Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

RADIOIMMUNOTHERAPY IN TREATMENT OF UNRESECTABLE HEPATOMA－A REPORT OF 43 CASES

Forty-three patients with surgically verified unresectable hepatoma had been treated by radioimmunotherapy(RIT)using￣(131)I antiferritin antibidy as a part of multimodality treatment during 1985 - 1990.The shortand long-term responses were compared with those in control group of 39 patients with unresectable hepatoma receiving conventional multimodality treatment in the same period.The rates of the tumor shrinkage,serum AFP decline and sequence resction were 67. 4% (29/43),69.6%(16/23)and 30.2%(13/43)respectively,which were significantly higher than those in contrul group[23.1%(15/39),40.0%(8/20)and 10.3%(4/39),respectively].The 1-,3- and 5-year survival rates were 61.5%,40.4%and 35.4%,respectively,for the RIT group,and 51.2%,20.1% and 15.5% ,respectrely,for the control group.The tumor size,dose of RIT and sequence resection were identified as significant factors (P=0.005,0.025 and 0.006,respectively, with Cox analysis model in 13 influencing factors.The results indicate that RIT was an effective one in multimodality treatment,particularly in the conversion of unresectable to resectable tumor.

Current status of esophageal cancer treatment

Esophageal cancer(EC) remains one of the most common and aggressive diseases worldwide.This review discusses some debates in the modern management of the disease.Endoscopic procedures for early cancer(T1a-b) are now embedded in routine care and the challenge will be to more accurately select patients for endoscopic resection with or without adjuvant therapy.Perioperative multimodal therapies are associated with improved survival compared to surgery alone for locally advanced esophageal cancer.However, there is no global consensus on the optimal regimen.Furthermore, histological subtype(adenocarcinoma vs.squamous cell cancer) plays a role in the choice for treatment.New studies are underway to resolve some issues.The extent of the lymphadenectomy during esophagectomy remains controversial especially after neoadjuvant chemoradiation.The ideal operation balances between limiting surgical trauma and optimizing survival.Minimally invasive esophagectomy and enhanced recovery pathways are associated with decreased morbidity and faster recovery albeit there is no consensus yet what approach should be used.Finally, immune checkpoint inhibitors present promising preliminary results in the novel treatment of advanced or metastatic EC but their widespread application in clinical practice is still awaited.

Multimodal treatment in oligometastatic gastric cancer

Gastric cancer is generally diagnosed at an advanced stage,especially in countries without screening programs.Previously,the metastatic stage was synonymous with palliative management,and surgical indications were only for symptomatic relief.However,this therapeutic option is associated with poor prognosis.A subgroup of patients with limited metastatic disease could benefit from intensive treatment.A combination of chemotherapy,immunotherapy,and targeted therapy could help either maintain a resectable state for oligometastatic disease or diminish the metastasis size to obtain a complete resection configuration.This latter strategy is known as conversion therapy and has growing evidence with favorable outcomes.Oncosurgical approach of metastatic disease could prolong survival in selected patients.The challenge for the surgeon and oncologist is to identify these specific patients to offer the best multimodal management.We review in this article the actual evidence for the treatment of oligometastatic gastric cancer with curative intent.

Comprehensive multimodal management of borderline resectable pancreatic cancer:Current status and progress

Borderline resectable pancreatic cancer(BRPC)is a complex clinical entity with specific biological features.Criteria for resectability need to be assessed in combination with tumor anatomy and oncology.Neoadjuvant therapy(NAT)for BRPC patients is associated with additional survival benefits.Research is currently focused on exploring the optimal NAT regimen and more reliable ways of assessing response to NAT.More attention to management standards during NAT,including biliary drainage and nutritional support,is needed.Surgery remains the cornerstone of BRPC treatment and multidisciplinary teams can help to evaluate whether patients are suitable for surgery and provide individualized management during the perioperative period,including NAT responsiveness and the selection of surgical timing.

Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma

BACKGROUND: Curable outcome of unresectable hepato- cellular carcinoma ( HCC) was seldom encountered in the past. This study was designed to assess the role of down- staging followed by resection ( downstaging-resection) in the improvement of prognosis of unresectable HCC. METHODS: During the period of 1958-2003 , a total of 1085 patients were verified surgically to be unresectable. Of these patients, 139 received downstaging-resection, with a rate of 84.2% for coexisting cirrhosis and a median tumor diame- ter of 11.1 cm. Resection of the right lobe, hepatic hilum and bilateral cancer accounted for 97. 8% of the patients. Downstaging including hepatic artery ligation ( HAL) + he- patic artery chemo-infusion ( HAI ) was performed in 65.5% of the patients, HAL + HAI + radiotherapy/radioim- munotherapy in 29. 5%, and HAL or HAI alone in 5.0%. Retrospective analysis was made of the survival of patients with unresectable HCC, downstaging-resection rate and treatment pattern. RESULTS: In the 139 patients with downstaging-resection, the median interval between the first and second operation was 7.2 months and the 5-year survival rate calculated from the first operation was 48. 7%. In the 1085 patients with un- resectable HCC, their 5-year survival was 0% in the period of 1958-1973, 11.5% in the period of 1974-1988 and 19.3% in the period of 1989-2003. These figures were correlated with the increasing downstaging-resection rate from 0%, 9.0% to 15.6%, and the increasing percentage of triple or double combination treatment from 32.2%, 60.4% to 69.7%. The 5-year survival in triple treatment group was 24. 9%, double treatment 15.2%, and single treatment only 10.9%, which was also correlated with the downstaging-re- section rate of 34.6%, 16.2% and 1.8% respectively. CONCLUSIONS: Downstaging-resection plays a role in improving prognosis of unresectable HCC. Triple and double treatments provide a higher downstaging-resection rate and may result in better prognosis.

Preoperative therapy in locally advanced esophageal cancer

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer(T2 or greater or node positive); however, a high rate of disease recurrence(systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment(preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy(radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

PRIMARY MALIGNANT MELANOMA OF ESOPHAGUS: REPORT OF FOUR CASES AND REVIEW OF THE LITERATURES

Objective: To investigate the clinical features and prognosis of the primary malignant melanoma of esophagus, to try to find out a rational therapy and to evaluate the value of surgical resection. Methods: Retrospective study was conducted for four cases with Primary malignant melanoma of esophagus hospitalized from May 1975 to April 1999. The relevant literatures of primary malignant melanoma of esophagus in recent years were also reviewed. Results: Four patients received multimodality therapy including surgical resection. The survival time is 16 years, 53 months, 5 months and 6 months, respectively. Conclusion: Primary malignant melanoma of the esophagus has a poor prognosis. Surgical resection plays an important role and is indispensable. The patterns of combination treatment modality need further investigation. Preoperative therapy combined with surgical resection and post-operative therapy may be a better management.

Primary large cell neuroendocrine carcinoma in the common bile duct:First Asian case report

Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.

palliative care and end-stage colorectal cancer management:The surgeon meets the oncologist

Colorectal cancer (CRC) is a common neoplasia in the Western countries, with considerable morbidity and mortality. Every fifth patient with CRC presents with metastatic disease, which is not curable with radical intent in roughly 80% of cases. Traditionally approached surgically, by resection of the primitive tumor or stoma, the management to incurable stage IV CRC patients has significantly changed over the last three decades and is nowadays multidisciplinary, with a pivotal role played by chemotherapy (CHT). This latter have allowed for a dramatic increase in survival, whereas the role of colonic and liver surgery is nowadays matter of debate. Although any generalization is difficult, two main situations are considered, asymptomatic (or minimally symptomatic) and severely symptomatic patients needing aggressive management, including emergency cases. In asymptomatic patients, new CHT regimens allow today long survival in selected patients, also exceeding two years. The role of colonic resection in this group has been challenged in recent years, as it is not clear whether the resection of primary CRC may imply a further increase in survival, thus justifying surgery-related morbidity/mortality in such a class of short-living patients. Secondary surgery of liver metastasis is gaining acceptance since, under new generation CHT regimens, an increasing amount of patients with distant metastasis initially considered non resectable become resectable, with a significant increase in long term survival. The management of CRC emergency patients still represents a major issue in Western countries, and is associated to high morbidity/mortality. Obstruction is traditionally approached surgically by colonic resection, stoma or internal by-pass, although nowadays CRC stenting is a feasible option. Nevertheless, CRC stent has peculiar contraindications and complications, and its long-term cost-effectiveness is questionable, especially in the light of recently increased survival. Perforation is associated with the highest mortality and remains mostly matter for surgeons, by abdominal lavage/drainage, colonic resection and/or stoma. Bleeding and other CRC-related symptoms (pain, tenesmus, etc.) may be managed by several mini-invasive approaches, including radiotherapy, laser therapy and other transanal procedures.

MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases

Non-invasive image-guided precise photothermal/photodynamic therapy(PTT/PDT)has been proven to be an effective local treatment modality but incompetent against metastases.Hence,the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication.Herein,a magnetic resonance imaging(MRI)-visualized PTT/PDT agent(SIDP NMs)was constructed,and the efficacy of its multimodal combination with a programmed cell death 1(PD-1)inhibitor in the treatment of melanoma and metastases was studied.Due to the hydrophobic encapsulation of indocyanine green within the micellar core,SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser.In vitro cell experiments showed that SIDP NMs had a good killing effect.After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min,cell viability decreased significantly.Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs.When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI,the temperature of the tumor area rapidly increased from 32℃to 60.7℃in 5 min.In mouse melanoma ablation and distant tumor immunotherapy studies,SIDP NMs provided excellent MRI-guided PTT/PDT results and,when combined with PD-1 inhibitor,have great potential to cure primary tumors and eradicate metastases.

Post liver transplant recurrence in patients with hepatocellular carcinoma:not necessarily the end of the road!

Aim:We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma(HCC)recurrence post living donor liver transplantation(LDLT).Methods:Of 2363 LDLT’s performed between 2005 to mid 2018,435(18.4%)were for HCC within our expanded selection criteria(absence of extrahepatic disease and vascular invasion,irrespective of tumor size and number).Survival after recurrence,and prognostic factors for these patients were studied.Results:Of 435 LDLT patients,51%had HCC beyond Milan and 43%beyond UCSF criteria at the time of LDLT.pre-LT AFP>100 ng/mL and tumour FDG-18 PET avidity predicted overall survival(OS),whereas pre-LT AFP>100 ng/mL,UCSF criteria,and FDG-18 PET avidity predicted recurrence-free survival.Hundred patients(23%)developed HCC recurrence at a median time of 16 months(range 2-108 months)post LDLT.Lungs(53%),liver(37%),and bone(21%)were the most common sites of recurrence.Ninety-five patients received tyrosine kinase inhibitors(TKI)after recurrence and 62 received mTOR inhibitors(protocol-based after LDLT,or post recurrence).Surgical resection of metastases was performed in 14 patients,15 received stereotactic body radiotherapy,and 18 underwent ablation(radiofrequency,microwave ablation,transarterial chemoembolisation,or percutaneous ethanol injection).One-and 3-yr OS after recurrence were 57%,and 24%respectively,with a maximum post recurrence survival of 7.5 years.HCC recurrence within one year after LDLT(P=0.004,HR=2.38,95%CI:1.325-4.276),AFP>200 ng/mL at the time of recurrence(P=0.02,HR=2.075,95%CI:1.121-3.841),and recurrence at multiple sites(P=0.047,HR=1.831,95%CI:1.009-3.321)were poor prognostics factors for post recurrence survival.Multimodality management of recurrence using combined medical,surgical,ablative treatments and radiotherapy significantly improved survival compared to the use of TKI’s or mTORi’s alone,or in combination.Conclusion:In patients accepted for LDLT beyond the conventional size-number criteria,even after HCC recurrence,an aggressive approach using multimodality therapy,when possible,aids in further prolongation of survival.

Cancer: An unknown territory;rethinking before going ahead

Cancer is a disease of altered signaling and metabolism,causing uncontrolled divi-sion and survival of transformed cells.A host of molecules,factors,and conditions have been designated as underlying causes for the inception and progression of the disease.An enormous amount of data is available,system-wide interaction networks of the genes and proteins are generated over the years and have now reached up to a level of saturation,where we need to shift our focus to the more advanced and comprehensive methods and approaches of data analysis and visualization.Even with the availability of enormous literature on this one of the most pressing pathological conditions,a successful cure of the disease seems to be obscure.New treatment plans,like immunotherapy and precision medicine,are being employed for different studies.Nevertheless,their actual benefits to the patients would be known only after the evaluation of clinical data over the next few years.Therefore,we need to look at few fundamental challenges that should be addressed in more depth before we could devise bet-ter,rigorous,and comprehensive treatment plans and may successfully reach a possible cure of the disease.This article aims at bringing attention towards some fundamental gaps in our approach towards the disease that leads to failure in devising successful therapeutics.