Salvage Therapy for Alveolar Echinococcosis—A Case Series
Abstract
:1. Introduction
2. Results
3. Discussion
- (1)
- It seems better not to stop treatment, even if the effectiveness is questionable. In situations with advanced AE, in which treatment has been stopped completely due to complications or critically ill patients, fast progression with consecutive death was observed.
- (2)
- BMZs are currently the most effective drugs and are usually well tolerated. If not, several re-exposures with low dosages and switch from ABZ to MBZ are worth trying, as in most cases, BMZs can be introduced successfully and are then effective.
- (3)
- However, in the case of impending treatment failure or permanent intolerance, it seems best not to wait too long before starting salvage therapy, as lower effectiveness than BMZs has to be expected. A period of three, maximum six, months should be set for re-evaluation of the situation and treatment plan, with consequent escalation, if necessary.
- (4)
- Non-pharmaceutical interventions, such as a biliary stent, have to be evaluated to control complications, as well as ‘rescue’ surgery.
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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All Patients | AMB | NTZ | ||
---|---|---|---|---|
N | 13 | 11 | 4 | |
Sex | Female, n (%) | 6 (46.2%) | 4 (36.4%) | 2 (50.0%) |
Male, n (%) | 7 (53.8%) | 7 (63.6%) | 2 (50.0%) | |
Median age at first diagnosis, years (IQR) | 43.0 (23.0) | 43.0 (21.5) | 46.0 (12.5) | |
Median time of salvage therapy imitation after first diagnosis, years (IQR) | 5.0 (11.0) | 10.0 (12.0) | 8.0 (10.875) | |
Reason for salvage therapy | BMZ intolerance, n (%) | 7 (53.8%) | 5 (45.5%) | 3 (75%) |
BMZ treatment failure, n (%) | 6 (46.2%) | 6 (54.5%) | 1 (25%) | |
Cumulative time of salvage therapy, years | 50.8 | 42.7 | 9.2 | |
Median duration of salvage therapy | 2.0 (3.75) | 1.5 (3.0) | 1.7 (1.0) |
Diagnosis | WHO Stage, Case Definition | Manifestations | Age at Diagnosis, Gender | Surgical Treatment | Medical Treatment before AMB | Time of AMB after Diagnosis | Duration of AMB | Reason for AMB | Initial Application | Side Effects of AMB | Serological Outcome | Radiological and Clinical Outcome |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1976 | P?N1M1, stage IV, confirmed | Liver, lung, CNS, mamma, paracardial | 42, F | Partial liver resection 1976, CNS resection 1976 | ABZ, MBZ (few months), Interferon γ (1.5 years), praziquantel (7 months) | 24 years | 3 years | BMZ intolerance | Non-liposomal AMB 0.5 mg/kg BW/3×/week | Nephrotoxicity, ECC reduction | Stable IHA-AB, partial reduction IgE | Stable with AMB, but advanced disease, side effects require dose reduction, deceased at 69 due to AE-related heart failure |
1992 | PxN1M0, stage IIIB, confirmed | Liver continuing to thoracic wall (post-operative relapse), subcutaneous manifestation, paracardial | 49, M | Left hemihepatectomy 1992, subxiphoid resection 1998 | ABZ (1 year), MBZ (1 year), NTZ (9 months) | 15 years | 16 years | BMZ intolerance | i.v. AMB-D 0.8 mg/kg BW 3×/week, changed to lipAMB 3 mg/kg every 1–3/weeks | Nephrotoxicity requiring dose reduction | Increase in IHA AB and slightly IgE concomitant with radiological progress | Long, stable disease, progress with dose reduction after 13 years |
1992 | P?N1M1, stage IV, confirmed | Liver, lumbar spine, retroperitoneum, CNS (intrathecal lesions) | 43, M | Right hemihepatectomy 1992, vertebrectomy 1995, laminectomy and myelon decompression 2000 | ABZ (12 years), MBZ (3 years) | 12 years | 13 months | BMZ treatment failure | Intrathecal AMB-D 0.2 mg 3×/week | Catheter infection | Not evaluable | Partial regression, stop due to catheter explantation, deceased at 57 due to sepsis with ABZ |
1992 | P?N?M1, stage IV, confirmed | Extensive liver, hyper-IgE syndrome | 7, M | Partial liver resection 1993 and 1999 | MBZ (10 years), praziquantel (pre-operatively 1999) | 10 years | 1.5 years | BMZ treatment failure | i.v. AMB-D 0.5 mg/kg BW 3×/week, reduced to 2×/week | Nephrotoxicity requiring dose reduction and pausing | Not evaluable | Less progressive disease under AMB, repeated stops with critical illness (cholangitis), deceased with liver failure/cholangitis |
1997 | P4N1M0, stage IV, probable | Liver with extended portal vein and inferior vena cava thrombosis, hepatic encephalopathy | 28, F | Partial liver resection 1997 (R2), listed for transplant, ultima ratio explorative laparotomy and partial cystectomy February 2021 | ABZ (11 years), MBZ (4 months) | 23 years | 17 months in combination with ABZ | BMZ treatment failure | lipAMB 3 mg/kg BW/week * | Nephrotoxicity | Slight increase in IgE, stable IgG AB, borderline IHA | Progress under AMB, post-operative death |
2009 | P4N1M0, stage IV, confirmed | Disseminated liver with secondary sclerotic cholangitis | 57, M | Inoperable, listed for transplant | ABZ (10 years) | 10 years | 5 months in combination with mefloquine | BMZ treatment failure | lipAMB 3 mg/kg BW/week * | Nephrotoxicity | EM-AB IgG stable | Deceased due to cholangitis, AMB not evaluable |
15 Dec | P4N1M0, stage IV, confirmed | Right liver lobe, probably kidney | 75, M | Inoperable | ABZ (6 months), MBZ (1 months) | 5 years | 10 months | BMZ intolerance | lipAMB 3 mg/kg BW/week * | nephrotoxicity | Decrease in IgE, EM-AB IgG constantly high | Stable disease |
18 Nov | P3N0M0, stage IIIa, confirmed | Right liver lobe with contact to right portal vein | 39, M | Extended right hemihepatectomy November 2020 | ABZ (3 months), MBZ (1 months) | 1 year | 15 months | BMZ intolerance | lipAMB 3 mg/kg BW/week * | - | Decrease in EM-AB IgG, post-operatively negative | Pre-operative progression with AMB, currently post-operative remission with AMB |
19 May | P4N1M0, stage IV, confirmed | Liver with portal vein thrombosis, stenosis of DHC, left renal vein, truncus coeliacus and AMS | 60, F | Palliative surgery with debulking 09/21 | ABZ (4 months), MBZ (4 months) | 2 years | 8 months | BMZ intolerance | lipAMB 3 mg/kg BW/week * | - | Post-operative decrease in IgE, constant EM-AB IgG | Stable disease |
19 Nov | P4N1M1, stage IV, probable | Disseminated liver, spleen, peritoneum | 59, M | Inoperable | ABZ (5 months), MBZ (2 months) | 1 year | 1 year | BMZ intolerance | lipAMB 3 mg/kg BW/week * | - | Strong increase in EM-AB IgG, slight decrease IgE | Progress, currently re-exposure MBZ |
21 Jan | P4NxMo, stage IIIB, confirmed | Left liver lobe with life-threatening cholestasis and cholangitis | 34, F | Inoperable | ABZ (10 months) | 8 months | 5 months in combination with ABZ | Combination therapy due to life-threatening condition, BMZ treatment failure and intolerance | lipAMB 3 mg/kg BW 3 times/week * | - | Decrease in EM-AB IgG and normalisation of IgE | Stable disease with combination treatment, re-evaluation operation planned |
Nitazoxanide | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Diagnosis | WHO Stage, Case Definition | Manifestations | Age at Diagnosis, Gender | Surgical Treatment | Medical Treatment before NTZ | Time of NTZ after Diagnosis | Duration of NTZ | Reason for NTZ | Dosage | Side Effects of NTZ | Serological Outcome | Clinical Outcome |
1992 | PxN1M0, stage IIIb, confirmed | Liver continuing to thoracic wall (post-operative relapse), subcutaneous manifestations, paracardial | 49, M | Left hemihepatectomy 1992, subxiphoid resection 1998 | ABZ (1 year), MBZ (1 year) | 13 years | 9 months | BMZ intolerance | 2 × 500 mg/day (4 months), reduced to 2 × 500 mg/week | Hepatotoxicity | Increase in IHA AK, IgE within normal limits | Progression, severe hepatotoxicity limited dosage |
1992 | P?N1M1, stage IV, confirmed | Liver, lumbar spine, retroperitoneum, CNS (intrathecal lesions) | 43, M | Vertebrectomy 1995, laminectomy and myelon decompression 2000 | ABZ (12 years), MBZ (3 years), AMB-D (13 months) | 14 years | 17 months | BMZ treatment failure | 2 × 500 mg/day | Nephrotoxicity, interaction with ABZ (increased serum levels of ABZ) | Partial regression of IHA AK | Partial regression, stopped due to acute chronic kidney failure, deceased at 57 due to sepsis, with ABZ |
3 June | P3N0M0, stage IIIa, confirmed | Right liver lobe | 17, F | Right hemihepatectomy 01/04 | ABZ and MBZ (together 4 months) | 6 months | 2 years | BMZ intolerance | Cyclical 2 × 1 G/day for 30 days and 3 months break peri-operatively for 6 cycles (2 years) | - | Increase in IHA AK concomitant with relapse | Relapse 1 year after stopping NTZ with BMZ (9 years) regression, currently on STI |
3 Dec | P3N0M0, stage IIIa, probable | Extended liver disease | 49, F | Inoperable | ABZ and MBZ (together 2 years on/off) | 3 years | 5 years (initial attempt to combine with BMZ failed) | BMZ intolerance | 500 mg BID | - | Decrease in IgE, constantly high IHA AK | Partial regression and stable disease since STI 11 years ago |
4 June | P3N1M0, stage IIIb, probable | Extended liver disease | 22, M | Inoperable | ABZ (2 years) | 2 years | 2.5 years (1.5 in combination with ABZ) | BMZ intolerance | 500 mg BID | Gastrointestinal side effects | Increase in IHA with monotherapy, decrease in IgE with either treatment | Slight progress with NTZ monotherapy, stable with combination therapy and ABZ monotherapy |
Mefloquine | ||||||||||||
2009 | P4N1M0, stage IV, confirmed | Disseminated liver with secondary sclerotic cholangitis | 57, M | Inoperable, listed for transplant | ABZ (10 years) | 10 years | 8 months (in combination with ABZ or AMB) | BMZ treatment failure | 250 mg/week | Nephrotoxicity | EM-AB IgG stable | Deceased due to cholangitis, no treatment response seen after 7 months |
Pembrolizumab | ||||||||||||
16 Feb | P4N1?M0, stage IV, confirmed | Right liver lobe | 64, M | Diagnostical laparotomy and partial resection 02/16 | ABZ | 2.5 years | 2 years | Urothelial carcinoma | 200 mg every 3 weeks, followed by 400 mg every 6 weeks | Dermatotoxicity | Increase in IgE | Suspicion of progressive AE |
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Burkert, S.; Peters, L.; Bloehdorn, J.; Grüner, B. Salvage Therapy for Alveolar Echinococcosis—A Case Series. Pathogens 2022, 11, 333. https://doi.org/10.3390/pathogens11030333
Burkert S, Peters L, Bloehdorn J, Grüner B. Salvage Therapy for Alveolar Echinococcosis—A Case Series. Pathogens. 2022; 11(3):333. https://doi.org/10.3390/pathogens11030333
Chicago/Turabian StyleBurkert, Sanne, Lynn Peters, Johannes Bloehdorn, and Beate Grüner. 2022. "Salvage Therapy for Alveolar Echinococcosis—A Case Series" Pathogens 11, no. 3: 333. https://doi.org/10.3390/pathogens11030333
APA StyleBurkert, S., Peters, L., Bloehdorn, J., & Grüner, B. (2022). Salvage Therapy for Alveolar Echinococcosis—A Case Series. Pathogens, 11(3), 333. https://doi.org/10.3390/pathogens11030333