Use of endoscopic ultrasound-guided gallbladder drainage as a rescue approach in cases of unsuccessful biliary drainage

This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.

Local recurrence rate as quality indicator in surgery for pancreatic cancer?

To the Editor: As we all know, even with the current advancements regarding novel chemotherapy regimens, patients affected by pancreatic cancer(PC) have an extremely dismal prognosis(5-year survival rate 12% for all stages in the National Cancer Institute SEER database). Among the patients undergoing surgical treatment, the prognosis is mostly affected by recurrence. PC after surgery has mainly four patterns of recurrence, isolated or variously associated with each other: local, lymph nodal, peritoneal or distant(liver, lung, other sites).

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Problems faced by evidence-based medicine in evaluating lymphadenectomy for gastric cancer

Gastric cancer surgical management differs between Eastern Asia and Western countries. Extended lymphadenectomy (D2) is the standard of care in Japan and South Korea since decades, while the majority of United States patients receive at most a limited lymphadenectomy (D1). United States and Northern Europe are considered the scientific leaders in medicine and evidence-based procedures are the cornerstone of their clinical practice. However, surgeons in Eastern Asia are more experienced, as there are more new cases of gastric cancer in Japan (107898 in 2012) than in the entire European Union (81592), or in South Korea (31269) than in the entire United States (21155). For quite a long time evidence-based medicine (EBM) did not solve the question whether D2 improves long-term prognosis with respect to D1. Indeed, eastern surgeons were reluctant to perform D1 even in the frame of a clinical trial, as their patients had a very good prognosis after D2. Evidence-based surgical indications provided by Western trials were questioned, as surgical procedures could not be properly standardized. In the present study we analyzed indications about the optimal extension of lymphadenectomy in gastric cancer according to current scientific literature (2008-2012) and surgical guidelines. We searched PubMed for papers using the key words “lymphadenectomy or D1 or D2” AND “gastric cancer” from 2008 to 2012. Moreover, we reviewed national guidelines for gastric cancer management. The support to D2 lymphadenectomy increased progressively from 2008 to 2012: since 2010 papers supporting D2 have achieved a higher overall impact factor than the other papers. Till 2011, D2 was the procedure of choice according to experts’ opinion, while three meta-analyses found no survival advantage after D2 with respect to D1. In 2012-2013, however, two meta-analyses reported that D2 improves prognosis with respect to D1. D2 lymphadenectomy was proposed as the standard of care for advanced gastric cancer by Japanese National Guidelines since 1981 and was adopted as the standard procedure by the Italian Research Group for Gastric Cancer since the Nineties. D2 is now indicated as the standard of surgical treatment with curative intent by the German, British and ESMO-ESSO-ESTRO guidelines. At variance American NCCN guidelines recommend a D1+ or a modified D2 lymph node dissection. In conclusion, D2 lymphadenectomy, originally developed by Eastern surgeons, is now becoming the procedure of choice also in the West. In gastric cancer surgery EBM is lagging behind national guidelines, rather than preceding and orienting them. To eliminate this lag, EBM should value to a larger extent Eastern Asian literature and should evaluate not only the quality of the study design but also the quality of surgical procedures.

Microbiota-gut-brain axis and its affect inflammatory bowel disease:Pathophysiological concepts and insights for clinicians

Despite the bi-directional interaction between gut microbiota and the brain not being fully understood,there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease(IBD)pathogenesis,with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves,by acting on the different components of this system,mainly by modifying the microbiota.With the emergence of precision medicine,strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients.The aim of this narrative review is to elaborate on the concept of the gutbrain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature,and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.

Hyperthermic intraperitoneal chemotherapy and colorectal cancer:From physiology to surgery

The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy(HIPEC) and cytoreductive surgery(CRS) used in colorectal cancer(CRC).We focus on principal biological aspects of CRC,hyperthermia effects,and surgical procedures.We searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment(CRS + HIPEC) against local and advanced CRC.In the literature,from several studies,it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall survival.Despite these studies,there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with CRC.Even if the concept is still not very clear and shared,after a careful evaluation of the published data,and after some technical and pathophysiological descriptions,we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced(pT4) CRC with peritoneal metastases.

Hepatocellular carcinoma in viral and autoimmune liver diseases:Role of CD4+CD25+Foxp3+regulatory T cells in the immune microenvironment

More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.

Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas

Objective:Squamous cell carcinoma(SCC)represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma(OSCC),a tumor associated with different clinical outcomes and linked to human papilloma virus(HPV)status.Translational research has few available in vitro models with which to study the different pathophysiological behavior of OSCCs.The present study proposes a 3-dimensional(3 D)biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix(ECM)and cancer cells.Methods:We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on scaffolds.We also explored cancer cell adaptation to the 3 D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary cultures.Results:HPV-positive and HPV-negative cell lines were successfully grown in the 3 D model and displayed different collagen fiber organization.The 3 D cultures induced an increased expression of markers related to epithelial–mesenchymal transition(EMT)and to matrix interactions and showed different migration behavior,as confirmed by zebrafish embryo xenografts.The expression of hypoxia-inducible factor 1α(1α)and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold area.Furthermore,the 3 D cultures activated drug-resistance signaling pathways in both cell lines and primary cultures.Conclusions:Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of OSCCs.Moreover,3 D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.

Some pathogenic characters of paratyphoid Salmonella enterica strains isolated from poultry

Objective: To investigate some pathogenic characters of Salmonella enterica strains isolated from poultry.Methods: Twenty-three genetically distinct Salmonella enterica strains, of different serovars and pulsotype, were examined for virulence traits. Resistance to gastric acid environment was estimated by measuring the percentage of survived bacterial cells after exposure for 2 h to a synthetic gastric juice. Strains were analyzed with PCR for the presence of the following virulence genes: mgtC and rhu M located on SPI-3, sopB and pipB located on SPI-5, Salmonella virulence plasmid(spv)R(spvR), spvB and spvC located on Salmonella plasmid virulence and sodCI, sopE, and gipA located on prophage.Finally, resistance to 21 antibiotics was tested with Kirby–Bauer method.Results: A percentage of 82.60% of strains were resistant to gastric environment after induction and 60.87% of the strains exhibited constitutive resistance too. Nineteen different virulence profiles were detected. The phage related genes sodCI and sopE and the plasmid mediated operon spvR, spvB and spvC(spvRBC) were detected in 82.60%,47.82% and 52.17% of strains, respectively. Typhimurium and Enteritidis strains showed the highest number of virulence genes. Twenty-one different antibiotic resistance profiles were obtained and two isolates(Typhimurium and Enteritidis) resulted sensible to all the tested molecules. The ampicillin, streptomycin, sulfonamide and tetracycline resistance profile was detected in seven isolates(30.43%).Conclusion: Our results show that paratyphoid Salmonella strains with several characters of pathogenicity, that may be cause of severe pathology in animals and humans, are circulating among poultry.

Prediction of genetic value for sweet cherry fruit maturity among environments using a 6K SNP array

The timing of fruit maturity is an important trait in sweet cherry production and breeding.Phenotypic variation for phenology of fruit maturity in sweet cherry appears to be under strong genetic control,but that control might be complicated by phenotypic instability across environments.Although such genotype-by-environment interaction(G×E)is a common phenomenon in crop plants,knowledge about it is lacking for fruit maturity timing and other sweet cherry traits.In this study,1673 genome-wide SNP markers were used to estimate genomic relationships among 597 weakly pedigree-connected individuals evaluated over two seasons at three locations in Europe and one location in the USA,thus sampling eight‘environments’.The combined dataset enabled a single meta-analysis to investigate the environmental stability of genomic predictions.Linkage disequilibrium among marker loci declined rapidly with physical distance,and ordination of the relationship matrix suggested no strong structure among germplasm.The most parsimonious G×E model allowed heterogeneous genetic variance and pairwise covariances among environments.Narrow-sense genomic heritability was very high(0.60–0.83),as was accuracy of predicted breeding values(>0.62).Average correlation of additive effects among environments was high(0.96)and breeding values were highly correlated across locations.Results indicated that genomic models can be used in cherry to accurately predict date of fruit maturity for untested individuals in new environments.Limited G×E for this trait indicated that phenotypes of individuals will be stable across similar environments.Equivalent analyses for other sweet cherry traits,for which multiple years of data are commonly available among breeders and cultivar testers,would be informative for predicting performance of elite selections and cultivars in new environments.

Dengue and falciparum malaria co-infection in travelers returning from Burkina Faso:Report of two cases in Northeastern Italy

Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus(DENV) concurrent infection is possible and often under-recognized in geographical areas where these infections are both endemic.Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014.Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated;the treatment of dengue was symptomatic.Outcomes: The patients were discharged in good general condition.Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection.

Multiple quantitative trait loci contribute to resistance to bacterial canker incited by Pseudomonas syringae pv.actinidiae in kiwifruit(Actinidia chinensis)

Pseudomonas syringae pv.actinidiae(Psa)biovar 3,a virulent,canker-inducing pathogen is an economic threat to the kiwifruit(Actinidia spp.)industry worldwide.The commercially grown diploid(2×)A.chinensis var.chinensis is more susceptible to Psa than tetraploid and hexaploid kiwifruit.However information on the genetic loci modulating Psa resistance in kiwifruit is not available.Here we report mapping of quantitative trait loci(QTLs)regulating resistance to Psa in a diploid kiwifruit population,derived from a cross between an elite Psa-susceptible‘Hort16A’and a resistant male breeding parent P1.Using high-density genetic maps and intensive phenotyping,we identified a single QTL for Psa resistance on Linkage Group(LG)27 of‘Hort16A’revealing 16–19%phenotypic variance and candidate alleles for susceptibility and resistance at this loci.In addition,six minor QTLs were identified in P1 on distinct LGs,exerting 4–9%variance.Resistance in the F1 population is improved by additive effects from‘Hort16A’and P1 QTLs providing evidence that divergent genetic pathways interact to combat the virulent Psa strain.Two different bioassays further identified new QTLs for tissue-specific responses to Psa.The genetic marker at LG27 QTL was further verified for association with Psa resistance in diploid Actinidia chinensis populations.Transcriptome analysis of Psa-resistant and susceptible genotypes in field revealed hallmarks of basal defense and provided candidate RNA-biomarkers for screening for Psa resistance in greenhouse conditions.

Follow-up after gastrectomy for cancer:results of an international web round table

Oncological follow-up after radical gastrectomy for cancer still represents a discrepancy in the field, with many retrospective series demonstrating that early diagnosis of recurrence does not result in an improvement in patient survival; yet, many centers with high quality of care still provide routine patient follow-up after surgery by clinical and instrumental controls. This was the topic for a web round table entitled “Rationale and limits of oncological follow-up after gastrectomy for cancer” that was launched one year before the 10th International Gastric Cancer Congress. Authors having specific expertise were invited to comment on their previous publications to provide the subject for an open debate. During a three-month-long discussion, 32 authors from 12 countries participated, and 2299 people visited the dedicated web page. Substantial differences emerged between the participants: authors from Japan, South Korea, Italy, Brazil, Germany and France currently engage in instrumental follow-up, whereas authors from Eastern Europe, Peru and India do not, and British and American surgeons practice it in a rather limited manner or in the context of experimental studies. Although endoscopy is still considered useful by most authors, all the authors recognized that computed tomography scanning is the method of choice to detect recurrence; however, many limit follow-up to clinical and biochemical examinations, and acknowledge the lack of improved survival with early detection.

Feasibility and safety of self-expandable metal stent in nonmalignant disease of the lower gastrointestinal tract

In recent years,self-expandable metal stents(SEMSs)have been employed to treat benign gastrointestinal strictures secondary to several conditions:Acute diverticulitis,radiation colitis,inflammatory bowel disease(IBD),and postanastomotic leakages and stenosis.Other applications include endometriosis and fistulas of the lower gastrointestinal tract.Although it may be technically feasible to proceed to stenting in the aforementioned benign diseases of the lower gastrointestinal tract,the outcome has been reported to be poor.In fact,in some settings(such as complicated diverticulitis and postsurgical anastomotic strictures),stenting seems to have a limited evidence-based benefit as a bridge to surgery,while in other settings(such as endometriosis,IBD,radiation colitis,etc.),even society guidelines are not able to guide the endoscopist through decisional algorithms for SEMS placement.The aim of this narrative paper is to review the scientific evidence regarding the use of SEMSs in nonmalignant diseases of the lower gastrointestinal tract,both in adult and pediatric settings.

Electrical storm in systemic sclerosis: Inside the electroanatomic substrate

We report the case of a 63-year-old woman affected by a severe form of systemic scleroderma with pul-monary involvement(interstitial fibrosis diagnosed by biopsy and moderate pulmonary hypertension) and cardiac involvement(paroxysmal atrial fibrillation, right atrial flutter treated by catheter ablation, ventricular tachyarrhythmias, previous dual chamber implantable cardioverter defibrillator implant). Because of recurrent electrical storms refractory to iv antiarrhythmic drugs the patient was referred to our institution to undergo catheter ablation. During electrophysiological proce-dure a 3D shell of cardiac anatomy was created with intracardiac echocardiography pointing out a significant right ventricular dilatation with a complex aneurysmal lesion characterized by thin walls and irregular multiple trabeculae. A substrate-guided strategy of catheter ab-lation was accomplished leading to a complete electri-cal isolation of the aneurism and to the abolishment of all abnormal electrical activities. The use of advanced strategies of imaging together with electroanatomical mapping added important information to the complex arrhythmogenic substrate and improved efficacy and safety.

Which octogenarian patients are at higher risk after cholecystectomy for symptomatic gallstone disease? A single center cohort study

BACKGROUND Incidence of gallstones in those aged≥80 years is as high as 38%-53%.The decision-making process to select those oldest old patients who could benefit from cholecystectomy is challenging.AIM To assess the risk of morbidity of the“oldest-old”patients treated with cholecystectomy in order to provide useful data that could help surgeons in the decision-making process leading to surgery in this population.METHODS A retrospective study was conducted between 2010 and 2019.Perioperative variables were collected and compared between patients who had postoperative complications.A model was created and tested to predict severe postoperative morbidity.RESULTS The 269 patients were included in the study(193 complicated).The 9.7%of complications were grade 3 or 4 according to the Clavien-Dindo classification.Bilirubin levels were lower in patients who did not have any postoperative complications.American Society of Anesthesiologists scale 4 patients,performing a choledocholithotomy and bilirubin levels were associated with Clavien-Dindo>2 complications(P<0.001).The decision curve analysis showed that the proposed model had a higher net benefit than the treating all/none options between threshold probabilities of 11%and 32%of developing a severe complication.CONCLUSION Patients with American Society of Anesthesiologists scale 4,higher level of bilirubin and need of choledocholithotomy are at the highest risk of a severely complicated postoperative course.Alternative endoscopic or percutaneous treatments should be considered in this subgroup of octogenarians.

Anesthetic management of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy procedures

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy procedure are performed with increasing frequency to treat patients with diffused peritoneal carcinomatosis. These procedures have showed to increase life expectancy in what was previously considered a "terminal condition". Anyway patients face major and life threatening derangements of their hemodynamic, respiratory and metabolic physiologic balance during the surgery and in the immediate postoperative period. Despite the need of an advanced organ monitoring and support all these derangements seem to be mild and short-lived when timely addressed, at least in the majority of patients. Intensive care physicians are involved in providing surveillance and organ support till the patient is effectively weaned after the operation. Moreover, the anesthesiologist as perioperative physician is involved in pain control, metabolic and nutritional support of this cohort of patients. This task can be challenging considering that part of the patients are already on a long list of pain control medication after previous surgery or chemotherapy. A malnourished state is common too and it is secondary to diffi cult feeding, wasting syndrome from the tumor and massive ascites. The last issue the anesthesiologists need to be aware of is the impact over the quality of life(Qo L) of this procedure. The patient's underlying pathology is unlikely to be defi nitively cured so no treatment is an acceptable choice. The possibility to withhold the treatments must be part of the consultation process like the discussion about the Qo L in the immediate, as well as in the long-term, after the operation. Careful monitoring and treatment of every aspect that can impact the Qo L must be taken and the efforts to be poured into an effective preservation of the Qo L must be doubled when compared with a patient scheduled for major abdominal surgery.

Impact of COVID-19 pandemic on the neuropsychiatric status of Wilson’s disease

We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.

Histopathological landscape of rare oesophageal neoplasms

The landscape of neoplastic pathology of the oesophagus is dominated by malignancies of epithelial origin,in particular by oesophageal adenocarcinoma and oesophageal squamous cell carcinoma.However,several other histopathological variants can be distinguished,some associated with peculiar histopathological profiles and prognostic behaviours and frequently underrecognized in clinical practice.The aim of this review is to provide a comprehensive characterization of the main morphological and clinical features of these rare variants of oesophageal neoplastic lesions.

Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.