A probabilistic neural twin for treatment planning in peripheral pulmonary artery stenosis.

The substantial computational cost of high-fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data-driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time-critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient. Since different degrees of success can be achieved in practice during treatment, we formulate the problem in probability, and solve it through a sample-based approach. We propose a new offline-online pipeline for probabilistic real-time treatment planning which combines offline assimilation of boundary conditions, model reduction, and training dataset generation with online estimation of marginal probabilities, possibly conditioned on the degree of augmentation observed in already repaired lesions. Moreover, we propose a new approach for the parametrization of arbitrarily shaped vascular repairs through iterative corrections of a zero-dimensional approximant. We demonstrate this pipeline for a diseased model of the pulmonary artery tree available through the Vascular Model Repository.

Laparoscopic Incisional and Ventral Hernia Repair with Absorbable Tacks in a Long Term Follow-up: A Retrospective Control Study.

BACKGROUND: Laparoscopic Incisional and Ventral Hernia Repair (LIVHR) is a safe and worldwide accepted procedure performed using absorbable tacks. The aim of the study was to evaluate recurrence rate in a long term follow-up and whether the results of laparoscopic IVH repair in the elderly (≥65 years old) are different with respect to results obtained in younger patients. METHODS: One hundred and twenty-nine consecutive patients (74 women and 55 men, median age 67 years, range = 30-87 years) with ventral (N = 42, 32.5%) or post incisional (N = 87, 67.5%) hernia were enrolled in the study. Patients were divided into two groups according to their age: group A (N = 55, 42.6%) aged <65 years and group B (N = 74, 57.4%) aged ≥65 years. RESULTS: The mean operative time was not significantly different between groups (66.7 ± 37 vs. 74 ± 48.4 min, p = 0.4). To the end of 2016, seven recurrences had occurred (group A = 3, group B = 4, p = 1). Complications occurred in 8 (16%) patients in group A and 21 (28.3%) patients in group B. CONCLUSION: In conclusion, our results confirm that the use of absorbable tacks does not increase recurrence frequency and laparoscopic incisional and ventral repair is a safety procedure also in elderly patients.

Reintervention After Heller Myotomy for Achalasia: Is It Inevitable?

BACKGROUND: Few studies of reintervention after Heller myotomy for achalasia set patients' expectations, assist therapeutic decision making, and direct follow-up. Therefore, we investigated the frequency and type of symptoms and reinterventions after myotomy based on achalasia type. METHODS: From January 2006 to March 2013, 248 patients who had preoperative high-resolution manometry and a timed barium esophagram (TBE) underwent Heller myotomy, 62 (25%) for type I, 162 (65%) for type II, and 24 (10%) for type III achalasia. Postoperative surveillance, including TBE, was performed at 8 weeks, then annually. Median follow-up was 36 months. End points were all symptom types and modes of reintervention, endoscopic or surgical. Reintervention was based on both symptoms and objective TBE measurements. RESULTS: Eventually most patients (169 of 218; 69%) experienced at least one symptom after myotomy. Fifty patients underwent 85 reinterventions, 41 endoscopic only, 4 surgical only, and 5 both. Five-year freedom from reintervention was 62% for type I, 74% for type II, and 87% for type III, most occurring within 6 months, although later in type III. At 5 years, number of reinterventions per 100 patients was 72 for type I, 51 for type II, and 13 for type III. After each reintervention, there was approximately a 50% chance of another within 2 years. CONCLUSIONS: Patients' expectations when undergoing Heller myotomy for achalasia must be that symptoms will only be palliated, and patients who have worse esophageal function-achalasia type I-may require one or more postoperative reinterventions. Thus, we recommend that patients with achalasia have lifelong annual surveillance after Heller myotomy that includes TBE.

Siewert III esophagogastric junction adenocarcinoma: does TNM 8th save us?

Siewert III cancers were classified as esophageal cancers by the TNM 7th edition (TNM7), while being defined as gastric cancers by the new TNM 8th edition (TNM8). Aim of this study was to compare previous and present TNM classifications of Siewert III. From 2000 to 2015, 309 patients with Siewert III adenocarcinoma were treated at ten high-volume centers, belonging to the GIRCG (Italian Research Group for Gastric Cancer). We retrospectively analyzed overall survival according to TNM classifications: gastric TNM8 was compared with either gastric TNM7 or esophageal TNM7. Median number of lymph nodes harvested was 31 (interquartile range 22-44). Agreement between gastric TNM7 and TNM8 was very good (weighted kappa 92.3%, IC 95% 90.3-94.1%). Accordingly, stage migration was observed in 54 of 309 patients (17.5%), with 12 patients upstaged (3.9%) and 42 downstaged (13.6%). Cox models including either gastric TNM7 or TNM8 achieved similar goodness-of-fit and c-index. Differences were much larger, when shifting from esophageal TNM7 to gastric TNM8: the agreement was much lower (weighted kappa 69.1%, 65.2-73.2%), with 196 of 309 patients (63.4%) downstaging. The corresponding Cox model presented the lowest goodness-of-fit and discrimination ability. Gastric TNM7 and TNM8 were largely superimposable, so that stage migration was minor and prognostic significance was similar. At variance, stage migration was substantial when shifting from esophageal TNM7 to TNM8. Moreover, survival models with esophageal TNM7 presented the worst goodness-of-fit and the lowest discrimination ability. This further supports placing Siewert III among gastric cancers, as done in TNM8.

Value of routine timed barium esophagram follow-up in achalasia after myotomy.

OBJECTIVES: The value of routine timed barium esophagram (TBE) in longitudinal follow-up of achalasia after Heller myotomy is unknown. We prospectively prescribed a yearly follow-up TBE. Purposes were to characterize esophageal emptying over time after myotomy, identify preoperative TBE measures associated with follow-up TBE, and characterize follow-up TBE over time in relationship to reintervention. METHODS: From March 1995 to April 2013, 635 patients underwent Heller myotomy for achalasia; 559 had at least 1 follow-up TBE. Temporal trends of 1335 follow-up TBEs in all nonreintervention and reintervention patients were assessed. Multivariable longitudinal analysis identified preoperative TBE measures associated with follow-up TBE. RESULTS: On average, TBE height and width at 1 and 5 minutes decreased approximately 50% and 60%, respectively, at first postoperative follow-up, and remained stable or slightly decreased for up to 5 years. Wider TBE width at 5 minutes was associated with greater follow-up TBE height and width at 1 minute. Of 118 patients undergoing reintervention, 64 (57%) had only 1 reintervention, with follow-up TBE returning to that of nonreintervention patients. Patients whose follow-up TBE remained abnormal underwent a further reintervention, some normalizing on subsequent TBE, and some not. CONCLUSIONS: Follow-up TBE is valuable postmyotomy, particularly if there is substantial esophageal dilatation preoperatively. Follow-up TBE reassures patients with stable or decreasing TBE measures, permitting decreased follow-up intensity. Reintervention should not be considered a myotomy failure, because a successful, single, nonsurgical reintervention often results in long-term successful palliation. More than 1 reintervention requires intensification of TBE follow-up, facilitating treatment planning.

Radical surgery for gastric cancer in octogenarian patients.

To valuate feasibility and results of radical surgery in octogenarian patients with gastric cancer. We collected data on 60 patients that underwent gastrectomy with an R0 resection at our Institution from 2010 to 2015. Patients were divided into two groups: octogenarian (OG) (n = 26), consisting of patients aged 80-89 years, and younger (YG) (n = 34), consisting of patients under 80 years of age. All patients were treated with total or subtotal gastrectomy with lymphadenectomy. A D2-lymphadenectomy was performed in 11 and 24 patients, a D1+ in 5 and 4, a D1 in 8 and 6, and a D0 in 2 and 0 cases in OG and YG respectively. The overall morbidity rate was 42.3% (11/26) in OG and 29.4% (10/34) in YG, while 90-days mortality was observed in four (15.4%) and one (2.9%) patients in OG and YG, respectively. The median hospital stay was 9 days (2-31) and 9.5 days (6-66) in OG and YG, respectively. Gastrectomy with radical resection and limited lymphadenectomy should be recommended for octogenarian patients with good performance status and low co-morbidity.

Siewert III adenocarcinoma: treatment update.

Siewert III cancer, although representing around 40% of EGJ cancers and being the EGJ cancer with worst prognosis, does not have a homogenous treatment, has few dedicated studies, and is often not considered in study protocols. Although staged as an esophageal cancer by the TNM 7th ed., it is considered a gastric cancer by new TNM 8th ed. Our aim was to consolidate the current literature on the indications and treatment options for Siewert III adenocarcinoma. A review of the literature was performed to better delineate treatment indications (according to stage, surgical margins, type of lymphatic spread and lymphadenectomy) and treatment strategy. The treatment approach is strictly dependent on cancer site and nodal diffusion. T1m cancers have insignificant risk of nodal metastases and can be safely treated with endoscopic resections. The risk of nodal metastases increases markedly starting from T1sm cancers and requires surgery with lymphadenectomy. The site of this type of cancer and the nodal diffusion require a total gastrectomy and distal esophagectomy, with 5 cm of clear proximal and distal margins and a D2 abdominal and inferior mediastinal lymphadenectomy. Multimodal treatments are indicated in all locally advanced and node positive cancers. Siewert III cancers are gastric cancers with some peculiarities and require dedicated studies and deserve more consideration in the current literature, especially because their treatment is particularly challenging.

ypN0: Does It Matter How You Get There? Nodal Downstaging in Esophageal Cancer.

BACKGROUND: ypN0 following induction treatment for advanced esophageal cancer improves survival. Importance of how ypN0 is achieved is unknown. This study evaluates survival in "natural" N0 (cN0/ypN0) and "downstaged" N0 (cN+/ypN0) patients. METHODS: Among patients treated with induction treatment and surgery, 83 CT scans were retrieved in digital format and re-evaluated by a radiologist, blinded to pathological nodal status: 28 natural N0, 37 downstaged N0, and 18 ypN+. Impact of N0 classification on survival and associations with survival were identified. RESULTS: Survival varied with ypN: 3-year survival was 84 % for natural N0 patients, 59 % for downstaged N0, and 20 % for ypN+ (p < .001). Compared with natural N0 patients, risk of cancer mortality was 3.8 for downstaged N0 and 7.6 for ypN+ (p = .01). Survival was also stratified by ypT: compared with ypT0 natural N0, who had the best survival, intermediate survival was seen in ypT+ natural N0 [hazard ratio (HR), 1.3] and ypT0 downstaged N0 (HR, 1.8), and poor survival in ypT+ downstaged N0 (HR, 9.5) and ypN+ (HR, 12.0) (p = .026). CONCLUSIONS: Natural N0 and downstaged N0 patients are different clinical entities: downstaging cN+ with induction treatment producing downstaged N0 improves survival only if there is concomitant primary cancer downstaging to ypT0. Intermediate survival is seen in downstaged N0 patients with complete tumor response. Natural N0 patients experience intermediate survival with incomplete response (ypT+). Complete response in natural N0 patients produces the best survival. Means of obtaining ypN0 status matters and requires a complete response for downstaged N0 patients to benefit from induction treatment.

Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response: a phase 2 study.

BACKGROUND: This phase 2 study was aimed at defining the pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, continuous infusion (c.i.) of 5-fluorouracil (5-FU) and concomitant radiotherapy (RT) in untreated stage II-III adenocarcinoma and squamous cell carcinoma of mid-distal thoracic esophagus. METHODS: The schedule consisted of a first phase of chemotherapy alone and of a second phase of concurrent chemoradiation. Doses were as follows: docetaxel 35 mg/m(2) and cisplatin 25 mg/m(2) on days 1, 8, 15, 29, 36, 43, 50, and 57 plus 5-FU c.i. (180 mg/m(2) on days 1-21 and 150 mg/m(2) on days 29-63); RT (50 Gy) started at day 29. Surgery was planned 6 to 8 weeks after the completion of chemoradiation. RESULTS: A total of 74 patients were enrolled; pathological complete remission (pCR) was found in 47% (35 of 74) and near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) (pnCR) in 15% of the patients (11 of 74). Grade 3-4 neutropenia, nonhematological toxicity, and toxic deaths occurred in 13.5%, 32.4%, and 4% of the patients, respectively. Median follow-up was 55 months (range, 3-108 months). Median survival of all 74 patients was 55 months, whereas it was not reached in the pCR subset. The 3- and 5-year survival rates were, respectively, 83% and 77% for pCR, 73% and 44% for pnCR, and 21% and 14% for Residual Tumor subsets (P < .001). CONCLUSIONS: This study shows that 1) this intensive weekly schedule produced a high pathological response rate, 2) responders had high and long-term durable survival rates.

Treatment of esophago-gastric junction adenocarcinoma.

AIM: The incidence of Adenocarcinoma of the esophagogastric junction (EGJ) is increasing and its treatment is still debated, primarily because of the non-uniform definition of EGJ. MATERIALS AND METHODS: The most used classification of EGJ cancer was proposed by Siewert and it divides the EGJ in three regions: from 5 to 1 cm above the Z line (Siewert type I or esophageal Adenocarcinoma), from 1 over to 2 below the Z line (Siewert type II or real Cardia cancer) and from 2 below to 5 below the Z line (Siewert type III or proximal Gastric cancer diffused to Cardia). The neoplasia is defined type I, II or III depending on where is the center of the cancer. DISCUSSION: This classification did not show to be related to differences in prognosis and survival, but it has been used to guide the surgical strategy based on the site of the tumor. Criticism about this classification focuses mainly on the non-uniform treatment, in the current literature, of Siewert Type II cancer. CONCLUSION: From January 2010, a new definition of EGJ carcinoma has been introduced by TNM. This new definition considers esophageal cancers all the ones whose centers falls inside a line drawn 5 cm below the Z line with invasion of the esophagus. This means that Siewert type I and II are now considered esophageal cancers, while type III can be esophageal or proximal gastric cancer depending if the esophagus is infiltrated or not. Criticism about this new definition rises on the border-line definition of former Siewert type III cancers.

[Prognostic significance of the Mandard TRG classification after induction therapy in carcinoma of the oesophagus and cardia]. / Significato prognostico della classificazione TRG di Mandard dopo terapia induttiva nel carcinoma di esofago e cardias.

Mandard's tumor regression grade (TRG) is widely used to evaluate the pathological response to induction therapy with concurrent chemoradiotherapy in cancer of the oesophagus or gastro-oesophageal junction. The aim of this study was to evaluate the prognostic significance and clinical applicability of TRG. From 2000 to 2007, 108 patients with squamous cell carcinoma of the oesophagus (57 cases) or Siewert type I and II adenocarcinoma of the cardia (51 cases) were treated with induction chemoradiotherapy followed by surgery in the 1st Division of General Surgery of the University of Verona. The treatment was identical for all patients and consisted of cisplatin, 5 FU and docetaxel together with 50 Gy of concurrent radiotherapy. The treatment-induced response was evaluated by TRG. Fifty-one, 24, 17, 9 and 7 patients were classified, respectively, as TRG1, 2, 3 4 and 5. Fifty-two patients died of the disease. Disease-related survival decreased with the increase in TRG class in node-negative patients (p < 0.001), while in N+ patients it was poor, irrespective of TRG class (p = 0.241). Mandard TRG is therefore useful for staging patients undergoing preoperative chemoradiotherapy, because it displays high prognostic significance. In our study, however, N was the main prognostic factor and for this reason it is mandatory to consider nodal status along with TRG. Moreover, among N negative patients, the prognosis of each different TRG class is statistically different and for this reason different TRG classes cannot be grouped together.