Letters to the Editor
aortic lymph nodes (Fig. 1a). We excised the black macule on his third toe of the left foot, but histopathological examination of the lesion revealed melanophages but no dysplastic cells. Then, we tried left groin dissection, and resection of the left pelvic and para-aortic lymph nodes as much as possible using the inguinal and pararectal approach. However, a part of the left pelvic and para-aortic lymph nodes, which were swollen, were not removed because of possible nerve injury and excess bleeding. Atypical epithelioid cells, which were positive for HMB-45, were found in the large part of the inguinal, pelvic and para-aortic lymph nodes (Fig. 1c,d). Hence, we considered that the primary lesion on the third toe of the left foot had spontaneously regressed, and malignant melanoma stage IV (pTxpN3M1a) was diagnosed. A combination chemotherapy including CDDP, DTIC, ACNU and tamoxifen (DAC-Tam) was not effective. Next, we performed percutaneous ethanol injection therapy (PEIT) with computed tomography (CT) guidance into the para-aortic nodes once a month in addition to i.d. injection of OK-432 once a week for 3 months (from August to October 2007). As a result, 34% reduction of the long axis of the para-aortic lymph node was achieved. After starting PEIT/OK-432 treatment, white macules appeared on the surgical site on his left inguinal region, thigh and face. Because the patient refused further treatment, no further antitumor therapy was conducted. Positron emission tomography/CT performed in November 2013 showed no accumulation (Fig. 1b). The patient has been healthy, having white macules on his face until February 2014. This case suggests that PEIT/OK-432 treatment after mass reduction surgery becomes an effective treatment for advanced melanoma with para-aortic lymph node metastasis. This finding is well compatible with a previous report which describes the rapid destruction of human melanoma by percutaneous injection of absolute ethanol,3 and another case report of advanced melanoma successfully treated with OK-432.4 The underlying mechanism of getting a long-term remission in this
patient may be due to induction of anti-melanoma immunity by destruction of melanoma cells in the metastatic lymph nodes. Immunohistochemical study of the metastatic lymph node revealed marked infiltration of CD11b- and PD-1-positive cells (Fig. 1e–h) around the melanoma cells into the lymph node, supporting the high anti-melanoma immunity in this patient. Now, nivolumab, a new biologic which targets PD-1, is available for the treatment of melanoma, indicating that immunotherapies may improve survival outcomes in melanoma.5
CONFLICT OF INTEREST:
None.
Kazuo MIZUMOTO,1 Hiroyuki NIIHARA,2 Kenji KUSATAKE,2 Eishin MORITA2 1
Department of Surgery, Ohda General Medicine Education Center, Ohda, and 2Department of Dermatology, Shimane University Faculty of Medicine, Izumo, Japan doi: 10.1111/1346-8138.12707
REFERENCES 1 Gogas H, Ioannovich J, Dafni U et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 2006; 354: 709–718. 2 Boasberg PD, Hoon DS, Piro LD et al. Enhanced survival associated with vitiligo expression during maintenance biotherapy for metastatic melanoma. J Invest Dermatol 2006; 126: 2658–2663. 3 Nakayama J, Toyofuku K, Kokuba H et al. Rapid destruction of murine and human melanomas by local injection of absolute ethanol: augmentation of the anti-proliferative effects with a combination of biological response modifiers. J Dermatol 1996; 23: 156–164. 4 Umeda M, Murata M, Suzuki H et al. A case of malignant melanoma of the oral cavity alive with liver metastasis for a long period with administration of a biologic response modifier, OK432. Kobe J Med Sci 2010; 56: E140–E147. C, Hodi FS et al. Durable benefit and the 5 McDermott D, Lebbe potential for long-term survival with immunotherapy in advanced melanoma. Cancer Treat Rev 2014; 40: 1056–1064.
Percutaneous cardiopulmonary support as a possible risk factor for symmetrical peripheral gangrene of the toes Dear Editor, Symmetrical peripheral gangrene (SPG) is characterized by rapid onset of peripheral gangrene, most commonly on the fingers and toes, while occlusive arterial disorders are absent. SPG may be associated with sepsis, low output states, vasospastic conditions, myeloproliferative disorders or hyperviscosity syndrome.1 Disseminated intravascular coagulation (DIC) is
observed in most cases of SPG. According to a recent report of 14 patients with SPG, five patients died and nine patients survived.2 Among the survivors, four patients had auto-amputation of the distal part of the fingers or toes, and surgical amputation was performed in two patients. A 40-year-old man was admitted to undergo endoscopic papillectomy for a tumor on the ampulla of Vater. The patient
Correspondence: Kazuyoshi Fukai, M.D., Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan. Email: [email protected]
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© 2014 Japanese Dermatological Association
Letters to the Editor
(a)
(b)
(c)
(d)
(g)
(e)
(f)
(h)
Figure 1. (a–d) Clinical manifestations on postoperative day (POD) 16 show extensive purpura on the dorsum of the right foot, including necrotic gangrene on the distal parts of the right first, second and fourth toes, and left first, second, third and fourth toes. Purpura was observed on all toes. Marked swelling of the dorsum of both feet was also noted. (e) Necrotic gangrene on all of the left toes cleared on POD 54. (f) Necrosis is evident only on the right great toe on POD 54. (g) The necrotic tissue on the right great toe was removed leaving a skin ulcer on POD 79. (h) The skin ulcer on the right great toe completely healed by POD 128.
had undergone a subtotal colectomy at the age of 16 years owing to familial adenomatous polyposis. On postoperative day (POD) 1, severe pancreatitis occurred. On POD 7, because of circulatory insufficiency and respiratory failure, the patient was transferred to the emergency care unit, where respiratory support, continuous hemodiafiltration and percutaneous cardiopulmonary support (PCPS) were initiated, along with i.v. administration of vasopressor drugs such as noradrenaline. On POD 8, the patient was diagnosed with DIC. Bilateral foot acrocyanosis was noted and noradrenaline treatment was stopped. On POD 10, soon after the PCPS was removed, acrocyanosis improved remarkably on both feet. On POD 11, the coagulation status of DIC recovered to normal, and therefore prostaglandin E1 infusion was started. Methicillin-resistant Staphylococcus aureus was detected in the feces. On POD 19, the respirator was removed. Prostaglandin E1 infusion was continued until POD 30. The skin ulcer was treated with topical 1% silver sulfadiazine cream. The skin ulcer on the right hallux was completely epithelized on POD 128 without any surgical intervention (Fig. 1). Overall, the patient followed the typical clinical course for symmetrical peripheral gangrene except for the possible involvement of PCPS. The differential diagnoses include cholesterol embolism and vascular occlusion, both of which do not show a symmetrical distribution of gangrene. Further, cholesterol embolism is associated with livedo reticularis. In addition, in our case, pedal pulses were palpable throughout the disease course. From POD 7 to 10, PCPS was introduced. Venous blood was taken from the catheter inserted into the left femoral vein, oxygenated within the machine and returned to the right femoral artery. This process may interfere more with the circulation of the right lower limb than the left lower limb,3,4 which is corroborated by the fact that gangrene on the
© 2014 Japanese Dermatological Association
right toes was more severe than that on the left toes. In fact, ischemia of the lower limb is one of the major complications of PCPS.3,4 In summary, we report a case of SPG after endoscopic papillectomy, which caused pancreatitis, toxic shock-likesyndrome and DIC. PCPS may modify circulation of the lower limbs and may be a risk factor underlying exacerbation of gangrene. Acrocyanotic changes on the toes during the operation of the PCPS machine may be a sign of not only ischemia but also SPG.
CONFLICT OF INTEREST:
None.
Nami SHIMIZU,1 Kazuyoshi FUKAI,1 Shigeto YANAGIHARA,1 Hirotsugu MARUYAMA,2 Tetsuo ARAKAWA,2 Daisuke TSURUTA1 Departments of 1Dermatology and 2Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan doi: 10.1111/1346-8138.12673
REFERENCES 1 Sharma BD, Kabra SR, Gupta B. Symmetrical peripheral gangrene. Trop Doct 2004; 34: 2–4. 2 Ghosh SK, Bandyopadhyay D, Ghosh A. Symmetrical peripheral gangrene: a prospective study of 14 consecutive cases in a tertiary-care hospital in eastern India. J Eur Acad Dermatol Venereol 2010; 24: 214–218. 3 Foley PJ, Morris RJ, Woo EY et al. Limb ischemia during femoral cannulation for cardiopulmonary support. J Vasc Surg 2010; 52: 850–853. 4 Bisdas T, Beutel G, Warnecke G et al. Vascular complications in patients undergoing femoral cannulation for extracorporeal membrane oxygenation support. Ann Thorac Surg 2011; 92: 626–631.
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aortic lymph nodes (Fig. 1a). We excised the black macule on his third toe of the left foot, but histopathological examination of the lesion revealed melanophages but no dysplastic cells. Then, we tried left groin dissection, and resection of the left pelvic and para-aortic lymph nodes as much as possible using the inguinal and pararectal approach. However, a part of the left pelvic and para-aortic lymph nodes, which were swollen, were not removed because of possible nerve injury and excess bleeding. Atypical epithelioid cells, which were positive for HMB-45, were found in the large part of the inguinal, pelvic and para-aortic lymph nodes (Fig. 1c,d). Hence, we considered that the primary lesion on the third toe of the left foot had spontaneously regressed, and malignant melanoma stage IV (pTxpN3M1a) was diagnosed. A combination chemotherapy including CDDP, DTIC, ACNU and tamoxifen (DAC-Tam) was not effective. Next, we performed percutaneous ethanol injection therapy (PEIT) with computed tomography (CT) guidance into the para-aortic nodes once a month in addition to i.d. injection of OK-432 once a week for 3 months (from August to October 2007). As a result, 34% reduction of the long axis of the para-aortic lymph node was achieved. After starting PEIT/OK-432 treatment, white macules appeared on the surgical site on his left inguinal region, thigh and face. Because the patient refused further treatment, no further antitumor therapy was conducted. Positron emission tomography/CT performed in November 2013 showed no accumulation (Fig. 1b). The patient has been healthy, having white macules on his face until February 2014. This case suggests that PEIT/OK-432 treatment after mass reduction surgery becomes an effective treatment for advanced melanoma with para-aortic lymph node metastasis. This finding is well compatible with a previous report which describes the rapid destruction of human melanoma by percutaneous injection of absolute ethanol,3 and another case report of advanced melanoma successfully treated with OK-432.4 The underlying mechanism of getting a long-term remission in this
patient may be due to induction of anti-melanoma immunity by destruction of melanoma cells in the metastatic lymph nodes. Immunohistochemical study of the metastatic lymph node revealed marked infiltration of CD11b- and PD-1-positive cells (Fig. 1e–h) around the melanoma cells into the lymph node, supporting the high anti-melanoma immunity in this patient. Now, nivolumab, a new biologic which targets PD-1, is available for the treatment of melanoma, indicating that immunotherapies may improve survival outcomes in melanoma.5
CONFLICT OF INTEREST:
None.
Kazuo MIZUMOTO,1 Hiroyuki NIIHARA,2 Kenji KUSATAKE,2 Eishin MORITA2 1
Department of Surgery, Ohda General Medicine Education Center, Ohda, and 2Department of Dermatology, Shimane University Faculty of Medicine, Izumo, Japan doi: 10.1111/1346-8138.12707
REFERENCES 1 Gogas H, Ioannovich J, Dafni U et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 2006; 354: 709–718. 2 Boasberg PD, Hoon DS, Piro LD et al. Enhanced survival associated with vitiligo expression during maintenance biotherapy for metastatic melanoma. J Invest Dermatol 2006; 126: 2658–2663. 3 Nakayama J, Toyofuku K, Kokuba H et al. Rapid destruction of murine and human melanomas by local injection of absolute ethanol: augmentation of the anti-proliferative effects with a combination of biological response modifiers. J Dermatol 1996; 23: 156–164. 4 Umeda M, Murata M, Suzuki H et al. A case of malignant melanoma of the oral cavity alive with liver metastasis for a long period with administration of a biologic response modifier, OK432. Kobe J Med Sci 2010; 56: E140–E147. C, Hodi FS et al. Durable benefit and the 5 McDermott D, Lebbe potential for long-term survival with immunotherapy in advanced melanoma. Cancer Treat Rev 2014; 40: 1056–1064.
Percutaneous cardiopulmonary support as a possible risk factor for symmetrical peripheral gangrene of the toes Dear Editor, Symmetrical peripheral gangrene (SPG) is characterized by rapid onset of peripheral gangrene, most commonly on the fingers and toes, while occlusive arterial disorders are absent. SPG may be associated with sepsis, low output states, vasospastic conditions, myeloproliferative disorders or hyperviscosity syndrome.1 Disseminated intravascular coagulation (DIC) is
observed in most cases of SPG. According to a recent report of 14 patients with SPG, five patients died and nine patients survived.2 Among the survivors, four patients had auto-amputation of the distal part of the fingers or toes, and surgical amputation was performed in two patients. A 40-year-old man was admitted to undergo endoscopic papillectomy for a tumor on the ampulla of Vater. The patient
Correspondence: Kazuyoshi Fukai, M.D., Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan. Email: [email protected]
1130
© 2014 Japanese Dermatological Association
Letters to the Editor
(a)
(b)
(c)
(d)
(g)
(e)
(f)
(h)
Figure 1. (a–d) Clinical manifestations on postoperative day (POD) 16 show extensive purpura on the dorsum of the right foot, including necrotic gangrene on the distal parts of the right first, second and fourth toes, and left first, second, third and fourth toes. Purpura was observed on all toes. Marked swelling of the dorsum of both feet was also noted. (e) Necrotic gangrene on all of the left toes cleared on POD 54. (f) Necrosis is evident only on the right great toe on POD 54. (g) The necrotic tissue on the right great toe was removed leaving a skin ulcer on POD 79. (h) The skin ulcer on the right great toe completely healed by POD 128.
had undergone a subtotal colectomy at the age of 16 years owing to familial adenomatous polyposis. On postoperative day (POD) 1, severe pancreatitis occurred. On POD 7, because of circulatory insufficiency and respiratory failure, the patient was transferred to the emergency care unit, where respiratory support, continuous hemodiafiltration and percutaneous cardiopulmonary support (PCPS) were initiated, along with i.v. administration of vasopressor drugs such as noradrenaline. On POD 8, the patient was diagnosed with DIC. Bilateral foot acrocyanosis was noted and noradrenaline treatment was stopped. On POD 10, soon after the PCPS was removed, acrocyanosis improved remarkably on both feet. On POD 11, the coagulation status of DIC recovered to normal, and therefore prostaglandin E1 infusion was started. Methicillin-resistant Staphylococcus aureus was detected in the feces. On POD 19, the respirator was removed. Prostaglandin E1 infusion was continued until POD 30. The skin ulcer was treated with topical 1% silver sulfadiazine cream. The skin ulcer on the right hallux was completely epithelized on POD 128 without any surgical intervention (Fig. 1). Overall, the patient followed the typical clinical course for symmetrical peripheral gangrene except for the possible involvement of PCPS. The differential diagnoses include cholesterol embolism and vascular occlusion, both of which do not show a symmetrical distribution of gangrene. Further, cholesterol embolism is associated with livedo reticularis. In addition, in our case, pedal pulses were palpable throughout the disease course. From POD 7 to 10, PCPS was introduced. Venous blood was taken from the catheter inserted into the left femoral vein, oxygenated within the machine and returned to the right femoral artery. This process may interfere more with the circulation of the right lower limb than the left lower limb,3,4 which is corroborated by the fact that gangrene on the
© 2014 Japanese Dermatological Association
right toes was more severe than that on the left toes. In fact, ischemia of the lower limb is one of the major complications of PCPS.3,4 In summary, we report a case of SPG after endoscopic papillectomy, which caused pancreatitis, toxic shock-likesyndrome and DIC. PCPS may modify circulation of the lower limbs and may be a risk factor underlying exacerbation of gangrene. Acrocyanotic changes on the toes during the operation of the PCPS machine may be a sign of not only ischemia but also SPG.
CONFLICT OF INTEREST:
None.
Nami SHIMIZU,1 Kazuyoshi FUKAI,1 Shigeto YANAGIHARA,1 Hirotsugu MARUYAMA,2 Tetsuo ARAKAWA,2 Daisuke TSURUTA1 Departments of 1Dermatology and 2Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan doi: 10.1111/1346-8138.12673
REFERENCES 1 Sharma BD, Kabra SR, Gupta B. Symmetrical peripheral gangrene. Trop Doct 2004; 34: 2–4. 2 Ghosh SK, Bandyopadhyay D, Ghosh A. Symmetrical peripheral gangrene: a prospective study of 14 consecutive cases in a tertiary-care hospital in eastern India. J Eur Acad Dermatol Venereol 2010; 24: 214–218. 3 Foley PJ, Morris RJ, Woo EY et al. Limb ischemia during femoral cannulation for cardiopulmonary support. J Vasc Surg 2010; 52: 850–853. 4 Bisdas T, Beutel G, Warnecke G et al. Vascular complications in patients undergoing femoral cannulation for extracorporeal membrane oxygenation support. Ann Thorac Surg 2011; 92: 626–631.
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