgroup of patients who developed early recurrence. The optimal cut-off value for dividing early recurrence after R0 resection of hilar cholangiocarcinoma was 12 months. Tumor differentiation, Bismuth classification, and perineural invasion were independent factors of overall survival in the subgroup of patients with early recurrence. Patients with risk factors should be monitored closely after curative surgery.

Comparative analysis of different hepatico-jejunostomy techniques for treating adult type I choledochal cyst.

OBJECTIVE: To compare Roux-en-Y hepatico-jejunostomy with complete resection of the cyst or incomplete resection with 1-cm remnant proximal cyst wall in treating adult type I choledochal cyst (CC). METHODS: The medical records of 267 adult patients with type I CC from January 1998 to December 2015 were reviewed retrospectively. Among them, 171 underwent Roux-en-Y hepatico-jejunostomy with complete resection (PBD 0-cm group) and 96 underwent Roux-en-Y hepatico-jejunostomy with 1-cm proximal cyst wall left (PBD 1-cm group). The short- and long-term post-operative complications were compared between the two groups. RESULTS: No significant difference was observed in operative time or anastomotic diameter between the two groups. The incidence of perioperative complications was significantly higher in the PBD 1-cm group than that in the PBD 0-cm group (28.1% vs 14.0%, p=0.005), especially post-operative cholangitis (7.3% vs 1.2%, p=0.021). The incidence of long-term post-operative complications was not significantly different, including anastomotic stricture, reflux cholangitis, intra-hepatic bile duct stones and bile leak (all p >0.05). Post-operative intra-pancreatic biliary malignancy occurred in one patient in the PBD 0-cm group at 25 months and one patient in the PBD 1-cm group at 5 month, respectively. Anatomical site malignancy was observed in one patient in the PBD 1-cm group at 10 months. CONCLUSION: Ease of performing anastomosis does not justify retaining a segment of choledochal cyst in type I CC due to its higher risk of post-operative complication and malignancy. A complete excision of the CC with anastomosis to the healthy proximal bile duct is necessary in treatment of type I CC.

Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required?

OBJECTIVE: The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. METHODS: We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. RESULTS: There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). CONCLUSIONS: Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.

Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma.

BACKGROUND: The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9). METHODS: Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated. RESULTS: A total of 228 patients were enrolled: 175 PM(-) without additional resection patients (group A), 21 PM(-) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months; P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05). CONCLUSIONS: HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.