Robotic intracorporeal “Padua Ileal Bladder”: Surgical technique, perioperative, oncologic and functional outcomes

==inizio abstract==

Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder reconstruction is a challenging procedure. The aim of this video is to illustrate our technique for RARC and totally intracorporeal orthotopic “Padua Ileal Bladder”.
From August 2012 to February 2014, 45 patients underwent RARC, extended pelvic lymph node dissection and intracorporeal partly stapled neobladder at a single tertiary referral centre. Surgical steps are demonstrated in the accompanying video. Demographics, clinical and pathological data were collected. Perioperative, 2-yr oncologic and 2-yr functional outcomes were reported.
Intraoperative transfusion or conversion to open surgery was not necessary in any case and intracorporeal neobladder was successfully performed in all 45 patients. Median operative time was 305 minutes (IQR 282-345). Median estimated blood loss was 210 ml (IQR 50-250). Median hospital stay was 9 days (IQR 7–12). The overall incidence of perioperative, 30-d and 180-d complications were 44.4%, 57.8% and 77.8%, respectively, while severe complications occurred in 17.8%, 17.8% and 35.5%, respectively. Two-yr daytime and night-time continence rates were 73.3% and 55.5%, respectively. Two-yr disease free survival, cancer specific survival and overall survival rates were 72.5%, 82.3% and 82.4%, respectively.
Our experience supports the feasibility of totally intracorporeal neobladder following 
RARC. Operative times and perioperative complication rate are likely to be reduced with increasing experience.

==fine abstract==

Anatomic robot assisted radical cystectomy in female: step by step technique

==inizio abstract==

Robot assisted radical cystectomy (RARC) in female is a challenging procedure. We describe step by step surgical technique, presenting perioperative outcomes of a 66 yr-old female patient with a cT1/N0/M0 high grade recurrent bladder cancer who underwent RARC with totally intracorporeal orthotopic neobladder (iON).

Key steps were: ligation of gonadic pedicles, dissection of umbilical and uterine arteries and the ureters, dissection of bladder pedicles, opening of the vagina and creation of the plane between vagina and bladder. Urethra was cut and Foley catheter secured with the entire specimen into an Endocatch bag to minimize any urine spillage. Specimen was removed through the vagina. Extended pelvic lymph node dissection. Vagina was sutured and a peritoneal flap used as posterior neobladder support.
Operative time was 295 minutes, EBL was 250 mL, time to flatus was 3 days. Hemoglobin and creatinine at discharge were 10.3 g/dL and 0.76 mg/dL, respectively. Pathologic stage was pT0 pN0. Nodes removed were 26. Postoperative course was uneventful. Daytime continence was recovered after 45 days.
A meticulous dissection of bladder vascular suppliers, a natural orifice specimen retrieval and the ease of posterior neobladder support, thanks to a perfect vision of the small pelvis anatomic structures, may contribute to minimize invasiveness, improving outcomes of RARC in female patients.

==fine abstract==

Intracorporeal partly stapled Padua Ileal Bladder using robotic staplers: surgical technique, perioperative and early functional outcomes of a prospective single center series

==inizio abstract==

In this prospective study (www.clinicaltrials.gov NCT02665156) we assessed the feasibility, safety and time efficiency of RARC with intracorporeal partly stapled “Padua Ileal Bladder” using robotic staplers.
Twenty-two consecutive patients with muscle invasive or high grade recurrent urothelial bladder carcinoma were treated between March 2016 and October 2016. Baseline, perioperative and follow-up data were prospectively collected. Key steps of surgery include: selection of 45 centimeters of ileum and division of the distal and proximal part of the ileum using robotic staplers; detubularization of the ileal loop; creation of the neo-bladder neck with one stapler load; double folding of the proximal ileal loop using two-three stapler loads; hand-sewing of the posterior neobladders wall with barbed suture; uretero-ileal anastomoses on JJ stents with a modified split-nipple technique; urethroneobladder anastomosis is performed according to Van Velthoven; hand-sewing of the anterior neobladders wall with barbed suture.
Median total operative time (“skin to skin”) was 270 minutes (IQR:255-295).
Median hospital stay was 9 days (IQR 8-11). Overall complication rate was 40.1% and overall severe complication incidence was 18.2%; at a median follow-up of 3 months, no patients developed recurrence, daytime continence rate was 59%.
We first report safety, feasibility and time efficiency in the use of robotic staplers to create orthotopic neobladder.

==fine abstract==

En bloc TUR of bladder tumours: a new standard?

==inizio objective==

Trans urethral resection (TUR) of bladder tumor is one of the most frequent procedures performed in urology. Indeed, it is one of the most controversial [1]. It clearly violates oncological basic principles inasmuch tumor must be fragmented to be resected and retrieved from the bladder. Fragmentation is at the base of two major flaws. First, the pathological examination of the specimen is frankly impaired. Margins cannot be properly assessed and infiltration of the sub-urothelial connective or of the muscular tissue may be underestimated or even missed. Second, seeding of urothelial cancerous cells, which may lead to recurrence, may easily occur after tumor resection and fragmentation. En bloc transurethral resection (EBTUR) is supposed to overcome the major flaws of conventional TUR. It is not a new procedure, since it has been described the first time in 1980 in Japan [2], but only in the last decade, the interest in technical improvements of TUR has been renewed [1]. We performed a literature review to assess up to date results of EBTUR and to answer the question if EBTUR may be considered as the new golden standard for endoscopic treatment of bladder tumors

==fine objective==

==inizio methodsresults==

We performed a systematic review of the available literature about EBTUR. A search across PUBMED was performed with the following keys “bladder cancer” [MESH term] & “en bloc” and “en bloc resection bladder tumor” in July, 20th, 2016. Respectively, 132 and 160 papers were found. After reading the abstract, 118 and 141 were excluded by Authors because they were off topic, reviews and opinions. After matching the list of the remaining 14 and 20 items, 14 were excluded because duplicates, 2 because case reports, and 2 because not written in English. Thus, a list of 16 original papers was included in the review [3-18]. Finally, after reading thoroughly the references of the selected papers, one more significant item was added [19]. Main outcomes were safety (complications rate), pathological assessment (incidence of detrusor muscle in the specimen and rate of appropriate staging), and oncological control (recurrence rate, surgical margins, rate of residual disease)

==fine methodsresults==

==inizio results==

Overall, 895 patients have been submitted to EBTUR, accounting for 1191 lesions. Forty complications (4%) were computed. Only 10 (1%) were grade III, mostly bladder perforation or bleeding. Fifty-nine conversions (6.5%) to conventional TUR have been reported because of “difficult” locations of tumors or failure to extract the specimen. Several series, accounting for 763 patients, report about incidence of detrusor muscle in the specimen. Overall, 731 (96%) cases with detrusor muscle were computed. Tumor stage remained uncertain only in 12 (1.5%) cases. Follow up data were available for 544 patients. Mean follow up ranged from 9.3 to 40 months. Recurrence rate varied from 6% to 55%. Most of the recurrence occurred outside primary tumor site. Mean weighted follow up across all series was 20 months, whereas overall recurrence rate was 23%.

==fine results==

==inizio discussions==

Conventional TUR of bladder tumor is generally performed with a 24/26 Ch continues flow resectoscope and standard loop. Tumor is fragmented in chips by the “incise and scatter” technique and extracted with a syringe or an Ellik evacuator through the working channel. Cell seeding may occur during resection as well as during extraction of tumor. Moreover, tumor fragmentation impairs pathological examination. There is no clear orientation of the specimen, muscular or sub connective tissue infiltration may be underestimated or even missed as well as a proper assessment of surgical margins is impossible, even if additional biopsies of the resection bed and of perilesional margins are performed. Conversely, EBTUR respects the oncological principle of specimen integrity with a safety margin of healthy tissue. Even if the first paper about EBTUR has been printed in the Eighties [2], it is yet in its infancy inasmuch only about a thousand of cases have been published up to date. Despite a similar surgical technique, a great variety of equipments for resection and for specimen extraction has been used, adding heterogeneity to the results interpretation [3-19]. Beyond technicalities, two main aspects must be underlined. First, EBTUR is safe; the risk of serious complications is negligible whereas the overall risk of complications is comparable to historical TUR series [20]. Second, pathological assessment is by any means far more precise. The incidence of detrusor muscle in the specimen, about 95%, and the rate of appropriate staging, about 99%, are really high if compared to standard TUR [20,21].

==fine discussions==

==inizio conclusion==

EBTUR is safe and feasible. Pathological assessment of en bloc specimen makes the difference with respect to conventional TUR, even if a clear statement on the matter has still to be reported by pathologists, who should change their way of describing the specimen, including margins as in whatever oncological histology report. Indeed, no advantages in terms of recurrence rate have been yet disclosed. What we do really need now is a standardization of the technique, especially when it comes to specimen extraction, and larger randomized study, adequately designed to observe an oncological advantage. In the meanwhile, when it is possible, every urologist should adopt EBTUR to ensure the best histological assessment possible.

==fine conclusion==

==inizio reference==

1) Wilby D, Thomas K, Ray E, et al. Bladder cancer: new TUR techniques. World J Urol 2009; 27:309-12

2) Kitamura K, Kataoka K, Fujioka H, et al. Transurethral resection of a bladder tumor by the use of a polypectomy snare. J Urol 1980; 124:808-9

3) Hurle R, Lazzeri M, Colombo P, et al. “En Bloc” Resection of Nonmuscle Invasive Bladder Cancer: A Prospective Single-center Study. Urology 2016; 90:126-30

4) Migliari R, Buffardi A, Ghabin H. Thulium Laser Endoscopic En Bloc Enucleation
of Nonmuscle-Invasive Bladder Cancer. J Endourol. 2015; 29:1258-62

5) Chen X, Liao J, Chen L, et al. En bloc transurethral resection with 2-micron continuous-wave laser for primary non-muscle-invasive bladder cancer: a randomized controlled trial. World J Urol
2015; 33:989-95

6) Kramer MW, Rassweiler JJ, Klein J, et al. En bloc resection of urothelium carcinoma of the bladder (EBRUC): a European multicenter study to compare safety, efficacy, and outcome of laser and electrical en bloc transurethral resection of bladder tumor. World J Urol 2015; 33:1937-43

7) He D, Fan J, Wu K, et al. Novel green-light KTP laser en bloc enucleation for nonmuscle-invasive bladder cancer: technique and initial clinical experience. J Endourol 2014; 28:975-9

8) Muto G, Collura D, Giacobbe A, et al. Thulium:yttrium-aluminum-garnet laser for en bloc resection of bladder cancer: clinical and histopathologic advantages. Urology 2014; 83:851-5

9) Sureka SK, Agarwal V, Agnihotri S, et al. Is en-bloc transurethral resection of bladder tumor for non-muscle invasive bladder carcinoma better than conventional technique in terms of recurrence and progression?: A prospective study. Indian J Urol 2014; 30:144-9

10) Upadhyay R, Kapoor R, Srivastava A, et al. Does En-bloc transurethral resection of bladder tumor give a better yield in terms of presence of detrusor muscle in the biopsy specimen? Indian J Urol 2012; 28:275-9

11) Maurice MJ, Vricella GJ, MacLennan G, et al. Endoscopic snare resection of bladder tumors: evaluation of an alternative technique for bladder tumor resection. J Endourol 2012; 26:614-7

12) Naselli A, Introini C, Germinale F, et al. En bloc transurethral resection of bladder lesions: a trick to retrieve specimens up to 4.5 cm. BJU Int 2012; 109:960-3

13) Fritsche HM, Otto W, Eder F, Hofstädter F, et al. Water-jet-aided transurethral dissection of urothelial carcinoma: a prospective clinical study. J Endourol 2011; 25:1599-603

14) Wolters M, Kramer MW, Becker JU, et al. Tm:YAG laser en bloc mucosectomy for accurate staging of primary bladder cancer: early experience. World J Urol 2011; 29:429-32

15) Nagele U, Kugler M, Nicklas A, et al. Waterjet hydrodissection: first experiences and short-term outcomes of a novel approach to bladder tumor resection. World J Urol; 29:423-7

16) Ukai R, Hashimoto K, Iwasa T, et al. Transurethral resection in one piece (TURBO) is an accurate tool for pathological staging of bladder tumor. Int J Urol 2010; 17:708-14

17) Lodde M, Lusuardi L, Palermo S, et al. En bloc transurethral resection of bladder tumors: use and limits. Urology 2003; 62:1089-91

18) Saito S. Transurethral en bloc resection of bladder tumors. J Urol 2001; 166:2148-50

19) Ukai R, Kawashita E, Ikeda H. A new technique for transurethral resection of superficial bladder tumor in 1 piece. J Urol 2000; 163:878-9

20) Herr HW, Donat SM. Quality control in transurethral resection of bladder tumours. BJU Int 2008; 102:1242-6

21) Babjuk M, Böhle A, Burger M, et al. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol 2016 Jun 17 [Epub ahead of print]

==fine reference==

Oncological outcomes of laparoscopic and open treatment (nephroureterectomy) for urothelial tumors of upper urinary tract

==inizio objective==

The open radical nephroureterectomy (ORN) with distal ureter and removal of a bladder cuff is considered the current standard of care for the treatment of carcinoma of the upper urinary tract (1). However, laparoscopy has been shown to be equally effective with lower perioperative morbidity (2). Laparoscopic nephroureterectomy (LRN), therefore it is emerging as a viable alternative minimally invasive. But the question remains on the safety and efficacy of oncological LRN and its equivalence to ORN.
Some authors have suggested that the dissection of the tumor and the high pressure of the gas that are established for the pneumoperitoneum during the LRN associated with a higher risk of bladder recurrence, local recurrence as well as metastases on Trocar sites (3).
The differential effect of LRN compared ORN on oncological outcomes after radical nephroureterectomy (RN) remains controversial. Although many recent studies report oncological results comparable between ORN and LRN in well selected patients (4-5 and 8), others reported a higher risk of intravesical recurrence of disease compared with LRN ORN (6-7).

We wanted to evaluate our clinical results between ORN and LRN, analyzing the data of 61 NUL performed between 2006 and 2016 and compared retrospectively with data from 37 NUO performed in the years 2002 to 2005 (it was pre-laparoscopy ).

==fine objective==

==inizio methodsresults==

We evaluated data collected retrospectively on 37 consecutive patients treated with ORN between 2002 and 2005 (it was pre-laparoscopy) and 61 patients undergoing LRN between 2006 and 2016.

ORN was performed according to the standard criteria, ie, the dissection of the kidney with the entire length of the ureter bladder and removal of a headset with a second short incision. Lymphadenectomy was not routinely performed unless the patient had no macroscopically or radiographically evident lymph nodes.
The laparoscopic technique has been performed with transperitoneal approach in 45 patients and with retroperitoneal approach 15. The excision of the bladder cuff has been carried out with open technique using the incision to remove the piece. In table 1, 2 and 3, the characteristics of patients and interventions
Patients were followed every 3 months for the first year, every 4 months for the second year, every 6 months starting from the third to fifth year and each year thereafter. The follow-up consisted of history, physical examination, routine blood tests, urine cytology, chest X-ray, CT uretrocistoscopica and Uro.
The average was 32 months follow-up in patients undergoing LRN and 52 months for those treated with ORN. We evaluated particularly cancer recurrence, the recurrence and survival site.

==fine methodsresults==

==inizio results==

We had local recurrence in 7 patients (11.4%) after LRN and in 2 (6.25%) after ORN.
2 patients undergoing LRN (5.5%) died from metastatic disease at 9 and 12 months, 3 patients underwent ORN (9.3%) died from metastases to 12, 16 and 23 months.
Was found bladder recurrence in 9 patients undergoing LRN and 4 after ORN.
The most frequent tumor recurrence sites were: local recurrence (7 LRN-2 ORN), 1 recurrence of laparoscopic port, 3 recurrences in the regional lymph nodes (6 LRN, 1 ORN), bladder (LRN 9, 4 ORN) .There were no significant differences in recurrence and even the survival rates at 1 and 3 years old are not very different results between the two techniques.

Some researchers have suggested that the manipulation of the tumor during the LRN can lead to a migration of tumor cells with the possible plant to secondary sites, and in the bladder, due to the high gas pressure required for the laparoscopic procedure (3).
Moreover, it was also reported as a possible concern with the LRN of tumoral cells of the plant in Trocar sites (3). However, these potential risks of LRN are controversial and have not gotten feedback in the various works carried out (11).

In agreement with many previous studies, we found no significant difference in recurrence, recurrence in the bladder, and in the specific cause of death from the disease among patients treated with ORN and those with LRN (4-5- 8-9). Also as in other studies (5, 8 and 9), we found no significant association between surgical approach and death due to illness.

==fine results==

==inizio discussions==

Some researchers have suggested that the manipulation of the tumor during the LRN can lead to a migration of tumor cells with the possible plant to secondary sites, and in the bladder, due to the high gas pressure required for the laparoscopic procedure (3).
Moreover, it was also reported as a possible concern with the LRN of tumoral cells of the plant in Trocar sites (3). However, these potential risks of LRN are controversial and have not gotten feedback in the various works carried out (11).

In agreement with many previous studies, we found no significant difference in recurrence, recurrence in the bladder, and in the specific cause of death from the disease among patients treated with ORN and those with LRN (4-5- 8-9). Also as in other studies (5, 8 and 9), we found no significant association between surgical approach and death due to illness.

==fine discussions==

==inizio conclusion==

The grade and stage of the cancer affect the incidence of metastatic disease, and is a poor prognostic factor in the primitive location of the disease (pelvis-ureter-both), rather than the surgical technique used.
There is no evidence so that the cancer control is compromised in patients treated with LRN rather than by ORN.

==fine conclusion==

==inizio reference==

1. Oosterlinck W, Solsona E, van der Meijden APM et al. EAU guidelines on diagnosis and treatment of upper urinary tract transitional cell carcinoma. Eur Urol 2004;46:14
2. S.Y. Eskicorapci, D. Teber, M. Schulze, M. Ates, C. Stock, J.J. Rassweiler. Laparoscopic radical nephrectomy: the new gold standard surgical treatment for localized renal cell carcinoma. ScientificWorldJournal 7 (2007) (825 – 836)
3. S. Micali, A. Celia, P. Bove, et al.. Tumor seeding in urological laparoscopy: an international survey. J Urol 171 (2004) (2151 – 2154)
4. F. Greco, S. Wagner, R. Hoda, A. Hamza, P. Fornara. Laparoscopic vs open radical nephroureterectomy for upper urinary tract urothelial cancer: oncological outcomes and 5-year follow-up. BJU Int 104 (2009) (1274 – 1278)
5. U. Capitanio, S.F. Shariat, H. Isbarn, et al.. Comparison of oncologic outcomes for open and laparoscopic nephroureterectomy: a multi-institutional analysis of 1249 cases. Eur Urol 56 (2009) (1 – 9)
6. O. Kamihira, R. Hattori, A. Yamaguchi, et al.. Laparoscopic radical nephroureterectomy: a multicenter analysis in Japan. Eur Urol 55 (2009) (1397 – 1409)
7. Y. Matsui, N. Utsunomiya, K. Ichioka, et al.. Risk factors for subsequent development of bladder cancer after primary transitional cell carcinoma of the upper urinary tract. Urology 65 (2005) (279 – 283)
8. M. Waldert, M. Remzi, H. Klingler, L. Mueller, M. Marberger. The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy. BJU Int 103 (2009) (66 – 70)
9. D. Manabe, T. Saika, S. Ebara, et al.. Comparative study of oncologic outcome of laparoscopic nephroureterectomy and standard nephroureterectomy for upper urinary tract transitional cell carcinoma. Urology 69 (2007) (457 – 461)
10. M. Muntener, E. Schaeffer, F. Romero, et al.. Incidence of local recurrence and port site metastasis after laparoscopic radical nephroureterectomy. Urology 70 (2007) (864 – 868)
11. G. Simone, R. Papalia, S. Guaglianone, et al.. Laparoscopic versus open nephroureterectomy: perioperative and oncologic outcomes from a randomised prospective study. Eur Urol 56 (2009) (520 – 526)

==fine reference==

EN BLOC RESECTION OF NON MUSCLE INVASIVE BLADDER CANCER: EXPERIENCE IN SANT’ANNA HOSPITAL – COMO

==inizio objective==

The goal of traditional trans-urethral resection of bladder tumors (TURBT) is to remove all visible cancers and obtain tissue for pathological diagnosis, with minimal morbidity to the patient, even if the tumor is removed in piecemeal. Additionally, detrusor muscle (DM) is absent in up to 50% of cases. Moreover, residual disease is diagnosed in the final pathology in up to 76% of cases of the restaging TURBT. Recently, the urologists’ approach to the management of superficial bladder cancer has been evolving and the basic principle of oncologic surgery of removing the entire tumor “en bloc” by dissecting through normal tissue to prevent the scatter of malignant cells and positive surgical margins is becoming more and more important.
The aim of the present study is the description of both “en-bloc” technique in Our Centre and the medium-term results of our single-center experience with “en-bloc resection of bladder tumors” (ERBT) in a selected group of patients.

==fine objective==

==inizio methodsresults==

We retrospectively analyzed the story of 24 patients consecutively underwent to ERBT. A single expert urologist executed the procedure using a mono-polar or bipolar Storz 24 Ch resector.
The surgeon executed a “U-shaped” incision anteriorly to the lesion, with a mucosal margin of 3 mm, including macroscopically sane tissue. Thus, the incision was conducted in retrograde way going under the lesion, until obtaining a complete detachment from the bladder wall. Laterally, the incision included the margin of sane mucosa. The depth of the incision included the muscle layer.
A trans-urethral catheter was positioned after the operation; the same was removed after 48 hours.
We also compared our experience with data literature, searching for the key words: “En bloc resection”, “Trans-urethral resection” and “Non Muscle Invasive Bladder Cancer”.

==fine methodsresults==

==inizio results==

We enrolled 24 patients (21 males and 3 females); all showed a Non Muscle Invasive Bladder Cancer (NMIBC) urothelial carcinoma; among these, 3 had High grade NMIBC, 1 Carcinoma in Situ, 1 PULMP, and 20 showed low grade NMIBC at the definitive pathology. All the ERBT samples showed the presence of DM. The mean age at diagnosis was 69 years (range 53-87), presenting with a mean tumor diameter of  8± 3 mm and a median number of resected tumors per patients of 1 (range 1-3). In 7 case the procedure (first in all patients) was associated with early instillation of epirubicin within 30 minutes after TUR. In 6 cases the ERBT was not the first TUR in the history of the patients. The mean follow-up was 25 months (range 7-60 months) and there was a recurrence rate in 7/24 patients, with low grade final pathology. The main limitation of the study consists in the absence of a control group.

==fine results==

==inizio discussions==

SEE RESULTS

==fine discussions==

==inizio conclusion==

Our findings confirmed the feasibility and safety of en bloc resection of bladder tumor, with a recurrence-free survival of 71%.

==fine conclusion==

==inizio reference==

1. Herrmann TR, Wolters M, Kramer MW. Transurethral en bloc resection of nonmuscle invasive bladder cancer: trend or hype. Curr Opin Urol. 2016 Dec 28. doi: 10.1097/MOU.0000000000000377.

2. Hurle R, Lazzeri M, Colombo P, Buffi N, Morenghi E, Peschechera R, Castaldo L, Pasini L, Casale P, Seveso M, Zandegiacomo S, Taverna G, Benetti A, Lughezzani G, Fiorini G, Guazzoni G. “En Bloc” Resection of Nonmuscle Invasive Bladder Cancer: A Prospective Single-center Study. Urology 2016; 90: 126-30.

3. kramer MW, Rassweiler JJ, Klein J, Martov A, Baykov N, Lusuardi L, Janetschek G, Hurle R, Wolters M, Abbas M, von Klot CA, Leitenberger A, Riedl M, Nagele U, Merseburger AS, Kuczyk MA, Babjuk M, Herrmann TR.En bloc resection of urothelium carcinoma of the bladder (EBRUC): a European multicenter study to compare safety, efficacy, and outcome of laser and electrical en bloc transurethral resection of bladder tumor. World J Urol 2015; 33 (12):1937-43.

==fine reference==

Ethical consultation for radical urological surgery in fragile elderly people

==inizio objective==

1) Objective

The care of fragile patient is an aspect still largely debated. In the past was encouraged economic assistance with low clinical content; in this context find place an evaluation also based on ethical clinic. We don’t want to discuss surgical methods or medical results, but we would like to demonstrate the way we answered an explicit (or sometimes tacit) question when we decided to perform surgery on a patient with these characteristics: “It really needs to perform surgery on him at his age?”

==fine objective==

==inizio methodsresults==

2) Materials and Methods

The word “fragile” identifies a condition of risk and vulnerability, with unstable equilibrium towards negative events. Elderly people, due to aging process and intercurrent diseases, become more vulnerable and many conditions can change homeostatic balance of their organism (1). It is defined essentially by two paradigms:
Biomedical: this condition is considered a physiological syndrome defined by reduction of functional reserves and weak resistance to “stressors”, resulting from cumulative decline of multiple physiological systems causing vulnerability and adverse consequences (2)
BioPsychosocial : this condition is considered like “dynamic state affecting people who experience losses in one or more functional domains (Physical, Psychic, Social) caused by multiple variables that increase risk of adverse events for health” (3,4). To evaluate fragile patients we applied the Multidimensional Oncological Geriatric Evaluation (MOGE) and the scale: Vulnerable Elders Survey (VES – 13), and screening tool (G8) (5,6). We defined three categories of patients:
FIT: absence of disability or comorbidity, standard treatment can be applied.
UNFIT/VULNERABLE: presence of many comorbidity and/or disability and /or Geriatric Syndrome; treatments conformed to general clinical conditions can be applied to improve quality of life.
UNFIT/FRAIL: cannot be included in previous two categories¸ personalized treatment to improve quality of life and survival can be applied
We scanned the caregiver. Cancer changes family architecture. Caregiver takes care of sick people in first person, is an integrated figure in the care of oncological patient with important caretaking and ethical tasks and is involved in many aspects of the care through several phases of oncological disease: drugs administration, symptoms management, nutritional assistance, treatments supervision, emotional support.

==fine methodsresults==

==inizio results==

3) Results

In the second half of 2016 we perform surgery on 12 patients that can be defined fragile elderly people. In 5 patients we perform radical cystectomy with ureteroileocutaneostomy (Bricker). In 3 patients we must perform radical nephrectomy (in addition to cystectomy), with monolateral ureterocutaneostomy, in 2 patients we perform radical nephrectomy and in the last 2 patients conservative renal surgery. Actually 10 patients are in follow-up. 2 patients died (one for pulmonary thromboembolism during surgery and one after 4 months for pulmonary infection).

==fine results==

==inizio discussions==

4) Discussion

Combining data from MOGE (VMG) and data from interview with caregiver (that we consider fundamental because relationship between caregiver and health professionals have important ethical and social implications) (7), we got to analyze the whole question according to ethical clinic using bioethical foundations, contractualism, utilitarianism, ontology based personalism (8), but in particular inspired by Bioethics of everyday life (9,10,11) that want to face daily life themes of professionals of care process so that ethics become an operative tool stimulating a change for improvement of health intervention.

==fine discussions==

==inizio conclusion==

5) Conclusions

Ethical consultation allows to help any health worker, patient, caregiver who need advice in facing hard or suffered decisions. In particular helps doctors to answer the initial question: “It really needs to perform surgery on him at his age?”, not only with the guidelines indications, but also in the perspective of total care so that the narrative medicine based (12) approach became always more important in health resorts

==fine conclusion==

==inizio reference==

6) References

1) La fragilità nell’anziano: una prospettiva clinica. A. Giordano et all. J Gerontol 2007;55:2-6
2) Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. Journals of Gerontology. Series A: Biological and Medical Sciences; 59(3): 255-263; 2004 Fried LP et al.
3) Gobbens R.J. et al. In search of an integral conceptual definition of frailty: opinions of experts. J Am Med Dir Assoc; 11(5): 338-43; Jun 2010
4) La fragilità dell’anziano. Linea guida Regione Toscana 2013
5) Tumori dell’anziano .Linee Guida AIOM 2016
6) Gestione del paziente unfil/trail : il punto di vista dell’Urologo. A. Giacobbe Convegno renal care Verona 7-8 Marzo 2014
7) Family caregivers, patients and physicians: ethical guidance to optimize relationships. Mitnick S., Leffler C., Hood V.L. J Gen Intern Med 2010; 25: 255-260.
8) Dalla parte della vita . Itinerari di Bioetica Vol. 1 E. Larghero . Effatà Editore 2010
9) Bioetica del Quotidiano. S. Spinsanti Medico e Bambino 1/1997 pag.59-64
10) Bioetica Quotidiana. G. Berlinguer. Giunti Editore 2000
11) La Bioetica del Quotidiano. E. Sgreccia Vita e Pensiero Editore 2006
12) Bioetica e medicina narrativa: nuove prospettive di cura . E. Larghero Edizioni Camilliane 2013

==fine reference==

Neuroendocrine Carcinoma of the Bladder

==inizio objective==

Primary neuroendocrine cancer of the bladder is a rare histological occurrence, constituting 0.48–1% of all bladder cancers. The 5-year survival rate is around 8% and the prognosis is extremely unfavorable. Due to the morphology of the tumor, treatments based on small cell lung cancer have been performed. In this study, we treated a case in which chemotherapy was performed with cisplatin (CDDP) and etoposide (VP-16) forneuroendocrine cancer that occurred in the bladder; here, we report the results.

==fine objective==

==inizio methodsresults==

Our patient was a 49 year old male. His previous history included hypertension. He had no family history in particular. In June 2014, the patient visited our department because of voiding obstructive and irritative symptoms. He was evaluated by ultrasound examination, thoracic and pelvic CT scan, urinary cytology and cystoscopy without evidence of bladder pathology. He was treated with alpha lytic therapy because of his obstructive symptoms. Nine months later he returned with intensive irritative voiding symptoms and haematuria. An ultrasound examination revealed a thickening on the right bladder wall. A thoracic and pelvic CT scan revealed a flat lesion of 4 cm on the right bladder wall and metastasis to right external iliac lymph nodes with a diameter of 2.5 cm, resulting in a diagnosis of clinical stage T3bN1M0. No obvious distal metastasis was detected by bone scintigraphy and thoracic pelvic CT. In April 2015 the patient was hospitalized for the purpose of undergoing a transurethral resection of the bladder tumor (TUR-Bt). In the histopathological findings, there were a number of large and small solid alveoli of atypical cells accompanied by infiltrative growth into the interstitium. The atypical cells had a high N/C ratio and rough chromatin, and the neoplastic alveoli also suggested differentiation into the neuroendocrine system. When immunohistological staining was performed, the tumor cells were partially positive for CD56 and chromogranin A and negative for synaptophysin. Based on the morphology and the results of immunohistological staining, the patient was diagnosed with neuroendocrine cancer. Radical cystectomy was performed in June 2015 with bilateral ureterocutaneostomy.

==fine methodsresults==

==inizio results==

In September 2015 a positron emission tomography-computed tomography (PETCT) performed before chemotherapy revealed no distal metastasis. Based on the protocol for small cell lung cancer, chemotherapy with cisplatin (CDDP) and etoposide (VP-16) was performed along with PE therapy (P: 80 mg/body, E: 100 mg/body). Two other PETCT in March 2016 and November 2016 revealed no recurrence.

==fine results==

==inizio discussions==

Since first being reported by Cramer et al. in 1981, neuroendocrine bladder cancer has often been reported as primary small cell cancer of the bladder. Histologically, it is believed that this condition exhibits a similar histological appearance as small cell lung cancer, where the tumor cells are small, the nuclei are rich in chromatin and are circular or spindle-shaped, and tumor cells with scarce cytoplasm solidly proliferate. For immunostaining, CD56, synaptophysin, and chromogranin A are used. In this study, CD56 and chromogranin A were shown to be partially positive. The case in this study involved a high-grade neuroendocrine cancer according to the World Health Organization classification, and using the classifications of lung cancer, many parts had morphologies equivalent to those of small cell cancer, while some parts exhibited morphologies of large cell cancer. Blomjous et al. have reported that primary neuroendocrine cancer of the bladder constitutes approximately 0.48% of all bladder tumors in autopsy cases. At the time of diagnosis, primary neuroendocrine cancer of the bladder is detected as an advanced cancer occurring in T3 and T4 in 70% and 16.3% of cases, respectively. In addition, the 5-year survival rate has been reported to be 8.1–19%, and the prognosis is extremely unfavorable. Regarding treatment, multimodality therapy combining surgical therapy and chemotherapy/radiation therapy is often implemented; however, this is not yet an established therapy. Based on cases of small cell lung cancer, chemotherapy is mainly performed with PE therapy using a combination of cisplatin (CDDP) and etoposide (VP-16), and there are reports in which the prognosis was improved.

==fine discussions==

==inizio conclusion==

Primary neuroendocrine cancer of the bladder is a rare histological occurrence, constituting 0.48–1% of all bladder cancers. The 5-year survival rate is around 8% and the prognosis is extremely unfavorable. This case is to be signaled because of the age of the patient and the rapid evolution of pathology.

==fine conclusion==

==inizio reference==

1 Cramer SF, Aikawa M, Cebelin M: Neurosecretory granules in small cell invasive carcinoma of the urinary bladder. Cancer 1981;47:724–730.
2 Blomjous CE, Vos W, Schipper NW, et al: Morphometric and flow cytometric analysis of small cell undifferentiated carcinoma of the bladder. J Clin Path 1989;42:1032–1039.
3 Abbas F, Civantos F, Benedetto P, et al: Small cell carcinoma of the bladder andprostate.
Urology 1995;46:617–630.
4 Mackey JR, Au HJ, Venner P, et al: Genetourinary small cell carcinoma of the bladder: a report of 25 cases. J Urol 1998;153:1820–1822.

==fine reference==

Role of re-staging transurethral resection for T1 non-muscle invasive bladder cancer: a systematic review and meta-analysis

==inizio objective==

Repeated transurethral resection of bladder tumor (reTUR), the fourth most common cancer [1], has been advocated as an essential step to obtain a complete tumor clearance in T1 stage and an appropriate staging. Several standardized national and international guidelines recommend the procedure, especially in patients with high grade and/or T1 bladder cancer [2]. The main reason is the high prevalence of residual tumor found after reTUR and its clinical implications [2]. However, experts’ opinion on the topic is not concordant. Some suggest that reTUR may be not useful when an adequate first TUR has been performed [3]. Moreover, to our knowledge, the last meta-analysis were published respectively in 2011 and 2014 [4,5]. Since then many series, including a great number of cases, properly stratified upon the status of detrusor muscle of the first TUR, have been reported. Therefore, we believe it is necessary to re assess the impact of the procedure by means of a systematic review of literature and meta-analysis of available datasets, distributed in a period of 30 years, to find out potential discrepancies and support guidelines commitment.

==fine objective==

==inizio methodsresults==

The whole process of evidence acquisition and synthesis has been carried in order to accomplish to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist [6]. After definition of the population and of the outcome a systematic search of available literature in English from 1980 to 2016 was performed. Articles included in the study [7-35] were assessed for risk of bias using two domains of the Quality in Prognosis Studies tool (QUIPS) relevant to observational studies (study participation and outcome measurement). Pooled prevalence of residual tumor and of upstage at reTUR was assessed and computed by means of random effects model to take into account heterogeneity showed by I squared and Cochran’s Q values. A sensitivity analysis was conducted to exclude excessive influence by a single study.

==fine methodsresults==

==inizio results==

Among papers identified, 29 items were selected. A total of 3566 and 2556 cases formed the study population to assess the prevalence of residual tumor and upstaging respectively. The respective figures for the subgroup with detrusor muscle in the specimen of TUR were respectively 1565 and 1187. Pooled residual tumor prevalence at reTUR and upstaging to T2 were 0.56 (95% CI 0.48 – 0.63) and 0.1 (95% CI 0.06 – 0.14). Respective figures for the subgroup were 0.47 (95% CI 0.33 – 0.62) and 0.1 (95% CI 0.06 – 0.14). Analysis of series at low risk of bias disclosed a limited impact of heterogeneity, especially in regards to up staging. Pooled prevalence of residual disease was 0.42 (95% CI 0.27 – 0.58) and of upstaging to invasive disease 0.11 (95% CI 0.06 – 0.18). Sensitivity analysis excluded excessive influence from each of the study examined.

==fine results==

==inizio discussions==

Findings from our systematic review and meta-analysis showed that the rate of persistence of disease in T1 cases is really high and stable among studies belonging to different decades. Pooled prevalence of persistent disease is about 50% whereas pooled prevalence of upstaging to invasive disease is about 10% overall or about one third of the cases with residual cancer. Intriguingly, results are similar including only cases with a sample of muscle in the specimen of the initial TUR or including only series at low risk of bias. A meta-analysis, published in 2011, came to similar findings analyzing a group of 2248 patients, including 1432 T1 cases [4]. Interestingly, Authors observed similar pooled prevalence rate among cases with single and multiple primary lesion [4]. Another meta-analysis, including 3 randomized trials and 4 prospective clinical studies on reTUR for Ta and T1 tumors, showed a rate of residual disease of about one third, raging from 3.7 to 17.6% for cases with a complete first TUR [6].

==fine discussions==

==inizio conclusion==

The rate of residual disease and of upstaging also in prospective nowadays series including cases with a “clinically and pathologically” complete previous TUR suggest that reTUR should remain a cornerstone in the treatment of non muscle invasive bladder cancer as recommended in guidelines

==fine conclusion==

==inizio reference==

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[2] Burger M, Oosterlinck W, Konety B, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2013; 63:36-44
[3] Brausi MA. Challenging the EAU Guidelines Regarding Early Repeat Transurethral Resection. Eur Urol Suppl 2011;3:e5 – e7
[4] Vianello A, Costantini E, Del Zingaro M, et al. Repeated white light transurethral resection of the bladder in nonmuscle-invasive urothelial bladder cancers: systematic review and meta-analysis. J Endourol 2011; 25:1703-12
[5] Dobruch J, Borówka A, Herr HW. Clinical value of transurethral second resection of bladder tumor: systematic review. Urology 2014; 84:881-5
[6] Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 21:339:b2535
[7] Klan R, Loy V, Huland H. Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. J Urol 1991;146:316–18
[8] Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999; 162:74–76
[9] Brauers A, Buttner R, Jakse G. 2nd Resection and prognosis in primary high risk superficial bladder cancer. J Urol 2001; 165:808–10
[10] Ozen H, Ekici S, Uygur MC, Akbal C, Sahin A. Repeated transurethral resection and intravesical BCG for extensive superficial bladder tumors. J Endourol 2001; 15:863-7
[11] Schips L, Augustin H, Zigeuner RE, et al. Is repeated transurethral resection justified in patients with newly diagnosed superficial bladder cancer? Urology 2002; 59:220–23
[12] Dalbagni G, Herr HW, Reuter VE. Impact of a second transurethral resection on the staging of T1 bladder cancer. Urology 2002; 60:822-824
[13] Grimm M, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. J Urol 2003; 170:433-37
[14] Zurkirchen MA, Sulser T, Gaspert A, Hauri D. Second transurethral resection of superficial transitional cell carcinoma of the bladder: a must even for experienced urologists. Urol Int 2004; 72:99–102
[15] Schwaibold HE, Sivalingam S, May F, Hartung R. The value of a second transurethral resection for T1 bladder cancer. BJU Int 2006; 97:1199-1201
[16] Divrik T, Yildirim U, Eroğlu AS, Zorlu F, Ozen H. Is a second transurethral resection necessary for newly diagnosed pT1 bladder cancer? J Urol 2006; 175:1258–61
[17] Han KS, Joung JY, Cho KS, et al. Results of repeated transurethral resection for a second opinion in patients referred for non muscle invasive bladder cancer: the referral cancer center experience and review of the literature. J Endourol 2008; 22:2699-2704
[18] Herr HW, Donat MS. Quality control in transurethral resection of bladder tumors. BJU Int 2008; 102:1242–46
[19] Divrik RT, Sahin AF, Yildirim U, Altok M, Zorlu F. Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate and disease-specific survival: a prospective randomised clinical trial. Eur Urol 2010; 58:185–90
[20] Parkin J, O’Keefe K, Bhatt RI, et al. G3T1 bladder cancer: Is early re-resection necessary? Br J Med Surg Urol 2011; 4:13–17
[21] Ali MH, Ismail IY, Eltobgy A, Gobeish A. Evaluation of second-look transurethral resection in restaging of patients with non-muscle- invasive bladder cancer. J Endourol 2010; 24:2047-2050
[22] Yucel M, Hatipoglu NK, Atakanli C, et al. Is repeat transurethral resection effective and necessary in patients with T1 bladder carcinoma? Urol Int 2010; 85:276-80
[23] Katumalla FS, Devasia A, Kumar R, Kumar S, Chacko N, Kekre N. Second transurethral resection in T1G3 bladder tumors – Selective avoidable? Indian J Urol 2011; 27:176-79
[24] Aning JJ, Hotston M, Pisipatti S, et al. Early re-resction for T1 transitioanl cell carcinoma of the bladder-A study of current practice in the South West of England. Br J Med Surg Urol 2011; 4:18-23
[25] Fujikawa A, Yumura Y, Yao M, Tsuchiya F, Iwasaki A, Moriyama M. An evaluation to define the role of repeat transurethral resection in a treatment algorithm for non-muscle-invasive bladder cancer. Indian J Urol. 2012 Jul; 28:267-70
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==fine reference==

Open versus robot assisted radical cystectomy and orthotopic neobladder: Mid-term single center propensity score matched analysis of perioperative and oncologic outcomes

==inizio objective==

Oncologic equivalence open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) remains a debatable issue and prospective randomized trials comparing these two approaches are hard to perform. In this study we compared oncologic outcomes of propensity score matched cohorts of patients treated with either ORC and orthotopic neobladder (ON) or RARC and intracorporeal ON.

==fine objective==

==inizio methodsresults==

The institutional review board approved prospective bladder cancer database was queried for “cystectomy with curative intent” and “neobladder”. A 1:1 PSM analysis was used to minimize the potential biases of a retrospective analysis of data. Kaplan-Meier method was used to compare the oncologic outcomes of the PSM cohorts. Survival rates were computed at 2, 3 and 4 years after surgery and the log rank test was applied to assess statistical significance between the two PSM groups.

==fine methodsresults==

==inizio results==

Overall 363 patients with a minimum follow-up length of 2 years were included, 299 of which treated with ORC and 64 with RARC.
Patients treated with open surgery were less frequently male (p=0.08), with higher pT stage (p=0.003), higher incidence of non-urothelial histologies (0.05) and lesser adoption of neoadjuvant chemotherapy (<0.001). After applying the PSM, 64 RARC patients were matched with 46 ORC cases. The two groups did not differ for all clinical and pathologic variables included in the analysis (all p ≥0.22). All data are summarized in table 1. At Kaplan-Meier analysis RARC and ORC cohorts displayed comparable disease free survival (log rank p= 0.894; Figure 1a), cancer specific survival (log rank p=0.8; Figure 1b) and overall survival rates (log rank p= 0.97; Figure 1c). ==fine results== ==inizio discussions== ==fine discussions== ==inizio conclusion== RARC with intracorporeal neobladder provides an optimal control of soft tissue surgical margins and of LN yield. Preliminary oncologic outcomes suggest that patients treated with RARC and intracorporeal neobladder display comparable disease free survival of patients treated with open surgery. ==fine conclusion== ==inizio reference== - Robotic Intracorporeal Padua Ileal Bladder: Surgical Technique, Perioperative, Oncologic and Functional Outcomes. Simone G, Papalia R, Misuraca L, Tuderti G, Minisola F, Ferriero M, Vallati G, Guaglianone S, Gallucci M. Eur Urol. 2016 Oct 22. pii: S0302-2838(16)30721-7. doi: 10.1016/j.eururo.2016.10.018. [Epub ahead of print] - Perioperative and oncologic outcomes of robot-assisted vs. open radical cystectomy in bladder cancer patients: A comparison of two high-volume referral centers. Gandaglia G, Karl A, Novara G, de Groote R, Buchner A, D'Hondt F, Montorsi F, Stief C, Mottrie A, Gratzke C. Eur J Surg Oncol. 2016 Nov;42(11):1736-1743. doi: 10.1016/j.ejso.2016.02.254. ==fine reference==