Localized RCC: Nephron Sparing Surgery and alternative treatments Saleh A.Binsaleh

Introduction The incidence of small incidental renal tumors is increasing.The incidence of small incidental renal tumors is increasing. Nowadays the trend in managing these tumors is toward nephron-conserving surgery.Nowadays the trend in managing these tumors is toward nephron-conserving surgery. Open partial nephrectomy with its excellent 5 and 10 yrs oncologic follow-up data is the gold standard,against which all other MINSS should be compared.Open partial nephrectomy with its excellent 5 and 10 yrs oncologic follow-up data is the gold standard,against which all other MINSS should be compared. NSS provides cancer control comparable with radical nephrectomy in selected pts with a small(4 cm or less) localized RCC.NSS provides cancer control comparable with radical nephrectomy in selected pts with a small(4 cm or less) localized RCC. (Uzzo&Novick,J.Urol 2001;166:6).

Introduction Minimally invasive NSS is relatively recent advance that has gain considerable interest in the urologic community.Minimally invasive NSS is relatively recent advance that has gain considerable interest in the urologic community. Some of the newer technologies still investigational.Some of the newer technologies still investigational.

MINSS Lap. Partial nephrectomyLap. Partial nephrectomy Renal cryotherapyRenal cryotherapy RFARFA HIFUHIFU Microwave thermotherapyMicrowave thermotherapy Intracavitary photon irradiationIntracavitary photon irradiation

MINSS Laparoscopic Partial Nephrectomy

Introduction The first LPN was described by Winfield et al for a woman with a lower pole caliceal diverticulum containing a stone. (J. Endourol,7:521,1993).The first LPN was described by Winfield et al for a woman with a lower pole caliceal diverticulum containing a stone. (J. Endourol,7:521,1993). As compared to laparoscopic Radical Nephrectomy, it is more technically challenging procedure.As compared to laparoscopic Radical Nephrectomy, it is more technically challenging procedure. Technical difficulties are encountered when securing renal hypothermia,renal parenchymal hemostasis, pelvicaliceal reconstruction, and renorraphy.Technical difficulties are encountered when securing renal hypothermia,renal parenchymal hemostasis, pelvicaliceal reconstruction, and renorraphy. Steps are essentially duplicating those of open partial nephrectomy.Steps are essentially duplicating those of open partial nephrectomy.

Indications Classical indications:Classical indications: -small renal tumors. -Peripheral location. -Superficial. -Exophytic. As the surgeon s experience increases:As the surgeon s experience increases: more complex tumors can be done (tumors invading the parenchyma to the collecting system,or renal sinus, complete intrarenal tumors,tumor in a solitary kidney). more complex tumors can be done (tumors invading the parenchyma to the collecting system,or renal sinus, complete intrarenal tumors,tumor in a solitary kidney).

Contraindications Renal vein thrombus/ IVC thrombus.Renal vein thrombus/ IVC thrombus. Multiple renal tumors( more than two).Multiple renal tumors( more than two). Locally advanced disease.Locally advanced disease. Bleeding diathesis.Bleeding diathesis. Morbid obesity.Morbid obesity. Prior renal surgery.Prior renal surgery. General C/I to laparoscopic surgery.General C/I to laparoscopic surgery.

C/I to Lap. surgery Absolute contraindications:Absolute contraindications: -uncorrectable coagulopathy -Intestinal obstruction -Abdominal wall infection -Massive hemoperitonium -Generalized peritonitis -Suspected malignant ascites.

C/I to Lap. surgery Relative contraindications:Relative contraindications: -Morbid obesity. -Extensive Prior Abdominal or Pelvic Surgery. -Pelvic Fibrosis. -Organomegaly. -Ascites -Pregnancy. -Hernia. -Iliac or Aortic Aneurysm.

Pre-op. Preparation Same as for open approach.Same as for open approach. Basic blood work.Basic blood work. Accurate staging.Accurate staging. Three dimensional CT scan.Three dimensional CT scan.

Surgical technique Transperitoneal. anterior,anterolateral,lateral,upper pole apical tumors. anterior,anterolateral,lateral,upper pole apical tumors. Retroperitoneal posterior,posterolateral tumors. posterior,posterolateral tumors.

Surgical technique -Cystoscopy, ureteral catheterization - Port placement. - Hilar dissection and preparation for vessels cross-clamping. - Mobilize and defat kidney. - Identify tumor. -Laparoscopic ultrasonography and circumferential scoring. -Renal hypothermia (if needed). cooling jacket,retrograde cold perfusion,ice-slush. cooling jacket,retrograde cold perfusion,ice-slush. -Hilar cross-clamping (preceded by intravenous mannitol).

Surgical technique -Tumor excision. -Renal tumor bed biopsy and frozen section. - Pelvicaliceal repair (if necessary). - Specific figure-of-eight sutures to control transected parenchymal vessels. - Hemostatic renorraphy over bolsters. - Unclamp hilum, confirm hemostasis. - Jackson-Pratt drain.

Hemostatic techniques: - Argon beam coagulator. -Electrocautery. -Harmonic scalpel. -Fibrin glue. -Gelatin sponges. -Ultrasonic surgical aspirator. -Laser. -Microwave tissue coagulator.

Surgical technique

Lap. Partial nephrectomy Transperitoneal laparoscopic partial nephrectomy. Individual dissection of the renal artery and vein is not necessary, and a laparoscopic Satinsky clamp is used to control the renal hilum en bloc. The inset shows a four- port arrangement, with a 2-mm needle port positioned laterally.

Lap. Partial nephrectomy Retroperitoneal laparoscopic partial nephrectomy. Owing to the somewhat restricted retroperitoneal operative space, the Satinsky clamp is not used. Instead, the renal artery and vein are dissected individually and controlled with separate laparoscopic bulldog clamps. Inset shows the three-port retroperitoneoscopic approach.

Lap. Partial nephrectomy Tumor excision performed with cold Endoshears in a bloodless operative field. The calyx abutting the tumor is entered deliberately, as necessary, to maintain an adequate parenchymal margin.

Lap. Partial nephrectomy Retrograde injection of dilute indigo carmine through an indwelling ureteral catheter precisely delineates the site of caliceal entry in the partial nephrectomy bed.

Lap. Partial nephrectomy Caliceal suture repair performed using intracorporeal freehand laparoscopic suturing. A CT-1 needle with 2-0 Vicryl is employed to achieve a watertight closure.

Lap. Partial nephrectomy Renal parenchymal reconstruction. A GS-25 needle with 0 Vicryl is employed to place wide parenchymal sutures. Typically, three to four sutures are needed.

Lap. Partial nephrectomy Pre-prepared bolsters of Surgicel are placed in the parenchymal defect before cinching down the sutures.

Hand-Assisted LPN Only one report of 11 cases has been published.Only one report of 11 cases has been published. Stifelman et al, J Endourol,15:161,2001. Stifelman et al, J Endourol,15:161,2001. Higher cost(hand port device).Higher cost(hand port device). Larger incision.Larger incision. Shorter operation time.Shorter operation time. ? More secure hemostasis ( hand compression).? More secure hemostasis ( hand compression).

Complications Parenchymal hemorrhage.Parenchymal hemorrhage. Ureteral injury.Ureteral injury. Bowel injury.Bowel injury. Urinary leakage.Urinary leakage. Perirenal hematoma.Perirenal hematoma. Hematuria.Hematuria. CHF,PE.CHF,PE. Renal failure.Renal failure. Tumor cell seeding.Tumor cell seeding.

Oncologic Data Lap.Vs open partial nephrectomyLap.Vs open partial nephrectomy -Gill IS,Matin,Desai, et al;J Urol. 2003 -200 cases( 100 in each arm.)

Lap.Vs open partial nephrectomy ItemLap.Open P value No. of pts. 100100 Med. Tumor size. 2.8 cm 3.3 cm 0.005 Solitary kidney 7280.001 Central tumor 35%33%0.83 Med.Preop.Creatinine 1.0 mg/dL Med. Surgical time 3 hours 3.9 hours < 0.001

Lap.Vs open partial nephrectomy ItemLap.Open P value Blood loss 125ml250ml < 0.001 Warm ischemia time 28 min 18 min < 0.001 Analgesia requirement 20.2 mg MS 252.5 mg MS < 0.001 Hospital stay 2 days 5 days < 0.001 Convalescence 4 weeks 6 weeks < 0.001 Intraop. Comp. 5%0%0.02 Postop. Comp. 9%14%0.27

Lap.Vs open partial nephrectomy ItemLap.Open P value Postop.creatinine 1.0 mg/dL 1.1 mg/dL 0.99 + surgical margin 300.11 Med. Width of margin 4mm4mm0.11 Lost kidneys due to warm ischemia 00 Local recurrences 00 Port site recurrences 0N/A

Oncologic Data World wide single institution World wide single institution experiences with lap. Partial experiences with lap. Partial Nephrectomy. Nephrectomy.

Oncologic Data

Financial analysis Steinberg, Desai, Gill, et al.Steinberg, Desai, Gill, et al. -financial analysis of lap. Vs open partial nephrectomy. -J Endourol. (in press). -Retrospective analysis of 30 pts undergoing either partial lap.(15),or open(15) nephrectomy. -All pts had normal contralateral kidney -Uncomplicated perioperative course.

Financial analysis ItemLap.Open P value Tumor size 2.4 cm 2.5 cm 0.50 Intraop. Cost 20.1% greater < 0.001 Postop. cost 55% lesser < 0.001 Overall hospital cost 15.6% lesser 0.002

Conclusions Advanced procedure.Advanced procedure. Carries higher intraop./postoperative complications.Carries higher intraop./postoperative complications. As surgeon experience increases, the rate of complications decreases, and the indications for more complex cases increases.As surgeon experience increases, the rate of complications decreases, and the indications for more complex cases increases. Emerging as a viable and efficient treatment option in the minimally invasive armamentarium.Emerging as a viable and efficient treatment option in the minimally invasive armamentarium.

MINSS Renal Cryotherapy

Introduction First known report of renal cryotherapy in human was by Uchida et al (Br J Urol,75:132,1995).First known report of renal cryotherapy in human was by Uchida et al (Br J Urol,75:132,1995). An energy-based tissue ablation.An energy-based tissue ablation. One of the most studied ablative technique.One of the most studied ablative technique. The aim is to achieve targeted destruction of a predetermined volume of tissue (the tumor and a surrounding margin of healthy parenchyma).The aim is to achieve targeted destruction of a predetermined volume of tissue (the tumor and a surrounding margin of healthy parenchyma). Can be done laparoscopic or percutanous.Can be done laparoscopic or percutanous. Various modalities available, differ in the type of ablation energy.Various modalities available, differ in the type of ablation energy.

M/A The targeted tissue is rapidly frozen in situ, followed by sloughing of the devitalized tissue and healing by secondary intention over time.The targeted tissue is rapidly frozen in situ, followed by sloughing of the devitalized tissue and healing by secondary intention over time. Essential features:rapid freezing,slow thawing, and repetition of the freeze-thaw cycle.Essential features:rapid freezing,slow thawing, and repetition of the freeze-thaw cycle. Cytonecrosis is the result of two step process:Cytonecrosis is the result of two step process: 1- rapid intracellular ice formation 2- delayed microcirculatory failure during the thaw phase of the cycle.

M/A The lethal temp. required for death of normal and cancerous renal cells is near 40C.The lethal temp. required for death of normal and cancerous renal cells is near 40C. (Chosy et al.predictor of tissue necrosis in swine. J Urol.1998;159:1370). (Chosy et al.predictor of tissue necrosis in swine. J Urol.1998;159:1370). Others: 20C (Chosy et al, 1996; Campbell et al, 1998; Bishoff et al, 1999; Gill and Novick, 1999). Various cryogens available (for freezing): liquid argon, and liquid nitrogen are the two most commonly used.Various cryogens available (for freezing): liquid argon, and liquid nitrogen are the two most commonly used. For thawing phase helium gas usually used.For thawing phase helium gas usually used. The cryoprobe affect the size and efficiency of the cryolesion.The cryoprobe affect the size and efficiency of the cryolesion.

M/A Cryolesion created by a 3.4 mm diameter cryoprobe.

Indications Small lesions(less than 3cm).Small lesions(less than 3cm). - larger lesions will require 2 or more probes,technically difficult, might leave residual tumor. - larger lesions will require 2 or more probes,technically difficult, might leave residual tumor. Solitary lesion.Solitary lesion. Located away from the collecting system.Located away from the collecting system. Elderly pts.Elderly pts.

Contraindications Coagulopathy.Coagulopathy. Significant post op. adhesions.Significant post op. adhesions. Intrarenal,centrally located tumor.Intrarenal,centrally located tumor.

Technique Open,laparoscopic or percutanous.Open,laparoscopic or percutanous. Real-time imaging of the tumor.Real-time imaging of the tumor. - CT/MRI not proven reliable modality for detection the progression of the ice-ball. - CT/MRI not proven reliable modality for detection the progression of the ice-ball. - USS with color Doppler appears promising. - USS with color Doppler appears promising. Pre-plan the angle and depth of the probe.Pre-plan the angle and depth of the probe. Needle biopsy of the tumor.Needle biopsy of the tumor. Insert the cryoprobe to the center of the tumor, and advance up to or just beyond the inner(deep) margin of the tumor.Insert the cryoprobe to the center of the tumor, and advance up to or just beyond the inner(deep) margin of the tumor. Cryolesion should be 1cm larger than the tumor.Cryolesion should be 1cm larger than the tumor. Use lap. USS, or MRI compatible cryosystem for the percutanous route.Use lap. USS, or MRI compatible cryosystem for the percutanous route.

Cryotherapy

Complications Potential complications include:Potential complications include: -urinary fistula. -Post-op hemorrhage. -Injury to the collecting system. -Injury to the adjacent structures(bowel,liver).

Clinical points Renal artery clamping does not facilitate the freezing process, and has no clinical significance, as evident by canine model.Renal artery clamping does not facilitate the freezing process, and has no clinical significance, as evident by canine model. Cryoinjury to the collecting system with the ice ball in the absence of physical puncture with the probe tip does not seem to result in urinary extravasations.Cryoinjury to the collecting system with the ice ball in the absence of physical puncture with the probe tip does not seem to result in urinary extravasations. Cryoablation does not lead to significant systemic hypothermia, or hypertension.Cryoablation does not lead to significant systemic hypothermia, or hypertension. The ischemic necrotic renal cryolesion, which remains in situ does not have significant impact on the renal function over long term follow-up of up to 20 months.The ischemic necrotic renal cryolesion, which remains in situ does not have significant impact on the renal function over long term follow-up of up to 20 months. (Carvalhal et al. Urology 2001;58:357-61). (Carvalhal et al. Urology 2001;58:357-61).

Oncologic data 5 years follow-up data still lacking.5 years follow-up data still lacking. Gill et al, Urology 2000;56:748.Gill et al, Urology 2000;56:748. -32 pts -Lap.trans./retroperitoneal approach. -Mean tumor size=2.3 cm. -Double freeze-thaw cycle. -Mean surgical time=2.9 hours. -The cryoablation time=15.1 min. -Blood loss=66.8ml. -Hospital stay: less than 23 hours in 69%. -20 pts completed 1 yr F/U: 5 pts no tumor seen in subsequent MRI, tumor reduction by 66% in the remaining 15 pts.

Oncologic data Shingleton et al.J Urol 2002;167:167.Shingleton et al.J Urol 2002;167:167. -55 pts. -Percutanous cryoablation. -2 or 3 mm cryoprobe used under MRI. -18 months F/U. -50 pts had no radiologic evidence of local disease recurrence. -7 pts(14%) required more than one treatment session,due to incomplete tumor ablation. -2 pts had local residual disease. -No complications intraoperatively. -No post op. biopsy data or serial measurment of the cryolesions post op. reported.

Oncologic data Steinberg A. et al. 3yrs F/U of lap. Renal cryoablationSteinberg A. et al. 3yrs F/U of lap. Renal cryoablation (in press). (in press). -25 pts. -F/U includes: abdominal MRI on post op. day 1, months1,3,6,12, and semiannually after.CXR,CT guided tru-cut biopsy of the lesion at 6 months post op. -3 years follow-up ( the longest F/U clinical data). -The mean tumor size:2.3 cm. -Pre-op. biopsy confirming RCC:61%. -Mean cryolesion diameter at 1,2,3 years:2,1.4,0.9 cm respectively. -No lesions seen at the last MRI: 31%. -2 pts had residual tumor with F/U CT biopsy, both had uneventful lap. Radical nephrectomy.

Conclusion The most clinically applied procedure among all probe-ablative techniques.The most clinically applied procedure among all probe-ablative techniques. Important critique: lack of histologic data after cryoablation to ascertain completeness of tumor destruction or to verify surgical margins.Important critique: lack of histologic data after cryoablation to ascertain completeness of tumor destruction or to verify surgical margins. Needs long term F/U with MRI/CT scanning complimented by needle biopsy evaluation.Needs long term F/U with MRI/CT scanning complimented by needle biopsy evaluation. Should be still developmental, and limited to selected pts.Should be still developmental, and limited to selected pts.

MINSS Radiofrequency ablation (RFA)

Introduction Heat-based tissue ablation.Heat-based tissue ablation. High-frequency electrical current creates molecular friction, denaturation of cellular protein, and cell membrane disintegration.High-frequency electrical current creates molecular friction, denaturation of cellular protein, and cell membrane disintegration. The necessary temp. required for tissue destruction is 40-70 C.The necessary temp. required for tissue destruction is 40-70 C.

Techniques Laparoscopic or percutaneous.Laparoscopic or percutaneous. RFA can be performed using a dry or wet technique.RFA can be performed using a dry or wet technique. In the wet type: hypertonic saline is used, which promotes centrifugal dissipation of the RF energy, resulting in rapid creation of larger radiolesions without the early tissue desiccation as seen in the dry type.In the wet type: hypertonic saline is used, which promotes centrifugal dissipation of the RF energy, resulting in rapid creation of larger radiolesions without the early tissue desiccation as seen in the dry type. USS,CT,or MRI is used to roughly monitor the boundaries of the treatment.USS,CT,or MRI is used to roughly monitor the boundaries of the treatment. Post operatively monitoring by loss of contrast enhancement on CT scan.Post operatively monitoring by loss of contrast enhancement on CT scan.

RFA RF probe, with its semicircular umbrella-shaped tines.

RFA Gross photograph of a radiolesion at day 7 denotes clear horizontal demarcation of the nonviable radioablated lower pole. (From Hsu TH, Fidler ME, Gill IS. Radiofrequency ablation of the kidney: acute and chronic histology in porcine model. Urology 2000;56:872).

Oncologic data First described in 1999 by Zlotta et al, and nowadays there are 4 institutions reported their initial clinical experience.First described in 1999 by Zlotta et al, and nowadays there are 4 institutions reported their initial clinical experience. 1-National institute of health:2002 - 21 pts/24 percutaneous renal RFA. - tumor size:3 cm or less. -19 pts with VHL syndrome. -50 W,460 kHz electrosurgical generator. -15 G coaxial probe used. -At least two, 10-15 min ablation cycles. -Under USS or CT scan guidance. -Conscious sedation used. -F/U at 2 months, tumor size decreased from 2.4 cm to 2cm, and 79% of tumors ceased to enhance on contrast CT scan. -No post op. biopsy data were reported.

Oncologic data 2- Massachusetts General Hospital:2000 -24 P/C RFA done 9 pts with RCC. -6 tumors had no enhancement post op, while 9 tumors(33%) required repeat treatment due to continuous enhancement post op. 3- Johns Hopkins experience:2002 -22 CT guided P/C RFA. -17 poor surgical risk pts. -Mean tumor size: 1.9 cm. -2-3.5 cm probe was used. -One pt required repeat treatment due to persistence enhancement post op. -The remaining 21 lesions had no evidence of enhancement on F/U imaging at a mean time of 3.2 months.

Oncologic data 4- Randon et al,Toronto,2002: -10 pts with small renal lesions. -Acute group:4 pts,open RFA followed by immediate open partial or radical nephrectomy. -Delayed group:6 pts,P/C RFA under LA followed 7 days later by open partial or radical nephrectomy. -Mean tumor size:2.4 cm. -A median of 2 RFA cycles used, with a mean heating time of 17 mins. -Residual tumor on histopathology exam in 4 of 5 tumors(80%) in the acute group, and in 3 of 6 tumors(50%) in the delayed group. -One pt complication: hepatic hematoma,biliary fistula,and pneumonia. -Concluded:complete cell death was difficult to achieve with the current treatment protocol.

Conclusion RFA still developmental for renal use.RFA still developmental for renal use. Long term prospective trials still lacking.Long term prospective trials still lacking. So far for monitoring the RFA intensity intra-op., there is no imaging modality that can in real time ensure a sufficient extent of tissue ablation while avoiding injury to normal adjacent parenchyma.So far for monitoring the RFA intensity intra-op., there is no imaging modality that can in real time ensure a sufficient extent of tissue ablation while avoiding injury to normal adjacent parenchyma.

MINSS High-intensity focused ultrasound (HIFU)

HIFU Potentially the least invasive tumor ablation technique (Extracorporeal).Potentially the least invasive tumor ablation technique (Extracorporeal). Employs beams of ablative US frequency,generated by piezoelectric element,focused by a paraboloid reflector.Employs beams of ablative US frequency,generated by piezoelectric element,focused by a paraboloid reflector. This beam is focused on the lesion, like ESWL, US lithotripsy.This beam is focused on the lesion, like ESWL, US lithotripsy. Resulting in thermal destruction - tissue cooking (temp. raise by 70-80 C in the target lesion).Resulting in thermal destruction - tissue cooking (temp. raise by 70-80 C in the target lesion). Initially used for BPH,and Pca.Initially used for BPH,and Pca. Lots of concerns in regard to incomplete tumor ablation, and superficial skin burns.Lots of concerns in regard to incomplete tumor ablation, and superficial skin burns.

HIFU Several studies report the use of HIFU to treat benign and malignant kidney tumors of animals, and one report in human.Several studies report the use of HIFU to treat benign and malignant kidney tumors of animals, and one report in human.

HIFU Kohrmann et al, 2002:Kohrmann et al, 2002: -report on one pt with 3 renal tumors(2.3,1.4,2.8cm), who had HIFU in 3 sessions under general or sedation anesthesia. -US pulses used at intervals of 15 sec.,and duration of 4 sec. -F/U with MRI: necrosis of the two lower pole tumors within 17,48 days respectively. -The upper pole tumor was not affected due to absorption of the energy by the interposed ribs. -At 6 months F/U: the two lower pole tumors had shrunken in size to 8,11mm respectively. -Concluded:HIFU is a potential effective technique,once the visualization problem of the target lesion, skin protection against burns have been solved.

Conclusions HIFU offers complete noninvasive ablation.HIFU offers complete noninvasive ablation. Challenges include control over energy deposition,monitoring of treatment,adjustment for target movement.Challenges include control over energy deposition,monitoring of treatment,adjustment for target movement. Data on safety,histologic effect,clinical efficacy still lacking.Data on safety,histologic effect,clinical efficacy still lacking.

MINSS Intracavitary photon radiation

A steriotactic radio-surgery.A steriotactic radio-surgery. Used initially for brain tumors.Used initially for brain tumors. Also applied for radio-resistant RCC metastatic lesions.Also applied for radio-resistant RCC metastatic lesions. Deliver targeted high dose radiation for a precise site causing coagulative necrosis, while preserving normal surrounding tissues.Deliver targeted high dose radiation for a precise site causing coagulative necrosis, while preserving normal surrounding tissues. Additional experimental and clinical work is necessary to evaluate its role in renal cancer.Additional experimental and clinical work is necessary to evaluate its role in renal cancer.

MINSS Microwave thermotherapy

Experimental in rabbit kidneys.Experimental in rabbit kidneys. Major experience with the prostate.Major experience with the prostate. Maintaining temperature greater than 60C for 60 sec., causes coagulative necrosis.Maintaining temperature greater than 60C for 60 sec., causes coagulative necrosis. Can be done by laparoscopic or percutaneous approach.Can be done by laparoscopic or percutaneous approach. No significant clinical data have been reported to date using this modality.No significant clinical data have been reported to date using this modality.

Documents

Localized RCC: Nephron Sparing Surgery and alternative treatments Saleh A.Binsaleh