The correlation between the grade of dyskaryosis on cervical smear, grade of cervical intraepithelial neoplasia (CIN) on punch biopsy and the final histological diagnosis on cone biopsies of the cervix

This study was carried out to assess how reliably a punch biopsy of the cervix predicts the maximum grade of CIN present and whether a colposcopically directed punch biopsy is more reliable than cytology in predicting the grade of intraepithelial neoplasia present in the cervix. The grade of CIN in 107 cone biopsy specimens was compared with the grade of CIN and dyskaryosis in punch biopsies and smears from the same patients. Exact correlations were identified between the highest grade lesions on cone biopsy and those in 63% of punch biopsies and 49% of cervical smears. fie conclude that punch biopsy provides a more reliable estimate of the highest grade of CIN present in a subsequent cone biopsy than cervical cytology, but nonetheless fails to give a consistent estimate of the final grade of CIN in a significant percentage of cases.     

Carcinoma In Situ of the Uterine Cervix—A Review of Some Present Clinical Problems

The vaginal smear reveals a spectrum of borderline lesions of the uterine cervix. This spectrum is the source of new clinical problems involving both the recognition and treatment of these various entities. A review of the literature of the past decade indicates that vaginal smears should be obtained regularly every year or two in all women beginning at the onset of sexual activity, but the initial smear may be falsely negative in 10 to 30 percent of cases. When patients have abnormal smears, the precise diagnosis can be established more accurately by cold-knife conization than by multiple punch biopsy.While hysterectomy has been considered “definitive treatment,” late recurrence in the vagina occurs in 1.24 percent of patients so treated. A compilation of 1,100 patients with carcinoma in situ of the cervix treated by conization and follow-up smear reveals that in over 90 percent the disease was controlled by the cone alone, and the remainder by repeat cone or hysterectomy.Precise definition is required in treatment decisions concerning micro-invasive lesions, but these may be well treated by non-radical measures. In almost 500 patients so treated, no death occurred from therapy or tumor metastasis.When carcinoma in situ is found during pregnancy, a coexisting invasive carcinoma must be excluded by appropriate conization or punch biopsy and definitive therapy completed after vaginal delivery.     

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells

J. Slama, P. Freitag, P. Dundr, J. Duskova, D. Fischerova, M. Zikan, I. Pinkavova and D. Cibula
Outcomes of pregnant patients with Pap smears classified as atypical glandular cells Objectives: The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy. Methods: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC‐NOS), five favour neoplasia (AGC‐FN) and one adenocarcinoma in situ (AIS). Thirty‐one with high‐grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC‐NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC‐FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow‐up controls were carried out every 8–12 weeks and, if there were no signs of progression, revaluation was scheduled 6–8 weeks after delivery. Results: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group. Conclusions: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre‐cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC‐FN or AIS. Triage of persistent AGC‐NOS with HPV testing is useful in distinguishing significant underlying lesions.     

Secretory leukocyte protease inhibitor in punch biopsies from human colonic mucosa.

Secretory leukocyte protease inhibitor (SLPI) is a well-known protease inhibitor. Its function is thought to be protease/protease-inhibitor balance. Free proteolytic activity, mainly pancreatic elastase, anionic trypsin and granulocytic elastase, has been demonstrated in faecal extracts from patients with ulcerative colitis. We wanted to verify that SLPI is actually secreted from normal human colonic mucosa. Also, we wanted to ascertain whether studies of SLPI secretion based on punch biopsies were dependent on biopsy area or on biopsy circumference. Normal colonic mucosa was sampled during surgery for colonic cancer. A total of 36 samples from four patients were used. Mucosa preparation was carried out using a punch biopsy technique, and samples of 3, 4 and 6 mm diameter were used. All media contained SLPI at varying concentrations. When expressed in terms of the sample area, the secretion per millimetre-squared seemed to decrease with increasing area. When calculated as secretion per circumference, secretion seemed to be constant. In conclusion, SLPI was secreted from normal human colonic mucosa. The SLPI secretion seemed dependent on the circumference of the biopsy rather than on the area of the biopsy.     

Isolated glomerulonephritis with mesangial IgA deposits.

Mesangial deposits of IgA, occurring in the absence of systemic disease known to be associated with nephritis, were detected by immunofluorescence microscopy in renal biopsy specimens from 25 patients (4% of 630 specimens studied). Associated deposits of C3 were always present, usually with IgG, but IgM deposits were less common and C1q was never seen. On light microscopy most of the biopsy specimens showed mesangial of focal nuclear proliferation though some were normal. Fifteen of the 25 patients presented with macroscopic haematuria, which was usually recurrent and preceded by a sore throat, whereas the remaining, and usually older, patients presented with persistent proteinuria and were more likely to have impaired renal function. This incidence of "mesangial IgA disease" is less than that reported by French workers. There was a significantly high incidence of familial renal disease among these patients. No abnormalities of serum complement or IgA concentration were found.     

DIAGNOSIS AND TREATMENT OF JOINT TUBERCULOSIS

Tuberculosis of the joints is not a clinical oddity and a diagnosis of tuberculous infection must be considered in all joint lesions if diagnosis is to be made early. A history of insidious onset of pain, especially if accompanied by pulmonary symptoms or a history of contact with a tuberculous person, should alert the clinician to the possibility of this diagnosis. The tuberculin test, roentgenograms, culture of aspirated fluids and biopsy, by anthrotomy or punch, continue to be the standard procedures for establishing the diagnosis. The differential diagnosis must include the entire gamut of bone and joint disease.Chemotherapy combining streptomycin and dihydrostreptomycin with isonicotinic acid hydrazid and para-aminosalicylic acid is of extreme value in the eradication of draining sinuses and in the advancement of the ideal surgical date; but general physical and mental hygiene, rest and the prevention or correction of deformities is a continuing therapeutic necessity. Fusion of the affected area is advocated in almost all lesions although there is some hope that functioning joints may be preserved with early diagnosis, conservative surgical treatment and more efficient antibiotics. A postoperative regime similar to the preoperative treatment must be continued until the stabilization is firm or until there is no evidence of activity.     

MANAGEMENT OF EARLY PROSTATIC CARCINOMA

It is important to make a diagnosis of prostatic carcinoma as early as possible, because early treatment gives the best results whether radical prostatectomy is done or endocrine therapy used. Open perineal biopsy is the most accurate method of making a diagnosis. Perineal needle biopsy or the newer approach of transrectal needle biopsy is probably about 75 per cent accurate in making a diagnosis.Ten-year survival with conservative therapy, as determined in a review of a series of cases, was 50 per cent—about the same as that following radical prostatectomy; but the patients with prostatectomy are clinically free of malignant disease whereas the former are not. Radical prostatectomy is indicated in a few selected cases.The results from endocrine therapy begun immediately after diagnosis are significantly better than those from delayed treatment. Orchiectomy and estrogens promise a little longer survival than estrogens alone.     

Residual Disease and HPV Persistence after Cryotherapy for Cervical Intraepithelial Neoplasia Grade 2/3 in HIV-Positive Women in Kenya

Objective

To assess residual cervical intraepithelial neoplasia (CIN) 2/3 disease and clearance of high-risk (hr) human papillomavirus (HPV) infections at 6 months after cryotherapy among HIV-positive women.

Design

Follow-up study.

Methods

79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy) and after cryotherapy (cells).

Results

At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI): 66.4–85.9). 18 women (22.8%) had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART) were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2–15.0) among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9–70). The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively.

Conclusions

Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity.     

Relative accuracy of cervical and anal cytology for detection of high grade lesions by colposcope guided biopsy: a cut-point meta-analytic comparison

Background

We recently reported, using a receiver operating characteristic area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe histopathologic lesions by magnification directed punch biopsy. The aim of the present research was to meta-analytically examine cut-point specific operating characteristics (sensitivity, specificity) of cervical and anal cytology in detecting high grade squamous intraepithelial lesion (HSIL) histopathology by colposcope directed punch biopsy.

Methodology/Principal Findings

The primary eligibility requirement was availability of tabulated cytology (normal, atypical cells of unclear significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical squamous cells cannot rule out high grade [ASC-H]) and biopsy (Conclusions/SignificanceUsing a cytology cut-point of HSIL or ASC-H, anal cytology is less sensitive but comparably specific to cervical cytology. However, using a cut-point of ASCUS, differences in accuracy were of borderline significance.     

A morphometric study of the protective effect of cryotherapy on oral mucositis in cancer patients treated with 5-fluorouracil

We investigated cytological changes in oral mucosa smears from patients treated with cryotherapy to determine whether cryotherapy prevented mucositis caused by 5-fluorouracil (5-FU) therapy. Patients with gastrointestinal malignancies were divided into four groups; control patients before 5-FU therapy, patients after 5-FU therapy without cryotherapy, patients with cryotherapy before 5-FU therapy and patients with cryotherapy after 5-FU therapy. Oral mucosa samples from all patients were assessed at the beginning and on day 14 of chemotherapy. We used exfoliative cytology to evaluate cellular changes in the oral mucosa that were caused by 5-FU. Smears from each patient were stained using the Papanicolaou method and analyzed using stereology. Smears were taken from each group before and after 5-FU infusion. We found that nuclear volume was decreased significantly in cells of the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. We also found significantly decreased cytoplasmic volumes in the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. The results of cytomorphometric estimations revealed that cryotherapy may be used to prevent damage to oral tissue and may decrease the frequency and duration of oral mucositis caused by 5-FU.     

Fibroblast sources: Where can we get them?

Fibroblasts are cells widely used in cell culture, both for transient primary cell culture or permanent as transformed cell lines. Lately, fibroblasts become cell sources for use in disease modeling after cell reprogramming because it is easily accessible in the body. Fibroblasts in patients will maintain all genetic background during reprogramming into induced pluripotent stem cells. In spite of their large use, fibroblasts are obtained after an invasive procedure, a superficial punch skin biopsy, collected under patient’s local anesthesia. Taking into consideration the minimum patient’s discomfort during and after the biopsy procedure, as well as the aesthetics aspect, it is essential to reflect on the best site of the body for the biopsy procedure combined with the success of getting robust fibroblast cultures in the lab. For this purpose, we compared the efficiency of four biopsy sites of the body (skin from eyelid, back of the ear, abdominal cesarean scar and groin). Cell proliferation assays and viability after cryopreservation were measured. Our results revealed that scar tissue provided fibroblasts with higher proliferative rates. Also, fibroblasts from scar tissues presented a higher viability after the thawing process.     

Laparoscopy and laparotomy combined with bone marrow biopsy in staging Hodgkin's disease.

The relative merits of laparoscopy with liver and spleen biopsy and staging laparotomy were studied in 91 unselected patients with Hodgkin''s disease. Laparoscopy with liver and spleen biopsy were combined with needle biopsy of the bone marrow and laparotomy was combined with open bone marrow biopsy. In 65 untreated patients six out of seven with liver or marrow disease, or both, were shown to have extranodal lymphomas in these sites by laparoscopy plus needle marrow biopsy. Among 26 patients who had been treated this finding occurred in six out of 10 patients. Spleen biopsies during laparoscopy detected infiltration by lymphoma in 14 out of 37 (38%) patients with diseases spleens. Morbidity was higher after laparotomy than after laparoscopy. Laparoscopy produced abdominal bleeding secondary to splenic biopsy in two patients. All patients with Hodgkin''s disease should be subjected to laparoscopy plus needle marrow biopsy before undergoing laparotomy.     

A Cervical Cytology Program in General Practice

In a six-year period 723 women were examined using cervical cytology smears. Fifteen cancers of the cervix were discovered, including two invasive growths and 13 carcinoma in situ. A careful follow-up was carried out, and the later appearance of cancer was noted in 12 of 41 patients who initially showed only atypical cells. It is recommended that all patients showing “positive” cells (atypical, suspicious, or cancer morphology cells) undergo cone biopsy for definitive histological diagnosis. Target lesions should have punch biopsy. Four cancers were found in 170 obstetrical patients, and it is recommended that this proved high-risk group be screened both prenatally and postnatally. The importance of annual screening of all women over 20 years of age for cancer of the cervix by cytological methods is emphasized.     

Duodenal somatostatinoma of the ampulla of vater diagnosed by endoscopic fine needle aspiration biopsy: a case report

BACKGROUND: Duodenal somatostatinoma is a rare neuroendocrine neoplasm. A better prognosis can be obtained if these tumors are resected at an early clinical stage. Endoscopic punch biopsy has been the method most commonly used for the preoperative diagnosis of neuroendocrine duodenal tumors. To the best of our knowledge, endoscopic fine needle aspiration biopsy (FNAB) of duodenal somatostatinoma has not been reported before. CASE: A 41-year-old, black female presented with upper gastrointestinal bleeding as well as elevated bilirubin, liver enzymes and glucose. Computed tomography, esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography (ERCP) detected a mass at the region of the ampulla of Vater partially obstructing the pancreatic duct. The initial punch biopsy yielded only intestinal mucosa. Subsequent endoscopic FNAB suggested the diagnosis of a neuroendocrine neoplasm, as confirmed by additional punch biopsies. Immunohistochemical and electron microscopic studies disclosed somatostatin production by the tumor, which was resected through a modified Whipple procedure. The patient recovered fully. CONCLUSION: This case demonstrates the usefulness of endoscopic FNAB in diagnosing submucosal gastrointestinal neuroendocrine tumors.     

Renal Impairment in Hepatic Cryotherapy

Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following cryotherapy, and its etiology is unknown. The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Ten of 204 patients with renal impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2 days postprocedure) were identified. One patient had postoperative pancreatitis with late renal impairment (20 days) and was excluded. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19). Two patients required temporary hemodialysis. Only one patient, who had significant cardiac disease, had associated pulmonary injury and shock. Demographic data in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194). Patients in the renal impairment group had a greater number of lesions than those of the nonrenal impairment group (3.4 vs 2.1,P< 0.01), as well as larger lesion diameter (2.9 vs 1.9,P< 0.01), increased freezing time (74.7 vs 44.3,P< 0.01), and a higher aspartate transaminase (AST) (2254 vs 1157,P< 0.01). This study suggests that renal impairment is more likely to be seen in patients undergoing more extensive cryotherapy. The number and diameter of lesions together with AST data link renal injury with magnitude of liver injury—all renal impairment patients had an AST > 1000, compared with only 28% of patients who did not.     

In Vivo Long-Term Monitoring of Circulating Tumor Cells Fluctuation during Medical Interventions

The goal of this research was to study the long-term impact of medical interventions on circulating tumor cell (CTC) dynamics. We have explored whether tumor compression, punch biopsy or tumor resection cause dissemination of CTCs into peripheral blood circulation using in vivo fluorescent flow cytometry and breast cancer-bearing mouse model inoculated with MDA-MB-231-Luc2-GFP cells in the mammary gland. Two weeks after tumor inoculation, three groups of mice were the subject of the following interventions: (1) tumor compression for 15 minutes using 400 g weight to approximate the pressure during mammography; (2) punch biopsy; or (3) surgery. The CTC dynamics were determined before, during and six weeks after these interventions. An additional group of tumor-bearing mice was used as control and did not receive an intervention. The CTC dynamics in all mice were monitored weekly for eight weeks after tumor inoculation. We determined that tumor compression did not significantly affect CTC dynamics, either during the procedure itself (P = 0.28), or during the 6-week follow-up. In the punch biopsy group, we observed a significant increase in CTC immediately after the biopsy (P = 0.02), and the rate stayed elevated up to six weeks after the procedure in comparison to the tumor control group. The CTCs in the group of mice that received a tumor resection disappeared immediately after the surgery (P = 0.03). However, CTC recurrence in small numbers was detected during six weeks after the surgery. In the future, to prevent these side effects of medical interventions, the defined dynamics of intervention-induced CTCs may be used as a basis for initiation of aggressive anti-CTC therapy at time-points of increasing CTC number.     

Comparative study of cytology and punch biopsy in cervical intraepithelial neoplasia during pregnancy. A preliminary report

To elucidate the accuracy of cytology in diagnosing cervical intraepithelial neoplasia (CIN) during pregnancy, cytologic screenings for uterine cervical cancer in pregnant women were reviewed for a five-year period. Of the 967 pregnant women screened, abnormal cytologic findings were recorded for 15 (1.6%). Only nine of these were subsequently examined by colposcopy and punch biopsy, which demonstrated CIN in all cases, for an incidence of documented CIN during pregnancy of 0.93%. Including two referral cases also examined by colposcopy and biopsy, cytology and histology agreed on the degree of CIN in four cases and disagreed by one degree in four cases, by two degrees in two cases and by three degrees (mild dysplasia versus carcinoma in situ) in one case. Review of the specimens from these cases did not readily explain the poor concordance between cytology and punch biopsy; some findings suggest that overestimation of the punch biopsy sample may be the explanation.     

Biopsy of canine ear tissue for detection of Borrelia burgdorferi following Ixodes dammini feeding

A punch biopsy method was developed to detect and cultivate Borrelia burgdorferi from canine ear tissue. The biopsy procedure was sensitive in that spirochetes were detected in 100% of the dogs upon which infected ticks had fed. B. burgdorferi could be cultured as early as 6 days after tick feeding at which time the organisms could not be concurrently recovered from peripheral blood. The ear punch biopsy provides a reliable method for sampling live canines and should prove useful for detecting early B. burgdorferi infection and for monitoring duration of non-disseminated infection. Additionally, the procedure will aid in the development of an animal model for evaluation of preventive and therapeutic treatment modalities.     

Cryotherapy protocols for metastatic breast cancer after failure of radical surgery

To retrospectively assess the effect of cryotherapy in patients with metastatic breast cancer (MBC) but without local recurrence after resection of the primary lesion, we divided 120 MBC patients into cryotherapy (91 patients) and chemotherapy (29 patients) groups. In the cryotherapy group, 37 patients with tumor recurrence received multiple cryoablations, while 54 patients received only a single cryoablation. Moreover, 62 cryotherapy-group patients underwent cryoablation immediately after the detection of metastases (timely cryotherapy); 35 patients received simultaneous immunotherapy (cryo-immunotherapy), and 29 patients underwent cryoablation in our hospital 3 months after receiving chemotherapy in other centers (chemo-cryotherapy and delayed cryotherapy). Overall survival (OS) after the diagnosis of MBC was assessed after a 10-year follow-up. The median OS was higher in the cryotherapy group (55 months) than in the chemotherapy group (27 months; P < 0.0001). In the cryotherapy group, longer median OS was associated with multiple (76 months) rather than single cryoablations (48 months; P = 0.0005) and with timely (67 months) rather than delayed cryoablation (48 months; P = 0.0012). The median OS was higher after cryo-immunotherapy (83 months) than after chemo-cryotherapy (48 months) or cryotherapy alone (43 months; P < 0.0001 for both). In conclusion, timely and multiple cryoablations, especially when combined with immunotherapy, offer significant advantages over chemotherapy in extending the OS of MBC patients.     

Fine needle aspiration biopsy of the liver. A study of 102 consecutive cases

One hundred five CT-guided or ultrasound-guided fine needle aspirations of liver in 102 consecutive patients were reviewed. Adequate histologic confirmation or clinical follow-up of the final diagnosis was available for 86 of the 105 aspirations. A definite diagnosis of malignancy was made in 53 of the 61 aspirations performed on patients with malignant hepatic disease (86.9%). There were no false positives. The most common tumors detected were metastatic adenocarcinomas from an unknown primary or from the colon and rectum. The tumors were typed correctly in nearly all cases. Benign lesions encountered included cysts, abscesses, hemangiomas, cirrhosis and fatty metamorphosis. No serious complications were encountered as a result of aspiration. Guided fine needle aspiration biopsy of focal liver lesions appears to be an accurate, safe and relatively inexpensive method of diagnosis.