The esophageal pull-down technique improves the outcome of laparoscopic Heller-Dor myotomy in end-stage achalasia.

BACKGROUND: The treatment of patients with end-stage achalasia with a sigmoid-shaped esophagus is particularly challenging. A modified technique (pull-down technique) has been developed to straighten the esophageal axis, but only a limited number of studies on this topic are available in the literature. This study aimed to compare the outcome of patients who underwent the pull-down technique with that of patients who had a classical laparoscopic Heller-Dor (CLHD) myotomy. METHODS: All patients with a radiologic diagnosis of end-stage achalasia who underwent an LHD myotomy between 1995 and 2022 were considered eligible for the study. All patients underwent symptom score, barium swallow, endoscopy, and manometry tests before and after the procedure was performed. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score (ES) of >3 or the need for retreatment. RESULTS: Of the 94 patients who were diagnosed with end-stage achalasia (male-to-female ratio of 52:42), 60 were treated with CLHD myotomy, and 34 were treated with the pull-down technique. Of note, 2 patients (2.1%), both belonging to the CLHD myotomy group, developed a squamous cell carcinoma during the follow-up. The overall success of LHD myotomy was seen in 76 of 92 patients (82.6%). All patients in both groups achieved a lower ES after surgery. The failure rates were 27.6% (16/58) in the CLHD myotomy group and 5.9% (2/34) in the pull-down technique group (P < .01). CONCLUSION: Our findings confirm that LHD myotomy is an effective treatment of end-stage achalasia and that the pull-down technique further improves the outcome in patients with end-stage achalasia who are difficult to treat.

Paraneoplastic myopathy-related rhabdomyolysis and pancreatic cancer: A case report and review of the literature.

BACKGROUND: Rhabdomyolysis is a life-threatening condition, often leading to progressive renal failure and death. It is caused by destruction of skeletal muscle and the release of myoglobin and other intracellular contents into the circulation. The most frequent cause of this condition is "crush syndrome", although several others have been described and paraneoplastic inflammatory myopathies associated with various types of cancer are repeatedly reported. CASE SUMMARY: We describe a rare case of a patient with pancreatic cancer who developed rhabdomyolysis early on, possibly due to paraneoplastic myositis leading to acute renal failure and eventually to rapid death. A 78-year-old Caucasian woman was referred to our hospital for obstructive jaundice and weight loss due to a lesion in the pancreatic head. She presented increasingly severe renal insufficiency with anuria, a dramatic increase in creatine phosphokinase (36000 U/L, n.v. 20-180 U/L) and myoglobin (> 120000 µg/L, n.v. 12-70 µg/L). On clinical examination, the patient showed increasing pain in the lower limbs associated with muscle weakness which was severe enough to immobilize her. Paraneoplastic myopathy linked to the malignant lesion of the pancreatic head was suspected. The patient was treated with hemodialysis and intravenous methylprednisolone. Despite all the efforts to prepare the patient for surgery, her general condition rapidly deteriorated and she eventually died 30 d after hospital admission. CONCLUSION: The possible causes of rhabdomyolysis in this patient with pancreatic cancer are discussed, the development of paraneoplastic myopathy being the most likely. Clinicians should bear in mind that these syndromes may become clinically manifest at any stage of the cancer course and their early diagnosis and treatment could improve the patient's prognosis.

Minimally invasive Ivor Lewis esophagectomy in the elderly patient: a multicenter retrospective matched-cohort study.

Introduction: Several studies reported the advantages of minimally invasive esophagectomy over the conventional open approach, particularly in terms of postoperative morbidity and mortality. The literature regarding the elderly population is however scarce and it is still not clear whether elderly patients may benefit from a minimally invasive approach as the general population. We sought to evaluate whether thoracoscopic/ laparoscopic (MIE) or fully robotic (RAMIE) Ivor-Lewis esophagectomy significantly reduces postoperative morbidity in the elderly population. Methods: We analyzed data of patients who underwent open esophagectomy or MIE/RAMIE at Mainz University Hospital and at Padova University Hospital between 2016 and 2021. Elderly patients were defined as those ≥ 75 years old. Clinical characteristics and the postoperative outcomes were compared between elderly patients who underwent open esophagectomy or MIE/RAMIE. A 1-to-1 matched comparison was also performed. Patients < 75 years old were evaluated as a control group. Results: Among elderly patients MIE/RAMIE were associated with a lower overall morbidity (39.7% vs. 62.7%, p=0.005), less pulmonary complications (32.8 vs. 56.9%, p=0.003) and a shorter hospital stay (13 vs. 18 days, p=0.03). Comparable findings were obtained after matching. Similarly, among < 75 years-old patients, a reduced morbidity (31.2% vs. 43.5%, p=0.01) and less pulmonary complications (22% vs. 36%, p=0.001) were detected in the minimally invasive group. Discussion: Minimally invasive esophagectomy improves the postoperative course of elderly patients reducing the overall incidence of postoperative complications, particularly of pulmonary complications.

Safety and Efficacy of Surgery for Metastatic Tumor to the Pancreas: A Single-Center Experience.

Pancreatic metastases from other neoplasms are rare. The role of surgery for this clinical entity is unclear. The aim of this study was to investigate the role of resection in patients with pancreatic secondary lesions. We observed 44 patients with pancreatic metastases from other tumors. Renal cell carcinoma was the most common primary tumor (n = 19, 43.2%). Thirty-seven patients underwent surgery, and pancreatic resection with curative intent was feasible in 35 cases. Fifteen patients (43.2%) experienced major postoperative complications (Clavien-Dindo > 2), and postoperative mortality rate was 5.4%. The median overall survival and disease-free survival were 38 (range 0-186) and 11 (range 0-186) months, respectively. Overall survival and disease-free survival were significantly longer for pancreatic metastases from renal cell carcinoma when compared to other primary tumors. Multivariate analysis confirmed a pathological diagnosis of metastasis from RCC as an independent prognostic factor for overall survival (OR 2.48; 95% CI, 1.00-6.14; p = 0.05). In conclusion, radical resection of metastases to the pancreas is feasible and safe, and may confer a survival benefit for selected patients. There is a clear benefit of metastasectomy in terms of patient survival for metastases from renal cell carcinoma, while for those with other primary tumors, surgery seems to be mainly palliative.

Laparoscopic Heller-Dor is an effective long-term treatment for end-stage achalasia.

BACKGROUND: The end-stage achalasia is a difficult condition to treat, for the esophageal diameter and conformation of the gullet, that may progress to a sigmoid shape. The aim of this study was to examine the outcome of Laparoscopic Heller-Dor in patients with end-stage achalasia, comparing them with patients who had mega-esophagus without a sigmoid shape. METHODS: From 1992 to 2020, patients with a diagnosis of sigmoid esophagus, or radiological stage IV achalasia (the SE group), and patients with a straight esophagus larger than 6 cm in diameter, or radiological stage III achalasia (the NSE group), were all treated with LHD. The two groups were compared in terms of patients' symptoms, based on the Eckardt score, and on barium swallow, endoscopy and manometry performed before and after the treatment. The failure of the treatment was defined as an Eckardt score > 3, or the need for further treatment. RESULTS: The study involved 164 patients: 73 in the SE group and 91 in the NSE group. No intra- or postoperative mortality was recorded. The median follow-up was 51 months (IQR 25-107). The outcome was satisfactory in 71.2% of patients in the SE group, and in 89% of those in the NSE group (p = 0.005). CONCLUSIONS: SE is certainly the worst condition of the disease and the final outcome of LHD, in term of symptom control, is inferior compared to NSE. Despite this, almost 3/4 of the SE patients experienced a significant relieve in symptoms after LHD, which may therefore still be the first surgical option to offer to these patients, before considering esophagectomy.

Multimodal treatment of radiation-induced esophageal cancer: Results of a case-matched comparative study from a single center.

PURPOSE: Radiation-induced esophageal cancer (RIEC) is a rare but severe late consequence of radiotherapy. The literature regarding this topic is predominately limited in describing the risk of this disease. Tumor behavior, treatment strategies, and prognosis of this cancer remain poorly defined. PATIENTS AND METHODS: We collected data of patients who were referred to our unit between 2000 and 2020 for RIEC. After tumor board discussion, upfront surgery or neoadjuvant therapy and surgery were indicated as the main treatment. Preoperative characteristics, long-term and short-term postoperative outcomes of RIEC patients were compared with a 1:1 clustering-matched cohort of patients affected by primary esophageal cancer (PEC). RESULTS: At pre-matching, 54 RIEC and 936 PEC patients were enrolled. The median time between primary irradiation and diagnosis of RIEC was 13.5 years, and the median primary radiation dose was 60 Gy. Compared to the unmatched cohort of PECs, RIEC patients were more frequently female (p = 0.0007), had earlier detection of disease (p = 0.03) and presented more frequently with upper esophageal cancers (p < 0.0001). Neoadjuvant treatment was used less frequently in RIEC patients (p < 0.0001). After matching, the 51 RIEC and 50 PEC patients showed comparable results in terms of exposure to neoadjuvant treatment, surgical radicality and survival outcomes. RIEC patients had more severe postoperative complications (p = 0.04) and a higher proportion of pulmonary complications (p = 0.04). CONCLUSIONS: Curative treatments are feasible for RIEC. Neoadjuvant chemotherapy or chemoradiation can be used in this subgroup, treatment response and long-term outcomes are comparable to those of PEC. The risk of postoperative complications is probably related to the detrimental effect of primary irradiation on lung function.

Could the Pittsburgh Severity Score guide the treatment of esophageal perforation? Experience of a single referral center.

BACKGROUND: Esophageal perforation (EP) is characterized by high morbidity and mortality. The Pittsburgh Severity Score (PSS) is a scoring system based on clinical factors at the time of EP presentation, intended to guide treatment. The aim of the study is to verify PSS usefulness in stratifying EP severity and in guiding clinical decisions. METHODS: All patients referred to our unit for EP between January 2005 and January 2020 were enrolled. Patients were stratified according to their PSS into three groups (PSS ≤ 2, 3-5, and >5): the postoperative outcomes were compared. The predictive value of the PSS was evaluated by simple linear and logistic regression for the following outcomes: need for surgery, complications, in-hospital mortality, intensive care unit (ICU) and hospital stay, time to refeeding, and need for reintervention. RESULTS: Seventy-three patients were referred for EP (male/female, 46/27). Perforations were more frequently iatrogenic (41.1%) or spontaneous (38.3%). The median PSS was 4 (interquartile range, 2-6). Surgery was required in 60.3% of cases. Pittsburgh Severity Score was associated with ICU admission, hospital stay, need for surgery and reintervention, postperforation complications and mortality. After regression analysis, PSS was significantly predictive of postperforation complications (p < 0.01), in-hospital mortality (p = 0.01), ICU admission (p < 0.01), need for surgical treatment (p < 0.01), and need for reintervention (p = 0.02). CONCLUSION: Pittsburgh Severity Score is useful in stratifying patients in risk groups with different morbidity and mortality. It is also useful in guiding the therapeutic conduct, selecting patients for nonoperative management. Prospective studies are needed to confirm the role of the PSS in the treatment of esophageal perforation. LEVEL OF EVIDENCE: Management, Therapeutic/Care; level IV.

Pharyngo-Esophageal Perforation Following Anterior Cervical Spine Surgery: A Single Center Experience and a Systematic Review of the Literature.

STUDY DESIGN: Case series and systematic review of the Literature. OBJECTIVES: Pharyngo-esophageal perforation (PEP) is a rare, life-threatening complication of anterior cervical spine surgery (ACSS). Best management of these patients remains poorly defined. The aim of this study is to present our experience with this entity and to perform a systematic Literature review to better clarify the appropriate treatment of these patients. METHODS: Patients referred to our center for PEP following ACSS (January 2002-December 2018) were identified from our database. Moreover, an extensive review of the English Literature was conducted according to the 2009 PRISMA guidelines. RESULTS: Twelve patients were referred to our Institution for PEP following ACSS. Indications for ACSS were trauma (n = 10), vertebral metastases (n = 1) and disc herniation (n = 1). All patients underwent hardware placement at the time of ACSS. There were 6 early and 6 delayed PEP. Surgical treatment was performed in 11 patients with total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement, anatomical suture of the fistula and suture line reinforcement with myoplasty. Complete resolution of PEP was observed in 6 patients. Five patients experienced PEP persistence, requiring further surgical management in 2 cases. At a median follow-up of 18.8 months, all patients exhibited permanent resolution of the perforation. CONCLUSIONS: PEP following ACSS is a rare but dreadful complication. Partial or total removal of the fixation devices, direct suture of the esophageal defect and coverage with tissue flaps seems to be an effective surgical approach in these patients.

The Prognostic Value of Low Muscle Mass in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis.

Low muscle mass is associated with reduced survival in patients with different cancer types. The interest in preoperative sarcopenia and pancreatic cancer has risen in the last decade as muscle mass loss seems to be associated with poorer survival, higher postoperative morbidity, and mortality. The aim of the present study was to review the literature to compare the impact of low muscle mass on the outcomes of patients undergoing surgery for pancreatic adenocarcinoma. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 10 articles were analyzed in detail and included in the meta-analysis. Data were retrieved on 2811 patients undergoing surgery for pancreatic cancer. Meta-analysis identified that patients with low muscle mass demonstrated a significantly reduced OS when compared to patients without alterations of the muscle mass (ROM 0.86; 95% CI: 0.81-0.91, p < 0.001), resulting in a 14% loss for the former. Meta-analysis failed to identify an increase in the postoperative complications and length of stay of patients with low muscle mass. Our analysis confirms the role of low muscle mass in influencing oncologic outcomes in pancreatic cancer. Its role on surgical outcomes remains to be established.

Optimal Treatment of cT2N0 Esophageal Carcinoma: Is Upfront Surgery Really the Way?

BACKGROUND: Staging is inaccurate for cT2N0 esophageal cancer, and patients often are clinically mis-staged. This study aimed to evaluate the outcome after upfront surgery or neoadjuvant therapy, considering the impact of clinical "mis-staging." METHODS: This study reviewed patients with squamous cell carcinoma (SCC) or adenocarcinoma (ADK) of the esophagus who underwent upfront surgery (S group) or neoadjuvant treatment (chemoradiotherapy [CRT] group) for cT2N0 cancer. Overall survival (OS), disease-free survival (DFS), morbidity, and mortality were evaluated. Correctly staged (cTNM = pTNM), understaged (cTNM < pTNM), and overstaged (cTNM > pTNM) patients in the S group and the CRT group were analyzed. Risk factors for unexpected lymph-node involvement were identified in the S group and for cancer-related death in the whole study cohort. RESULTS: The study enrolled 229 patients with cT2N0 esophageal cancer. The 5-year OS rate was 34.2% in the S group versus 55.7% in the CRT group (p = 0.0088). The DFS also was significantly higher (p = 0.01). The morbidity and mortality rates were similar. In the S group, the cTNM was correctly staged for 21.4% and understaged for 63.4% of the patients, with 48.7% of the patients showing unexpected nodal involvement. A tumor length of 3 cm or more was an independent predictor of nodal metastases in SCC (p = 0.03), as was lymphovascular invasion (LVI) in ADK (p < 0.01). Cancer-related mortality was independently associated with lymph-node metastases (p = 0.03) and treatment by upfront surgery (p = 0.01). CONCLUSION: Given the high rate of understaged patients in this study (63.4%), the authors advocate for combining the induction therapy with surgery in cT2N0, achieving better survival with similar morbidity and mortality.

Laparoscopic Revisional Surgery After Failed Heller Myotomy for Esophageal Achalasia: Long-Term Outcome at a Single Tertiary Center.

BACKGROUND: Laparoscopic Heller myotomy (HM) has gained acceptance as the gold standard of treatment for achalasia. However, 10-20% of the patients will experience symptom recurrence, thus requiring further treatment including pneumodilations (PD) or revisional surgery. The aim of our study was to assess the long-term outcome of laparoscopic redo HM. METHODS: Patients who underwent redo HM at our center between 2000 and 2019 were enrolled. Postoperative outcomes of redo HM patients (redo group) were compared with that of patients who underwent primary laparoscopic HM in the same time span (control group). For the control group, we randomly selected patients matched for age, sex, FU time, Eckardt score (ES), previous PD, and radiological stage. Failure was defined as an Eckardt score > 3 or the need for re-treatment. RESULTS: Forty-nine patients underwent laparoscopic redo HM after failed primary HM. A new myotomy on the right lateral wall of the EGJ was the procedure of choice in the majority of patients (83.7%). In 36 patients (73.5%) an anti-reflux procedure was deemed necessary. Postoperative outcomes were somewhat less satisfactory, albeit comparable to the control group; the incidence of postoperative GERD was higher in the redo group (p < 0.01). At a median 5-year FU time, a good outcome was obtained in 71.4% of patients in the redo group; further 5 patients (10.2%) obtained a long-term symptom control after complementary PD, thus bringing the overall success rate to 81.6%. Stage IV disease at presentation was independently associated with a poor outcome of revisional LHD (p = 0.003). CONCLUSIONS: This study reports the largest case series of laparoscopic redo HM to date. The procedure, albeit difficult, is safe and effective in relieving symptoms in this group of patients with a highly refractory disease. The failure rate, albeit not significantly, and the post-operative reflux are higher than after primary HM. Patients with stage IV disease are at high risk of esophagectomy.

Laparoscopic Heller-Dor Is an Effective Treatment for Esophageal-Gastric Junction Outflow Obstruction.

BACKGROUND: The treatment of esophagogastric junction outflow obstruction (EGJOO) currently mirrors that of achalasia, but this is based on only a few studies on small case series. The aim of this prospective, controlled study was to assess the outcome of laparoscopic Heller-Dor (LHD) in patients with EGJOO, as compared with patients with esophageal achalasia. MATERIALS AND METHODS: Between 2016 and 2019, patients with manometric diagnosis of idiopathic EGJOO and patients with radiological stage I achalasia, both treated with LHD, were compared. The achalasia group was further analyzed by subgrouping the patients based on the manometric pattern. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score > 3 or the need for retreatment. RESULTS: During the study period, 150 patients were enrolled: 25 patients had EGJOO and 125 had radiological stage I achalasia (25 pattern I, 74 pattern II, and 26 pattern III). The median follow-up was 24 months (IQR: 34-16). Treatment was successful in 96% of patients in the EGJOO group and in 96% of achalasia patients with pattern I, 98.7% in those with pattern II, and 96.2% of those with pattern III (p=0.50). High-resolution manometry showed a reduction in the LES resting pressure and integrated relaxation pressure for all patients in all 4 groups (p<0.001). CONCLUSION: This is the first comparative study based on prospective data collection to assess the outcome of LHD in patients with EGJOO. LHD emerged as an effective treatment for EGJOO, with an excellent success rate, comparable with the procedure's efficacy in treating early-stage achalasia.

Histology of the spleen in immune thrombocytopenia: clinical-pathological characterization and prognostic implications.

OBJECTIVE: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. METHODS: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. RESULTS: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. CONCLUSION: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.

International guidelines and recommendations for surgery during Covid-19 pandemic: A Systematic Review.

BACKGROUND: During the COVID-19 pandemic, surgical departments were forced to re-schedule their activity giving priority to urgent procedures and non-deferrable oncological cases. There is a lack of evidence-based literature providing clinical and organizational guidelines for the management of a general surgery department. Aim of our study was to review the available recommendations published by general Surgery Societies and Health Institutions and evaluate the underlying Literature. MATERIALS AND METHODS: A review of the English Literature was conducted according to the AMSTAR and to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: After eligibility assessment, a total of 22 papers and statements were analyzed. Surgical societies have established criteria for triage and prioritization in order to identify procedures that can be postponed after the pandemic and those that should not. Prioritization among oncologic cases represents a difficult task: clinicians have to balance a possible delay in cancer diagnosis or treatment against the risk for a potential COVID-19 exposure. There is broad agreement among guidelines that indication to proceed with surgery should be discussed in virtual Tumor Boards taking into consideration alternative therapeutic approaches. Several guidelines deal with the role of laparoscopic surgery during the pandemic: a tailored approach is currently suggested, with a case-by-case evaluation provided that appropriate personal protective equipment is available in order to minimize the potential risk of transmission. Finally, there is a considerable agreement in the published Literature concerning the management of the personnel during the peri- and intraoperative phase and on the technical advices regarding the induction, operative and recover maneuvers in COVID-19 cases. CONCLUSIONS: During COVID-19 pandemic, it is of paramount importance to face the emergency in the most effective and efficient manner, retrieving resources from non-essential settings and, at the same time, providing care to high priority non-COVID-19 related diseases.

The Role of Positron Emission Tomography in Clinical Management of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas represent a heterogeneous group of tumors, increasingly diagnosed in clinical practice. An early differential diagnosis between malignant and benign lesions is crucial to patient management and the choice of surgery or observation. The therapeutic approach is currently based on a patient's clinical, biochemical, and morphological characteristics. The latest published International Consensus Guidelines (ICG) make no mention of the role of metabolic assessments of IPMNs. The aim of this study was to review the current literature, examining the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in IPMN management. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 10 articles were analyzed in detail, focusing on the value of PET as opposed to other standard imaging criteria. Data were retrieved on 419 patients. The 18-FDG-PET proved more sensitive, specific, and accurate than the ICG criteria in detecting malignant IPMNs (reaching 80%, 95%, and 87% vs. 67%, 58%, and 63%, respectively). Metabolic assessments may be used as an additional tool for the appropriate management of patients with doubtful imaging findings.

A Technical Modification to the Circular Stapling Anastomosis Technique During Minimally Invasive Ivor Lewis Procedure.

Background: The circular stapled (CS) technique with transoral placement of the anvil is commonly used to perform the esophagogastric anastomosis during minimally invasive esophagectomy (MIE). The procedure is safe, efficient, and highly reproducible; however, the intersection between the circular plane of the stapler and the linear staple line of the esophageal stump can expose the anastomosis to the formation of dog-ears and, therefore, increase the risk of anastomotic leak (AL). We describe a simple modification of the CS technique that consists of folding the linear esophageal transection line with a stitch around the anvil shaft, to include the staple line in the resection during the EEA™ firing. Methods: We prospectively collected data on a small group of patients who underwent MIE for cancer using our modified CS technique. Feasibility has been evaluated as the percentage of cases in which the modified anastomosis technique has been carried out successfully with the formation of a complete anastomotic ring. Safety has been defined as the absence of procedure-related complications. Results: MIE was performed in 10 patients using our modified CS technique. All the procedures were successfully completed with complete resection of the linear esophageal staple line and no intraoperative complications. Only one patient developed a postoperative AL that was only detected by barium swallow and did not cause any symptom or clinical sign. Conclusion: Our modified CS technique is feasible and did successfully prevent the occurrence of clinically relevant ALs in this small case series of patients.

Surgery for Recurrent Pancreatic Cancer: Is It Effective?

Despite improvements to surgical procedures and novel combinations of drugs for adjuvant and neoadjuvant therapies for pancreatic adenocarcinoma, the recurrence rate after radical surgery is still high. Little is known about the role of surgery in the treatment of isolated recurrences of pancreatic cancer. The aim of this study was to review the current literature dealing with surgery for recurrent pancreatic cancer in order to examine its feasibility and effectiveness. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 14 articles dealing with re-resections for recurrent pancreatic adenocarcinoma were analyzed, focusing on the characteristics of the primary neoplasm and its recurrence, the surgical procedures used, and patient outcomes. Data were retrieved on a total of 301 patients. The interval between surgery for primary pancreatic cancer and the detection of a recurrence ranged from 2 to 120 months. The recurrence was local or regional in 230 patients, and distant in 71. The median overall survival was 68.9 months (range 3-152) after resection of the primary tumor, and 26.0 months (range 0-112) after surgery for recurrent disease. The disease-free interval after the resection of recurrences was 14.2 months (range 4-29). Although data analysis was performed on a heterogeneous and limited number of patients, some of these may benefit from surgery for isolated recurrence of pancreatic adenocarcinoma. Further studies are needed to identify these cases.

Cervical Esophageal Cancer Treatment Strategies: A Cohort Study Appraising the Debated Role of Surgery.

BACKGROUND: Few studies have examined optimal treatment specifically for cervical esophageal carcinoma. This study evaluated the outcome of three common treatment strategies with a focus on the debated role of surgery. METHODS: All patients with cervical esophageal cancer treated at a single center were identified and their outcomes analyzed in terms of morbidity, mortality, and recurrence according to the treatment they received, i.e. surgery alone, definitive platinum-based chemoradiation (CRT), or CRT followed by surgery. RESULTS: The study population included 148 patients with cervical esophageal cancer from a prospective database of 3445 patients. Primary surgery was the treatment of choice for 56 (37.83%) patients, definitive CRT was the treatment of choice for 52 (35.13%) patients, and CRT followed by surgery was the treatment of choice for 40 (27.02%) patients. CRT-treated patients obtained 36.96% complete clinical response, with overall morbidity and mortality rates of 36.95 and 2.17%, respectively. Surgical complete resection was achieved in 71.88% of surgically treated cases, with morbidity and mortality rates of 52.17 and 6.25%, respectively. No significant survival difference existed among the three treatments, but patients who underwent surgery alone had a significantly lower stage of disease (p = 0.031). Compared with patients with complete response after CRT, surgery did not confer any significant survival benefit, and overall 5-year survival was lower than definitive CRT alone. In contrast, surgery improved survival significantly in patients with non-complete response after definitive CRT (p = 0.023). CONCLUSIONS: Definitive platinum-based CRT should be the treatment of choice for cervical esophageal cancer. Surgery has a role for patients with non-complete response as it adds significant survival benefit, with acceptable morbidity and mortality.

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia.