Pancreatic cancer–Surgery for recurrent disease

Recurrence of pancreatic ductal adenocarcinoma （PDAC） after a resection with curative intent is inevitable in the majority of cases. Approximately three-quarters of patients ultimately die from metastatic, local, or combined tumor recurrence . This may be due to the insufficient control over the disease after resecting the tumor and/or the existence of micrometastases at the time of the initial diagnosis. Even multimodality approaches including surgery, neoadjuvant radio-chemotherapy, adjuvant therapy, and novel targeted therapies offer only limited benefit and are not able to prevent recurrence in most of the patients.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma

Sarcomas are a large family of cancers originating in the mesenchyme.Composed of more than 100 histological subtypes,soft tissue and bone sarcomas remain clinically challenging,particularly in children and adolescents in whom sarcomas are the second most common malignant entities.Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant.The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity.In the last decade,the notion of cancer stem-like cells(CSCs)has emerged.This subset of cancer cells has been linked to drug resistance properties,recurrence of the disease,and therapeutic failure.Although CSCs remain controversial,many elements are in favor of them playing a role in the development of the drug resistance profile.The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities.Their use as promising therapeutic targets is discussed.

Ultrasonographic study of postcibal gastro-esophageal reflux and gastric emptying in infants with recurrent respiratory disease

AIM: To check the utility of postcibal ultrasonography for the evaluation of reflux in relation to gastric emptying in infants with recurrent respiratory symptoms and to link imaging with clinical data.METHODS: Esophageal reflux (hyperechoic retrograde filling) and gastric emptying (antral areas) were quantified before and after ingestion of a standard formula in 35 untreated infants (13 with chronic cough,22 with recurrent bronchitis) and in 31 controls.RESULTS: The prevalence of abnormal (≥8 episodes)postcibal refluxes was 74% in patients and 3% in controls. Number, duration of the longest episode and extent of refluxes were significantly higher in patients compared to controls. Number of refluxes was higher in patients with symptomatic refluxes than in those without.Infants with recurrent bronchitis had more refluxes than those with chronic cough and controls. Extent and timing of gastric emptying were similar in patients and controls.CONCLUSION: Esophageal ultrasonography is a useful and physiological test in infants with recurrent respiratory diseases, which have a high prevalence of abnormal postcibal esophageal reflux and a gastric emptying similar to that of normal controls. Esophageal reflux is more severe in subjects with recurrent bronchitis than in those with chronic cough.

Laparoscopic surgery for complex and recurrent Crohn's disease

Crohn's disease(CD) is a chronic inflammatory disease of digestive tract. Approximately 70% of patients with CD require surgical intervention within 10 years of their initial diagnosis, despite advanced medical treatment alternatives including biologics, immune suppressive drugs and steroids. Refractory to medical treatment in CD patients is the common indication for surgery. Unfortunately, surgery cannot cure the disease. Minimally invasive treatment modalities can be suitable for CD patients due to the benign nature of the disease especially at the time of index surgery. However,laparoscopic management in fistulizing or recurrent disease is controversial. Intractable fibrotic strictures with obstruction, fistulas with abscess formation and hemorrhage are the surgical indications of recurrent CD,which are also complicating laparoscopic treatments.Nevertheless, laparoscopy can be performed in selected CD patients with safety, and may provide better outcomes compared to open surgery. The common complication after laparoscopic intervention is postoperative ileus seems and this may strongly relate excessive manipulation of the bowel during dissection. But additionally, unsuccessful laparoscopic attempts requiring conversion to open surgery have been a major concern due to presumed risk of worse outcomes. However, recent data show that conversions do not to worsen the outcomes of colorectal surgery in experienced hands. In conclusion, laparoscopic treatment modalities in recurrent CD patients have promising outcomes when it is used selectively.

Role of adrenalectomy in treating recurrent Cushing's disease:A report of 43 cases

Objective To evaluate the efficacy of laparoscopic adrenalectomy and open adrenalectomy in treating recurrent Cushing ’s disease. Methods Forty-three patients ( 29 females and 14 males) with recurrent Cushing’s disease treated with laparoscopic adrenalectomy ( LA,n = 32) or open ( OA,n = 11) adrenalectomy from 2000

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk(± 5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments(antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections(type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year(± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance(MR) score ≥ MR1.RESULTS:Twenty-nine patients(55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76(range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29(13.7%) developed clinical recurrence,6/29(20.7%) endoscopic recurrence and 7/19(36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance was found between clinical-endoscopic recurrence(k = 0.76,P < 0.001) and clinical-morphological recurrence(k = 0.63,P = 0.003).Correlation between endoscopic and radiological findings was good(comparing the 5-point Rutgeerts score with the 4-point MR score,a score of i4 was classified as MR3,i3 as MR2,and i2-i1 as MR1)(P < 0.001,r s = 0.825).During follow-up,five(17.2%) patients needed adalimumab dose intensification(40 mg/wk);Mean time to intensification after the introduction of adalimumab treatment was 8 mo(range:5 to 11 mo).In three cases(10.3%),a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk.One patient suffered an adverse event.CONCLUSION:Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

Prevention of post-operative recurrence of Crohn's disease

Endoscopic and clinical recurrence of Crohn&#x02019;s disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

Biliary fistula and late recurrence of liver hydatid cyst:Role of cystobiliary communication:A prospective multicenter study

BACKGROUND Hydatid cyst disease(HCD)is common in certain locations.Surgery is associated with postoperative biliary fistula(POBF)and recurrence.The primary aim of this study was to identify whether occult cysto-biliary communication(CBC)can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase(ALP)levels in predicting POBF and recurrent HCD.AIM To identify whether occult CBC can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD.METHODS From September 2010 to September 2016,a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty.Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence.RESULTS There was a highly statistically significant association(P≤0.001)between cystic fluid biochemical indices and the development of biliary complications(of 16 patients with POBF,15 patients had high cyst fluid bilirubin and ALP levels),where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications.There was a highly statistically significant association(P≤0.001)between biliary complications,biochemical indices,and the occurrence of recurrent HCD(of 30 patients with recurrent HCD,15 patients had high cyst fluid bilirubin and ALP;all 16 patients who had POBF later developed recurrent HCD),where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts,respectively.CONCLUSION Occult CBC can predict recurrent HCD.Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.

Liver retransplantation: indications and outcomes

BACKGROUND: Liver transplantation is a life-saving the- rapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% pa- tients may lose the grafts caused by a variety of reasons. This review covers the most frequent indications for liver retransplantation as well as the results and specific problems with each indication. DATA RESOURCES: Searching MEDLINE (1997-2003) for articles on liver retransplantation. RESULTS: The most frequent indications of liver retrans- plantation are primary non-function, hepatic artery throm- bosis, graft rejection and recurrent diseases. The results af- ter liver retransplantation remain inferior to those after first transplantation. CONCLUSION: Liver retransplantation, which is the only means of prolonging survival in those patients whose initial graft has failed, makes an important contribution to overall survival.

Diagnosis and management of late hepatic allograft dysfunction

Late hepatic allograft dysfunction (LHAD) is common after liver transplantation (LT) and can cause graft failure,retransplantation,or even death.A variety of etiologies including rejection,vascular complications,bile duct complications,recurrent diseases,infections,de novo diseases,neoplasms and drug toxicity can result in LHAD.The recurrent diseases have the potential to become the most serious problems facing LT in the future.It is difficult to differentiate late acute rejection from recurrent viral or autoimmune hepatitis.Accurate diagnosis of the cause of LHAD has therapeutic importance.

Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

Myocardial infarction with ST-segment elevation in old patient with history of takotsubo syndrome

Takotsubo syndrome （TTS） is a rare condition that af- fects mainly aging women. TTS was first reported in 1990r and is characterized by clinical symptoms, ECG changes and regional wall motion abnormalities without changes in the coronary arteries. However, some reports admit the pos- sibility of coexistence of TTS and coronary artery disease. We present a patient who had not had any changes in coro- nary arteries until four years later when she had myocardial infarction associated with right coronary artery narrowing, despite the fact that the risk factors of coronary heart disease were closely monitored.

The lncRNA BORG: a novel inducer of TNBC metastasis, chemoresistance, and disease recurrence

Although greater than 90% of breast cancer-related mortality can be attributed to metastases, the molecular mechanisms underpinning the dissemination of primary breast tumor cells and their ability to establish malignant lesions in distant tissues remain incompletely understood. Genomic and transcriptomic analyses identified a class of transcripts called long noncoding RNA (lncRNA), which interact both directly and indirectly with key components of gene regulatory networks to alter cell proliferation, invasion, and metastasis. We identified a pro-metastatic lncRNA BMP/OP-Responsive Gene (BORG) whose aberrant expression promotes metastatic relapse by reactivating proliferative programs in dormant disseminated tumor cells (DTCs). BORG expression is broadly and strongly induced by environmental and chemotherapeutic stresses, a transcriptional response that facilitates the survival of DTCs. Transcriptomic reprogramming in response to BORG resulted in robust signaling via survival and viability pathways, as well as decreased activation of cell death pathways. As such, BORG expression acts as a (1) marker capable of predicting which breast cancer patients are predisposed to develop secondary metastatic lesions;and (2) unique therapeutic target to maximize chemosensitivity of DTCs. Here we review the molecular and cellular factors that contribute to the pathophysiological activities of BORG during its regulation of breast cancer metastasis, chemoresistance, and disease recurrence.