Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma

AIM To evaluate the long-term effectiveness and late toxicities of paclitaxel(PTX) plus cisplatin(DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer.METHODS Between 2008 and 2011, 76 patients were enrolled in a phase Ⅱ study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy(68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP(25 mg/m^2 per day for 3 d) and PTX(175 mg/m^2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern.RESULTS A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient(heart failure). In log-rank analysis, the pretreatment stage(stage Ⅱ + Ⅲ: 36.1 mo vs stage Ⅳ: 14.9 mo) and the completed cycle(1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors(P = 0.037 < 0.05 and P = 0.013 < 0.05).CONCLUSION Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer.

Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread

The most common malignancy of biliary tract is gallbladder cancer(GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a verypoor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer(GC) is locoregional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography(CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly.

Loco-regional intervention for hepatocellular carcinoma

Anatomic location/size and number of lesions,inadequate volume of future liver remnant,or poor coexisting premorbid conditions preclude surgery in the majority of patients with hepatocellular carcinoma(HCC).Liver transplantation can cure some patients with poor liver function,but few patients are eligible because of scarcity of donors.Without specific anti-cancer treatment,the prognosis of HCC is poor.Various locoregional therapies are used to treat patients who are not candidates for surgery,and have emerged as tools for palliation,tumor downstaging,and bridging therapy prior to liver transplantation.Currently,local ablative therapy even competes with partial hepatectomy and liver transplantation as a primary treatment for small HCC.HCC is well suited to treatment with loco-regional therapy because it has a tendency to stay within the liver,with distant metastasis generally occurring late in the course of disease.This suggests that an effective local-regional therapy can have a great impact on HCC patients who are not candidates for surgical treatment.Loco-regional therapy can further be justified because patients with HCC usually die of liver failure consequent to intrahepatic growth resulting in liver tissue destruction,rather than extrahepatic metastases.

Outcomes of loco-regional therapy for down-staging of hepatocellular carcinoma prior to liver transplantation

BACKGROUND: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade. Many patients with HCC who were beyond the Milan criteria were allowed to receive a liver transplantation (LT) once the HCC was successfully down-staged. This retrospective study aimed to analyze the outcomes of LRTs prior to LT in patients with HCC beyond the Milan criteria. METHODS: We analyzed 56 patients treated from June 2006 to March 2010: 22 met the Milan criteria (T1+T2, 39.3%), 16 had T3 tumors (28.6%), and 11 had T4a tumors (19.6%), while 7 were suspected of tumor vascular invasion (T4b, 12.5%). All patients underwent preoperative LRTs, including transcatheter arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, liver resection, and/or microwave coagulation therapy. The number of the patients who were successfully down-staged before LT, the types of LRTs used before LT, and their outcomes after LT were recorded. RESULTS: Eleven patients had necrotic tumors (pT0, 19.6%); 6 had pT1 tumors (10.7%), 22 had pT2 tumors (39.3%), 6 had pT3 tumors (10.7%), 5 had pT4a tumors (8.9%), and 6 had pT4b tumors (10.7%). The histopathologic tumors of 39 patients (69.6%) were down-staged and met the established Milan criteria (pT0-2). Imaging-proven under-staging was present in 5 HCC patients (8.9%) who had tumors involving the intrahepatic venous system. Twenty-three patients (41.1%) had stable HCC and 10 (17.9%) died. The 1-, 3- and 4-year survival rates were 96%, 73% and 61%, respectively, with a mean survival time of 22.29±1.63 months. Six patients died of tumorrecurrence. The 1-, 3- and 4-year recurrence-free survival (RFS) rates were 88%, 75% and 66%, respectively. The 3-year RFS of patients with pT0-2 tumors was 82%, which was markedly greater than that of patients with pT3 tumors (63%, P=0.018) or pT4 tumors (17%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was greater than that of patients with pT4 tumors, the difference was not significant. CONCLUSIONS: Successful down-staging of HCCs can be achieved in the majority of carefully selected patients by LRTs. Importantly, patients who are successfully down-staged and undergo LT may have a higher RFS rate.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

Globe penetration during loco-regional anesthesia: prevalence and review of cases

AIM: To describe prevalence and different clinical signs and management of cases with penetrating eye injuries during loco-regional anesthesia for ophthalmic surgery. METHODS: A retrospective review of clinical records was carried out, identifying cases of globe penetration secondary to peribulbar anesthesia injection during 5 y activity in Centro de Oftalmología Barraquer. RESULTS: A total of 17 460 needle-based ocular anesthesia procedures were performed in our centre and 4 cases of globe penetration were recorded with an estimated prevalence of 0.024%. Globe penetrations were always detected in the first 24 h after surgery. Vitreous haemorrhage was found in all the cases. Two eyes presented retinal detachment and two eyes choroidal detachment(CD). The initial surgical approach was performed within the first 48 h. Silicone oil was used as tamponade in three eyes and the fourth case remained only with air. Detachments were solved successfully in all the cases. Functional results varied among cases, depending on ocular remarkable antecedent and globe penetration with or without retinal or CD.CONCLUSION: Prevalence of globe penetration during loco-regional anesthesia is low in our centre. Physicians should consider the possibility of globe penetration in eyes with postoperative atypical appearance after locoregional anesthesia. Immediate B-scan ultrasonography is recommended in suspicious cases with a dense vitreous haemorrhage. An early vitrectomy surgery in conjunction with laser or cryotherapy at the penetration sites is essential for good anatomical and functional results.

Accuracy of Ultrasound Examination of Loco-Regional Lymph Nodes in Breast Cancer Follow-Up and Its Role in the Axillary Surgical Management

Objective: Major international guidelines have not standardized the sequence of diagnostic examinations during the follow-up of a patient with a diagnosed breast cancer. The aim of this study is to investigate the accuracy of sonography in the diagnosis of loco-regional lymphatic recurrences in comparison to the core needle biopsy results. Materials and Methods: Among 6455 patients who were followed up with clinical examination, mammography and ultrasound between January 2004 and November 2011, 125 (1.93%) patients had to be investigated with a core needle biopsy of a sonographically suspicious loco-regional lymph node. Results: Among the whole series, a total of 142 ultrasound-guided core needle biopsies were performed. Follow-up for the primary tumor lasted for a median time of 6.1 years (range 1 - 27 years). Ultrasound of suspicious loco-regional lymph nodes showed a sensitivity of 89.5%, a specificity of 87.1% and a positive predictive value of 89.5%. Conclusions: In our experience, ultrasound of suspicious loco-regional lymph nodes showed good accuracy and it should be a part of the standard examinations performed during follow-up for breast cancer.

Outcomes associated with the intention of loco-regional therapy prior to living donor liver transplantation for hepatocellular carcinoma

BACKGROUND Loco-regional therapy for hepatocellular carcinoma(HCC) during the period awaiting liver transplantation(LT) appears to be a logical approach to reduce the risk of tumor progression and dropout in the waitlist.Living donor LT(LDLT)offers a flexible timing for transplantation providing timeframe for well preparation of transplantation.AIM To investigate outcomes in relation to the intention of pre-transplantation locoregional therapy in LDLT for HCC patients.METHODS A total of 308 consecutive patients undergoing LDLTs for HCC between August2004 and December 2018 were retrospectively analyzed.Patients were grouped according to the intention of loco-regional therapy prior to LT,and outcomes of patients were analyzed and compared between groups.RESULTS Overall,38 patients(12.3%) were detected with HCC recurrence during the follow-up period after LDLT.Patients who were radiologically beyond the University of California at San Francisco criteria and received loco-regional therapy as down-staging therapy had significant inferior outcomes to other groups for both recurrence-free survival(RFS,P < 0.0005) and overall survival(P= 0.046).Moreover,patients with defined profound tumor necrosis(TN) by locoregional therapy had a superior RFS(5-year of 93.8%) as compared with others(P= 0.010).CONCLUSION LDLT features a flexible timely transplantation for patient with HCC.However,the loco-regional therapy prior to LDLT does not seem to provide benefit unless a certain effect in terms of profound TN is noted.

Impact and the delivery of loco-regional treatment for hepatocellular carcinoma during the COVID-19 pandemic

Hepatocellular carcinoma(HCC)is the second most lethal tumour,with therapies broadly divided into curative and palliative intent.Unfortunately,the majority of HCCs were found to be unresectable at diagnosis.Advances in novel loco-regional therapies have given patients with unresectable HCC a vital chance for disease control and survival.However,the COVID-19 pandemic has greatly shaped and impacted treatment protocols and delivery for HCC patients.This review article aims to describe the impact of the COVID-19 pandemic on the delivery of locoregional treatment modalities for HCC and compare treatment trends between the pre-pandemic and pandemic eras.Treatment of HCC involves complex collaboration between clinical professionals within their local and global healthcare institutions.The COVID-19 pandemic has had a profound impact on the treatment of HCC.The delivery of loco-regional treatment for HCC will need to adapt to each healthcare system’s unique structure.

Irreversible electroporation for the management of pancreatic cancer: Current data and future directions

Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.

Postoperative Analgesia for Abdominal Laparoscopic Surgery: Tap Block vs Peri-Orificial Infiltrations

Introduction/Purpose: The “transverse abdominal plane block” or TAP block was described by Rafi in 2001. It describes an approach to the neurofascial plane of the transverse abdominal muscle via the Jean-Louis Petit triangle and provides analgesia of the entire homolateral hemi abdomen. The aim of our study was to compare post-operative analgesia and post-operative morphine requirements between transverse abdominal plane block (TAP) and peri-orificial infiltration during laparoscopic abdominal surgery. Material and method: Prospective, randomized study conducted over a 2-year period. The study was conducted in the operating theatre of the Saint Louis Regional Hospital in Senegal. All adult patients undergoing laparoscopic abdominal surgery were included. Clinical aspects, pain scales and morphine consumption were analyzed. Results: A total of 60 patients were enrolled: 30 patients in the TAP group and 30 patients in the infiltration group. The average age was 32.9 years. The indications for laparoscopy were acute appendicitis in 50% of cases, gallbladder stones in 16% and inguinal hernia in 8%. For the TAP group, the mean numerical pain scale was 3.9 at 6 hours post-operatively and 2.1 at 24 hours post-operatively. For the infiltration group, the mean numerical pain scale was 4.3 at 6 hours post-op and 3 at 24 hours post-op. Morphine consumption at 6 hours post-op was on average 0.4 mg/patient for the TAP group and 0.9 mg/patient for the infiltration group. Discussion/conclusion: Analgesia provided by ultrasound-guided TAP block for laparoscopic abdominal surgery appears to be identical to periorificial infiltration. However, the simplicity and reproducibility of ultrasound-guided TAP block gives it a definite advantage.

Current status of radiofrequency ablation of hepatocellular carcinoma

Loco-regional treatments for hepatocellular carcinoma(HCC) are important alternatives to curative transplantation or resection.Among them,radiofrequency ablation(RFA) is accepted as the most popular technique showing excellent local tumor control and acceptable morbidity.The current role of RFA is well documented in the evidence-based practice guidelines of European Association of Study of Liver,American Association of Study of the Liver Disease and Japanese academic societies.Several randomized controlled trials have confirmed that RFA is superior to percutaneous ethanol injections in terms of local tumor control and survival.The overall survival after RFA is comparable to after surgical resection in a selected group of patients with smaller(< 3 cm) tumors.Currently,the clinical benefits of combined RFA with transarterial chemoembolization for intermediate stage HCC are increasingly being explored.Here we review the ongoing technical advancements of RFA and future potential.

Rationale and techniques of cytoreductive surgery and peritoneal chemohyperthermia

The evolution of loco-regional treatments has occurred in the last two decades and has deeply changed the natural history of primitive and secondary peritoneal surface malignancies.Several phase Ⅱ-Ⅲ studies have proved the effectiveness of the combination of cytoreductive surgery with peritoneal chemohyperthermia.Cytoreductive surgery allows the reduction of the neoplastic mass and increases tumoral chemosensitivity.The development of chemohyperthermia finds its origins in the necessity to exceed the limits of intraperitoneal chemotherapy performed in normothermia.It permits a continuous high concentration gradient of chemotherapeutic drugs between the peritoneal cavity and the plasma compartment to and a more uniform distribution throughout the abdominal cavity compared to systemic administration.

Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common cause of liver malignancy and the fourth leading cause of cancer deaths universally.Cure can be achieved for early stage HCC,which is defined as 3 or fewer lesions less than or equal to 3 cm in the setting of Child-Pugh A or B and an ECOG of 0.Patients outside of these criteria who can be down-staged with loco-regional therapies to resection or liver transplantation(LT)also achieve curative outcomes.Traditionally,surgical resection,LT,and ablation are considered curative therapies for early HCC.However,results from recently conducted LEGACY study and DOSISPHERE trial demonstrate that transarterial radio-embolization has curative outcomes for early HCC,leading to its recent incorporation into the Barcelona clinic liver criteria guidelines for early HCC.This review is based on current evidence for curativeintent loco-regional therapies including radioembolization for early-stage HCC.

Radiological imaging and non-surgical local treatments for cholangiocarcinoma

Cholangiocarcinoma(CC)is a malignancy with a very heterogeneous spectrum of morphopathological and prognostic characteristics.Diagnostic imaging is fundamental for early detection,preoperative staging,and resectability assessment,as well as early recognition of prognostic factors.Radical surgical treatment is limited by disease stage and technical feasibility.Interventional radiology has acquired a critical function in addressing disease control and survival improvement through loco-regional therapies,specifically in the setting of intrahepatic CC.In this review,we will describe the current state of art of diagnostic imaging,focusing on intrahepatic CC and proximal extrahepatic CC,and delineate the available loco-regional therapies strategies for unresectable intrahepatic CC.