Study of neoadjuvant chemotherapy in advanced malignant ovarian germ cell tumors at a tertiary center in western India.

OBJECTIVE: To study clinical characters and outcomes in patients of malignant ovarian germ cell tumor (MOGCT) undergoing surgery following neoadjuvant chemotherapy (NACT). METHODS: Retrospective study of patients undergoing surgery following NACT for MOGCT at our institute. Platinum based chemotherapy was given in all patients in NACT. RESULTS: Between March 2013 and February 2023, 30 patients had surgery after NACT. Patient's median age was 22 years (range, 12 to 35 years) and median follow up 42months (range, 6 to 132 months). Majority had endodermal sinus tumor (n=12), dysgerminoma (n=9) and mixed GCT (n=7). All had either International Federation of Gynecology and Obstetrics (FIGO) stage 3 (n=19) or FIGO stage 4 disease (n=11). Complete response to NACT seen in 5 patients and 23 patients had partial response. Fertility sparing surgery in 18 patients and complete surgery in 12 patients. Suboptimal surgery was seen in 4 patients. Currently, 20 of 30 patients are alive and disease free, 3 lost for follow up and 7 patients had progression after adjuvant therapy. Five patients had mortality-4 with progression and 1 with bleomycin toxicity. Fifteen of 17 eligible patients have resumed menstruation and one had successful pregnancy. Prognostic factors noted in study are stage, optimal surgery and viable tumor in histopathology. Dysgerminoma had better outcome than other histology. CONCLUSION: NACT may be a reasonable option in patients with extensive unresectable disease or in whom fertility sparing is not possible or in the poor general condition. Fertility sparing surgery can be attempted post neoadjuvant chemotherapy without adversely affecting prognosis.

Retrospective Analysis of 32 Cases of Ovarian Granulosa Cell Tumours.

INTRODUCTION: Granulosa cell tumour (GCT) comprises 2-5% of ovarian malignancies. They are hormonally active tumours and may present with menstrual complaints, abdominal distension or infertility. Prognosis is generally favourable because of the early stage at diagnosis and less aggressive behaviour. MATERIALS AND METHODS: Medical records of 32 cases presenting from January 2008 to December 2014 were retrospectively analysed for the patient characteristics, tumour characteristics and the treatment received. RESULTS: The mean age was 42.75 ± 10.25 years (range: 22 to 70 years). The most common presenting symptom was abdominal distension (50.00%) followed by menstrual complaints. The mean tumour diameter was 15.24 cm (range: 4-25 cm). Endometrial pathology was found in 4 patients (12.50%), and all had simple hyperplasia without atypia. Twenty-four patients underwent primary staging surgery; one patient underwent interval debulking surgery after neo-adjuvant chemotherapy. Seven patients had undergone surgery elsewhere of which 4 underwent re-staging and three were given chemotherapy. All patients had the final histopathology of adult granulosa cell tumour except one patient with juvenile granulosa cell tumour. Most patients had stage I disease (81.25%). Post-operative chemotherapy was administered to 22 patients. The most commonly used regimen was paclitaxel and carboplatin. The overall 5-year survival rate was 90%. The mean overall survival was 36.95 ± 34.08 months (range: 0.50 to 112.00 months). Two patients had recurrence at 38 and 44 months, respectively. CONCLUSION: GCT of the ovary is a rare tumour with a tendency for late relapse. Survival is generally excellent as majority of the patients present in early stages.

Ovarian Fibroma: A Clinico-pathological Study of 23 Cases with Review of Literature.

PURPOSE: The purpose of this study was to correlate the clinical findings, RMI-4 index and frozen section, in cases of ovarian fibroma with the final histopathology. METHODS: This is a retrospective study of clinical and pathological features of 23 patients of ovarian fibroma. The patient's age ranged from 34 to 66 years (mean-49 years). The most common presenting symptom was abdominal pain. On clinical examination, the mean size of ovarian tumor was 9.5 cm, CA-125 levels were found to be raised in 14 patients, and it was associated with ascites in 10 patients. USG showed a well-circumscribed mass (with a mean size of 14 cm), on the left side in 14 cases and on the right side in 9 patients. RMI-4 was calculated in all the patients, and it revealed the possibility of a benign histology in 17 patients. All patients underwent exploratory laparotomy with the removal of ovarian tumor followed by frozen section examination. All but one (22/23) patient had positive correlation among frozen section and final histopathological findings. RESULT: Ovarian fibroma generally tends to occur in post-menopausal women. All the patients in our study of ovarian fibroma were symptomatic, with the presence of palpable mass in majority of patients. RMI-4 Index correlated very well with benign nature of disease. Frozen section has an invaluable role at surgery; fertility-conserving surgery is the choice in young women. CONCLUSION: Clinical findings, RMI-4 Index and frozen section, play vital roles before and during surgery in cases of benign ovarian tumors.

Ovarian carcinoma or abdominal tuberculosis?-A diagnostic dilemma: study of fifteen cases.

OBJECTIVE: To evaluate the clinical, laboratory, and diagnostic features in women with abdominal tuberculosis that resembled advanced ovarian malignancy. METHODS: A retrospective review of women with abdominal tuberculosis who were managed at GCRI Ahmedabad from 1996 to 2001 was undertaken. RESULTS: Fifteen patients (3.06 %) with suspected ovarian cancer cases, finally diagnosed as abdominal tuberculosis over a 6-year period (1996-2001), are analyzed. During this period, 492 patients were operated for suspected ovarian malignancy. Pre-operatively, ultrasound-guided biopsies were inconclusive in 14 cases and hence, exploratory laparotomy was planned. They underwent laparotomy and biopsy for final diagnosis. Frozen sections-of peritoneal/omental biopsies in 11 cases and ovarian tumour in three cases-were indicative of tuberculosis in all the 14 cases. CONCLUSION: The data of this study indicate that the majority of the cases with peritoneal tuberculosis can be diagnosed intra-operatively through the use of frozen section in conjunction with clinical features. Ascites and high levels of Ca125 do not necessarily indicate that the clinical picture is malignant in reproductive women. Laparoscopic tissue biopsy may be a fundamental tool in the management of such cases to avoid extended surgery.

Lack of association of outcomes with treatment duration and microbiologic susceptibility data in Clostridium difficile infections in a non-NAP1/BI/027 setting.

BACKGROUND: Concerns regarding the poor response of severe Clostridium difficile infection (CDI) treated with metronidazole have arisen over the last 5 y. METHODS: We conducted a prospective, non-interventional study of CDI cases at our institution to evaluate the role of drug resistance, co-morbidities, and the emergence of hypervirulent strains on patient outcomes. A total of 118 adult inpatients with diarrhea and a positive stool for C. difficile toxin immunoassay had positive stool cultures and were included in the study. All 118 isolates had vancomycin and metronidazole susceptibility testing via the E-test method; rep-PCR was performed on 47 isolates. Of the 118 study patients, 107 were treated with either metronidazole or vancomycin. RESULTS: Initial therapy was metronidazole in 98.1% (n = 105) and vancomycin in 1.9% (n = 2) patients. Evaluable clinical response within 5 days of treatment was noted in 52.5% (52/99) of cases. The mean duration of treatment was 11.7 ± 7.2 days. The 30-day all-cause mortality rate was 24.6% (29/118). Recurrence occurred in 23.6% (21/89). A recent stay in the intensive care unit was associated with increased 30-day mortality (odds ratio 3.58, p = 0.012). There were no isolates resistant to metronidazole or vancomycin. Only 1 isolate was possibly related to the NAP1/BI/027 reference strain. No strain-related differences in deaths or recurrence were noted. CONCLUSIONS: Deaths related to CDI in our study appear to be related to multiple factors and did not appear to be independently related to antibiotic susceptibility, strain type, or treatment duration.

The impact of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in patients with Clostridium difficile infection.

There is increasing frequency and severity of disease due to Clostridium difficile infection (CDI). In addition, failure of initial antibiotic therapy is increasing. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARBs) may have local and systemic anti-inflammatory properties to reduce severity of disease in CDI. We performed a retrospective study of 306 patients with CDI over 23 months at a single center in Detroit, Michigan. Patient outcomes (death, death due to CDAD and relapse rates) were compared based on the use of ACEI or ARB during an episode of CDI. A total of 116 (37.9%) patients received an ACEI/ARB and 190 (62.1%) did not. The groups were similar except ACEI/ARB patients were older (71.9 vs. 64.3, P<0.0005) and had a higher frequency of congestive heart failure (50.9% vs. 30.2%, P<0.0005) and chronic obstructive pulmonary diseases (44.8% vs. 30.2%, P<0.010). ACEI/ARB patients had lower overall mortality rates (9.5% vs. 23.3%, P<0.002) as well as mortality due to CDI (2.6% vs. 8.6%, P<0.036). The rate of CDI relapse was not significantly different between the groups (5.2% in ACEI/ARB vs. 10.0%, P=0.135). Logistic regression analysis demonstrated that ACEI/ARB use was associated with lower overall mortality rate (OR 0.26; 95% CI, 0.12-0.55) and mortality due to CDI (OR 0.29; 95% CI, 0.08-1.02). Our findings suggest that ACEI/ARBs may have a role as an adjuvant therapy to antibiotics in patients with CDI. Prospective studies are needed to confirm these results.

Management of drug resistant gestational trophoblastic neoplasia.

OBJECTIVE: To determine the outcome of secondary management in drug-resistant gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Sixteen of 60 patients with GTN (8 low-risk and 8 high-risk) who developed resistance to primary chemotherapy were studied retrospectively. Primary chemotherapy was methotrexate-folinic acid rescue (MTX-FA) for low risk and etoposide/methotrexate/actinomycin D/cyclophosphamide/vincristine (EMA-CO) for high risk. Secondary chemotherapy for the low-risk group was either actinomycin D or EMA-CO, depending on serum beta human chorionic gonadotropin (hCG) levels at resistance. For the high-risk group, etoposide/methotrexate/actinomycin D/cisplatinum (EMA-EP) or bleomycin/etoposide/cisplatin (BEP) was given. Third-line chemotherapy was vincristine/actinomycin D/cyclophosphamide (VAC) or vincristine/ iphosphamide/cisplatin (VIP). Surgery and radiotherapy were used in selected patients. RESULTS: Survival after salvage therapy in low-risk patients was 100%: 2 with EMA-CO and 6 with actinomycin D. Of high-risk cases 75% were cured with EMA-EP or BEP. Third-line chemotherapy was given in 2 patients: 1 was lost to follow-up and the other died. Survival was significantly influenced by both hCG level at the start of secondary therapy and site of metastasis. CONCLUSION: Prognosis in GTN is excellent. Optimization of treatment strategies for those who develop drug resistance remains a key challenge.

Early onset of tenofovir-induced renal failure: case report and review of the literature.

Tenofovir is an acyclic nucleotide analogue reverse transcriptase inhibitor that is commonly prescribed as part of a highly active antiretroviral therapy (HAART) regimen in HIV-infected patients. Although it is generally well tolerated, renal insufficiency has been associated with its use. We report a biopsy-proven case of acute renal failure that developed within weeks of initiating a HAART regimen containing tenofovir, and review the literature with specific attention to cases of renal failure occurring within 8 weeks of tenofovir initiation. Our patient developed renal insufficiency within 3 weeks of initiating tenofovir-containing HAART and overt renal failure was noted within 5 weeks. Renal biopsy demonstrated histopathologic changes suggestive of HIV nephropathy, despite normal baseline serum creatinine values. Thirty additional cases of tenofovir-associated renal failure have been reported. In the majority (n = 22, 73%), renal failure occurred months after initiating therapy (range: 5-26 months). However, in a significant subset (n = 8, 27%), renal failure occurred within 8 weeks of treatment initiation. Our data suggest that some patients are at risk for developing renal failure within weeks of tenofovir initiation. Thorough evaluation of renal function should be undertaken before prescription of tenofovir-containing HAART. For those in whom subclinical renal disease is discerned, added vigilance when monitoring renal function may be warranted.

Monotherapy versus combination therapy.

The science of antibiotic therapy for infectious diseases continues to evolve. In many instances where empiric coverage is necessary, treatment with more than one agent is considered prudent. If an etiology is identified, antibiotics are modified based on culture and susceptibility data. Even when the organism is known, more than one antibiotic may be needed. Decisions about antibiotics should be made after assessments of pertinent clinical information, laboratory and microbiology information, ease of administration, patient compliance, potential adverse effects, cost, and available evidence supporting various treatment options. Clinicians also need to consider synergy and local resistance patterns in selecting therapeutic options. In this article, the authors outline monotherapy and combination therapy options for several common infectious diseases.

Breakthrough Candida infections in patients receiving voriconazole.

OBJECTIVE: To describe 2 instances of breakthrough Candida infection in 2 patients on treatment doses of voriconazole. CASE SUMMARIES: A 27-year-old woman with systemic lupus erythematosus was receiving high-dose voriconazole (400 mg twice daily) for central nervous system lesions of unknown origin and developed oral thrush. The patient was receiving concomitant therapy with phenytoin 400 mg/day. The voriconazole dose was increased to 400 mg 3 times daily, and the thrush resolved. A 50-year-old man with HIV infection was receiving enfuvirtide, lamivudine, tenofovir, and efavirenz 600 mg/day, as well as prophylactic trimethoprim/sulfamethoxazole and azithromycin. He was started on voriconazole 200 mg twice daily for pulmonary aspergillosis and developed esophageal candidiasis. The voriconazole dose was increased to 350 mg twice daily, and the thrush eventually resolved. DISCUSSION: Both reactions were probable according to the Naranjo probability scale. Significant drug interactions may have played a role in the development of breakthrough infections in these patients, specifically with phenytoin and efavirenz. Voriconazole is metabolized primarily by CYP2C19, as well as CYP2C9 and CYP3A4. Voriconazole is also known to inhibit these enzymes, and the manufacturer reports an extensive list of drugs that interact with voriconazole. CONCLUSIONS: Although requiring systematic evaluation, there may be a role for voriconazole serum concentration monitoring to ensure therapeutic efficacy when significant drug interactions are suspected.

Serious adverse cutaneous and hepatic toxicities associated with nevirapine use by non-HIV-infected individuals.

BACKGROUND: Nevirapine is a nonnucleoside reverse transcriptase antiretroviral agent. Among HIV-infected individuals, rare instances (<1%) of serious cutaneous and hepatic toxicity have been reported. Because of its favorable pharmacokinetic profile, non-HIV-infected individuals have received nevirapine-containing postexposure prophylaxis (PEP). OBJECTIVE: To describe the clinical features of cutaneous and hepatic toxicity that occurred when nevirapine was administered to non-HIV-infected individuals. METHODS: Reports of nevirapine-associated cutaneous or hepatic toxicity occurring among non-HIV-infected individuals were obtained from the US Food and Drug Administration's adverse event reporting system, the pharmaceutic manufacturer, occupational health programs in Chicago, physicians, and case reports. The Eastern Cooperative Oncology Group (ECOG) scoring system was used to grade toxicity. RESULTS: Twelve non-HIV-infected individuals developed severe cutaneous toxicity, including 3 with Stevens-Johnson syndrome, after 7 to 12 days of nevirapine-containing PEP regimens. Thirty non-HIV-infected individuals developed hepatotoxicity after 8 to 35 days of single-agent nevirapine (n = 8) or a nevirapine-containing PEP regimen (n = 22). Findings included ECOG grade 3 or 4 hepatotoxicity (n = 14), fevers (n = 11), skin rashes (n = 8), eosinophilia (n = 6), and fulminant hepatic necrosis requiring an orthotopic liver transplant (n = 1). Rates of severe hepatotoxicity (grade 3 or 4) in non-HIV-infected individuals ranged from 10% (4/41) to 62% (5/8). Liver biopsy material from 2 individuals was consistent with a hypersensitivity syndrome. CONCLUSIONS: Serious hepatic and cutaneous toxicities can occur in non-HIV-infected individuals who receive short-term nevirapine therapy. The rate of severe hepatotoxicity appears to be greater in non-HIV-infected individuals than in HIV-infected persons and may be associated with higher CD4 counts. The use of PEP regimens containing nevirapine should be discouraged.