Nirmish Singla, MD

“Challenging Cases in Urology” is a new Urology Times section in which residents from the nation’s leading urology programs present their toughest cases and how they ultimately managed them. Cases inform readers of the problem-solving process and provide a lesson from the authors’ experience.

A 63-year-old African-American male presents to the emergency department with sudden onset of painless gross hematuria for one day. He reports dark red urine with clots causing occasional dysuria, difficulty emptying, and light-headedness.

He had undergone a robot-assisted laparoscopic prostatectomy 12 years prior for pT2aN0 Gleason 3+4=7 prostate cancer, with negative surgical margins. His preoperative PSA was 8.6 ng/dL and his postoperative PSA nadir was <0.05 ng/dL 3 months after surgery. He was lost to follow-up until his current presentation. The patient notes that he received no further treatment for prostate cancer since his surgery.

His remaining past medical history is significant for hypertension, well-managed type 2 diabetes mellitus, and Paget’s disease of bone. He does not take any noteworthy medications. He denies family history of genitourinary malignancies and denies any history of smoking. He works as an MRI technician.

The patient is afebrile and presents with blood pressure of 133/90 mm Hg and heart rate of 97 bpm. His BMI is 30 kg/m

. He appears to have a slight pallor. His respirations are unlabored. His abdominal exam reveals a soft, non-tender, non-distended abdomen with well-healed port sites and a small, easily reducible umbilical hernia.

The patient’s genitourinary exam shows a circumcised phallus and bilaterally descended testes with no remarkable findings. His capillary refill time is 3 seconds. On insertion of a Foley catheter, there is return of cherry red-colored urine with clots.

Laboratory evaluation reveals creatinine 0.89 mg/dL, white blood cell count 12.3 x10

/µL, hemoglobin 8.4 g/dL, hematocrit 24.8%, and platelets 125 x10

/µL. Electrolytes are within normal range. His PSA is 0.12 ng/mL. His voided urinalysis demonstrates >45 red blood cells, 5 white blood cells, trace leukocyte esterase, negative nitrite, and no bacteria.

A CT urogram is obtained (figure 1). Imaging reveals a heterogeneous 4cm enhancing mass at the right aspect of the bladder anterolaterally, with some stranding changes noted in the fat adjacent to this lesion. No hydronephrosis, pelvic lymphadenopathy, or sites of metastatic disease are found.

 Large anterior enhancing bladder mass on CT urogram

The patient’s catheter is manually irrigated in the ED, with removal of a significant volume of clot. He is initiated on continuous bladder irrigation (CBI) and admitted for observation. On hospital day 2 his urine remains cherry red on moderate rate CBI. His vitals are notable for a pulse of 105 bpm with a blood pressure within the normal range. Hemoglobin and hematocrit are now 7.0 g/dL and 21.0%, respectively. His bladder is manually irrigated with a significant volume of clot removed again.

In light of his progressive anemia, he is transfused 2 units of packed red blood cells and taken to the operating room urgently for clot evacuation. Cystoscopic evaluation reveals no obstruction or obvious prostatic regrowth at his vesicourethral anastomosis. On entry into the bladder, a sizable, well-formed clot is appreciated. Following extensive clot resection, irrigation, and evacuation, a >5-cm tumor at the right lateral dome with a hemorrhagic surface and wide base is seen.

Resection of the mass is performed, but only partially, given the thin adjacent bladder wall. Tumor extension is noted well beyond this point. Once hemostasis is obtained, the procedure is terminated and the patient is reinitiated on CBI. The ureteral orifices are not identified intraoperatively but are not felt to be involved by the mass.

By hospital day 5, the patient remains on CBI and is transfusion dependent, and the decision is made to reevaluate his bladder cystoscopically. He is found to have several areas of bleeding that are fulgurated extensively. Postoperatively, he is successfully weaned off his CBI and discharged on hospital day 6 voiding clear urine.

Two days later, he re-presents to the ED with gross hematuria, normal vital signs, and stable hemoglobin. He denies any difficulty with voiding, and a post-void bladder scan reveals 0 cc. He expresses his strong desire to avoid catheterization. He is admitted for close observation, as he does not want to leave with active bleeding.

Fortunately, his pathology had returned earlier that day. Histologic evaluation of his tumor shows spindle cells in myxoid background extending into the muscularis propria and perivesical fat peripherally, consistent with inflammatory myofibroblastic tumor (IMT) (figures 2 and 3). IMTs, or inflammatory pseudotumors, are rare, typically benign, spindle-cell tumors felt to be associated with prior inflammatory processes, including trauma, prior instrumentation, infection, and autoimmune disease. The true cause is not well elucidated, however. On the molecular level, there is some evidence that these tumors develop due to a disruption in an RNA degradation pathway 

 Inflammatory myofibroblastic tumor, histologically demonstrating spindle cells in a myxoid background, extending into the muscularis propria

 IMT with involvement of the perivesical fat cells peripherally

IMTs can present throughout the body, with the lung being the most common site. According to a recent review of the literature, there are nearly 200 reported cases of bladder IMTs, the majority of which come from single case reports 

). The most common presenting symptom is gross hematuria, seen in over 70% of these cases, but other presenting symptoms may be subtler and include dysuria, frequency, abdominal pain, and loin pain. While this patient presented with symptomatic anemia, only 6% of patients with bladder IMTs ever develop anemia.

Histologically, IMTs are defined by myofibroblastic and fibroblastic spindle cells with inflammatory infiltrate of lymphocytes, plasma cells, eosinophils, and histiocytes. They are typically well vascularized. Grossly, they tend to be large, smooth, broad-based tumors with a propensity to bleed, as in this case, and have a mean tumor size is 4.5 cm 

"While there are typical histologic features noted in IMTs, there is room for diagnostic uncertainty"

While there are typical histologic features noted in IMTs, there is room for diagnostic uncertainty. There have been at least two cases of IMTs (in a study of 46 cases) that were found to be sarcomatoid carcinoma on re-transurethral resection of bladder tumor (TURBT) 

). The malignant potential of IMTs, however, remains controversial, as the largest series on the entity demonstrate no cases of metastases.

There are a handful of case reports of this occurrence from organs other than the bladder 

). In the largest literature review available, however, 0/120 patients with a mean follow-up time of 30 months had distant metastasis 

The mainstay of treatment for bladder IMTs is surgical resection, with the most commonly selected option in roughly 60% of cases 

). This is followed by partial cystectomy in approximately 30% of cases and radical cystectomy in almost 10% of cases. In this same review, only 4/120 patients had local recurrence at a mean follow-up of 30 months, although it is notable that 18/120 (15%) of patients in this series required a second surgical procedure due to presumed incomplete resection by initial TURBT.

For patients with tumors not amenable to resection or for whom surgery would present an undue risk, there are investigational treatment modalities that have shown some promise. Berger et al reported success in use of neoadjuvant prednisone and COX-2 inhibitors to shrink an IMT in a 3-year-old boy that was sitting close to the bladder neck 

Neoadjuvant platinum-based chemotherapy has also been used successfully to achieve resection of unresectable locally invasive IMTs 

. Germanides et al reported a near-complete regression of an aggressive gastrointestinal IMT with infliximab (Remicade) monotherapy 

). There are no reports of TNF-alpha inhibition treatment having been utilized in bladder IMTs, although this could be a promising area for investigation as TNF-alpha is a potent mediator of inflammation, which is believed to be critical to the formation and propagation of IMTs.

The success of these interventions, theoretically, could be limited by their systemic effects. In the era of targeted biologic therapy, there is a push to identify novel targets unique to the malignancy, thus limiting the undesirable systemic effects of medical treatment. Approximately 50% to 60% of IMTs express various rearrangements of anaplastic lymphoma kinase 

), a tyrosine kinase at the chromosome 2p23 locus.

Interestingly, this rearrangement was found in our patient. Numerous authors have investigated the prognostic implications of ALK expression and it appears that it is correlated with higher local recurrence rates, but reduced rates of metastasis in cases of non-bladder IMTs 

). Butrynski et al reported a case of a man with diffuse abdominopelvic IMT treated with neoadjuvant and adjuvant crizotinib, an ALK inhibitor, who achieved a sustained remission of his disease despite incomplete surgical resection 

Despite early successes with novel medical therapies, surgery is the only intervention that has proven curative for IMTs. Given the reported success in treatment of bladder IMTs in the available literature, urologists should pursue resection, by TURBT or partial cystectomy, barring exceptional circumstances and an IRB-approved research protocol.

The patient underwent a robot-assisted partial cystectomy. The decision to pursue partial cystectomy rather than repeat TURBT was made based on the extent of the tumor and difficulty in achieving complete resection endoscopically. The robotic approach was made more difficult by his prior robot-assisted laparoscopic prostatectomy, but the anterior bladder was successfully mobilized. Identification of the residual tumor-a 4 cm tumor on the right anterior surface of the bladder, sparing the ureteral orifices-was achieved with the assistance of concomitant flexible cystsoscopy. This lesion was successfully excised with a small mucosal margin via a vertical midline cystotomy and adequate residual bladder volume (figure 4).

 Robotic partial cystectomy with mucosal margin around IMT. Bladder closed in two layers.

Following cystorrhaphy, a drain was left in the pelvis through a right robotic port site. The patient was discharged home on postoperative day 2 without a drain after drain creatinine revealed no evidence of a urine leak. His Foley catheter was removed on postoperative day 7. Final pathology revealed IMT with negative surgical margins. At his 6-month follow-up, the patient had no residual hematuria or voiding complaints. A repeat cystoscopy was performed and revealed no residual bladder masses. Given the benign nature of his pathology, no further cystoscopic evaluations have been indicated. He continues to be followed for routine prostate cancer surveillance, and his PSA currently remains undetectable 2 years following his partial cystectomy.

 is assistant instructor and fellow, and 

 is professor of urology and radiology at UT Southwestern Medical Center, Dallas.

Articles

Challenging case: Hematuria in man with a history of prostate Ca

 is chief resident of urology at the University of Texas Southwestern Medical Center, Dallas. 

 blogs present opinions, advice, and news from urologists and other urology professionals. Opinions expressed by bloggers are their own, and do not necessarily reflect the views of 

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	The shift that occurs during medical school from the classroom to the clinical setting undoubtedly marks an important transition. The radical change in the learning environment is perhaps most apparent in that we no longer rely solely on textbooks and lectures to acquire knowledge, but rather contextualize the clinical questions that we encounter daily and integrate the dynamically evolving body of literature into the care of patients.

	Beyond redefining the approach to learning, this transition also symbolizes a shift in our primary focus from ourselves (the student) to the patient. No longer is our education simply centered on passing examinations and advancing to the next career stage, but rather on improving outcomes for the patients we encounter and treat.

Life after residency: Is a fellowship in your future?

	While medical school serves as a transition point, residency is a transformation. In the 5-6 demanding years that it takes to become a board-eligible urologist, we learn the foundational knowledge of a unique specialty, how to answer consults effectively, how to counsel patients based on the latest research in our field, and how to operate as surgeons and perform procedures skillfully. In short, we learn the skills needed to become a practicing urologist.

	Aside from the technical aspects of training, residency offers many lessons along the way. There is a particular maturity that develops throughout residency that extends beyond the curriculum.

	Now in the final year of my own residency training, perhaps the most important lesson I have learned is the value of responsibility. This may seem obvious at first glance, as patient care sits at the core of shared responsibility for the health care team.

	As a chief resident, though, I have come to appreciate that responsibility assumes many forms and should not be underestimated. Understanding the meaning of responsibility is crucial to effectively transition from a trainee to a urologic surgeon.

	In the context of patient accountability, it is worthwhile to revisit one of the basic tenets of medical ethics frequently cited: Primum non nocere, or first, do no harm. As surgeons, and particularly as surgical trainees, we must respect the privilege that we have been granted by our patients. They entrust their lives to us and surrender their bodies to allow us to operate on them to our discretion.

	As trainees, we are indebted to these patients for supporting our surgical education and enabling us to learn from them. We must further respect the legal liability that our attending surgeons are willing to risk for their patients in order to provide us with education and train the next generation of urologists.

	In return, we owe it to both our patients and our teachers to assume full ownership for our patients’ care and well-being. This means not only reading about, practicing, and preparing for operative cases, but also ensuring medical optimization for the operating room, paying attention to details in postoperative management (eg, intravenous fluids, thromboembolic chemoprophylaxis, social issues) and feeling a sense of personal accountability when complications arise.

	In hospital settings where immediate supervision is less direct, resident autonomy may be celebrated but comes with even greater responsibility. In such settings, perhaps more important than learning how to operate is recognizing when not to operate in the interest of upholding the principle of non-maleficence during the evaluation and counseling of patients.

Next - Promotion to chief resident: Paying it forward

Promotion to chief resident: Paying it forward

	Promotion to the chief resident year comes with yet another form of responsibility, in that we inherently become responsible for our junior residents and medical students. We assume the guise of leaders and role models for our mentees and transition into teachers-in conferences, in the clinic, on rounds, and in the operating room. I have gained an increasing appreciation for the patience that my own mentors and attending surgeons have demonstrated for me, and now I have the opportunity to pay the debt forward.

Visiting professorships offer unique benefit to residents

	By assuming the administrative responsibility of distributing operative case assignments among residents and dictating the content of educational conferences, I share the responsibility of ensuring that junior residents are progressing appropriately in their training.

	Indeed, the journey to become a urologist has taught me several valuable lessons that extend beyond the curriculum found in our textbooks. Certainly, the knowledge and technical skills that we learn as trainees are imperative for clinical practice. However, we must also learn to appreciate the privilege that we are gifted as physicians and surgeons. In order to complete our transformation into urologists, we must learn to understand and respect the multifaceted importance of responsibility for our patients, our teachers, and our mentees.

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"In order to complete our transformation into urologists, we must learn to understand and respect the multifaceted importance of responsibility for our patients, our teachers, and our mentees," writes Nirmish Singla, MD.

Lessons of residency extend beyond the technical

 section in which residents from the nation’s leading urology programs present their toughest cases and how they ultimately managed them. Cases inform readers of the problem-solving process and provide a lesson from the authors’ experience.  

 is professor of urology and chief of urologic oncology at the University of Texas Southwestern, Dallas.

	A 48-year-old male is referred from an outside provider for evaluation of gross hematuria for several weeks. He denies any dysuria or subjective difficulty with voiding. His medical history is remarkable for prune belly syndrome, atrial fibrillation, hypertension, and type II diabetes mellitus. Records regarding his childhood surgical history are unfortunately scant, though notable for a remote vesicostomy that was subsequently closed, an enterocystoplasty, and abdominoplasty.

	More recently, he had undergone a right simple nephrectomy 5 years prior for a non-functional kidney in the setting of recurrent urinary tract infections. The patient reports a long history of intermittent management with a urethral catheter, although he notes that he currently evacuates his bladder via spontaneous voiding without difficulty. He denies any family history of malignancies and notes that he did smoke approximately a half-pack per day of cigarettes for 2 years, from 1984 to 1986.

	On physical examination, the patient’s body mass index is 32 kg/m

, and he is noted to have a well-healed, large, left-sided paramedian scar from the pubic bone to above the umbilicus; a midline scar at his prior vesicostomy site; and laxity of his abdominal wall with redundancy of his overlying skin. Testes are palpable bilaterally. Laboratory evaluation reveals creatinine of 1.5 mg/dL (calculated GFR of 50 mL/min/1.73 m

); hemoglobin and hematocrit are 9.9 g/dL and 30.1%, respectively. Electrolytes, platelets, coagulation profile, liver function tests, and remainder of lab results are within normal range.

Persistent ureteral stone in a 76-year-old male

	To his initial appointment, the patient brings MR images of his abdomen and pelvis, displayed in the figure. The imaging reveals a 5.6 x 4.3 x 4.5-cm mass at the anterior bladder dome with inflammation extending to the perivesical fat. No pelvic lymphadenopathy or sites of metastatic disease are found. Severe left-sided hydoureteronephrosis extends to the level of an abnormally conformed bladder, consistent with a patulous collecting system, with ureteral insertion into the dome. His abdominal wall musculature appears thin, and his prostate appears diminutive with an apparent atrophic left seminal vesicle.

	Figure. MRI of the abdomen and pelvis reveal a solitary left kidney with severe hydroureteronephrosis seen in axial (A) and coronal T2-weighted (B) views. A 5.6 x 4.3 x 4.5-cm mass is seen at the anterior bladder dome (C) with inflammation extending to the perivesical fat on T1-weighted imaging in axial view (yellow circle). No pelvic lymphadenopathy or sites of metastatic disease are found. (Figure courtesy of Nirmish Singla, MD, and Yair Lotan, MD)

	He undergoes a transurethral resection of the tumor that reveals muscle-invasive urothelial carcinoma with >90% squamous differentiation and no lymphovascular invasion. The bladder appears to have been augmented with small bowel, and the tumor is located within the native portion of the bladder.

A case of hydronephrosis, sepsis, and pain

	The concern for a potentially increased risk of intravesical malignancy following augmentation enterocystoplasty has generated considerable interest. At present, however, we lack definitive evidence supporting this association. In 2010, Higuchi et al reported that bladder augmentation was not an independent risk factor in the development of bladder cancer in a relatively sizable cohort of patients with congenital bladder abnormalities 

), though their study is limited by its single-institution, retrospective nature.

	Given the controversy surrounding this topic, there are currently no guidelines to routinely screen asymptomatic patients with prior bladder augmentation for intravesical malignancy. Nonetheless, many urologists would still elect to pursue some means of monitoring, whether through urine studies, imaging, cystoscopic evaluation, or some combination thereof.

	The present case further highlights the issue of transitional care, commonly faced by pediatric urologists. Indeed, there are several challenges inherent in transitioning pediatric urology patients to adult providers-a process that must be carefully orchestrated. Some obstacles to this transition include locating adult urologists with special expertise, maintaining comprehensive documentation regarding childhood medical and surgical care, coordinating care with other adult specialties such as nephrology, and navigating the adult health care environment (

	In our patient’s case, unfortunately much was unknown regarding his prior history, such as the original indications for bladder augmentation, whether ureteral reimplantation was pursued, and the type and length of bowel segment used, which are all important to know prior to offering surgical intervention.

Metallic stents efficacious for malignant ureteral obstruction

	There are additional challenges worth consideration in the subsequent management of our patient’s malignancy. First, the role of neoadjuvant chemotherapy remains unclear in the setting of variant histology, as endorsed by the 2017 AUA guideline on muscle-invasive bladder cancer 

). Several operative challenges during radical cystectomy can be anticipated in his case as well. Given his multiple prior abdominal surgeries including bowel resection, extensive scarring can be anticipated, and preoperative consultation with a general surgeon may be worthwhile for intraoperative assistance with adhesiolysis and dissection.

Next: "Deciding on a type of diversion poses another challenge"

	Deciding on a type of diversion poses another challenge. Given his patulous ureter and unclear degree of bowel resection for prior reconstructions, the possibility of utilizing a cutaneous ureterostomy is worth consideration. Although long-term outcomes of ureterostomies in adults are not well known, the likelihood of stenosis is conceivably low in his case, while obviating the need to resect further bowel. Finally, given his history of prune belly syndrome, fascial closure must be meticulous, and the increased risk of parastomal hernia warrants discussion as well.

	Given his predominantly squamous histology and baseline renal dysfunction in the setting of a solitary kidney, the decision was ultimately made to proceed with upfront radical cystectomy. A midline incision was initially made. Several dense adhesions were encountered and lysed with the assistance of our general surgery colleagues, including adhesions between the small bowel and augmented bladder. The patulous left ureter was located coursing into the augmented bladder segment, and following its ligation, appeared to have a diameter larger than that of the small bowel lumen.

Multivitamin use may reduce prostate Ca recurrence

	A large bladder mass was palpable at the anterior portion of the bladder. Once the bladder was successfully removed en bloc with the prostate, the left ureter was noted to have been tunneled under the sigmoid mesentery proximally. There were significant adhesions proximally with the bowel and mesentery that made the dissection of the left ureter challenging, and it was felt that an attempt to free it to allow for a cutaneous ureterostomy would be precarious and possibly injure its blood supply. As such, a decision was made to bridge the gap between the ureter and skin using an ileal conduit, which was anastomosed to the solitary left ureter in an end-to-end fashion.

	Postoperatively, the patient had a relatively uncomplicated course, and his final pathology revealed pT3bN0 high-grade urothelial carcinoma with squamous and sarcomatoid differentiation arising in the dome, anterior, and posterior walls of the bladder with invasion into the perivesical soft tissues. Lymphovascular invasion was present, and all margins were negative. He is currently under consideration for adjuvant systemic immune therapy trials with our medical oncology colleagues.

	In summary, we present the unique case of a 48-year-old male with prune belly syndrome, solitary left kidney, and prior enterocystoplasty, who was found to have muscle-invasive bladder cancer with extensive squamous differentiation. Our case highlights multiple complexities in his management, including the role for multimodal care, operative challenges necessitating consultation with other surgical colleagues, and the importance of having multiple strategies in the operating room should the initial plans prove less desirable.

	Our case also highlights the controversy surrounding the development of and screening for intravesical malignancy in patients with prior enterocystoplasty, for which a stronger level of clinical evidence is necessary. Finally, our case more broadly underscores the challenges inherent in transitional care within urology.

Setting up an emergency fund: What you need to know

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Imaging reveals a mass at the anterior bladder dome with inflammation extending to the perivesical fat. No pelvic lymphadenopathy or sites of metastatic disease are found.

Challenging cases in urology: Hematuria in a man with prune belly syndrome

	Dr. Singla is a urology resident at the University of Texas Southwestern, Dallas

	From choosing a college major to pursuing a doctorate degree to selecting a specialty, we are constantly confronted with the need to narrow our career focus and define our meaning in life. Like a stem cell, we are initially faced with limitless opportunities, but progressively choose a direction that resonates with our identified interests and goals, which are often moving targets.

	For myself, part of the interest to pursue an MD stemmed from the versatility of the degree and the ability to pursue a broad variety of interests, including clinical care, research, education, and administration, among others. Selecting a specialty in medical school can be challenging, especially for those who enjoy thinking about every organ system and who wish to remain involved with every discipline in the field: the jack-of-all-trades mentality. That being said, all physicians must inevitably identify some niche for themselves, however broad or subspecialized it may be.

	Urology was enticing to me given the range of techniques (endoscopy, laparoscopy/robotics, open surgery, medical management) and the patient diversity that it affords. It has allowed me to develop a broad skill set while gaining expertise in a focused area-perhaps a similar sentiment held by many urologists. Despite the lengthy training process to become a urologist, 5-6 years of residency go by quickly, and the need to select a post-residency path-ie, the decision to pursue or forego subspecialty fellowship training-seemingly arrives sooner than anticipated. Making that choice can be another challenging process as well.

	Just as selecting a medical specialty requires some degree of soul-searching, a similar process is necessary for deciding what to do following residency. The decision to pursue a fellowship and the type of fellowship should ideally be made at least 2 years before graduation. Despite already being a specialty area, urology remarkably offers several subspecialty fellowship training programs, including andrology/infertility/male reproductive health, female pelvic medicine and reconstruction, oncology, pediatrics, trauma and reconstruction, endourology, minimally invasive surgery, and transplant. This means that an informed decision needs to be made with potentially limited exposure to some of these areas.

	For residents who are still trying to figure out what to do next, start by envisioning the type of practice setting in which you hope to work, the responsibilities you wish to assume (eg, research-based or education-based activities), and the skills you hope to gain.

	Next, prioritize your career goals and investigate the means necessary for fulfillment. Evaluate the skills and exposure you will gain on completion of your residency training, and assess whether or not investing 1-3 additional years in subspecialty training will significantly enhance your skillset or provide “political” gains to achieve your goals.

	For example, although not a requisite for an academic career, completing a fellowship may enhance your candidacy for an academic position or help carve a defined niche. Having a research and/or multidisciplinary didactic component in fellowship can also help mold the way urologists think about our field’s critical issues and gaps. In private practice, fellowship training could be useful by potentially improving your marketability or supplementing a surgical skillset.

	If you are interested in pursuing fellowship but unsure which of the many options to choose, it may be a helpful exercise to set aside some protected time to reflect on the types of cases you enjoy doing, areas you like reading and thinking about, mentors you admire, and patients you enjoy working with. Likewise, it similarly helps to identify aspects of urology that are less appealing for a long-term career.

	Try to immerse yourself within each subspecialty area within urology to see if it is a good fit-familiarize yourself with the contemporary literature, become involved with research projects, gain exposure to relevant operative cases and specialty clinics, attend any subspecialty conferences or educational sessions, and encourage discussions with attendings and fellows in each area. Taken together, these considerations may not only help equip you to make a more informed career decision, but also serve to better understand yourself as a budding urologist.

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Nirmish Singla, MD, offers career planning tips to urology residents who may be approaching the end of their training.