Surgical salvage therapy of anal cancer

AIM:To evaluate the results of salvage resection in the management of persistent or locally recurrent anal canal cancer.METHODS: Details of all patients with anal canal cancer treated from 1978 to 1994 at Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) were reviewed retrospectively.Sixteen patients who presented with persistent or locally recurrent anal canal cancer received salvage surgery. Before surgery all of the patients had received radiotherapy alone as their primary treatments.RESULTS:Of the 16 patients, 14 received salvage abdominoperineal resection (APR) and two had transanal local excision. There were no deaths attributable to operation.Delayed healing of the perineal wound occurred in eight patients. Complications unrelated to the perineal wound were found in five patients. The median follow-up time was 120 (range 5-245) months after salvage surgery. Nine patients died of disease progression, with a median survival time of 16 (range 5-27) months. Six patients had a long-term survival.CONCLUSION:Salvage resection after radiotherapy can yield a long-time survival in selected patients with anal canal cancer. However it offers little hope to patients with T4 and/or N2-3 tumors.

Clinical analysis of HCPT plus FOLFOX4 regimen as salvage therapy for patients with advanced gastric cancer

Objective: To evaluate the therapeutic as well as side effects of hydroxycamptothecin (HCPT) plus FOLFOX4 regimen as salvage therapy for patients with advanced gastric cancer. Methods: A total of 19 patients with advanced gastric cancer received HCPT plus FOLFOX4 as salvage therapy, in detail, Oxaliplatin 85 mg/m2 was given intravenously on day 1, CF 200 mg/m2, 5-Fu 400 mg/m2 given in bolus immediately after CF, days 1-2; 5-Fu 600 mg/m2 given continuously after bolus for 22 h on day 1, day 2, HCPT given intravenously at dosage of 10 mg/m2 on days 1-2. Therapeutic effects were evaluated at least after two cycles of treatment. Results: 17 cases among the 19 patients were valid for response evaluation, with CR 1 , PR 6, SD 4, PD 6. The response rate was 41.2%. For the 12 patients with liver metastasis, response rate of the liver foci was 50%. The main toxicities were bone marrow suppression, nausea and vomiting, and peripheral neuropathy; there were no chemotherapy-related deaths. Conclusion: The combination regimen with HCPT plus FOFLOX4 regimen was effective as salvage therapy for patients with advanced gastric cancer, with particularly high response rate for liver metastasis, and the side effects were tolerable and manageable.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Salvage locoregional therapies for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the second most common cause of cancerrelated death worldwide.Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies,recurrence rates remain high.In contrast to first-line treatment for HCC,which relies on several factors,including clinical staging,tumor burden,and liver function,there is no consensus or general treatment recommendations for recurrent HCC(R-HCC).Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC.Herein,we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.

Repeat peroral endoscopic myotomy with simultaneous submucosal and muscle dissection as a salvage option for recurrent achalasia

BACKGROUND For recurrent achalasia after initial peroral endoscopic myotomy(POEM)failure,repeat POEM(Re-POEM)has been reported as a treatment option.However,severe esophageal interlayer adhesions caused by previous procedures impede the successful establishment of a submucosal tunnel and lead to aborted Re-POEM procedures.Our team previously described POEM with simultaneous submucosal and muscle dissection(POEM-SSMD)as a feasible solution for achalasia with severe interlayer adhesions.AIM To investigate the effectiveness and safety of Re-POEM with simultaneous submucosal and muscle dissection(Re-POEM-SSMD).METHODS A total of 1049 patients with achalasia who underwent successful endoscopic myotomy at the Digestive Endoscopic Center of Chinese PLA General Hospital from December 2014 to May 2022 were reviewed.Patients with recurrent achalasia who experienced initial POEM clinical failure were retrospectively included in this study.The primary endpoint was retreatment clinical success,defined as an Eckardt score≤3 during the postretreatment follow-up and no need for additional treatment.Procedure-related adverse events,changes in manometric lower esophageal sphincter(LES)pressure and reflux complications,as well as procedure-related parameters,were recorded.RESULTS Sixteen patients underwent Re-POEM(9 patients)or Re-POEM-SSMD(7 patients)successfully at a median of 45.5 mo(range,4-95 mo)after initial POEM.During a median followup period of 31 mo(range,7-96 mo),clinical success(Eckardt score≤3)was achieved in 8(88.9%)and 6(85.7%)patients after Re-POEM and Re-POEM-SSMD,respectively(P=0.849).The median Eckardt score dropped from 4(range,3-8)at preretreatment to 1(range,0-5)at postretreatment in the Re-POEM group(P=0.025)and from 5(range,2-8)to 2(range,0-4)in the Re-POEM-SSMD group(P<0.001).The mean manometric LES pressure decreased from 23.78±9.04 mmHg to 11.45±5.37 mmHg after Re-POEM(P<0.001)and from 26.80±7.48 mmHg to 11.05±4.38 mmHg after Re-POEM-SSMD(P<0.001).No serious adverse events were recorded in both groups.CONCLUSION In conclusion,Re-POEM-SSMD appears to be a safe and effective salvage therapy for recurrent achalasia with severe interlayer adhesions.

Chidamide,Decitabine,Cytarabine,Aclarubicin,and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia:A Retrospective Study from a Single-Center

Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.

CLAG-M chemotherapy followed by umbilical cord blood stem cell transplantation for primary refractory acute myeloid leukaemia in a child:A case report

BACKGROUND The prognosis of paediatric primary refractory/relapsed acute myeloid leukaemia(R/R AML)remains poor.Intensive therapy is typically used as salvage treatment for those with R/R AML.No data are currently available about the use of the CLAG-M protocol as salvage therapy in paediatric patients with R/R AML.CASE SUMMARY An 8-year-old patient was diagnosed with acute myeloid leukaemia by bone marrow morphology and immunophenotype.The patient showed poor response to two cycles of induction therapy with 60%blast cells in the bone marrow after the second induction cycle.The patient achieved complete remission after being treated with the CLAG-M protocol as salvage therapy before undergoing umbilical cord blood stem cell transplantation.Morphological complete remission with haematological recovery has hitherto been maintained over 4 mo.Abnormal gene mutations detected at diagnosis were undetectable after haematopoietic stem cell transplantation.CONCLUSION Here we present a paediatric patient with primary refractory acute myeloid leukaemia who was successfully treated with the CLAG-M protocol.Given the positive results of the presented patient,large-scale clinical studies are required to assess the role of the CLAG-M protocol in the salvage treatment of refractory or relapsed AML in childhood.

Second and third line treatment options for Helicobacter pylori eradication

Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and thirdline treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.

Difficult treatment decisions in autoimmune hepatitis

Treatment decisions in autoimmune hepatitis are complicated by the diversity of its clinical presentations,uncertainties about its natural history,evolving opinions regarding treatment end points,varied nature of refractory disease,and plethora of alternative immu-nosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in au-toimmune hepatitis were identifi ed by Medline search up to October 2009 and 32 years of personal experi-ence. Autoimmune hepatitis may have an acute severe presentation,mild in? ammatory activity,lack autoan-tibodies,exhibit atypical histological changes (centri-lobular zone 3 necrosis or bile duct injury),or have variant features reminiscent of another disease (overlap syndrome). Corticosteroid therapy must be instituted early,applied despite the absence of symptoms,or modified in an individualized fashion. Pursuit of normal liver tests and tissue is the ideal treatment end point,but this objective must be tempered against the risk of side effects. Relapse after treatment withdrawal requires long-term maintenance therapy,preferably with azathioprine. Treatment failure or an incomplete response warrants salvage therapy that can include conventional medications in modified dose or empiricaltherapies with calcineurin inhibitors or mycophenolate mofetil. Liver transplantation supersedes empirical drug therapy in decompensated patients. Elderly and pregnant patients warrant treatment modifications. Difficult treatment decisions in autoimmune hepatitis can be simplified by recognizing its diverse manifestations and individualizing treatment,pursuing realistic goals,applying appropriate salvage regimens,and identifying problematic patients early.

Management of autoimmune hepatitis:Focus on pharmacologic treatments beyond corticosteroids

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use butit can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

Early oral tongue cancer initially managed with surgery alone:Treatment of recurrence

Objective:To report T1-2N0 tongue cancer recurrences initially treated with sur-gery alone. Methods:Between 1990 and 2010, 27 patients at tertiary hospital referral center institution were treated with curative intent for locoregional recurrence after initial glossectomy with or without neck dissection for T1-2N0 tongue cancer. None had received adjuvant postopera-tive radiation as a component of the original treatment. Results:Median time to locoregional recurrence was 12 months (range 5e39 months) and 78%of failures occurred in the first 2 years. Most treatment failures were local (63%). Salvage strat-egy was risk-adapted by individual patient. The 5-year disease specific survival (DSS) was 61%. Patients with local recurrences alone fared significantly better than those with regional recur-rences (5-yr DSS:86%vs. 22%, P Z 0.0018). Local recurrences were usually treated by surgery alone, while regional recurrences were more commonly treated with combined modality treat-ment (PZ 0.005).Conclusions:Recurrence of early stage oral tongue cancer can be successfully salvaged in a majority of cases. Patients developing regional recurrence have significantly worse prognosis than those with local failures.